Microbiology Block 4 - we out this bish

How many serotypes of Dengue virus are there?

*5* Classic Dengue Fever follows: - *infection by any serotype of virus in previously uninfected individual* Humans part of life cycle - chukungunya, dengue, yellow fever, zike (CD YZ) RT-PCR on patient serum

Amantadine inhibits

*Influenza A virus M2 protein activity* Amantadine - binds to M2 protein on influenza A virus --> inhibits ion pore = prevents uncoating of virus

Vaccine used for lifelong immunity to Hepatitis A

*"killed" vaccine (formalin inactivated) gives good protection* *PAIR* Salk *P*olio H*A*V *I*nfluenza (Injected) *R*abies

A US Park Service worker in the Blue Ridge Parkway was bitten by a raccoon while conducting a nature talk. The animal was killed and brain tissue from the animal subsequently tested positive for rabies antigen. The Park Ranger, who was current on all his vaccinations (including rabies), should receive prompt aggressive first aid, including washing the wound with soap and water,

*& a booster series of human rabies vaccine* ssRNA --> + icos --> enveloped --> C*R*FT --> Retro = HIV, HTLV

(TEST): The MMR vaccine is given at

*1 year of age because if given earlier, e.g., at 2 months along with other childhood vaccines, it would likely fail to induce immunity in a large percentage of children.* ssRNA --> - helical --> enveloped --> BAD*P*ROF --> PaRaMyxo = Parainfluenza, *RSV, Mumps, Measles*/Rubeola

GSS mutations

*10 families from 9 countries have a proline to leucine mutation at codon 102* Gerstmann-Straussler-Scheinker syndrome (GSS) = rare, usually familial, fatal neurodegenerative disease - transmissible spongiform encephalopathies

Symptoms of Measles/Rubeola

*4 "C"'s* Cough Coryza (runny/stuffy nose) Conjunctivitis Koplik spots (bluish white spots on red background of buccal mucosa) - fever ~ 4 day - *maculopapular rash = head --> trunk --> extremities* - confluent rash starts on face & moves downward (centrifugal) - pneumonia - SSPE (subacute sclerosing panencephalitis)

Polio Vaccination

*4 doses IPV given at 2, 4, 6-18 months, and 4 - 6 years...for control in the USA.* - Pediarix = DTaP, HepB, IPV prior to 2000 = oral polio vaccine (OPV) via live poliovirus 2000 --> US switched to inactivated polio vaccine (IPV) - given as shot in arm or leg - 4 doses given at 2, 4, 6-18 months, & 4-6 years

A 34-year-old woman comes to the physician because of a painful, tingling lesion on her upper lip. What is the most likely causal agent?

*A double-stranded DNA virus that is enveloped & icosahedral*

(TEST): Echinococcus hydatid cyst mode of transmission

*Ingesting the infective stage in fecally contaminated food or water*

can lead to uncontrolled growth of warts all over body. Due to rare genetic defect

Epidermodysplasia verruciformis - HPV-1 or 2

(TEST): Which of the following is common to both NK-mediated and CTL-mediated cell killing?

*Activation of caspases*

PAMPS unique to most viruses

*dsRNA* - Reovirus = DS linear = 10-12 segments = icosahedral (double) ssRNA --> + icos. --> naked --> (ds)Reo - Rotavirus; Coltivirus

(TEST): Human infection with what parasite results from penetration of skin with infectious filfariform larvae?

*Ancylostoma duodenale, Strongyloides stercoralis, Necator americanus* Ancylostoma duodenale, Necator americanus (hookworms) - intestinal infection causing anemia by sucking blood from intestinal wall - larvae penetrate skin - treatment = bendazoles or pyrantel pamoate Strongyloides stercoralis (threadworm) - intestinal infection causing vomiting, diarrhea, epigastric pain - larvae in soil penetrate skin - treatment = ivermectin or bendazoles

A viral protein that is thought to induce tumors by binding to a cellular tumor suppressor protein is

*Adenovirus E1A* - in permissive cells, it is involved in the replication process, but in nonpermissive cells, it can bind to cellular tumor suppressor protein p110Rb & inactivates its normal cellular function = cellular transformation

Number one cause of tonsilitis

*Adenovirus* - naked - most commonly affects dirty little children - outbreaks in military barracks - swimmers at public pools - causes hemorrhagic cystitis - common cause of viral conjunctivitis - live attenuated vaccine for miliatry recruits DNA positive icos --> naked --> Adeno

Pharyngoconjunctivitis, especially in children swimming the same pool, may be due to what virus?

*Adenovirus* = non-enveloped (naked), linear, icosahedral, naked double-stranded DNA viruses - acute respiratory disease, pharyngoconjunctivitis, epidemic keratoconjunctivitis, gastroenteritis - adenovirus subgroup B types 3 & 7 = most common isolates

Recognize Candida albicans in lab

- feet on plate - budding cells - germ tube

Both Yellow fever virus & Dengue transmitted by

*Aedes Egyptei mosquitos* Flaviviruses - SS positive linear - enveloped - icosahedral - HCV, Yellow fever, Dengue, St. Louis encephalitis, West Nile virus

(TEST): Infection with Trichuris trichiura (whipworm), which can cause dysentery, is treated with

*Albendazole* Trichuris trichiura (whipworm) - often asymptomatic - loose stools/anemia, rectal prolapse in children (heavy infection) - fecal-oral - diagnosis via effs in fresh stool sample - *treatment = bendazoles*

Why are there no serological ways to diagnose HPV

*All L1s are cross-reactive under all of the tests* L1, L2 - capsid proteins only produced in upper levels of lesion - late genes - vaccines (Gardasil, Cervarix) = composed of L1, L2

Inhibits M2. No uncoating in influenza

*Amantadine/Rimantadine* - inhibits viral uncoating - no longer recommended because of *high level of resistance* and only work against influenza A - can help treat Parkinson

Why is there not yet a HCV vaccine?

*Anti-HCV Ig from patients not protective* Effective vaccine *not* available to protect against HCV because... - Abs against HCV surface proteins not capable of neutralizing HCV infection

Ab + virus → increased uptake and replication in macrophages --> release of NO and TNF alpha --> increased vascular permeability.

*Antibody-dependent Enhancement (ADE, Dengue)* - cross-react but don't neutralize = hemorragic fever in Dengue fever

A 27-year-old man who is a football coach at a middle school has a history of sickle cell anemia. He notices that one of his players develops a red rash on his cheeks. Two days later, the rash spreads to the student's shoulders, upper chest, & upper arms with a blotchy, net-like appearance. If the teacher becomes infected, he is most likely at increased risk of developing what?

*Aplastic crisis* Fifth disease / erythema infectiosum - via *parvovirus B19* = spread human to human - contagious prior to start of rash - typical "slapped-cheek" rash begins = student no longer contagious Parvovirus = cause of pure red cell aplasia - may be responsible for *aplastic crises* in patients with sickle-cell anemia - exposure of pregnant woman in first trimester may = fetus with aplastic anemia = *non-immune hydrops fetalis* - infects immature erythrocytes = severe anemia = fetus dies of cardiac failure

A 19-year-old man who is a summer camp counselor in Mississippi is brought to the ED because of a headache, vomiting, & confusion. He has a temperature of 38.9 C (102 F) & appears disoriented to time & place. Physical exam shows gait ataxia when walking & the patient complains of double vision. Over the next several hours, the patient's confusion progresses to stupor. Exam of CSF obtained by lumbar puncture shows 300 lymphocytes/mm^3, glucose of 50 mg/dL & total protein of 80 mg/dL. Serum glucose (2 hours post-prandial) is 78 mg/dL. MRI analysis reveals no abnormalities. What is the means of transmission of the most likely causal agent?

*Arthropod* Viral encephalitis - presence or absence of normal brain function = primary ways to differentiate between encephalitits & meningitis - *encephalitis = abnormalities in brain function* - *during summer months, viral encephalitis transmitted by mosquitos should be considered* - examples of arthropod-born viruses = St. Louis virus, West Nile encephalitis virus (Flaviviridae), & Eastern equine, Western equine, & Venezuelan equine encephalitis (Togaviridae)

Roundworm likely to be transmitted by ingestion of food or water contaminated with feces

*Ascaris lumbricoides* - *fecal-oral*

A 47-year-old woman comes to the physician because of abdominal pain, nausea, & vomiting for 4 days. She recently emigrated from the Philippines. Physical exam shows a distended abdomen. High-pitched ("tinkly") bowel sounds are heard over the abdomen are those of small intestinal obstruction. What is the most likely underlying cause of these findings?

*Ascaris lumbricoides* - Ascariasis = common nematode (roundworm) infeciton worldwide - can occur from contaminated soil contact with hands or feet, or from ingestion of eggs - eggs can hatch in small intestines - when sounds coupled with distended abdomen = jejunal or ileal small intestinal obstruction - *causes of jejunal & ileal obstruction in adults* = hernias, adhesions, tumors of small intestine, foreign body, Meckel's diverticulum, Crohn's disease, *Ascaris* infection, midgut volvulus, intussusception by tumor

(TEST): This large roundworm, which can cause failure to thrive syndrome (FTT) and intestinal blockage in heavy infections of small children, is acquired by ingestion of fecally contaminated food or water

*Ascaris lumbricoides* / Giant roundworm - #1 nematode global - may cause obstruction at ileocecal valve, biliary obstruction, intestinal perforation, migrates from nose/mouth - fecal-oral - knobby-coated, oval eggs seen in feces - treatment = bendazoles

(TEST): Loeffler's Syndrome, a pneumonitis plus peripheral eosinophilia due to larval forms migrating thru the lung, is observed during human infection for each member of this group.

*Ascaris lumbricoides, Necator americanus, Strongyloides stercoralis*

(TEST): Loeffler's Syndrome, a pneumonitis plus peripheral eosinophilia due to larval forms migrating thru the lung, is observed during human infection for each member of this group.

*Ascaris lumbricoides, Necator americanus, Strongyoides stercoralis* Intestinal Nematodes / Roundworms - larval form that migrates through tissue & into lung at some stage of their life cycle --> larvae grow in lung = coughed up & swallowed into intestine --> grow into adult worms

Similar to caliciviruses in shape and genome organization. Major cause of childhood diarrhea worldwide.

*Astroviruses* - non-segmented, single stranded, positive sense RNA genome within non-enveloped icosahedral capsile

A 42-year-old man is brought to the ED after experiencing a grand mal seizure. He recently returned from a 2-month vacation in Honduras. He has not history of seizures or major medical illness & takes no medications. He drinks alcohol occasionally bud does not use illicit drugs. He appears alert & oriented & neurologic exam shows no abnormalities. A CT scan of the head shows multiple punctate calcifications & two cystic lesions with surrounding edema. What is the most likely underlying cause of this condition?

*Autoinfection in a human* Cysticercosis via larval cysts of tapeworm Taenia solium - patients ingests egg, either through ingestion of human feces-contaminated water or food or by *autoinfection* of person infected with adult worm who transmits eggs from perianal area to mouth via contaminated fingers - once in stomach, eggs hatch --> release embryo/oncosphere --> crosses intestinal wall to enter circulation --> gains access to tissue --> differentiates in a cysticercus - treatment for neurocysticercosis = albendazole, praziquantel, or both

(TEST): A 35-year-old woman, the mother of three children ages 1 - 6, presents with joint inflammation and pain. She states that life has been hectic juggling a job and the three kids, two of whom were sick a couple of months ago with a mild flu-like illness that was followed by a mild rash. Moreover, the 1-year-old has just received her array of childhood vaccinations, and the 6 -year-old just received the MMR vaccine, and both were "cranky" afterwards. In the differential diagnosis, you should consider the possibility that this woman has been infected with

*B19 virus* - *In adults, parvovirus leads to pure RBC aplasia & rheumatoid arthritis-like symptoms*

Segmented viruses

*BOAR* Bunyavirus - CA encephalitis, crimean-congo, hanta, rift valley/sandfly, lacrosse Orthomyxo - influenza Arenavirus - lassa/LMCV Reovirus - rotavirus, colitivirus (colorado tick fever virus)

Pathogen associated with Filoviridae: Ebolavirus, Marburg Virus

*BSL-4 pathogen* ssRNA --> - helical --> enveloped --> BADPRO*F* --> Filo = large Ebola & Marburg viruses

Overgrowth of gram-negative bacteria in vagina

*Bacterial vaginosis* - elevated vaginal pH (> 4.5) - +KOH whiff test - no inflammation - thin, white discharge - fishy odor - clue cells - treatment = metronidazole

Can be used to directly quantify the total number of viral particles present in Influenza

Hemagglutination (HA) - both infectious & non-infectious

(TEST): Your M2 classmate, Beauregard, confided in you that he sustained a needlestick injury from an improperly disposed needle while volunteering at a free clinic two months ago, but did not want to "bother" the supervising physician, since he is hoping for a strong letter of recommendation. He was concerned about the possibility of being infected by bloodborne pathogens, so he surreptitiously drew some of his own blood and ordered tests for HIV and acute hepatitis. The results come back negative for anti-HIV and anti-HCV antibodies. He was vaccinated against HBV upon entry into Medical School, so he is somewhat mystified to learn that his test was positive for hepatitis B surface antigen (HBsAg) but negative for hepatitis B core IgM antibody. Other than the recent needlestick, he denies other exposure to blood and has no history of unprotected sex. He does report that he and some frat buddies celebrated the completion of the first of several attempts at the MCAT by drinking excessively and getting tattoos saying "MD2B" on their biceps. What is the most likely explanation of the lab findings? What would be most appropriate treatment for Beauregard's treatment

*Beauregard was infected with HBV when he got his tattoo* - HbsAg = acute or chronic infection *Inteferon + Lamivudine* - lamivudine treats both HIV & HBV = NRTI

(TEST): What is true concerning HIV & HAART therapy imapact on transmission from mother to infants?

*Before the advent of HAART, 20 to 30% of HIV-positive mothers transmitted virus to their unborn or newly born children*

(TEST): Treatment for Trypanosoma cruzi (Chagas disease)

*Benznidazole* or Nifurtimox

(TEST): Bob, an otherwise healthy 36-year-old adult, presents in your office on Monday with fever and headache and reports he went camping over the past weekend and was "bit by a gillion mosquitoes." You suspect viral meningitis, draw blood, and send it out for testing. Results come back showing a high level of antibody against West Nile virus (WNV). This result suggests

*Bob was infected with WNV some time prior to 2-3 weeks ago; the current illness is due to another agent*

(TEST): Select the group in which each parasite infects humans via the bite of an insect vector.

*Brugia malayi, Trypanosoma cruzi, Onchocerca volvulus*

Diseases caused by Coronavirus

*Common cold, SARS, MERS* ssRNA --> positive icosahedral --> enveloped --> helical --> Corona = corona, SARS, MERS, common cold

What blocks HIV entry in some individuals?

*CCL3L1* - binding of CCL3L1 to CCR5 inhibits HIV entry

A 38-year-old man with a history of hemophilia has had multiple infusions of clotting factors in his lifetime. Lab studies of ten batches of clotting factors administered to this patient show contamination with the HIV, yet he has remained HIV-negative. The patient's CD4 count is 900/uL & reverse transcriptase polymerase chain reaction (RT-PCR) for the virus is negative. Absence of what best explains the findings in this patient?

*CCR5* = receptor for chemokines = co-receptor for HIV internalization into macrophages - 1% of Caucasians in the US are homozygous for protective CCR5 variant; 20% are heterozygotes HIV does not always progress to overt AIDS = nonprogressors remain asymptomatic with stable CD4 count & low/undetectable viremia - some are resistant because they carry *two defective copies of gene encoding CCR5 co-receptor*

EBV envelope glycoprotein binds

*CD21 to infect B cells* - not infected B cells but reactive cytotoxic T cells

When are AIDS patients extremely susceptible to CMV?

*CD4 count < 40* - CMV retinitis CD4+ cell count < 100 = following infections... - Aspergillus fumigatus - Candida albicans - CMV - Cryptococcus neoformans Cryptsporidium - EBV - Mycobacterium avium - intracellulare, Mycobacterium avium complex - Toxoplasma gondii

(TEST): In which one of the following do all of the herpesviruses listed posess genomes which exist in multiple isoforms?

*CMV, HSV-1, VZV*

What technique would you use to determine total number of influenza virus particles?

Hemagglutination Assay

Structure of HBV particles

*Dane particles* contain cores infectious *S particles* lack cores non-infectious

Roseola/Exanthema subitem is clinically characterized by

- fever lasting 4 days - febrile seizures - occurs in children, 6 months - 2 years - after fever: diffuse lacy body rash that spares face = asymptomatic rose-colored macules on body - high grade temp - No FDA approved medication = HHV-6 & -7

Member of Togavirus fam. World distribution. Maintenance hosts = Aedies aegypti, A. albopictus, nonhuman primates. *Man is part of the cycle.* Mosquito bite = mode of transmission.

*Chikungunya Virus* - high fever - polyarthralgia - maculopapular rash - bullous lesions - hemorrhagic manifestations - symptomatic - PCR in addition to ELISA, etc - respiratory and cardiac failure, hepatitis Humans part of cycle = CD.YZ = chickungunya, dengue, yellow fever, zika ssRNA --> + icos --> enveloped --> CRF*T* --> Togavirus = Rubella, EEV, NEV, Cikungunya

(TEST): Togaviruses with *intrauterine* infections

*Chikungunya* - can lead to Guillan Barre ssRNA --> + icos --> enveloped --> CRF*T* --> *Togavirus* = REC = Rubella, Equine viruses, *Chikungunya*

Apoptosis characterized by

*Chromatin condensation* *DNA fragmentation* = karyorrhexis = via endonuclease-mediate cleaveage Membrane *Blebbing* *Membrane reversal* - cell membrane remains intact without significant inflammation *Caspase activation* Apoptosis = ATP-dependent = cell shrinkage - apoptotic bodies --> phagocytosed - deeply eosinophilic cytoplasm - basophilic nucleus - DNA laddering = fragments in multiples of 180 bp = sensitive indicator

Treatment for Genital Warts: Chemotherapy

*Cisplatin* - cross-links DNA - testicular, bladder, ovary, & lung carcinomas - dose-limiting toxicity = vomiting

(TEST): Infection with this organism results in obstructive jaundice, cholecystitis, biliary colic, hepatomegaly and eosinophilia

*Clonorchis sinensis* - biliary tract inflammation --> pigmented gallstones - associated with cholangiocarcinoma - via undercooked fish - treatment = praziquantel

A 32-year-old woman who recently emigrated from Southeast Asia comes to the ED because of severe right upper quadrant pain. An ultrasound of the gallbladder shows high echogenicity & she undergoes a cholecystectomy. Exam of the gallbladder shows a large number of dark-colored, faceted stones with irregular shapes. Infection with what organisms is most likely associated with this type of stone?

*Clonorchis sinensis* - transmitted from freshwater snails (1st intermediate host) to fish (2nd intermediate host) to humans (definitive host), where they take up residence in liver Pigment stones - calcium bilirubinate - less common - risk factors = cirrhosis, hemolytic anemias, liver fluke infection, Oriental liver fluke Clonorchis sinensis

(TEST): A novel influenza A virus, H7N9, has been isolated from approximately 100 patients hospitalized with pneumonia and high fever. The current case fatality rate is 22%. All patients to date have a history of exposure to poultry at live animal markets. Although there is no evidence of human-to-human transfer yet, this is always a concern. Which of the following public health measures would most likely reduce the spread of the virus?

*Closure of live animal markets*

Recognize *histoplasmosis* on slant

- fuzzy appearance

(TEST): A 23-year-old male patient presents to the local emergency department with acute onset of flu-like symptoms, headache, ocular pain, and photophobia. Laboratory findings include leukopenia and lymphocytes in the CSF. On physical exam, the patient has a rash and conjunctival injection. The patient reports that he has just returned from a 2 week backcountry camping trip to Rocky Mountain National Park. He reports finding several attached ticks on his legs at the end of his backcountry trek. The most probable diagnosis is

*Colorado Tick Fever* *ds*RNA --> + icos --> naked --> Reo = Rotavirus, *Coltivirus* = Colorado tick fever

Only family of positive-strand viruses with a helical nucleocapsid

*Coronavirus* - crown is helical/round ssRNA --> positive icosa --> enveloped --> coronavirus = crown helical = corona, SARS, MERS, common cold

(TEST): Some members of this virus family cause the common cold whereas others trigger serious life threatening respiratory disease.

*Coronavirus* ssRNA --> + icos --> enveloped --> *C*RFT --> Coronavirus = *corona, SARS, MERS, common cold* only 2 viruses that cause common cold = rhino, *corona*

What family are SARS & MERS in?

*Coronavirus* - & common cold - SARS & MERS = *zoonotic infections*

Transmitted by mosquito bites. Present in Caribbean. Causes "breakbone fever."

*Dengue virus* ssRNA --> + icos --> Flavivirus --> Yellow Fever, St. Louis Encephalitis, Dengue, WNV, HCV

(TEST): Humans are part of the life cycle for which of the following arthropod borne diseases?

*Dengue virus* ssRNA --> + icos --> enveloped --> CRFT: Flavivirus = WNV, St. Louis, HCV, *Dengue*, Yellow Fever Humans part of life cycle for: *chikungunya, dengue, yellow fever, zika* (CD YZ)

18 yo boy with advanced HIV (CD 4 count of 50, viral load of 500,000) presents with severe headaches, vomiting and fevers. What should you worry about?

*Cryptococcus* CD4+ cell count < 100/mm^3 = diseases... - Aspergillus fumigatus - Candida albicans - *CMV* - *Cryptococcus neoformans* - Cryptosporidium - EBV - Mycobacterium avium-intracellulare - Toxoplasma gondii

Infection with this organism causes a profuse, large volume, watery diarrhea which can be life-threatening in immunocompromised (HIV+) patients.

*Cryptosporidium parvum* - severe diarrhea in AIDS - mild disease (watery diarrhea) in immunocompetent hosts - oocysts in water - prevention by filtering city water supplies - nitazoxanide in immunocompetent hosts

Select the group of organisms that is diagnosed by a modified acid fast stain of a stool specimen.

*Cyclospora spp., Cryptosporidium parvum, Isospora belli* Isospora & Cyclospora - can cause sever diarrhea in immunocompromised - fecal-oral route - cyclospora associated with contaminated raspberries - acid-fast stain - treatment = trimethoprim-sulfamethoxazole

Most common cause of seizures in Latin America

*Cysticercosis* - via T. solium - via ingestion of eggs contaminated with human feces

(TEST): Target cells displaying peptides derived from internal viral proteins such as polymerases

*Cytotoxic T cells* - kill virus-infected, neoplastic, & donor graft cells by inducing apoptosis - release cytotoxic granules containing preformed proteins (perforin, granzume B) - cytotoxic T cells have CD8 --> binds to MHC I on virus-infected cells

Tick paralysis mostly via

*Dermacentor* Tick paralysis - neurotoxin produced in tick's salivary gland - can experience severe respiratory distress (similar to anaphylaxis)

A 35-year-old man with a history of chronic myelogenous leukemia receives an allogeneic bone marrow transplant from an HLA-matched donor. Treatment with cyclosporine & prednisone is begun to reduce graft-vs-host disease. Two months after transplantation, he develops a low-grade fever & a dry cough. A photomicrograph of the patient's sputum is shown. What best describes the most likely causal virus?

*Double-stranded DNA, enveloped, icosahedral virus* Cytomegalovirus (CMV) - common problem among immunosuppressed patients - *owl's eye inclusion* = basophilic intranuclear inclusion body - found throughout body & in urinary sediment - *Herpesvirus family* = *double-stranded DNA* that takes its *envelope form the nuclear membrane* - all DNA viruses are icosahedral except pox viruses

Point-of-Care Tests for Flu Diagnosis

Flu OIA or Binax NOW influenza A & B - Antibody detection of viral core antigens (mainly NP) - In use at UMC

Sialic acid residues of influenza are bound by

Hemagglutinin (HA) - promotes viral entry - determines cell tropism

A patient whose major source of protein is smoked & cooked fish develops what appears to be pernicious anemia. What parasite is noted for causing a look-alike vitamin B12 anemia in certain genetically predisoposed infected individuals?

*Diphyllobothrium latum* - tapeworm associated with anemia - transmitted in fish found in cool lake regions - vitamin B12 deficiency (tapeworm competes for B12 in intestine) --> megaloblastic anemia - ingestion of larvae from raw freshwater fish - treatment = praziquantel

A 23-year-old man is brought to the ED because of a sudden high fever, severe dyspnea, & malaise. He has a history of intravenous drug abuse. One hour later, he develops progressive respiratory distress & supplemental oxygen is provided. His CD4 cell count is 73/mm^3. A chest x-ray shows bilateral, diffuse, fine, granular-appearing interstitial opacification. What tests is most appropriate for confirming identity of most likely causal agent of his fever & respiratory symptoms?

*Direct fluoresecent antibody test* Most common atypical pneumonia in AIDS = Pneumocystis jirovecii - difficulty producing sputum, so bronchial lavage or transmural biopsy required --> sample submitted to *direct fluorescent antibody test* or stained with Gomori *methenamine silver stain* to visualize = characteristic cup or boat shape

Worldwide zoonotic filarial infection of dogs and wild mammals / heartworms in dogs

*Dirofilariasis* - coin lesions - nematodes/roundworms - dirofilaria immitis = dog heartworm - spread by mosquitos

Aspartic acid to asparagine mutation at codon 178 associated with

*FFI (Fatal Familial Insomnia) in individuals with met at codon 129, CJD in individual with val at 129*

(TEST): Myc translocations are almost always present along with

*EBV in Burkitt's lymphoma* Myc - contains sequences similar to Ig switch regions

(TEST): This virus causes oral leukoplakia in AIDS patients.

*EBV* Hairy leukoplakia - irregular, white, painless plaques on lateral tongue that cannot be scraped off - *EBV mediated* - occurs in HIV-positive patients, organ transplant recipients = precancerous

A 19-year-old man has had fever, headache, sore throat, and swelling of the cervical lymph nodes for 5 days. His temperature is 40°C (104°F), pulse is 120/min, respirations are 20/min, and blood pressure is 125/85 mm Hg. The pharynx is red and swollen with enlarged tonsils and exudate. There is tender cervical adenopathy and palpable lymph nodes in the axillary and inguinal areas. The spleen tip is palpable. Leukocyte count is 14,000/mm3 (25% segmented neutrophils, 60% atypical lymphocytes, and 15% monocytes). A throat culture is obtained. Which of the following is the most likely pathogen?

*EBV* Mononucleosis / Kissing Disease - disease of *young adults* - *fever, chills, sweats, headache, very painful pharyngitis* - *enlarged lymph nodes* (as B-cell multiply) & even enlarged spleens - blood work = high WBC count with *atypical lymphocytes* = large activated T-lymphocytes - heterophile antibody = Ab against EBV that cross reacts with & agglutinates sheep RBCs = can be used as rapid screening test for mononucleosis (Monospot test)

Member of Togavirus fam. Gulf & Atlantic States. Maintenance hosts = Culiseta mosquitos. Amplifier hosts = Culiseta & birds. Incidental hosts = man, horses. Mode of transmission = mosquitos.

*Eastern Equine Encephalitis Virus (EEV)* - humans and horses = dead-end - extremes of age = affected most - severe neuro symptoms in kids - ELISA diagnosis - incidence highest in summer

(TEST): The large, slow growing, but progressively expanding lesions of this parasite, which are most commonly seen in the liver, are usually diagnosed with CT scan, X-ray or sonography is performed.

*Echinococcus granulosis* - hydatid cysts (eggshell calcification) in *liver* - cyst rupture can = anaphylaxis - ingestion of eggs in food contaminated with *dog feces* - sheep = intermediate host - treatment = albendazole

A 34-year-old male farmer comes to the ED because of generalized abdominal pain, nausea, & three episodes of non-bilious non-bloody vomiting. Initially, there is concern for atypical appendicitis, & CT scan of the abdomen & pelvis is performed. The CT shows a round peripherally enhancing, centrally hypoattenuating lesion involving the liver. The patient is admitted to the hospital and started on intravenous fluids. The next day, he arrives at the intraventional radiology suite to undergo image-guided aspiration biopsy of the hepatic lesion. Within an hour of the procedure, the patient becomes tachycardic, tachypneic, & flushed. His pulse is 121/min, BP is 90/46 mmHg, respirations are 31/min, & O2 saturation is 92%. He is immediately administered intramuscular epinephrine & glucocorticoids with subsequent stabilization of his blod pressure. What infectious organisms is most likely responsible for this patient's symptoms?

*Echinococcus granulosus* Cestode --> hydatid cysts - colonized after ingesting eggs in dog feces - look for farm or rural setting because dogs acquire parasite from eating entrails of herd animals - *smooth cystic lesions of liver* - transaminasemia &/or eosinophilia - potential for anaphylaxis during procedural intervention - *albendazole*

K3L (vaccinia) is an

*ElF-2 decoy* E3L and K3L act to maintain protein synthesis in virus-infected cells. - E3L is a dsRNA binding protein. - K3L, via a region of sequence identity with eIF-2α, binds PKR as a pseudosubstrate and prevents the phosphorylation and inactivation of eIF-2α. - Host range wrinkle: Although E3L and K3L appear to achieve the same result, i.e., maintaining protein synthesis during viral infection, they are not necessarily redundant as one is more important in HeLa cells, and the other in BHK cells Vaccinia virus = poxvirus family - active constituent of vaccine that eradicated smallpox = first human disease to be eradicated

Sudden onset, low grade fever, *unilateral thoracic, pleuritic chest pain*...abdominal pain and vomitting may occur...cough/cold symptoms absent...generally a 4 day illness...milder in children than adults...complete recovery

*EnB (CxB): Bornholm Disease, "Devil's Grip"* - attacks of severe pain in lower chest, often on one side

Productive. Can spread viruses, like in buccal lesions.

*Enanthema* - rash on mucous membranes - *smallpox, measles, chicken pox, Roseola Infantum*

HBV prophylaxis

*HBV vaccine (since 1982)* - Recombinant HBsAg (all forms) expressed in yeast 3 dose series (infants) typical schedule 0, 1-2, 4-6 months no maximum time between doses no need to restart series or repeat missed doses 2 dose series (adult dose) licensed for > 11 years of age *For patients who canNOT have vaccine...* *HBIG: anti-HBs Ig from convalescent patients (HBIG)* Rarely used today useful for immunocompromised patients Can also be used therapeutically

Most common worm infection in USA

*Enterobius vermicularis / Pinworm* - intestinal infection = anal pruritus - diagnosed by seeing egg via tape test - fecal-oral - treatment = mebendazole

(TEST): Latent infection is a hallmark of infection with

*Epstein-Barr virus* Herpes: HSV-1, 2; EBV; CMV; VZV; HHV-6, 8

(TEST): This large intestinal fluke can cause eosinophilia and gastrointestinal symptoms including diarrhea, ulceration, intestinal blockage, edema and ascites in heavy infections.

*Fasciolopsis buski* - diagnosed via: *stool exam/egg & parasites*

2 stages of Hantavirus

*Febrile Stage* = 4-7 days *Renal Stage* - mucosal bleeding - oliguria - polyuria - mortality in Asian = 6%, but asymptomatic in Europeans ssRNA --> - helical --> enveloped --> *B*ADPROF --> Bunya = crimeon-congo, california encephalitis, *hanta*, lacrosse, rift valley, sandfly

(TEST): For which of the following viruses is the host immune response to virally infected cells the primary cause of viral pathology?

*HAV, HBV, HCV*

(TEST): Which of the following lists the hepatitis virus(es) which can be successfully treated using reverse transcriptase inhibitors?

*HBV only*

Associated with resolution of HBV infection. NOT NEUTRALIZING OR PROTECTIVE.

*HBeAb* - low transmissability - resolved

HBV: binds histone de/acetylases.

*HBx* - interacts directly with other important cell regulators

Stem cells are usually in what stage of cell cycle?

*G1* Labile cells - never go to G0 - divide rapidly with short G1 - most affected by chemo - bone marrow, gut epithelium, skin, hair follicles, germ cells

You see a 36-year-old male at a walk-in clinic for the homeless. He was diagnosed with HIV two years ago, but has been on antiretroviral therapy for the last 18 months and claims he is compliant. His chief complaint today is the appearance of soft, cauliflower-like warts on his lips, and flat, colorless growths on this tongue. He admits a past history of prostitution, including performing oral sex on male clients. Which of the following measures would have been most appropriate to prevent infection with the agent causing the growth?

*Gardasil*

(TEST): Which of the following lists the hepatitis virus(es) which can be successfully treated using protease inhibitors?

*HCV only*

A 35-year-old woman gives birth to a male baby. She had adequate prenatal care & had received all appropriate vaccinations prior to pregnancy. The newborn has multiple hemorrhagic cutaneous lesions on the trunk, head, & neck. On examination, the newborn does not respond to auditory stimuli. A CT scan of the head shows periventricular calcifications. What did the newborn's mother most likely develop during the first 16 weeks of gestation?

*Generalized lymphadenopathy* Congenital CMV infection = 1-2% of all live births in US - via transplacental acquisition of primary or recurrent maternal infection - *triad of cutaneous hemorrhages ("blueberry-muffin baby"), sensorineural deafness, periventricular CNS calcifications suggests congenital CMV infection* = most common cause of intrauterine fetal viral infection - *Ganciclovir = drug of choice* - differential = *Toxoplasma gondii, cytomegalovirus (CMV), rubella* - mother's history of MMR vaccination = unlikely the mother is infected with rubella *TORCH infections*: *T*oxoplasmosis *O*ther (syphilis) *R*ubella *C*ytomegalovirus (CMV) *H*erpes simplex virus (HSV)

(TEST): A local television reporter, keen to get some footage for a "fluff" piece for the February 2 newscast, tried to "interview" a Groundhog (also known as a Woodchuck) at the local zoo. The animal became agitated and inflicted a deep gash on the reporter's arm, requiring several stitches. The animal tested negative for rabies, but electron microscopic examination of serum from the groundhog revealed the presence of what appeared to be virus particles with an icosahedral capsid enclosed in a lipid membrane. The Electron microscopist reported that they looked like ping-pong paddles or hand mirrors. Molecular testing showed that these apparent virus particles contained partially double-stranded circular DNA. This virus is most likely a member of which of the following virus families?

*Genomic sequencing*

(TEST): Failure to thrive syndrome (FTT) or growth retardation in small children can result from infection with

*Giardia lamblia* - bloating, flatulence, foul-smelling, fatty diarrhea (often seen in campers/hikers) - cysts in water - stool exam for ova (eggs) & parasites

Most prevalent herpesviruses

*HHV-6 & -7* - via saliva - roseola infantum (exanthem subitum) = high fever for several days --> seizures, followed by diffuse macular rash

Sites of viral replication in cytoplasm of Poxvirus

*Guarnierni bodies / Inclusion bodies* - only seen in cytoplasm = where it replicates DNA positive icosahedral --> enveloped --> Pox = cytoplasmic replication = smallpox, cowpox, molluscum contagiosum

Almost all due to direct contact with infected domestic poultry or wildfowl. Apparently spread by waterbird migration along Eurasian flyways.

*H5N1* haven't adapted to human-human spread May be due to HA receptor preference alpha2-3 SA- only found in mammalian lung, not present in URT

Can be used to quantify aniviral antibody

*HAI (Hemagglutination inhibition)* - hemagglutination assay = total # of influenza virus particles

(TEST): The mature extracellular virions of which of the following hepatitis virus(es) contain positive-sense single strand RNA?

*HAV & HCV* ssRNA --> + icos --> naked --> CHR*P* --> Picorna = PERCH --> *HAV* ssRNA --> + icos --> enveloped --> CR*F*T --> Flavivirus = *HCV*

(TEST): Mature virus particles contain positive sense ssRNA. Which hepatitis? (A, B, or C?)

*HAV and HCV, but not HBV* ssRNA --> + icos --> naked --> CHR*P* --> Picornavirus = PERCH: polio, echo, rhino, cox, *HAV* ssRNA --> + icos --> enveloped --> CR*F*T --> Flavivirus = *HCV*, WNV, yellow fever, Dengue, Zika, St. Louis, Japanese encephalitis HBV = DNA virus

(TEST): The parents of a 12-month-old girl bring her to see you because she has been having febrile seizures. Recently the parents had brought her to you because she had a spiking fever for a couple of days followed by a rash. You have a strong suspicion that the same virus that caused the fever and rash is also causing the seizures. The virus you suspect is

*HHV-6* - via saliva - roseola infantum (exanthem subitum) = high fevers for several days that can cause seizures, followed by diffuse macular rash

(TEST): Two viruses that impair immunity by targeting immune cells are

*HIV & Measles virus*

(TEST): The enzyme responsible for synthesizing HIV RNA genomes & viral mRNA is

*HOST RNA polymerase II*

Small DNA viruses (Papilloma, polyoma) recruit

*HOST* DNA polymerase

A 32-year-old man comes to the ED because of a 4-day history of fever, myalgias, & cough. He lives in a rural area in New Mexico & owns an automobile repair shop. He recently cleaned his garage, which was infested with mice. He is tachypneic & must use accessory respiratory muscles to breathe. Fine crackles are heard on auscultation of the lungs. What is the most likely causal agent?

*Hantavirus* - family = *Bunyviridiae (locations) = california encephalitis, crimean-congo, hanta, rift valley / sandly* = Sin Nombre (Spanish for "without a name") virus - via inhalation of aerosolized secretions from common deer mouse - typically begins with nonspecific prodrome (fever, generalized myalgia, GI disturbances), followed 4 to 5 days later by respiratory symptoms Hantavirus pulmonary syndrome - first reported in 1993 - fever, myalgia, rapid development of respiratory failure leading to death - initial cases mostly among Navajo Indians - most common in U.S. Four Corners states: New Mexico, Arizona, Colorado, Utah ssRNA --> negative helical --> enveloped --> Bunya = california encephalitis, crimean-congo, *hanta*, rift valley/sandfly

Only human viroid

*Hepatitis Delta virus* = smallest "virus" known to infect animals = originated from viroids Viroids = smallest infectious pathogens known = short strand of circular, single-stranded, RNA without protein coat ssRNA --> - helical --> enveloped --> BA*D*PROF --> deltavirus = HDV

(TEST): Which of the following tests will allow the total number of influenza viral particles, both infectious and defective, to be determined?

*Hemagglutination assay*

Fatal epizootic virus diseases.

*Hendra virus; Nipah virus* - Hendra = horses - Nipah = pigs - human cases associated with working with infected animals - initial reservoir = rats

(TEST): A local television reporter, keen to get some footage for a "fluff" piece for the February 2 newscast, tried to "interview" a Groundhog (also known as a Woodchuck) at the local zoo. The animal became agitated and inflicted a deep gash on the reporter's arm, requiring several stitches. The animal tested negative for rabies, but electron microscopic examination of serum from the groundhog revealed the presence of what appeared to be virus particles with an icosahedral capsid enclosed in a lipid membrane. The Electron microscopist reported that they looked like ping-pong paddles or hand mirrors. Molecular testing showed that these apparent virus particles contained partially double-stranded circular DNA. This virus is most likely a member of which of the following virus families?

*Hepadnaviridae* dsDNA --> enveloped --> HHP --> Hepadna = HBV - HBV = partially-stranded DNA!!!

A healthy 32-year-old primigravid woman at 6 weeks' gestation comes to the physician for a prenatal exam. She states that she emigrated from Southeast Asia and that three years ago, she had fatigue, nausea, anorexia, & jaundice. One month prior to these symptoms, she had fever, joint pains, & generalized skin lesions that slowly disappeared on its own. What lab tests should be ordered to investigate the patient's past illness?

*Hepatitis B surface antigen (HBsAg)* - recovered from hepatitis B - pregnant = need to find out if she still has agent in her liver (chronic hepatitis B infection) via performing test for HBsAg = negative if completely recovered but positive if chronic carrier

Dane particles are associated with

*Hepatitis B virus* - spherical virion of hepatitis B = Dane particle

The CDC & Prevention are alerted to a recent infectious outbreak in a small African community. The report states that thirteen cases of hepatitis were confirmed within this community. Of the thirteen cases, the mortality rate is particularly high among pregnant women. The women initially reported experiencing a varying degree of symptoms including jaundice, malaise, anorexia, nausea, vomiting, abdominal pain, & fever. The most likely causal organism belongs to what viral family?

*Hepeviridae* Hepatitis E = enterically transmitted acute hepatitis = self-limited acute infection - chronic hepatitis does *not* develop - spread primarily by fecally contaminated water in endemic areas - common in India, Asia, Africa, Central America - *very high mortality among third trimester pregnant women due to fulminant hepatitis*- *relatively immunocompromised state during third trimester of pregnancy likely plays a role* = 15-60 days of incubation period - *caused by naked capsid RNA virus belonging to Hepeviridae (formerly Caliciviridae)* ssRNA --> + icos --> naked --> Hepe --> HEV

Sufficient immunity protective against entire population, even to susceptible individuals

*Herd immunity* Important to protect those who: - Can't be vaccinated due to health status - Don't mount good immune response due to genetics

EnA, EnC (CxA): Rapid onset with fever lasting 2 - 4 days. Vomitting, myalgia, headache, sore throat...a few 2 - 4 mm papules that vesiculate, then ulcerate on soft palate at posterior of the mouth...lasts ~ 1 week.

*Herpangina* - mouth blisters, fever ssRNA --> + icos --> naked --> PERCH = polio, echo, rhino, cox, HAV Coxsackievirus - aseptic meningitis - hand, foot, mouth disease - myocarditis - pericarditis

(TEST): A 25-year-old woman presented with redness, pain, and diminution of vision that occurred 2 weeks after microkeratome-assisted laser in situ keratomileusis (LASIK). On presentation, corneal edema, Descemet membrane folds, keratic precipitates, stromal infiltrates, and flap necrosis were observed. Delayed post-LASIK microbial keratitis was diagnosed. Culture and scraping showed no organisms. The patient was started on oral valacyclovir, and progress was monitored through serial clinical photographs and anterior segment optical coherence tomography. Resolution began within 3 days of initiating treatment and was complete in 4 weeks. The most likely etiological agent in this case is

*Herpes Simplex Virus-1* - via respiratory secretions, saliva - gingivostomatitis - *keratoconjunctivitis* - herpes labialis - herpetic whitlow on finger - temporal lobe encephalitis - esophagitis - erythema multiforme

A primigravid woman delivers a newborn at 37 weeks' gestation. She did not receive any prenatal care throughout her pregnancy. She was able to deliver the newborn without any complications. After two days in the newborn nursery, both mother & baby were discharged from the hospital. About two weeks after delivery, the newborn develops erythema & vesicular lesions around the eyes. Over the next several days, he develops seizures, cranial nerve palsies, & lethargy, & he dies one week later. What is the most likely responsible for the dev't of these symptoms in this newborn?

*Herpes simplex* Herpes simplex-2 - acquired during delivery - causes devastating *neonatal encephalitis* - mortality = 65% *Adults herpes encephalitis (in immunocompetent individuals) usually due to herpes simplex-1, whereas neonatal & congenital herpes usually due to herpes simplex-2* - neonates = vesicular skin lesions

An 18-year-old man comes to the physician because of a 1-week history of fever, chills, & sore throat. His temperature is 38 C (100.4 F), pulse is 82/min, respirations are 20/min, & BP is 122/67 mmHg. Physical exam shows marked pharyngeal hyperemia, tonsillar exudates, & tender cervical lymphadenopathy. He has splenomegaly approximately 4 cm below the costal margin. What is the most likely commonly used test for probable diagnosis?

*Heterophile antibody test* Infectious mononucleosis via Epstein-Barr virus (EBV) - sore throat, headache, fever, malaise, tender lymphadenopathy, pharyngitis, tonsillitis, hepatosplenomegaly, periorbital edema, rash, palatal enanthem - diagnosis via *heterophile antibody testing (Monospot test)*, EBV Ab titers, lymphocytosis with atypical lymphocytes on peripheral smear Heterophile Abs = IgM Abs that react with sheep &/or horse RBCs & induce agglutination - restrict contact sports because hepatosplenomegaly places patient at increased risk of splenic rupture with physical contact

(TEST): Recent infection with HBV; infection with HIV months to years ago. What is the most appropriate therapy for your patient?

*Highly-active anti-retroviral therapy (HAART) including lamivudine* Lamivudine - NRTI - used for *HBV* infections - cytosine analog --> competes with deoxycytidine triphosphate = inhibits *HBV DNA polymerase* - *slows progress to liver fibrosis*

Retrovirus that causes tumors in people

*Human T cell Leukemia Virus (HTLV-1)* = Tropical Spastic Paraparesis (TSP) or HTLV-1 Associated Myleopathy (HAM) (1-2% of infected individuals): weakness/spasticity of extremities, hyperreflexia, Babinski signs, incontinence, mild peripheral sensory loss. - HTLV-1 --> adult T-cell leukemia - HTLV-2 --> human hairy cell leukemia

(TEST): This recently discovered virus is a cause of bronchilitis in infants and is generally clinically indistinguishable from respiratory syncytial virus.

*Human metapneumovirus (HPMV)* - negative-stranded RNA virus of family Pneumoviridae - second most common cause (after RSV) of lower respiratory infection in young children - occurs in slightly older children, less severe

(TEST): An infant born at 32 weeks gestation at the beginning of December is finally ready to go home by the end of January to a household that consists of a single mother, who plans to breast-feed her child, and two older siblings who are in daycare. Which of the following describes a prophylactic treatment that would commonly be given to such an infant to prevent a severe disease of viral origin?

*Humanized monoclonal antibody that neutralizes the F protein of RSV*

Rubeola =

*Measles* - paramyxovirus - 3 C's = cough, coryza, conjunctivitis --> followed by Koplik spots --> followed 1-2 days later by maculopapular rash (starts at head/neck --> spreads downward) - Warthin-Finkeldey giant cells = fused lymphocytes - SSPE (acute sclerosing panencephalitis) occurs years later - Vitamin A supplementation can reduce mortality, particularly in malnourished children

(TEST): A 16-year-old female heart-lung transplant patient shows evidence of a respiratory viral infection, and test positive for influenza B using a rapid test performed at the bedside. Her status declines rapidly and she is placed on mechanical ventilation. Which of the following would be the best choice to treat her viral infection?

*I.V. Rapivab (peramivir)* - treats influenza - neuraminidase inhibitor - suppose to be 18 & older

Ab + virus → glomerulonephritis

*Immune complex disease (LCMV)* - deposition of Ag-Ab complement complexes on surface of cells = chronic or acute inflammation - may be manifested by vasculitis, endocarditis, neuritis, or glomerulonephritis

How long does Smallpox vaccination last?

*Immunity wanes after 3 years; virtually absent after 20 years.* - live attenuated vaccine

NDM-1 mostly tracked back to what country

*India* New Delhi Metallo-beta-lactamse-1 - enzyme that makes bacteria resistant to broad range of beta-lactam antibiotics (includes carbapenem family)

An 8-year-old girl is brought to the physician by her mother because of crampy abdominal pain, nausea, & mild diarrhea for the past 2 weeks. Her mother states that the girl vomited a 20-cm (8-inch) long cyndrical white worm 24 hours ago. Vital signs are normal. Physical examination is unremarkable. Lab studies show eosinophilia in the blood & eggs in the stool. What best describes the most likely route of infection in this patient?

*Ingestion of eggs from human feces* Ascaris lumbricoides - *only helminth infection caused by cylindrical white worm of remarkably large size* - acquired directly with no intermediate host - from *fecal contamination from other humans* - stage of life cycle transmitted = egg --> *eggs hatch into larvae in intestine* - eggs hatch into larvae in intestine - larvae penetrate intestinal wall --> migrate to lungs - recent immigrants or travelers returning from Latin America or Asian countries are at risk - treatment = benzimidazoles: *albendazole & mebendazole* - ivermectin = alternative - pyrantel pamoate used in pregnant patients

How is Ascaris acquired?

*Ingestion of food contaminated with eggs* - fertilized Ascaris eggs released in feces may contaminate food or water --> consumed - doesn't attach to intestine but maintains its position by mobility - worm may become hypermotile --> migrates into appendix or bile duct

Member of Bunyavirus fam. Northcentral, Notheast US. Maintenance host = Aedes. Amplifier host = chipmunks & white tail deer. Incidental host = man.

*La Cross / California Encephalitis Group* - we don't have high enough viral amplification to pass it on - incubation period = short = 3-7 days - most cases asymptomatic - 90% of acute CNS disease in children <15 y/o - males more often - 75% of patients = abnormal ECG after infection - ELISA --> look for IgM & IgG

Therapy for HBV

*Interferon alpha (IntronA)* Enhances immune system function Reduces HBV replication directly modulates Pol levels Little effect on HBeAg- patients Generally used in combination with direct-acting antivirals *Lamivudine (3TC) * Nucleoside analogue RT inhibitor - chain terminator Frequently see mutations (YMDD) Some of these are "vaccine resistant" Recall: Pol and S ORFs overlap Pol mutants lose neutralizing epitope Also used in HIV *Adefovir* Nucleotide analogue RT inhibitor HBV specific Mutations less frequent Newer... Entecavir (Baraclude™) No HIV activity, but well tolerated alongside HIV ARV's Can be used in patients resistant to lamivudine Telbivudine (Tyzeka™) Potent anti-HIV activity L-isomer (i.e. mirror image) of thymidine More effective/less resistance than lamivudine/adefovir (clinical trial data) Tenofovir (Viread™) Potent anti-HIV activity

(TEST): A 28-year-old female physician sustained a needlestick injury with a needle contaminated with blood from a 49- year-old male HIV-negative hemophilia patient chronically infected with Hepatitis C virus (HCV) genotype 1a. At the time of the accident, the hemophilia patient was not receiving antiviral treatment due to prior treatment failure, and had a viral load of 7 × 105 IU/ml. Blood was drawn from the physician to establish background levels of plasma alanine aminotransferase (ALT) and antibodies to HCV. Her ALT results were normal, and no anti-HCV antibody was detected. Three months after the needlestick, a blood sample drawn from the physician was positive for HCV RNA (genotype 1a) and antibodies to HCV. Plasma ALT level was normal. A blood sample drawn at 4.5 months post exposure showed an HCV-RNA viral load of 5.1 × 104 IU/ml and the plasma ALT level was now 93 IU/liter (normal range, female: 9-52 IU/liter). She was otherwise asymptomatic at that time. What treatment options would you recommend for the physicians? For the original patient?

*Interferon plus ribavirin plus telapravir (or bocepravir)* - for both Ribavirin - *chronic HCV*, RSV Telapravir, Boceprevir - 1st-generation protease inhibitors introduced in 2011 for *HCV* - only effective against HCV genotype 1 - *used in combo with IFN alpha & ribavarin*

(TEST): Infection with each member of which of the following group of organisms can produce skin rashes or lesions?

*Leishmania major, Acanthamoeba spp., Onchocerca volvulus* Leishmania donovani - visceral & *cutaneous* leishmaniasis (skin ulcers)

A 6-month-old girl is brought to the physician by her mother because of a fever, labored breathing, & wheezing. Physical exam shows excessive nasal secretions, tachypnea & tachycardia. Bilateral expiratory wheezes are heard on auscultation of the chest. What is the firs step in pathogenesis after causal virus enters a host cell?

*It creates a complementary copy of its genome to use as mRNA using a virion-associated RNA-dependent RNA polymerase* Bronchiolitis via RSV - negative-sense, ss RNA virus in Paramyxovirus fam - negative-sense RNA viruses must carry *RNA-dependent RNA polymerase* within nucleocapside *so genome can be converted into positive-sense version* --> *first thing such a virus does upon entering a cell is use its won polymerases to create mRNA (positive-sense RNA)* so proteins can be created

Member of Flavivirus fam. Asia. Maintenance host = Culex trieniorhynchus. Amplifier hosts = birds, pigs. Incidental hosts = man, horses. Mode of transmission = mosquito bite.

*Japanese Encephalitis Virus* - JE vaccine recommended for travelers ssRNA--> + icos --> enveloped --> CR*F*T --> Flavivirus = mosquito viruses mostly = WNV, HCV, Zika, Japanese Encephalitis virus, Dengue, Yellow Fever, St. Louis

Two vaccines for influenza

*Killed injectable vaccine* - trivalent - quadravalent - most frequently used *Live intranasal vaccine* - contains temperature-sensitive mutant that replicates in nose but not in lung - administered intranasally

2 kinds of vaccine for flu

*LAIV* - live attenuated influenza vaccine *TIV* - trivalent influenza vaccine - disrupted --> must preserve virus - slow step = grow seed stock; grow in eggs - must make new vaccine every year - same seed stock = antigens are identical yearly

Inhibition of this reduces herpesvirus infection, shedding, and recurrence by promoting epigenetic suppression of viral genomes.

*LSD1* - heterochromatic suppression of the viral genome and blocks infection and reactivation in vitro

HPV 6 & 11 associated with what diseases?

*Laryngeal papillomatosis = recurrent respiratory papillomatosis* - tumors develop in airway - may be exposed during vaginal birth *Anogenital warts / Condyloma acuminata* - sexually active individuals

A 53-year-old woman who has diabetes mellitus comes to the employee health center for an annual exam. She has no complaints at this time. A review of her chart reveals that she is due for a few vaccinations, including the influenza vaccine. She questions the physician about the necessity of the vaccine because she just received one a year ago. What response by the physician is most appropriate?

*Last year's influenza vaccine may be ineffective today because influenza viruses undergo genetic drifts* - difficulty developing vaccine against influenza, especially influenza A, because influnza virus genome = 8 segments of single-stranded RNA - *minor antigenic changes (antigenic drift)* in surface antigens at point mutations in genes accumulate - does not confer lasting protection = yearly revaccination - Influenza virus = Orthomyxoviridae

Spliced and accumulate as stable introns. RNAs abundant during Herpes latency

*Latency-associated transcripts (LATs)* - repressed transcription, no DNA replication

Select the group of parasites which can cause anemia during infection.

*Leishmania donovani, Diphyllobothrium latum, Babesia microti* Leishmania donovani - via sandfly - visceral leishmaniasis; cutaneous leishmaniasis - macrophages containing amastigotes - treatment = amphotericin B, sodium stibogluconate Diphyllobothrium latum - vitamin B12 deficiency (tapeworm competes for B12 in intestine) --> megaloblastic anemia - ingestion of larvae in raw freshwater fish - treatment = praziquantel Babesia - babesiosis = fever & hemolytic anemia; predominately in northeastern US - asplenia increases risk of severe disease - via Ixodes tick - blood smear diagnosis

A newborn is born at 37 weeks' gestation with multiple medical problems. He is small for his gestational age & has cataracts, hepatosplenomegaly, & thrombocytopenia with purpura. An echocardiogram shows the presence of a patent ductus arteriosus, an x-ray of the lower limbs shows bone lucency, & an MRI of the brain shows meningoencephalitis. The patient's mother states that she had no prenatal care prior to her immigration from Somalia and had a mild maculopapular rash in mid-pregnancy. What practices would most likely have prevented this condition?

*Live attenuated vaccine* *Live MYRICSS* = *M*MR, *Y*ellow fever, *R*otavirus, *I*nfluenza (intranasal), *C*hickenpox (VZV), *S*mallpox, *S*abin polio virus Rubella - *first trimester infections = more common & more severe* - effects on fetus can range: *intrauterine growth retardation, involvement of senses & nervous system (meningoencephalitis, cataracts, retinopathy, hearing loss), cardiac involvement (patent ductus arteriosus, pulmonary arterial hypoplasia), hepatosplenomegaly, purpura (via thrombocytopenia), bluish-red skin lesions (secondary to dermal erythropoiesis), pneumonia* - treatment = supportive - *rubella vaccine = live attenuated vaccine = for women of childbearing age who are not pregnant at the time* = MMR / measles/mumps/rubella

Describe MMR - Measles Induced

*Live attenuated virus vaccine* Two doses: 1st at 12 - 15 mo; 2nd at 4 - 6 yr - maternal Ab may block virus replication and prevent development of immunity If given <9 months, - If given only once, 5% remain susceptible to infection. Side effects: fever and rash in <5% NB: There is now an MMR + VZV vaccine *Live MYRICSS* MMR = measles, mumps Yellow fever Rotavirus Influenza (intranasal) Chickenpox Smallpox Sabin polio virus

Ascaris: transient pulmonary infiltrates with peripheral eosinophilia

*Loeffler's Syndrome* - Ascaris lumbricoides - Necator americanus - Strongyloides stercoralis

Allows H+ to pass from lumen of acidified endosome to lumen of virus. required to release NP from M. wt 'flu A inhibited by amantadine- blocks H+

*M2 ion channel*

CCR5 inhibitor

*Maraviroc* = fusion inhibitor - binds CCR-5 on surface of T cells/monocytes --> inhibits interaction with gp120 = CCR5 receptor antagonist class

Treatment for pinworm infecton

*Mebendazole* - Treatment = albendazole, mebendazole, pyrantel, pamoate *PAM* has *P*inworms - avoid scratching - change sheets daily Enterobius vermicularis / Pinworm - simple life cycle: eggs ingested --> pinworms mature in cecum & ascending large intestine - female migrates to perianal area (usually at night) to lay her eggs --> become infectious 4-6 hours later - infection = severe perianal itching - diagnosis by placing scotch tape firmly on perianal area --> will pick up eggs = viewed under microscope - no eosinophilia since there is no tissue invasion

(TEST): A common mechanism for resistance to erythromycin

*Methylation of the ribosome* Aminoglycoside: Erythromycin - resistance = plasmid-encoded - prevalent in most strains of staphylococci - primarily due to active efflux or *ribosomal protection* by increased methylase production *MACE*: Macrolides = Azithromycin, Clarithryomycin, Erythromycin Resistance = Methylation of 23S rRNA-binding site prevents binding of drug

A 17 yo male with AML relapse underwent Hematopoietic Stem Cell transplant, he presents 3 months later with the sudden onset of left facial pain and swelling On P/E he looks ill, is febrile and tachycardic, He has tenderness upon palpation of the sinuses. What organism mare you mostly worried about? What is your next step?

*Mucor & Aspergillus* *Call ENT for emergency debridement* --> start *Amphotericin B* immediately Mucormycosis - disease in ketoacidotic diabetic &/or neutopenic patients (leukemia) - fungi proliferate in blood vessel walls, penetrate cribriform plate, enter brain - rhinocerebral, frontal lobe abscess - cavernous sinus thrombosis - headache, facial pane, black necrotic eschar on face

Classic sign of hookworm disease

*Microcytic & hypochromic iron deficient anemia* Necator americanus & Ancyclosotoma duodenale - diarrhea, abdominal pain, weight loss - sucks blood from intestine = iron deficiency anemia - intense itching & rash at site of penetration through skin (between toes) - local growth in lung = cough, infiltrate on chest x-ray, eosinophilia - diagnosis via identifying eggs in fresh fecal sample - treatment = mebendazole or albendazole

(TEST): Onchocerca volvulus method of diagnosis

*Microscopic exam of skin snips*

A 24-year-old man with HIV infection comes to the physician because of a headache, fever, vomiting, & generalized malaise for the past month. His last clinic visit was 5 years ago, at which time his CD4 count was 500/mm^3. He has been taking his antiretroviral meds intermittently because of the side effects. His temperature is 38.9 C (102 F), BP is 135/82, pulse is 106/min, & respirations are 18/min. Physical exam shows nuchal rigidity & photophobia. During the physical exam, the patient has a brief generalized seizure that lasts for 1 minute. A lumbar puncture is performed; the opening pressure is elevated. Lab studies of CSF show: Cells = 150 cells/uL, mostly lymphocytes Protein = 60 mg/dL Glucose = 35 mg/dL (serum gulcsoe = 95 mg/dL) What best describes the most likely causal gent?

*Monomorphic yeast* - not compliant with HIV meds - seizure + eningismus + CSF findings = meningitis Cryptococcus neoformans = monomorphic encapsulated yeast = common cause of meningitis in immunocompromised patients, especially in those with CD4 count less than 50 cells/mm^3 - treatment = amphotericin B, flucytosine, fluconazole Fungal infection via CSF: - 100-1000 cells, mostly lymphocytes - glucose < 45 mg/dL - protein > 50 mg/dL - opening pressure for lumbar puncture in patients with cryptococcal meningitis usually elevated

(TEST): Vector of filariasis (Wuchereria or Brugia infection)

*Mosquitos* Wuchereria bancrofti & Brugia malayi - lymphatic infection - chronic leg swelling - Pacific Islands & Africa - transmitted microfilariae mature into adults within lymphatic vessels & lymph nodes of genitals & lower extremities - areas become covered with thick, scaly skin - chronic disfiguring = elephantiasis - blood drawn at night time - treatment = diethylcarbamazine

Infestation of tissue with maggots

*Myiasis* - screwworm larvae eat living things = currently eating Florida Key deer :( 2 types 1. facultative - accidental or opportunistic - wound, death 2. obligate - required for bug's life cycle; adapted to this lifestyle - screwworm - have to live in living thing, so they eat it - mistake malodorous wound for death thing

(TEST): Deletion mutants involving this gene have been detected in attenuated retroviruses.

*NEF*

A 20-year-old woman comes to the physician because of a 2-week history of fever, chills, & sore throat. Her temperature is 38 C (100.4 F), pulse is 92/min, respirations are 20/min, & BP is 122/67 mmHg. Physical exam shows hyperemia of pharynx, tonsillar exudates, cervical lymphadenopathy, & splenomegaly. Treatment with ampicillin is begun. The patient returns to the physician 4 days later because of a generalized maculopapular rash. The most likely causal agent of this woman's initial condition is linked to the development of

*Nasopharyngeal carcinoma* Infectious mononucleosis via EBV - headache, fever, malaise, lymphadenopathy, pharingitis, hepatosplenomegaly, periorbital edema, rash, palatal enanthem - diagnosis via heterophile Ab testing (monospot) - *administration of penicillin derivatives (ampicillin) can lead to maculopapular rash* - EBV linked to mulitiple malignancies including Burkitt lymphoma, Hodgkin lymphoma,nasopharyngeal & other head & neck carcinomas, & T cell lymphoma

A 16-year-old woman, who immigrated from Africa 3 years ago, comes to the physician because of vague left-sided abdominal pain & bloating over the last 8 weeks. Her temperature is 37.4 C (99.4 F), pulse is 72/min, blood pressure is 124/78 mmHg, & respirations are 14/min. Physical exam shows a firm, 10-cm mass on the left lower quadrant of the abdomen. Abdominal CT scan shows an enlarged left ovary. Biopsy of the B cells with frequent mitoses & intermixed macrophages with abundant clear cytoplasm. The agent most likely associated with this disease is also associated with what malignancy?

*Nasopharyngeal carcinoma* Patient has Endemic/African form of Burkitt lymphoma = B-cell lymphoma - commonly presents as mass arising from jaw, GI tract (ileum, cecum), ovary, breast - most common in children & young adults but has been seen in adults up to 40 y/o EBV = DNA virus (Herpesviridae family) highly associated with African form of Burkitt lymphoma - infection & latency within B-lymphocytes, along with integration into host DNA = malignant transformation of cells Outside of Africa, sporadic & immune-deficiency forms of Burkitt lymphoma can presents with... - consititional symptoms & bulky abdominal organ, ovary, testis, liver & spleen involvement

(TEST): Heavy infection with this organism can cause a microcytic & hypochromic iron deficient anemia, especially in small children.

*Necator americanus* - via nematode (roundworm) - intestinal infection causing anemia by sucking blood form intestinal wall - cutaneous larve migrans - pruritic, serpiginous rash from walking barefoot on contaminated beach - transmission = larvae penetrate skin - treatment = bendazoles or pyrantel pamoate

A 3-month-old girl is brought to the physician because of a 3-day history of fever, cough, & poor feeding. Her temperature is 38.9 C (102 F) & respirations are 32/min. A chest x-ray shows bilateral infiltrates & chest auscultation reveals wheezing. What best describes the most likely causal organism responsible for these findings in this patient?

*Negative-sense, single-stranded RNA, nonsegmented, helical, enveloped virus* Respiratory syncytial virus (RSV) - most common cause of bronchiolitits & pneumonia in children younger than 1 y/o - chest x-rays = hyperinflated lung fields with diffuse increase in interstitial markings = *Paramyxoviridae = negative-sense, ssRNA viruses = nonsegmented, helical, enveloped* - supportive care - ribavarin may be promptly initiated at onset of infection to be effective at preventing viral replication ssRNA --> - helical --> enveloped --> PaRaMyxovirus = parainfluenza, RSV, measles, mumps

Cytoplasmic inclusions found in Rabies virus

*Negri bodies* - commonly found in: Purkinje cells of cerebellum & in hippocampal pyramidal neurons = eosinophilic

Cleaves sialic acid to release newly formed virions from host cell in influenza

*Neuraminidase* - part of mucin - cleaves neuramic acid --> disrupts mucin barrier = exposes sialic acid binding sites beneath - critical for release of newly formed virion from infected host cell

Target of Relenza/Zanamivir, Tamiflu / Oseltamivir

*Neuraminidase* = NA inhibitors - 9 know subtypes

A 32-year-old schoolteacher in her first trimester of pregnancy is concerned about a student in her class who develops a bright-red rash on her cheeks. Two days later, the student's shoulders, upper thorax, & upper arms become red, & develop a lacy, reticulated appearance. The physician should monitor this pregnancy closely for the dev't of what fetal conditions?

*Non-immune hydrops* Student's illness = *Fifth disease / erythema infectiosum* / Slapped cheek disease - caused by *parvovirus B19* = smallest icosahedral virus = ssDNA - spread from human to human - animals do not carry this particular parvovirus - disease is contagious prior to onset of rash - initial symptoms during period of contagion = nonspecific constitutional symptoms = fever, myalgia, lethargy, coryza, pharyngitis, abdominal pain - *when typical "slapped-cheek" rash begins, student is no longer contagious* - infectious of adults with blood dyscrasias such as sickle cell disease or thalassemia can lead to transient aplastic crisis Complications caused in pregnant women by Parvovirus infections - first trimester = *aplastic anemia* = *non-immune hydrops fetalis* - virus infects immature erythrocytes --> severe anemia --> fetus tries to compensate by increasing cardiac output but eventually dies of high-output cardiac failure

Most common Calicivirus

*Norovirus* = viral gastroenteritis - outbreaks common in day care centers & schools - consumption of shellfish - explosive watery diarrhea - Calicivirus = no envelope = SS positive linear RNA virus = icosahedral

Histoplasma antibodies are positive. How do you treat?

*Not always necessary, especially in immunocompetent patients whose symptoms resolve within 1 month, mediastinal or hilar adenopathy* - severe or disseminated = amphotericin B - mild to moderate = itraconazole

Vesicular "dew drops on a rose" rash

Varicella Zoster virus Herpes simplex virus

(TEST): The presence of unsheathed microfilaria in skin snip samples from a patient with corneal opacities, peripheral eosinophilia, dermatitis, and fibrous subcutaneous nodules on the head, is diagnostic of infection with the following parasite.

*Onchocerca volvulus* - skin changes, loss of elastic fibers, river blindness - allergic reaction to microfilaria possible - female blackfly - treatment = ivermectin

A biology graduate student who recently visited a tropical region of Africa presents with new visual impairment & the sensation that something is moving in her eye. She tells you that she is concerned bc she had been warned about eye disease transmitted by black flies. When in Africa, she was in a river area, & despite her best efforts she received a lot of black fly bites. She also has some subcutaneous nodules. If her infection was acquired by black fly bite, what is the most likely causative agent?

*Onchocerca volvulus* = second most infectious cause of blindness after trichoma - river blindness - snow flake corneal opacities - mazzotti reaction - filarial infection in Africa & Central & South America - microfilariae (larvae) mature into adults --> can be found coiled up in fibrous nodules in skin & subcutaneous tissue - after mating = microfilariae = pruritic skin rash with darkened pigmentation - microfilariae may migrate to eye --> blindness - treatment = ivermectin; nodulectomy

(TEST): 2 most common infectious causes of blindness in the world

*Onchocerca volvulus, Chlamydia trachomatis* Onchocerca volvulus - larvae transmitted to humans by bite of infected black flies - pruritic skin rash with darkened pigmentation - lizard skin - microfilariae may migrate into eye --> river blindness - microfilariae can often be seen in eye (cornea & anterior chamber) by slit lamp examination - treatment = ivermectin

(TEST): Select the group of parasites that can be found in the eye during infection

*Onchocerca volvulus, Taenia solium cysticercosis, Acanthamoeba spp.*

(TEST): The most appropriate antibiotic treatment, from the following list, for the treatment of hookworm infections is

*mebendazole* - depletion of glucose in helminth --> inhibits tubuling polymerization = loss of cytoplasmic microtubules in adult nematodes - *Hookworms: necator americanus, ancylostoma duodenale* - ascaris lumbricoides (& albendazole)

Neuraminidase inhibitors

*Oseltamivir/Zanamivir* - inhibit virion release - must be given early in course - treatment & prophylaxis of acute uncomplicated influenza infection - effective against both influenza A & B

Members of Picornavirus

*PERCH* on a "*peak*" (*pic*o) *P*oliovirus *E*chovirus *R*hinovirus *C*osackievirus *H*AV Enteroviruses = poliovirus, coxsackiviruses A & B Picornavirus - *RNA* translated into 1 large polypeptide --> cleaved by protease into functional viral proteins - all enteroviruses fecal-oral, except rhinovirus (respiratory) - positive-sense = replicates in cytoplasm - naked viruses

A 10-month-old infant is brought to the ED in early December after many children in his day care become ill with high fever, runny nose, cough, wheezing, & loss of appetite, in two cases requiring hospitalization. He has a history of prematurity & was born at 29 weeks gestation. He also has a history of chronic lung disease & required oxygen until he was 4 months of age. His temperature is 38 C (100.4 F), pulse is 113/min, & respirations are 28/min & oxygen saturation is 88% on room air. He is placed on 2 L nasal cannula & saturations improve to 96%. Physical exam reveals a small infant in no acute distress with wheezing bilaterally on auscultation. The infant has a significant amount of purulent nasal secretions. Lab studies show: WBC count = 15,500/mm^3 Neutrophils = 40% Lymphocytes = 45% Bands = 7% Monocytes = 8% Hemoglobin = 11.4 g/dL Hematocrit = 33.4% Platelets = 390,000m^3 Rapid RSV = positive Rapid influenza = negative What drugs could most likely have prevented this patient's condition?

*Palivizumab* = monoclonal antibody directed against fusion protein of RSV --> prevents infection of host cell = neutralizing & fusion-inhibitory activity against RSV - directed at epitope in A antigenic site of F protein on surface of RSV Respiratory syncytial virus (RSV) - can cause serious lower respiratory tract illnesses in infants - incidence high in winter months = most common cause of bronchiolitis & pneumonia in children younger than 1 year old = *paramyxovirus* = only respiratory pathogen that produces its most serious illness at time when maternal antibodies are still present - differs from rest of its kin by lacking both HA & NA glycoproteins

Treatment for pinworm (Enterobius vermicularis) infection

*mebendazole*, albendazole; pyrantel pamoate *PAM* has *P*inworms Enterobius vermicularis - intestinal infection = anal pruritis - diagnosed by seeing egg via tape test - fecal-oral transmission - itchy - children

(TEST): Infection with this organism, acquired in the United States by eating raw or poorly cooked crayfish, is characterized by fever, hemoptysis, dyspnea, and chest pain.

*Paragonimus kellicotti / North American lung fluke* - food-borne trematode infection - humans eat raw or undercooked crayfish meat that contains parasite larvae - common in Sub-Saharan Africa - after parasite has been ingested, it travels from intestines until it reaches lungs

A 17-year-old boy recently immigrated from Tajikistan is brought to the ED because of marked swelling of the left testis. His temperature is 35.9 C (96.7 F), pulse is 87/min, respirations are 16/min, & BP is 110/72 mmHg. He has a one-week history of marked bilateral swelling of the parotid glands. To what families does the most likely causal agent belong?

*Paramyxoviridae* Mumps = *negative-sense RNA virus in Paramyxovirus family* --> also includes parainfluenza virus, respiratory syncytial virus, & measles virus - Bilateral parotitis = present in 95% of symptomatic patients - inflammation of pancreas or testes = hallmarks - *Epididymo-orchitis = most common complication of mumps infection in adult males* - therapy of mumps parotitis = symptomatic = analgesics or antipyretics (aspirin, acetaminophen)

(TEST): Carol's 9 year old daughter develops a lace-like rash a week or so after a mild, flu-like illness. Within a week or so, Carol experiences arthritic like symptoms, but her husband and her two older sons remain healthy. It is possible that Carol is experiencing infection by

*Parvovirus B19* - in adults, leads to pure RBC aplasia & rheumatoid arthritis-like symptoms

*Linear, single*-stranded DNA is the genetic element of

*Parvovirus* ssDNA - --> naked --> PAPP: Parvovirus = B19

Type of immunization available for protection from Hepatitis A

*Passive immunization* - commercially available human immune globulin preparation available for pre-exposure & post-exposure prophylaxis for HAV ssRNA --> + icos --> naked --> picorna --> PERCH = polio, echo, rhino, cox, HAV Killed/inactivated vaccines: *RAIS*, then *Killed* *R*abies H*A*V *I*nfluenza (injected) *S*alk Polio

(TEST): What is true regarding acute HIV?

*Patient recently infected with HIV typically have viral loads in excess of 50,000 copies/mL within 4 weeks of infection.* - 3rd gen test = HIV negative test - highly infective when acutely infected

(TEST): A mother brings her 4-year-old child to your office and tells you that lately the child has been irritable, has had trouble sleeping, and suffers from nightmares. While you are discussing the case you notice the child is scratching his behind. Which of the following diagnostic test would be most likely to identify the cause of this child's symptoms?

*Perianal scotch tape prep* Enterobius vermicularis / Pinworm - treatment = albendazole, mebendazole, pyrantel pamoate, avoid scratching, change sheets daily

Detects presence of *viable* viruses.

*Plaque assay* - every plaque arises from *infectious particle* - holes in monolayer / plaques = presence of virus Disadvantages: Not all viruses form plaques Don't kill cells or lyse to release progeny Many viruses take a week or more Different strains of the same virus behave very differently Technically challenging Depends on state of cells

Select the group of parasites which are usually diagnosed by examination of blood smears for parasite stages.

*Plasmodium vivax, Wuchereria bancrofti, Babesia microti*

(TEST): An HIV patient presents with non-productive cough, respiratory distress, progressive loss of ventilatory capacity, respiratory failure and cyanosis. Chest films were abnormal with symmetrical cloudiness bilaterally and a honeycomb pattern of lobular collapse. Which organism is the most common cause of this condition?

*Pneumocystis jirovecii*

Major complication of influenza

*Pneumonia* Influenza can cause a primary pneumonia or weaken immunity to promote delayed secondary bacterial pneumonia or otitis media, typically caused by : *S aureus*, S pneumonia, H influenza

60% of Foodborne Illnesses (FBIs) caused by

*norovirus* - *calicivirus* (RNA) family - viral gastroenteritis = common on cruiseships ssRNA --> + icos --> naked --> *C*HRP = Corona

An investigator is studying virus life cycles. He creates a continuous culture of kidney fibroblasts that are suitable hosts for a large variet of viral agents. In one experiment, the nuclei of these cells are removed by cytosurgery, & various viral agents are added to the cultures. Following culture of the viruses with the enucleated cells, the yield of cytopathic units of virus is quantified. What viruses would be capable of replication in these enucleated cells?

*Poliovirus* - belong to family *Picornaviridae = non-enveloped = icosahedral nucleocapsid that contains positive-sense RNA* Most RNA viruses (poliovirus) replicate in cytoplasm = can replicate in enucleated cells - except Orthomyxoviruses & Retroviruses that have replicative stages in nuclei Picorna = PERCH = Polio, Echo, Rhino, Cox, HAV All DNA viruses require nucleus, except Poxviruses that can replicate in cytoplasm

Treatment for Fasciolopsis buski

*Praziquantel* - also treats Heterphyes heterophyes, Metagonimus yokogawai, Clonorchis sinensis, Schistosoma mansoni, Schistosoma japonicum, Schistosoma haematobium - broad spectrum anti-helminthic agent - covers cestodes & trematodes Fasciolopsis buski / giant intestinal fluke - common parasite of humans & pigs - most prevalent in Southern Asia - inhabit gut

(TEST): Treatment for infections with Taenia tapeworms

*Praziquantel* - paralysis of worm via increased cell membrane permeability of calcium - most effective drug against all types of fluke infections, including blood fluke infections (schistosomiasis), intestinal & liver fluke infections, & lung fluke infections (paragonimiasis) - also useful in treatment of tapeworm infections Albendazole for neurocysticercosis

Hallmark of *JC Polyomavirus*

*Progressive multifocal leukoencephalopathy* (PML) - over the half the population has this but only problem in immunocompromised - problem in HIV patients with CD4+ < 200 = *demyelinating disease of CNS* - *non-enhancing* multifocal brain lesions in white matter - reactivatino of JC virus infection - rapidly progressive, usually fatal - increased risk associated with natalizumab, rituximab - *patches of ill-defined destruction of white matter contain enlarged oligodendroglia with glassy nuclei*

Activated protein can modify eIF-2 involved in initiation of translation in viruses, required for cap-dependent initiation

*Protein Kinase R (PKR)* - either directly activated by dsRNA or by neighboring binding of interferon alpha & beta

Cytosolic receptors that recognize viral RNAs and induce production of type I interferons (IFNa and IFNb)

*RIG-1 like receptors (RLRs)*

(TEST): Retroviruses use this to synthesize viral genomes & messages

*RNA polymerase II* RNA --> DNA via reverse transcriptase DNA --> RNA via RNA polyerase II

Most common cause of pneumonia & bronchiolitis in infants

*RSV* - paramyxovirus - contains F-protein --> formation of multinucleated giant cells (syncytial cells) - lacks both HA & NA glycoproteins - *number one cause of pneumonia in young children, especially in infants less than 6 months of age* - can be prevented with palivizumab

(TEST): Which of the following assays would be most appropriate to detect an active Dengue virus (DENV) infection in a patient with suspected Dengue Shock Syndrome?

*RT-PCR on patient serum*

Have been used as expression vectors to introduce foreign antigens into cells or animals for smallpox vaccine vectors.

*Vaccinia, canarypox, MVA* - If safety considerations can be resolved, this may be a very good way to immunize against a number of pathogenic bacterial and viral agents

(TEST): Herpesviruses are usually transmitted by close contact; however, this member of the herpesvirus group is known to be transmitted by aerosols.

*Varicella Zoster Virus (VZV)* / HHV-3 - varicella-zoster (chickenpox, shingles), encephalitis, pneumonia - most common complication of shingles = *post-herpetic neuralgia*

Where does flu replicate?

*nucleus* All RNA viruses replicate in cytoplasm, except Orthomyxovirus (Influenza) & Retroviruses = have replicative stages in nuclei

Approved for emergency use (EUA) in pt with suspected/confirmed failing Ose/Zan or where oral/inhaled therapy not feasible (2009-10) Approved for general use in USA December 2014 (pt ≥ 18 only) See cross resistance with Ose in some cases.

*Rapidavir (Peramivir) - IV* = neuraminidase inhibitor

HHV-3

*Varicella-Zoster Virus* = alphaherpesvirus - only herpes virus for which we have vaccine, spread by respiratory drops - most common complication of shingles = post-herpetic neuralgia - smallest herpes virus - via respiratory secretions

An RNA virus that has a nuclear phase to its replication process is

*Retrovirus* & Orthomyxovirus

Reverse transcriptase (RNA-dependent, DNA-polymerase) activity is expressed by what viruses?

*Retroviruses* *Hepadnaviruses* - useful in recombinant DNA technology & gene therapy - *host cell DNA-dependent RNA polymerase II* synthesizes HIV-1 mRNAs - dsDN integrates into host genome

Host-cell tRNAs are involved in the genome replication of

*Retroviruses* - host-cell tRNAs = primers for synthesis of retrovirus DNA by reverse transciptase

2 viruses that only cause common cold

*Rhino- and Coronaviruses (229E)* Human Rhinovirus - acid labile - temperature restricted

Treatment for Hantavirus

*Ribavirin* Hantavirus Pulmonary Syndrome - early aggressive intensive care - inotropic agents = *Dobutamine* ssRNA --> - helical --> enveloped --> *B*ADPROF --> Hantavirus = Calfiornia encephalitis, Crimean-Congo, *Hanta*, Rift valley/sandfly, lacrosse

Treatment of RSV

*Ribavirin* - guanosine analog - administered as aerosol = RSV - oral formulations = treats influenza A & B *Prevent with Palivizumab* - humanized monoclonal Ab directed against F glycoprotein on surface of RSV - used in prevention of RSV in children & premature infants & children

(TEST): Purpose of a plaque assay

*number of infectious virus particles in a given sample.*

(TEST): These viruses are responsible for serious, life-threatening gastroenteritis in children, primarily in developing countries.

*Rotavirus* - most important global cause of infantile gastroenteritis - segmented dsRNA virus (reovirus) - RotaTeq vaccine = reassortment virus = live attenuated ssRNA --> + icos --> naked --> CH*R*P --> *ds*RNA = *Rotavirus*, Coltivirus

(TEST): Effective vaccines have been developed to lessen the disease burden induced by

*Rotavirus* Immunizing agent for Rotavirus vaccine (RotaTeq) = preparation of reassortment of viruses Live attenuated vacines: MYRICCS *M*MR *Y*ellow fever *R*otavirus *I*nfluenza (intranasal) *C*hickenpox (VZV) - Herpes zoster vaccine *S*mallpox *S*abin polio virus BCG

Viral oncogenes are present in

*Rous sarcoma virus* - v-src

A 7-year-old boy is brought to the physician because of a rash and a low-grade fever for 36 hours. The boy does not appear very ill and is playing happily. His temperature is 37.7 (99.8 F), pulse is 90/min, blood pressure is 110/65 mmHg, & respirations are 12/min. Physical exam shows mild conjunctivitis, normal tongue, a reddened throat with small red slightly raised lesions on the soft palate, & enlarged cervical nodes, including the occipital node. Skin exam shows a fine, erythematous, macular rash that is present on the face, neck, most pronounced on the trunk, & not involving the extremities. There are scratch marks at some parts of the rash. What is the most likely underlying condition?

*Rubella* / German/ Three-Day Measles - fine, non-blotchy, pruritic rash on face & trunk of child who is not very ill - via Togavirus = single-stranded RNA virus - via aerosolization & incubation 14-21 days after exposure - red papules on soft palate (Forchheimer's sign) can be seen in some patients - prominent lymphadenopathy = enlargement of occipital or post-auricular lymph nodes - rash starts on face --> spreads to trunk - in adult women = polyarthritis - IgM can be detected in serum within 1-2 days of developing rash

Patient had history of measles as a child or emigrated to US with no vaccinations. 5-15 years later = personality changes, seizures, coma, death. Anti-measles antibodies.

*SSPE (Subacute Sclerosing Panencephalitis)* - slow form of encephalitis caused by measles virus - years after measles --> child or adolescent = slowly progressing central nervous system disease - mental deterioration & incoordination

(TEST): The principal agent responsible for acute hemorrhagic conjunctivitis is

*one of several enteroviruses* Causes - enterovirus (picorna) - coxsackievirus A (picorna) - adenovirus

A 62-year-old woman comes to the physician because of a 5-month history of weight loss, fatigue, & lower abdominal pain. Her other medical history includes abdominal pain. Her other medical history includes hyperlipidemia & uterine fibroids, which were diagnosed incidentally. She currently takes atorvastatin & has no allergies to medication. Her temperature is 37.7 C (99.9 F), pulse is 79/min, blood pressure is 115/72 mmHg, & respirations are 12/min. Physical exam shows some tenderness to deep palpation of her lower abdomen. Imaging is performed. She is diagnosed with a tumor in the organ indicated by the arrow in the computerized tomography (CT) scan shown above. A biopsy of the tumor is performed. If the biopsy results reveal squamous cells carcinoma of the bladder. What would be the most likely predisposing risk factor?

*Schistosoma haematobium infection* = trematode = can chronically infect bladder mucosa --> painless hematuria & bladder fibrosis - intermediate hosts = snails - larval forms of parasite can infect humans by penetrating skin in infected water - chronic inflammation produced by parasite induces *squamous metaplasia of bladder's transitional epithelium*, which can progress to squamous cell carcinoma Patients symptoms - weight loss, abdominal pain, fatigue = suspicious for malignancy Squamous cell carcinoma of bladder = rare - risk factors = *Schistosoma haematobium, long-term indwelling Foley catheters, bladder stones*

(TEST): Infection with which ONE of these organisms is associated with hematuria, the presence of blood in the urine?

*Schistosoma hematobium / blood fluke* - second to malaria as cause of sickness in tropics - found in freshwater - penetrate skin --> invade venous system --> mate & lay eggs - eggs may enter lumen of intestine or bladder --> may be excreted via feces or urine into nearby stream or lake so they can continue life cycle

(TEST): A Peace Corps volunteer recently returned from Africa presents with fever, abdominal pain, and urticaria. Physical and laboratory examination reveal an enlarged liver and spleen, nonoperculate ova with a prominent lateral spine in the stool, and a significant eosinophilia. Further history reveals that the patient and several other Peace Corps colleagues had gone swimming in a local river near the village where they worked before returning to the U.S. The patient says that one of these colleagues is also experiencing similar symptoms. What is the most likely cause of this illness?

*Schistosoma mansoni*

(TEST): A Peace Corps volunteer who had recently returned from Africa presented with fever, abdominal pain, and urticaria. Physical and laboratory examination revealed an enlarged liver and spleen, non-operculate ova with a prominent lateral spine in the stool, and a significant eosinophilia. Further history revealed that the patient and several other Peace Corps colleagues had gone swimming in a local river near the village where they worked shortly before returning to the U.S. The patient says that one of these colleagues also is experiencing similar symptoms and has a neurological deficit of the lower extremities. What is the most likely cause of this illness?

*Schistosoma mansoni* - via trematodes (flukes) - liver & spleen enlargement = egg with lateral spine - fibrosis & inflammation - snails are host - cercariae penetrate skin of humans - treatment = praziquantel = South America & Africa - resides in intestinal tract - deposits eggs in feces - found in freshwater - practice molecular mimicry = tricks host's immune system into thinking schistosome are not foreign

A medical virology lab co-infects cells in a tissue culture flask with influenza A (H3N2) & influenza A (H1N1). The flask if incubated for 48 hours & the progeny viruses are analyzed. Four distinct variants of influenza A are isolated: H3N2, H1N1, H3N1, H1N2. What viral attributes most likely made the production of H3N1 & H1N2 variants possible?

*Segmented genome* Influenza A - undergoes *genetic shift / reassortment of pieces of its segmented genome* - genome of this RNA virus occurs in 8 separate segments = random rearrangements can occur when 2 related viruses infect a single cell - packaging of progeny viruses can become drastically changed --> *pandemics can result* in population due to sudden appearance of new antigenic types - 4 major pandemics of influenza since 1993 - *genetic drifts can occur only in viruses with segmented genomes* (pieces of RNA that can be exchanged in progeny) = slower process caused by accumulation of random mutations - can infected animals other than humans 4 families of viruses with segmented genomes: Reovirus, Orthomyxovirus, Bunyavirus, Arenavirus

One of the new anti-HIV drugs that is a CCR5 antagonist

*Selzentry* / Maraviroc

(TEST): Among DNA viruses such as herpesviruses and poxviruses, late viral gene expression is dependent on

*ongoing viral DNA synthesis*

Member of Flavivirus fam. North & Central America. Maintenance host = Culex species, birds. Amplifier hosts = birds. Incidental hosts = man. Mode of transmission = mosquito.

*St. Louis Encephalitis* - some cross-reactivity with West Nile Virus - most cases = asymptomatic - mainly elderly infected - fever with headache, aseptic meningitis, encephalitis

How is Schistosoma haematobium transmitted?

*Standing or swimming in contaminated water* - skin penetration via cervariae - snails = intermediate host Schistosoma haematobium = egg with terminal spine - can lead to squamous cell carcinoma of bladder (painless hematuria) & pulmonary hypertension - treatment = praziquantel

How would you manage recent, high risk exposure in context of PrEP

*Start post-exposure prophylaxis with tenofovir-em tricitabine + raltegravir, then continue PrEP alone after 28 days*

How would you manage recent, high risk exposure in the context of PrEP?

*Start post-exposure prophylaxis with tenofovir-em tricitabine + raltegravir, then continue PrEP alone after 28 days*

Radiographic finding of Croup / Parainfluenza / *Laryngotracheobronchitis*

*Steeple sign on x-ray* Croup - via parainfluenza (paramyxovirus) - virus membrane contains hemagglutinin (--> binds sialic acid --> promotes viral entry) & neuraminidase (--> promotes progeny virion release) antigens - seal-like barking cough - inspiratory stridor - severe = pulsus paradoxus secondary to upper airway obstruction

Family of Rubella

*Togavirus* ssRNA --> + icos --> enveloped --> CRF*T* --> Togavirus = REC = *Rubella*, Equine Viruses, Chikungunya

(TEST): A zoonotic infection characterized by skin lesions that is sometimes seen among sheep farmers, but rare in office workers, is triggered by

*orf virus*

(TEST): The presence of live larvae with a short buccal chamber in the stool of a patient suffering from epigastric pain, diarrhea, vomiting, and urticarial skin eruptions, is diagnostic for infection with

*Strongyloides stercoralis / Threadworm* - intestinal infection causing vomiting, diarrhea, epigastric pain (may mimic peptic ulcer) - transmission = larvae in soil penetrate skin - treatment = ivermectin or bendazoles

(TEST): A four-month-old female, originally taken to the Emergency Room of a small rural hospital for difficulty in breathing, was transferred to Batson Children's Hospital. She was born by vaginal delivery to a 14-year-old mother at home without medical assistance. The mother and her siblings are home-schooled, they have never been vaccinated due to parental objection, and the mother has never been seen by a gynecologist. On original admission, it was determined that she had life-threatening airway obstruction and endotracheal intubation was made difficult by an "epiglottic mass." On arrival at Batson, she was taken to the operating room for operative laryngoscopy and bronchoscopy that showed extensive supraglottic and glottic papilloma as well as multiple sessile tracheal lesions down to the carina. Histology confirmed benign papilloma, and viral typing showed mixed human papillomavirus (HPV) types 6 and 11. Which of the following is the most appropriate treatment for the four-month-old infant? What is the most likely prognosis for the four-month-old infant?

*Surgical debulking of lesions to maintain an airway* *Requirement for multiple rounds of surgery to maintain an airway*

(TEST): A 3-year-old boy is brought to the physician because of a 2-day history of fever and an itchy rash. The rash began on his face and then spread to his trunk, arms, and legs. Several children at his day-care center have had similar symptoms. His temperature is 38.9°C (102°F), pulse is 100/min, respirations are 20/min, and blood pressure is 110/60 mm Hg. Physical examination shows multiple red papules and vesicles over the face, trunk, and upper and lower extremities. Some vesicles contain clear fluid, whereas others are crusted. Which of the following is the most likely causative agent?

*Varicella-zoster virus*

A 27-year-old man develops a fever of 38.9 C (102 F). Physical exam shows bilateral parotid gland swelling & orchitis. Antibodies against the most likely causal agent are ineffective due to what property?

*Syncytial formation* Mumps - via paramyxovirus - rare in US because of live-attenuated MMR vaccine - highly contagious & spreads rapidly among unvaccinated individuals by *respiratory droplets*, direct contact, or possibly fomites - children = *transient inflammation of parotid glands* - tends to be more severe disease in adults than children - *in adults, mumps causes bilateral parotitis* & often involves testes - *aseptic meningitis* = most frequent extra-salivary complication of mumps paramyxoviruses = *negative-sense RNA viruses that spread from syncytia formation*

"Regulatory" Proteins of HIV-1: upregulates transcription

*TAT* - encodes transactivator protein -> binds to viral genome --> activates transcription - regulatory proteins = tat, rev, nef

Tapeworm acquired from eating undercooked pork

*Taenia solium* - pork tapeworm attaches to mucosa of intestine via hooks on its scolex - grows to length of 2-8 meters - releases its eggs in human feces - in animal's muscle tissue, larvae develop into another larval form, the cysticercus = round, fluid-filled bladder with larval form within - elevated eosinophils intestinal tapeworm - via ingestion of larvae encysted in undercooked port - treatment = praziquantel cystericosis, neurocysticercosis - via ingestion of eggs contaminated with human feces - treatment = praziquantel, albendazole for neurocysticercosis

(TEST): You see a 19-year-old female in your OB/GYN practice. This is her first visit to a gynecologist. She has a history of homelessness "on and off" from age 12 when she ran away as a result of sexual abuse from her mother's boyfriend. She reports multiple sexual partners, and exchanging sex for money or drugs. While she generally tried to insist on condom use, she admits multiple instances of unprotected sex while drunk or high. A pelvic exam shows no visible signs of active STIs, but she reports a history of cauliflower-like, non-vesicular growths in her genital region that persisted approximately one year, then disappeared. She now reports being in a steady relationship with her current boyfriend and is considering having a child with him. The best course of action for this patient would be to recommend

*Testing for STIs, vaccination with Gardasil, and yearly PAP testing* - was infected with HPV-6 or -11; the infection resolved spontaneously

An abandoned newborn is brought to the ED as authorities attempt to locate the biological mother. His temperature is 37 C (98.6 F), pulse is 135/min, & respirations are 32/min. Physical exam shows a well appearing, healthy newborn in no acute distress. HIV antigen/antibody combination immunoassays of serum are positive for HIV antibodies, but inconclusive for HIV-1 p24 antigen. What is the correct interpretation of these findings?

*The mother has been infected with HIV* FDA-approve antigen/antibody immunoassay - detects *HIV-1 & HIV-2 antibodies as well as HIV-1 p24 antigen* - baby positive for IgG HIV antibody but test for p24 is inconclusive - presence of HIV antibodies in newborn most strongly supports infection of mother because of HIV IgG antibodies can cross placenta - *all children born to HIV-positive mothers are born with positive immunoassay results* - *positive for both immunoassay & p24 antigen testing* should be interpreted as *positive for HIV infection* - if specimens are inconclusive, tests are repeated or PCR tests are conducted - *PCR detects integrate viral DNA (provirus) = necessary virological test to diagnose an infant with HIV infection*

(TEST): You isolate a retrovirus that you hypothesize causes prostate cancer, and find that it produces virions with two types of genomes: one type contains all three viral genes, gag, pol, and env, whereas the second genome displays massive deletions within gag and env, completely lacks any recognizable pol, but contains sequences coding for a novel protein. Based on this, which of the following statements is CORRECT?

*The novel protein is likely homologous to a cellular protein that plays a role in growth & differentiation*

The presence of eggs in fresh stool samples is diagnostic of human infection for each member of this group.

*Trichuris trichiura, Schistosoma mansoni, Diphyllobothrium latum* Trichuris trichiura / whipworm - often asymptomatic - loose stools/anemia - rectal prolapse in children (heavy infection) - fecal-oral - treatment = bendazoles

Treatment of Fasciola hepatica / Sheep liver fluke

*Triclabendazole (CDC)* - alternative = nitazoxanide - praziquantel = limited efficacy

*Visceral larval migrans* caused by

*Toxocara canis* / Dog roundworm - Can also cause *Ocular larval migrans (OLM)* --> can lead to blindness - covert toxocariasis = chronic exposure - worldwide-distributed helminth parasite of dogs - preventive anti-helmintic treatment of newborn puppies strongly recommended = pyrantel, fenbendazole

(TEST): One of the challenges of treating papillomaviruses is the lack of antivirals that specifically target viral functions. Which of following lists aspects of the HPV viral lifecycle performed by HOST derived enzymes?

*Transcription, translation, & DNA replication*

(TEST): One of the challenges of treating papillomaviruses is the lack of antivirals that specifically target viral functions. Which of following aspects of the HPV viral lifecycle are performed by HOST derived enzymes?

*Transcription, translation, DNA replication* - viral DNA integration into host chromosome - DNA replicates in nucleus, using host replication machinery - modulates host metabolism: t antigen - E4, E5 interact with host proteins

A 32-year-old primigravid woman at 32 weeks' gestation comes to the physician because of mild fever, headache, & a few painful genital lesions. She mentions that she has had these lesions a few times before pregnancy, but they went away. Physical exam shows two vesicular lesions on the labia & one similar cervical lesion. The physician explains that she should consider cesarean section prior to rupture of her membranes. What best describes the form of axonal transport that contributes to the latency of this organism?

*Transport is mediated by dynein* - woman = reactivated herpes simplex with active lesions, just prior to labor & delivery = indication for acyclovir & for elective cesarean section Herpesvirus, Poliovirus, Rabiesvirus, Tetanus toxin - use retrograde transport to establish latency & anterograde transport to establish secondary, reactivated infection - *motor dynein* = retrograde transport along microtubules of actin cytoskeleton

(TEST): A 10-year-old boy, who immigrated to the USA from Mexico, has been having worsening abdominal pain for 4 weeks. He also complains of high grade fevers, anorexia, weight loss and jaundice. On physical exam, you notice abdominal tenderness and hepatomegaly. An abdominal CT scan shows a liver abscess. What would you expect to see on Ova and Parasite analysis of a diarrheal stool sample from this patient?

*Trophozoites of Entamoeba histolytica with ingested erythrocytes*

Most common mutation of all found in cancer cells

*p53* - *SV40, HPV, KSHV target p53 --> prevents host cell from undergoing apoptosis*

Viruses spread in one of 5 ways:

*Via the bloodstream (polio, measles) - VIREMIA* *Cell-to-cell spread (e.g., respiratory pathogens)* Along axons (rabies) Through the lymphatic system (polio) Via cell-associated virus (HTLV-1, VZV, HIV-1)

Codes for the capsule of RNA strands in HIV

*gag = p24*

(TEST): To identify units of blood containing infectious HIV-1 prior to the development of anti-HIV-1 antibodies, blood in the USA is screened by PCR to identify the presence of HIV-1 RNA. For what other viruses is this PCR screen currently used?

*West Nile Virus (WNV)* ssRNA --> + icos --> enveloped --> CRFT --> Flavivirus = *WNV*, St. Louis, Dengue, Yellow Fever

A 64-year-old man living in southern Minnesota is brought on July 15 in the ER by his brother. The brother said the man had a 2-day history of fever, headache, & some vomiting, but today he appeared confused. He is confused by some of the simply questions you ask him. His spinal tap is clear with 75% PMNs & a head CT is normal. The most likely cause of his symptoms is

*West Nile virus* ssRNA --> + icos --> enveloped --> CR*F*T --> *Flavivirus* - yellow fever, dengue, HCV, WNV, zika, St. Louis encephalitis, japenes encephalitis

Peak times of Norovirus infections...

*Winter* Vomiting Disease - ssRNA --> + icos. --> naked --> calici = norovirus

Category of EBV

*gammaherpesvirus* - EBV (HHV-4) - Kaposi's sarcoma (HHV-8)

Member of Flavivirus fam. South America, Africa. Maintenance host = Aedes aegypti (urban), Aedes species (sylvanic, jungle), man, nonhuman primates. *Man is part of the cycle.*

*Yellow Fever Virus* - currently having outbreak in Brazil

(TEST): A 65-year-old native of Saudi Arabia who is now living in Jackson, MS presents with a severe pneumonia-like illness. He recently returned from a 3 week trip to Saudi Arabia and Jordan where he visited relatives. A virus that should be considered in the differential diagnosis is

*a coronavirus, such as the one responsible for Middle Eastern Respiratory Syndrome.* ssRNA --> +icos (corona = helical though) --> enveloped --> *C*RFT --> *Corona* = corona, SARS, *MERS*, common cold

(TEST): Antigenic shift in influenza viruses is best described as

*a mechanism of introducing entirely novel hemagglutinin (HA) and neuraminidase (NA) proteins into viruses capable of infecting humans.*

(TEST): A veterinarian who has recently returned from an exchange program in Australia, where she worked with wildlife including bats, is rushed to the hospital following a series of seizures. Her husband reports she had a history of fever and drowsiness for the prior 24 hours, and she rapidly becomes comatose upon admission. A CSF sample is obtained, from which is cultured a pleiomorphic, enveloped, virus which enters cells by direct fusion at the plasma membrane. The virus particles contain a single strand of negative-sense RNA, and it is determined that RNA replication occurs in the cytoplasm. This agent is most likely

*a paramyxovirus* - don't get tripped up by buzzwords ssRNA --> - helical --> enveloped --> BAD*P*ROF --> Paramyxo

(TEST): A Veterinarian recently returned from an exchange program in Australia, where she worked with wildlife including bats, is rushed to the hospital following a series of seizures. Her husband reports she had a history of fever and drowsiness for the prior 24 hours, and she rapidly becomes comatose upon admission. A CSF sample is obtained, from which is cultured a pleiomorphic, enveloped, virus which enters cells by direct fusion at the plasma membrane. The virus particles contain a single strand of negative-sense RNA, and it is determined that RNA replication occurs in the cytoplasm. This agent is most likely

*a paramyxovirus* ssRNA --> *- helical* --> enveloped --> BAR*P*ROF --> paramyxovirus = parainfluenza, RSV, mumps, measles/rubeola

(TEST): Synthesis of poliovirus mRNA and genomes is catalyzed by

*a virus-encoded RNA-dependent RNA polymerase* ssRNA --> + icos --> naked --> CHRP = picornavirus = poliovirus - *naked* birds *CHRP*

How does Rb turn cell cycle off?

*active form binds E2F* - HPV E7 activates cell cycle: disrupts Rb/E2f Rb - inhibits E2F - blocks G1 --> S phase - retinoblastoma, osteosarcoma

HBsAg present in

*acute & chronic infection* - Acute HBV - Chronic HBV (high infectivity) - Chronic HBV (low infectivity)

Most common manifestation of primary herpetic infection

*acute gingivostomatitis* - cervical lymphadenitis with fever common Herpes simplex virus-1 - via: respiratory secretions, saliva - *gingivostomatitis*, keratoconjunctivitis, herpes labialis, herpetic whitlow on finger, temporal lobe encephalitis, esophagitis, erythema multiforme - *most common form of sporadic encephalitis*

(TEST): A 4-year-old boy who has acute myelogenous leukemia is admitted with fever and neutropenia. His temperature on admission is 40°C and his absolute neutrophil count (ANC) is less than 100. No focus of infection is apparent on physical examination. Despite 5 days of cefepime (an advanced cephalosporin) and 3 days of vancomycin, he continues to spike high grade fevers and his ANC continues to be low. Of the following, the MOST appropriate next step would be to

*add antifungals (Amphotericin B or voriconazole) to the antibiotic regimen*

(TEST): Herpesvirus-encoded transcription factors kickstart virus replication in host cells and are often expressed with a kinetics categorized as

*alpha - immediate early* Alpha = immediate early = transcription factors Beta = early = DNA polymerase, thymidine kinase Gamma1 = late - can be transcribed *before* replication but transcription increases greatly after replication begins Gamma2 = late - can only be transcribed *after* replication begins - contains structural proteins, tegumen, capsid proteins, glycoproteins

(TEST): A veterinarian is bitten by a stray dog that was brought to his practice by a motorist who struck the dog on a busy street. The animal subsequently died and brain tissue from the animal tested positive for rabies antigen. The veterinarian, who was current on all his vaccinations, should receive prompt aggressive first aid, including washing the wound with soap and water,

*and the human rabies vaccine given in two doses* FIRSTAID: - postexposure prophylaxis = wound cleaning + immunization with killed vaccine & rabies immunoglobulin - example of passive-active immunization

(TEST): Classical dengue fever typically occurs following infection by

*any serotype in a previously uninfected individual*

Maintenance source of Ebola virus

*bats* - transmitted to non-human animals --> eaten by humans

(TEST): Compared to most humans, an individual who expresses 3 to 4 times the normal level of the CCR5 ligand would likely

*be more resistant to HIV infection*

Category of CMV

*betaherpesvirus* DNA positive icos --> Herpes: HSV-1, 2; EBV; *CMV*; VZV; HHV-6, 8 alpha: HSV-1, HSV-2, HHV-3 (VZV) beta - HHV-5, HHV-6, HHV-7 gamma - HHV-4, HHV-8

(TEST): The function of adenovirus VAI RNA and the vaccinia (poxvirus) E3L protein is to

*bind viral double-stranded RNA (dsRNA) and prevent PKR activation.* Also - activation of PKR by dsRNA

(TEST): The viral envelope can be obtained by

*budding through variety of cellular membranes* - generally, enveloped viruses acquire their envelopes from plasma membranes when they exit fro cell - exception = herpesviruses, which acquire envelopes from nuclear membrane

(TEST): SV40, HPV, and KSHV target the activity of to prevent the host cell from undergoing apoptosis.

*p53* = most common of all found in cancer cells - targetted by HPV E6, KSHV LABA - cell cycle moves from S to G2-phase even in presence of damaged DNA - HPV E6 blocks p53 signalling that can lead to apoptosis Some viruses evade apoptosis & killing by innate immunity

Disseminated strongyloidiasis can be induced by

*cellular immunity due to disease or therapy* Strongyloides stercoralis / Threadworm - intestinal infection causing vomiting, diarrhea, epigastric pain - larvae in soil penetrate skin - treatment = ivermectin, bendazoles - eosinophilia - larvae in stool

Vaccinia E3L binds

*dsRNA* Vaccinia... E3L binds dsRNA K3L = poxivirus fam = EIF-2 decoy

Where does Poxvirus replicate?

*cytoplasm* - unlike other DNA viruses = Guarniernia/inclusion bodies dsDNA --> enveloped --> HHP --> Poxvirus = smallpox, cowpox, molluscum contagiosum

(TEST): Classic Creutzfeldt-Jakob Disease (CJD), whether inherited, sporadic, or infectious, and variant CJD, associated with bovine transmissible spongiform encephalopathies, share a number of features. However, they differ dramatically in the age of onset of clinical disease and the percentage of patients who

*develop ataxia*

Viral triggers of Innate Immunity

*dsRNA* *uncapped RNA* = nucleic acids (viruses)

(TEST): A number of children in your child's day care have been reported sick with low grade fevers and vesicular lesions on their palms, within their mouths, and on the soles of their feet. The causative agent is most likely

*enterovirus* ssRNA --> +icos --> naked --> CHR*P* --> Picorna: PERCH = polio, echo, rhino, coxsackie (entero), HAV

(TEST): Within the first two to three weeks of initial infection with HIV, an infected individual will

*experience a marked rise in the viral load to as high as 10^6 RNA molecules/mL*

Histology of HBV

*ground glass cells* - larger - prominent nuclei - granular - eosinophilic - cytotoxic T cells mediate damage

Kaposi's sarcoma most commonly occurs where

*hard palate* Kaposi sarcoma - causes dysregulation of VEGF - endothelial malignancy - associated with HHV-8 & HIV - has lymphocytic infiltrate

(TEST): You are evaluating a 5-year-old boy who underwent Hematopoeitic Stem Cell Transplantation few weeks ago. When he developed fever, his work-up included a blood Aspergillus galactomannan antigen test, which came back positive. In addition to an invasive Aspergillus infection, the patient may test positive if he

*has another fungal infection*

(TEST): A 12-year-old boy presents with vesicular lesions only in his mouth. However, he also complains of aching muscles, a headache, and sore throat. The most likely diagnosis is

*herpangina caused by enterovirus*

(TEST): Human metapneumovirus (HMPV) mRNAs are transcribed, capped, and polyadelylylated in the cytoplasm by a single, multifunctional enzyme that utilizes an RNA template. This enzyme is

*packaged in the virion*

(TEST): Anti-poliovirus IgG

*is induced following vaccination with the inactivated (Salk) vaccine*

(TEST): Interferon "interferes" with virus replication by

*inducing the expression of several hundred proteins (e.g. PKR, 2'5'OAS, and RNAse L) that collectively enhance anti-viral immunity and/or block virus replication*

(TEST): A young man from Mississippi has just returned from his first trip outside the US where he worked for six months in Central America for a survey company. During this time, he developed classic Dengue Fever but had no hemorrhagic complications. Classic Dengue Fever typically occurs following

*infection by any serotype of the virus in a previously uninfected individual.* ssRNA --> + icos --> enveloped --> CR*F*T --> Flavivirus = WNV, *Dengue Fever*, Yellow Fever, HCV, Zika virus, St. Louis encephalitis

(TEST): Schistosoma japonicum mode of transmission

*infectious larvae penetrating the skin* - snails are hosts - cercariae penetrate skin of humans

Cutaneous Larva Migrans (CLM) via

*infective (filariform) dog & cat hookworm larva* Cutaneous Larva migrans = pruritic, serpiginous rash from walking barefoot on contaminated beach - via *Ancylostoma duodenale, Necator americanus (hookworms)* - larvae penetrate skin - rural southern US - blood stream --> lungs --> GI tract = iron deficiency anemia - treatment = bendazoles or pyrantel pamoate - eggs in stool - eosinophilia

(TEST): Babesia microti mode of transmission

*infective stage injected by insect bite* Babesia - Ixodes tick (same as Borrelia burgdorferi of Lyme disease; may coinfect human) - diagnosis = blood smear: ring form, "Maltese cross"; PCR - treatment = atovaquone + azithromycin

Most RNA viruses replicate in cytoplasm. Exception is

*influenza virus* (orthomyxovirus) & retroviruses

(TEST): Cysticercosis is acquired via

*ingestion of Taenia solium eggs in feces-contaminated food or drink*

(TEST): Infection with Trichinella spiralis is acquired by

*ingestion of larval forms in improperly cooked meat* Trichinella spiralis - larvae enter bloodstream, encyst in striated muscle --> muscle inflammation = trichinosis = fever, vomiting, nausea, periorbital edema, myalgia - transmission via *undercooked meat (especially pork); fecal-oral (less likely)* - treatment = bendazoles

(TEST): Anti-retroviral therapy is effective when it targets viral gene products that are essential for replication. Blocking the HIV TAT protein may prove useful because it would directly

*inhibits viral RNA synthesis* TAT = regulatory protein of HIV-1 - upregulates transcription

BK Virus (BKV) associated with

*kidney disease in (immunosuppressed) transplant patients* - cidofovir may be useful dsDNA (+ icos) --> naked --> Polyoma - JC, BK

(TEST): The viral proteins involved in HSV binding to host cells are encoded by

*late genes*

(TEST): If the goal of a vaccination scheme is to protect mucosal tissues from viral infection, and if safety issues have been resolved, the best vaccine to employ for this purpose would consist of

*live attenuated virus* - induces cellular & humoral responses - induces strong, often lifelong immunity MYRICSS MMR Yellow fever Rotavirus Influenza (intranasal) Chickenpox (VZV) Smallpox Sabin polio virus

Principal pathology of Paragonimus westermani is in the

*lungs* - cystic spaces - symptoms localized in pulmonary system = bad cough, bronchitis, blood in sputum / hemoptysis Paragonimus westermani / Japanese Lung Fluke / Oriental Lung Fluke - once in lung --> worm stimulates inflammatory response = covers itself in graunulation tissue forming a capsule - eggs in surrounding tissue become pseudotubercles - worm becomes disseminated --> gets into spinal cord = paralysis - capsules in heart can cause death

(TEST): A 23-year-old woman presents to a local emergency department in Rankin County with a fever, severe headache, and stiff neck. She has recently moved into a small trailer on her family farm and reports that she has had a "lot of trouble with mice" getting into her new home. A likely cause of this zoonosis is

*lymphoctic choriomeningitis virus (LCMV)* ssRNA --> - helical --> enveloped --> B*A*DPROF --> Arenavirus = Lassa/*LCMV* (via *mice*)

(TEST): Herpesviruses can establish latency in neurons and

*lymphocytes*

(TEST): A 23-year-old woman presents to a local emergency department in Rankin County with a fever, severe headache, and stiff neck. She has recently moved into a small trailer on her family farm and reports that she has had a "lot of trouble with mice" getting into her new home. A likely cause of this zoonosis is

*lymphocytic choriomeningitis virus (LCMV)* ssRNA --> - helical --> enveloped --> B*A*DPROF --> *Arenavirus* = Lassa, LCMV

(TEST): Virus infection is often accompanied by the down regulation of MHC Class I on infected cells. The reduction in MHC class I surface expression

*makes possible the killing of virus-infected cells by NK cells*

(TEST): Due to conserved antigens between members of this virus family, immunization with vaccinia virus may provide protection against

*molluscum contagiosum* - caused by poxvirus Vaccinia virus = vaccines - other poxviruses also used a s live recombinant vaccines

BK Polyomavirus causes

*nephropathy* hemorrhagic cystitis - adenovirus does this in young boys who go swimming

(TEST): A 51-year-old male, diagnosed as HIV-positive in 1995, reported the abrupt onset of fever, headache, and chills 24 hours prior to being seen at the emergency room. He was found to be positive for influenza B using a rapid test. His CD4 count was 180 cells/mm3 at his last appointment. He was admitted for observation, and oseltamivir (Tamiflu) therapy for influenza was initiated. Over the next four days, his condition worsened. A sputum sample was sent to the State Department of Health, from which oseltamivir-resistant influenza B virus was cultured. Genomic sequencing showed that the virus had acquired a key mutation not found in other influenza B viruses circulating in the general population. This mutation is most likely in the gene encoding

*neuraminidase (NA)*

(TEST): A sputum sample was sent to the State Department of Health, from which oseltamivir-resistant influenza B virus was cultured. Genomic sequencing showed that the virus had acquired a key mutation not found in other influenza B viruses circulating in the general population. This mutation is most likely in the gene encoding

*neuraminidase (NA)*

(TEST): The marked stability of noroviruses in the environment is likely a reflection of its

*non-enveloped icosahedral capsid* ssRNA --> + icos --> *naked* --> *C*HRP = Calici --> Norovirus

Enterovirus

*poliovirus (3), human enterovirus A (10), B (36), C (11), and D (2), nee Coxsackie A & B, ECHOvirus* - family = picornavirus - originally classified into four groups: poliovirus, Coxsackie A virus (CA), Coxsackie B viruses (CB), & echoviruses - fecal-oral route

Pretest probability depends on

*population* Pretest probability - varies directly with PPV - high pretest probability --> high PPV

Most DNA viruses replicate in nucleus. Exception is

*poxvirus* - carries own DNA-dependent RNA polymerase = brick-shaped complexes - envelope - DS & linear = largest DNA virus - smallpox eradicated world wide by use of live-attenuated vaccine - cowpox (milkmaid blisters) - molluscum contagiosum

Now routinely used for the rapid diagnosis of CMV infection in immunocompromised patients.

*pp65 CMV antigenemia test* - CMV antigen can be detected in blood, & is only present when virus is replicating Buffy coat: - CMV invades WBCs --> culturing buffy coat increases culture yield Polymerase Chain Reaction (PCR) - CMV DNA can be detected from blood - only detectable when virus is replicating

Appropriate therapy for trematode (fluke) infections

*praziquantel (Biltricide)* - causes paralysis of worm via increased cell membrane permeability of calcium - most effective drug against all types of *fluke infections*, including blood fluke infections (schistosomiasis), intestinal & liver fluke infections, & lung fluke infections (paragonimiasis) - also useful in treatment of tapeworm infections

Treatment for Taenia solium intestinal tapeworms

*praziquantel (Biltricide)* Taenia solium - intestinal tapeworm - ingestion of larvae encysted in undercooked pork - hooks on proglottid heads of T. solium seen on O&P - treatment = *praziquantel*

(TEST): The most appropriate treatment for human trematode (fluke) infections, with the exception of Fasciola infection, is

*praziquantel*

A vaccine is available for protection against Rotavirus. The immunizing agent for this vaccine is

*preparation of reassortment viruses* - segmented dsRNA genome of rotaviruses formed basis of prep of pentavalent rotavirus vaccine (RotaTeq) = reassortment viruses

(TEST): Viremia refers to

*presence of virus particles within blood*

Appropriate prophylaxis for malaria relapses from Plasmodium vivax infection

*primaquine phosphate* / 8-aminoquinoline - in combo with cloroquine: used to eliminate liver hypnozoites after expsosure to P. vivax or P. ovale for terminal prophylaxis & (radical) cure

The first viral-induced defense mechanism in a nonimmune individual is

*production of interferon* - induces antiviral replication proteins in neighboring cells - before appearance of any other viral-induced immune defense mechanisms

JC Virus (JCV) associated with

*progressive multifocal leukoencephalopathy (PML) patient* dsDNA --> PAP*P* --> Polyoma = *JC*, BK

(TEST): Treatment of rotavirus infections in children involves

*replacement of lost fluids and electrolytes*

Giving vaccine for previous exposure!!!

- booster - don't given immunoglobulin

(TEST): To help pay off your student loans, you are "moonlighting" in the emergency room of a small rural hospital over the Easter weekend in early April. At 2 am, parents of a 14-month-old boy bring him to the ER with symptoms of croup: runny nose, fever, and barking cough. He is otherwise healthy, and completely up-to-date on all of his vaccinations, including the trivalent influenza vaccine given in October. You examine his throat and note that his tonsils and throat appear normal, and a rapid antigen detection test for Streptococcus A is negative. The most MEDICALLY APPROPRIATE course of action would be to

*send the child home with no medications, but have the parents monitor for changes in the child's condition.* - treatment of croup = supportive care --> clears up in 3-5 days usually

All RNA viruses, except reovirus, are

*single stranded* Reovirus - no envelop - *DS linear* - 10-12 segments - icosahedral = Coltivirus - Colorado tick fever = Rotavirus = #1 cause of fatal diarrhea in children - via NSP4 toxin

(TEST): Fasciolopsis buski method of diagnosis

*stool exam for ova (eggs) & parasites*

(TEST): Giardia lamblia method of diagnosis

*stool exam for ova (eggs) & parasites* - multinucleated trophozoites or cysts in stool - antigen detection

(TEST): Epigenetic factors can influence viral latency by

*suppressing transcription of viral genome*

(TEST): HAART therapy is recommended for health care workers who

*sustain percutaneous exposure (needle stick) to blood from high- & increased-risk patients*

(TEST): A positive-strand RNA virus, such as poliovirus,

*synthesizes viral proteins as a polyprotein rather than as individual gene products.* - replicative feature common to both HIV-1 & poliovirus = presence of viral polyproteins

Polyomavirus: early gene. de-activates PP2A

*t antigen* dsDNA --> naked --> Polyoma = BK, JV

(TEST): Despite the fact that 100% of medical staff at a particular hospital were vaccinated with the current trivalent killed influenza vaccine, a number of workers reported influenza-like symptoms and were diagnosed as being positive for influenza A by a rapid antigen test. The most likely cause of this event is

*the fact that the vaccine is not 100% effective in all vacinees*

(TEST): Carol is a Mississippi spinner and weaver who spins wool from her own herd of sheep (Bah!!). She presents in your office with a festering sore on her right index finger. Among possible etiological agents, a likely possibility would be

*the poxvirus Orf*

(TEST): The replicative feature that is common to both HIV-1 and poliovirus is

*the presence of a viral polyprotein* - positive-stranded RNA virus, like poliovirus, synthesizes proteins as polyproteins rather than as individual gene products ssRNA --> + icos --> naked --> CHR*P* ssRNA --> + icos --> enveloped --> C*R*FT

Infection with Fasciola hepatica, a leaf-shaped worm which is acquired by eating encysted metacercariae on aquatic vegetation and infects the bile ducts, is usually diagnosed by

*the presence of operculated eggs in a stool sample.* Faciola hepatica / common liver fluke / sheep liver fluke = parasitic trematode - plant/food-borne trematode infection - acquired via eating *parasite metacercariae* encysted on plants - important parasite of sheep & cattle

(TEST): The Salk inactivated poliovirus vaccine triggers

*the production of anti-viral IgG that prevents paralysis.*

(TEST): Enteroviruses encode a protease that cleaves

*the viral polyprotein & generates viral structural & catalytic proteins*

BK Polyomavirus nephropathy classically seen in what patients?

*transplant patients* - commonly targets kidneys - can be confused with adeno (kid swimming in pool)

(TEST): In terms of protection from smallpox, variolation differs from vaccination in that variolation

*utilizes live smallpox virus as the immunogen* Variolation / Inoculation = method first used to immunize individual against smallpox (Variola) with material taken from patient or recently variolated individual in hope that mild, but protective infection would result

(TEST): The parents of a three-year-old boy newly diagnosed with acute lymphocytic leukemia are concerned about the possibility of his being exposed to influenza virus during travel to a specialist Children's Hospital where he will receive treatment. The best option for this child would be to

*vaccinate with a "killed" tetravalent influenza subunit vaccine only* Killed: *PAIR* Salk *P*olio H*A*V *I*nfluenza (*I*ntranasal) *R*abies

LARGE DNA viruses (Herpes, Adeno) use

*virally encoded* DNA polymerase

(TEST): Whether an enveloped virus is uncoated at the surface of the cell or within an endosome is primarily dependent upon

*whether the viral fusion protein requires an acid or neutral pH to be activated*

(TEST): Among the alternatives below, the greatest chance of an HIV-1 infected individual transmitting HIV-1 to an uninfected individual via a single sexual encounter would be

*within a week or two of the initial infection* - patients recently infected with HIV typically have viral loads in excess of 50,000 copies/mL within 4 weeks of infection - highly infective when acutely infected

Herpes Gladiatorum =

*wrestler's herpes or mat pox* - via HSV-1 - athletes usually - may develop lesions anywhere on face or body

Recognize Aspergillosis

- A. gumigatus - Bart Simpson's hair; all round = A. flavus

Rotavirus Vaccines

- An early vaccine (RotaShield, 1998) was withdrawn in 1999 due to the risk of intussusception. - Two vaccines are approved for the USA (RotaTeq [2006] and RotaRix [2008] ). - RotaTeq is a pentavalent, *live attenuated bovine-human reassortment* vaccine. - RotaRix given as two doses.

Be familial with HBV resolution

- HBsAg appearing = active transcription - HbeAg = diagnostic in the past = don't use it anymore - symptoms = CMI attack of liver - antibodies begin being produced, especially antiHBc - early = IgM, later = IgG (after first couple of months) - later = anti-HBs = resolution *IMMUNE TO FUTURE HBV INFECTIONS*!!!

Pathogenesis of Smallpox

- Infection of the URT via inhalation or exposure to infected scabs (less effective) - Incubation period (5 - 17D). - High fever, fatigue, myalgia, headache (2-4D) - Vesicular rash in the mouth (enanthem) (4D) - Pustular rash appears simultaneously on the body along with vomitting, diarrhea, bleeding (5D) - Pustules scab over and fall off (11D)

Be familial with HBV with no resolution

- No HBsAb - lots of HBsAg - don't have protective antibodies - worse in neonates; usually resolution in adults

Vaccination is contraindicated in *some* people (have what conditions)?

- immunosuppressed - history of allergy components: many vaccines produced in chicken eggs & can't be tolerate by people with extreme allergies to chicken eggs

Know how to read Western blot to confirm HIV infection

- need at least 2 matches - p24 looked for usually

Describe HPV genome

- origin of replication binds --> transcription - E6 & E7 made first - cells go back into cell cycle after - accumulation of E1 (replication protein) & E2 (transcription factor) - L1, L2 = capsid proteins = late stages only in differentiated

Recognize *disseminated Candidiasis*

- recognize lesions!!!

Know Poliovirus Proteases

- single copies = 5S particles - protomers form pentamers --> 12 of the pentamers form capsid = concentration-dependent = happens spontaneously

Classic vs. Variant CJD

- vCJD = BSE in humans

Chance of getting HIV after needle stick

0.33%

Most problematic serotype of Rabies virus

1

What triggers apoptosis

1. *Activation of PKR by dsRNA* 2. Receptor binding and inappropriate signaling 3. *Mitochondrial damage* 4. Unscheduled DNA synthesis 5. ER overload/Ca++ flux

Function of *2A protease* encoded by CxB4

1. The viral polyprotein 2. eIF-4G leading to host translational shut-off 3. Heart muscle dystrophin leading to cytoskeletal dysfunction. - Infection of heart muscle myocytes is a significant cause of acquired dilated cardiomyopathy in humans. EnB (Cosackie B): Bornholm Disease / Devil's Grip = attacks of severe pain in lower chest: one side

(TEST): The genome size of a typical herpesvirus is approximately

100 to 250 kilo base pairs (kbp)

The incidence of herpes zoster is higher among patients who are immuno-compromised. What is the approximate incidence of herpes zoster in HIV- infected patients compared with the general population?

15 times higher

If the viral load is below ____, there are no transmissions of HIV

1500

Cervarix covers what HPVs?

16, 18 (no protection against major genital wart types)

Bacteria generation time

20 minutes

What trimester is associated with the highest risk of congenital CMV?

2nd trimester - hydrops fetalis - heart failure --> severe edema with fluid accumulation in multiple compartments

In the event of an outbreak, vaccination needs to be given within

3 days of exposure to be effective - *no anti-viral drugs available for smallpox treatment* = prevent infection!!!

Emergence of Zoonotic Viruses From a Wildlife Reservoir

4 events required: 1. Interspecies contact 2. Cross-species virus transmission = spillover 3. Sustained transmission 4. Virus adaptation within spillover species

Number of PEP treatments given in the United States each year is unknown; however, it is estimated to be about

40,000-50,000 - Course of rabies immune globulin and four doses of vaccine given over a two-week period typically exceeds $3,000. - Estimated public health expenditures on rabies disease diagnostics, prevention, and control in the US is $245 to $510 million annually.

How many *segments* do Influenza A & B have?

8 - each segment codes 1-2 genes BOAR = 3, 8, 2, 11 - Hepatitis C = 7 - Thogoto & Dhori viruses = 6 = horses, camels - Isavirus = 8 = fish/salmon

Barrier that defines AIDS from HIV

<200 CD4+ cell/mm^3

Highly variable incubation period of Rabies

= 20-90 days = shorter for bites on head than extremities - only 6 cases = recovery - classic/furious rabies vs. paralytic/dumb (20%) rabies - hydrophobia = fear of water - muscle spasms in throat = can't swallow - neuro period followed by coma (2 weeks) & death

HHV-8

= Kaposi's = gammaherpesvirus

NPV

= TN/(TN + FN[false negative])*100% = How likely is a patient with a negative result to be a TN?

PPV

= TP/(TP + FP[false positive])*100% = How likely is it a patient with a positive result to be a TP?

Contact lens users are at risk for corneal infection characterized by keratitis with a ring infiltrate by which of the following organisms?

Acanthamoeba spp.

- converted by herpesvirus thymidine kinase to monophosphate - converted by cellular enzymes to dGTP analog which - inhibits viral DNA polymerase - Useful for HSV, VZV infections

Acyclovir/famciclovir

In 50% of children with Adenovirus, Abs against

Ad1, 2, 5

Serotypes of Adenovirus that cause Gastroenteritis and diarrhea in children

Ad40 & Ad41

Treatment for Fungal Sinusitis - Zygomycetes (Mucomycosis)

Aggressive debridement + Amphotericin B

Four genera of oncogenic viruses

Alpha (Rous Sarcoma Virus) Beta (Mouse Mammary Tumor Virus) Gamma (Feline Leukemia Virus) Delta (HTLV-1)

3 most common causes of vulvovaginitis in premenopausal women

Bacterial vaginosis Yeast (usually Candida species) Trichomonas vaginalis

(TEST): Administration of human interferon to a patient suffering from an unknown viral infection will

inhibit virus replication by inducing multiple anti-viral molecules (PKR)

Point mutations in viral genome, leading to changes in hemagglutinin &/or neuraminidase molecules.

Antigenic *drift* - epidemics, like seasonal flu = minor (antigenic drift)

Antigenic changes in which pieces of RNA are shared between different species

Antigenic *shift* - reassortment - pandemics = outbreaks over multiple continents/worldwide - segmented

Types of Togavirus

Arboviruses (Arthropod vector): Rubivirus: *Rubella* / German measles / 3-day measles - not an arbovirus because humans are the only infected creatures - via respiratory secretions - red maculopapular rash = forehead --> face --> extremities - young women can develop self-limiting arthritis = TORCH: first trimester worst - live attenuated rubella vaccine Alpha viruses: *Eastern equine encephalitis, Western equine encephalitis, Venezuelan equine encephalitis* = mosquito-borne - cause encephalitis, focal neurologic deficits

(TEST): Integration of viral DNA into the host chromosome is seen in the early stages of oncogenic transformation of some virus-infected cells. These integration events

represent a "dead end" for replication of HPV

Number one *nematode* infection worldwide

Ascaris lumbricoides / Roundworm

Loeffler's Syndrome, a pneumonitis plus peripheral eosinophilia due to larval forms migrating thru the lung, is observed during human infection for each member of this group.

Ascaris lumbricoides, Necator americanus, Strongyloides stercoralis

A 39-year-old man develops fever, cough, wheezing, & shortness of breath. The patient reports that he passed a worm in his stool, but could not bring himself to collect it. Lab analysis of a stool sample reveals characteristic eggs. A photomicrograph is shown. What immune mechanism does this body use against the most likely causal organism?

Ascaris lumbricoids - intestinal nematode - largest roundworm - most common helminth infestation worldwide - *body reacts to tissue parasite, such as nematodes, by coating them with IgE Abs, which trigger eosinophil-mediated cytotoxicity & release of vasoactive & spasmogenic substance from mast cells & basophils (type I HS)*

Halo sign on CT indicates

Aspergillosis - nodule with halo around it - air crescent eventually forms

Antigen for *Aspergillus*

Aspergillus *galactomannan* - also other fungal infections = not specific

Most Rabies are diagnosed when?

Autopsy - DFA staining of biopsy or necropsy (animal or human) the standard Saliva - RT-PCR/Isolation of virus in cell culture (BSL4, RG4) - Neck biopsy -RT-PCR & IF staining for viral antigen - Serum/CSF

AntiHBe antibody present in

resolved infections - window, chronic (low infectivity), or recovery

Hydrops fetalis

B19V uses the blood group cell receptor P antigen found on erthroblasts, megakaryoblasts, endothelial cells, and fetal myocardial cells. - <5% of B19V-infected pregnant women miscarry.

Examples of Live Attenuate Vaccines

BCG Influenza (intranasal) Measles Mumps Polio (Sabin) Rotavirus Rubella *Varicella* Yellow fever BIMM PRR VY

Only animal that survives rabies.

Bats

likely reservoirs for SARS, Nipah, Hendra, Marburg, and Ebola viruses.

Bats - May carry and shed virus for a long time without getting sick and without clearing the infection - Habitat degradation pushes them closer to humans. - Bats are frugivores, but don't swallow the fruit, they chew, extract the sugars, and spit out the rest. Other animals eat the droppings and acquire virus from them. - *may be reservoir for Paramyxovirus!*

(TEST): Which of the following has the steps of the lifecycle of an enveloped non-segmented negative sense single-stranded RNA virus such as Respiratory Syncytial virus ordered correctly?

Bind cell surface --> Fuse with plasma membrane --> Transcribe viral mRNA --> Translate viral Protein --> Replicate genome --> Assemble virions

(TEST): Vector of onchocerciasis (Onchocerca volvulus infection)

Black flies

Segmented negative strand virus. Causes neurological disease in horses, cattle sheep. Anti-Abs have been detected in humans with psychiatric diseases.

Bornavirus (Bornaviridae)

Often seen in Belize. Causes myiasis.

Botfly

What candida should *not* be treated with Amphotericin B

C. lusitaneiae

Selzentry targets / Maraviroc

CCR5 - cell etnry

HIV gains entry via what receptors?

CCR5 receptor in early stages - on macrophages CXCR4 in late stages - on T cells

Two factors are important in predicting progression to AIDS

CD4 counts *RNA levels as determined by qRT-PCR*

What cells does HIV-infect?

CD4+ cells - has ability to cause immunosuppression

What cells can be infected with HIV-1?

CD4-negative cells - CCR-negative cells cannot

Rabies: Neuronal attachment: binding to a ganglioside and independently to the neural adhesion molecule. Via

CD56

Biopsy of a patient with esophagitis reveals enlarged cells, intranuclear & cytoplasmic inclusions, & a *clear perinuclear halo*

CMV

Number one cause of sensorineural hearing loss in children

CMV

Owl's eyes inclusion suggests what virus?

CMV

Most common fetal viral infection

CMV - blueberry muffin rash - hepatosplenomegaly & jaundice - sensorineural deafness - ventriculomegaly - periventricular calcifications --> seizures = TORCH infection

(TEST): Infectious mononucleosis can be caused by

CMV or EBV

(TEST): Cysticercosis, infection with Taenia solium larval forms, is most frequently symptomatic when present in

CNS

What to do if patient has HIV and +RPR and neurologic signs:

CSF exam recommended

T-tropic uses a different co-receptor than M-tropic virus:

CXCR4 vs CCR3/5

What Candida species should *not* be treated with azoles?

Candida *krusei*

Cysteine aspartases

Caspases - series --> cascade

Red Bugs

Chiggers - itching for weeks after they leave - Scrub Typhus

(TEST): In what arboviruses are humans part of the cycle?

Chikungunya Dengue Yellow Fever Zika *CDYZ*

Most common STD in *US*

Chlamydia

Uncommon presentation of Histoplasmosis associated with calcifications

Chronic cavitary disseminated histoplasmosis

dCTP, converted by cellular enzymes to active triphosphate which inhibits DNA polymerase - thymidine kinase independent

Cidofovir

Antibiotic that can weaken condom

Clindamycin

Member of Coltivirus fam. Rocky mountains (above 4000 ft). Maintenance host is Dermacentor andersoni. Amplifier = ground squirrels & chipmunks. Incidental host = man.

Colorado Tick Fever Virus - incubation period = short = 3-4 days - symptoms look like flu - biphasic fever - leukopenia early on - ELISA diagnosis

First step of diagnosis of viral diseases

Constitutional symptoms

What family are SARS & MERS in?

Coronavirus

Five techniques of diagnosing viral diseases

Culture virus in vitro - Considered "Gold Standard" for many viral diseases Detect viral *antigens* - e.g. rapid tests for 'flu, RSV, etc - typically saliva - positive = line Detect antiviral *immune response* - ELISA and western blot tests for HIV - looking for antiviral antibody - *bead-based technologies work the same way- except the antigen is linked to a polystyrene microbead* Detect activity of viral enzymes - e.g. HIV RT assay, ZstatFlu Detect viral genomes - (RT)PCR, Hybridization assay (Southern blot, Northern blot) - HPV

Verruca vulgaris =

Cutaneous common wart - via HPV 1-4

Naked (nonenveloped) viruses include

DNA = *PAPP*y is naked Parvovirus - B19 Adeno Papilloma - HPV Polyoma - JC, BK RNA = *Naked* chicks *CHRP* Calici - Norovirus Hepe - HEV Reo - Rotavirus, Coltivirus Picorna - PERCH = polio, echo, rhino, COX, HAV

Herpes: beta genes mostly

DNA polymerase - early

Occurs when you are infected with a second serotype of Dengue

Dengue Hemorrhagic Fever --> can lead to Dengue Shock Syndrome - 2nd serotype interacts with antibodies = Ab-Dependent Enhancement

When HPV DNA is integrated into cancer...

E2 deleted --> losing modulation of transcription of E6 & E7 --> uncontrolled

(TEST): . Human papillomaviruses (HPV) are described as being high and low risk for progression to cervical cancer. High and low risk viruses differ as to whether or not their

E6 proteins can target cellular p53 for destruction

Screening for HIV done with

ELISA test - confirmation test done with Western blot

Major complication of West Nile Virus

Encephalitis - also causes flaccid paralysis, seizures, coma

Represents another mechanism of RV-induced diarrhea. However, it is likely that multiple mechanisms are responsible for the severe fluid loss associated with RV infection.

Enterotoxic activity of NSP4

Lice can transmit

Epidemic typhus - Rickettsia prowazekii Trench fever - Bartonella quintana Relapsing fever - Borrelia recurrentis

How frequently are Pap smears done?

Every 3 years under the age of 65

Undergoes huge conformation change for Paramyxoviruses

F protein - G protein of VSV does same thing

2 types of Myiasis

Facultative - accidental or opportunistic - wound, death Obligate - required for bug's life cycle - adapted to this lifestyle - screwworm - have to live in living thing, so they eat it - mistake malodorous wound for death thing

Infectious material on surfaces. Typically due to aerosol or droplets that has fallen on surface.

Fomites - wash yo hands!!!

VZV Prevention:

For urgent protection: passive immunization (Zoster immunoglobulin, ZIG) *Live attenuated vaccine* available Routine administration: 12-18 months of age Catch-up vaccination: 19 months through 12 years Shingles: vaccine for older adults who have not yet had shingles

Receptor binding protein of Rhabdo & Pneumo

G

West Nile virus NS1 protein blocks

complement activation

Converted by CMV phosphotransferase to monophosphate. Converted by cellular enzymes to triphosphate. Competitively inhibits dGTP incorporation and viral DNAp.

Ganciclovir

Treatments for CMV

Ganciclovir Foscarnet - when virus has UL97 gene mutation

Significance of Genotype 1 for Hepatitis C

Genotype 1 = no interferon response - STEP!!!

HPV *6, 11, 16, 18* inactivated subunit vaccine

Guardasil

(TEST): Pathology is caused by immune attack on virus infected cells, not directly by virus. Which hepatitis viruses (A, B, or C?)

HAV, HBV, HCV

Why is Hepatitis C RNA prone to frequent mutations?

HCV *lacks 3'-5' exonuclease activity* --> variation in antigenic structures of HCV envelop proteins ssRNA --> + icos --> enveloped --> CR*F*T --> Flavi = *HCV*, WNV, St .Louis encephalitis, Yellow Fever, Dengue

Knowing the genotype of the causative virus is important in determining the treatment of chronic

HCV infections - only genotypes 2 & 3 of HCV = likely to respond to currently recommended combo treatment with pegylated interferon-alpha & ribavirin for chronic HIV infections

HIV test for neonate

HIV RNA & HIV DNA nucleic acid amplification tests - virus itself & not the antibodies

Associated with clearance of chronic HBV

HLA-DR*04 *& DR*13* DNA (+ icos) --> enveloped --> Hepadna --> HBV

No vaccine is 100% effective in all people. Why?

HLA: some people don't respond well/at all to specific antigen based on genetic makeup - not making antibodies measured in vitro

Receptor binding protein of Paramyxo

HN (or H) - HN = parainfluenza, measles = neuraminidiase activity - H = mumps

Most common STD

HPV

this is a dead end for the virus- no infectious progeny can be produced! Cell lines: HeLa (HPV 18), SiHa (HPV 16)

HPV DNA integration in cancer

Why is there no convenient cell culture for HPV?

HPV only grows in primary keratinocytes, requires organotypic culture to produce high levels of DNA or capsid antigen.

Biopsy of a patient with esophagitis reveals large, pink, intranuclear inclusions & host cell chromatin that is pushed to the edge of the nucleus.

HSV

First identified human retrovirus

HTLV-1 - vertically to newborns - T-cell lymphomas

Partially stranded DNA - only human virus that does that =

Hepatitis B

A sexually active 37-year-old woman comes to the physician because of a 2-day history of pain in the area of her genitals. Pelvic examination shows shallow, small, extremely tender ulcers with red bases in the vulvar and vaginal regions. A Tzanck smear shows the presence of multinucleated giant cells. Which of the following infectious agents is the most likely cause of these findings?

Herpes simplex virus

CMV is in what DNA family?

Herpes virus family dsDNA (+ icos) --> enveloped --> H*H*P --> Herpes virus --> *CMV*

principal agent of croup in 0.5 - 3 year old children

HuPIV-1 - parainfluenza

second leading cause of bronchiolitis and pneumonia in 1 - 3 year olds.

HuPIV-3 - paralinfluenza

Most common congenital (1:150) infection in United States

Human Cytomegalovirus: = 2nd most common cause of mental retardation after Down's Syndrome Fetal mortality Sensorinueral hearing loss Blindness Mental retardation

Virus responsible for Roseola / Exanthema subitem

Human Herpes Virus 6 - DNA virus = Rose6ola = Herpes virus family

Responsible for 3 - 15% of URTIs. Estimated that ALL CHILDREN are seropositive by age 5 !

Human Metapneumovirus (HMPV)

Poxviruses block anti-viral cytokine responses by encoding soluble receptors for...

IFN gamma, TNF alpha, and IL-1

Serology Lab Diagnosis of CMV

IgG antibody indicates past infection IgM indicative of primary infection

(TEST): Vaccination with a live attenuate vaccine generates...

IgG, mucosal & serum IgA, & anti-viral CTLs

HAV diagnosis

IgM antibody to hepatitis A virus (anti-HAV) positive Elevated serum aminotransferase (ALT/AST) levels

Polymorphic variation in the PrP gene influence the pathogenesis of transmissible prion disease

In humans, polymorphism at codon 129 of the PrP gene, encoding either methionine or valine: MM, MV, VV Frequency of the human polymorphisms: - MM homozygotes: 38% - VV homozygotes: 11% - MV heterozygotes: 51% All vCJD patients to date have been MM In cases of sporadic and iatrogenic CJD, 89% and 93% (respectively) of patients are homozygotes (MM or VV)

Become infected but transmission from them does not occur with sufficient regularity for stable maintenance (*dead-end host*)

Incidental host

(TEST): Function of RIG-I

Induces type I interferon

Block integration of the HIV provirion into the host cell chromosome and thus prevent formation of HIV mRNA and genomes

Integrase Strand Transfer Inhibitors (ISTIs)

Infectious rhinitis: common cold caused by

coronavirus, rhinovirus, adenovirus, echovirus *race*

Influneza type that causes epidemics & pandemics

Influenza *A*

Vast majority of bird flu

Influenza A virus *H3N2* - can infect birds & mammals - abundance in seasonal influenza - first detected in people in July 2011 - first identified in US pigs in 2010

Resolves ongoing infection and may provide type specific (i.e., anti-type A virus) protection. Ineffective memory T-cell response?

Influenza virus-specific CTL

Genus of HIV

Lentivirus

Definition of Prion "Strains"

Isolates have specific incubation times in specific hosts Isolates have specific distribution of vacuolar lesions Isolates have distinct patterns of PrPsc accumulation in the CNS Isolates have distinct glycosylation patterns

MMR: Mumps Vaccine-induced protection

Jeryl Lynn attenuated strain Grown in chicken embryo fibroblasts - One dose of MMR is 73-91% clinically protective (prevents parotitis lasting > 2 days) - 2 doses are 76 - 95% protective. Transmission can occur among individuals in close contact (colleges, camps) when >10 yrs has passed since last immunization.

Most common Carbapenem-resistant Enterobacteriaceae (CRE) in US

Klebsiella pneumoniae Carbapenemases (KPC) - spread by clonal dissemination - Israel had early experience with this - highest ever reported moratlity for bacteremia - colistin was useful in treatment but China had resistance recently (mcr-1)

Target for nucleos(t)ide analogues (RT inhibitors/chain terminators)

Lamivudine (3TC- also used for HIV) nucleoside analogue frequently see active site mutations (YMDD) Adefovir (HBV specific) nucleotide analogue see YMDD mutants (pol active site) mutations at other sites as well - YMDD = classic tetrad of polymerization

First found in West Africa. Member of Arenavirus fam. Maintenance host = Mastomys huberti mouse. Incidental host = man. *Nosocomial & secondary person to person transmission.*

Lass Virus - common complication = *permanent* deafness - multi-organ failure - dangerous in pregnant women!!! - treatment = ribavirin; correctino of capillary leak syndrome

Vaccine for Varicella Zoster virus

Live attenuated vaccine for children

The herpes zoster vaccine is made from which of the following components?

Live attenuated virus

Incubation period of HBV

Long = 60-90 days

Binds to SLAMs (Signaling Lymphocyte Activation Molecules) found on activated T and B cells, Macrophages, and Dendritic cells.

Measles - infection of these cells --> immune suppression - would test negative on PPD test regardless ssRNA --> - helical --> enveloped --> PaRaMyxo = parainfluenza, RSV, mumps, measles

(TEST): Treatment for Ascaris (roundworm) and Enterobius (pinworm infections)

Mebendazole

Gold standard of diagnosis of viral diseases

culture virus *in vitro* - requires tissue culture cells or other biological material - often slow (>7 days) - some viruses not culturable (HPV, HCV)

Member of Arenavirus fam. Worldwide distribution. Incidental host = man. Mode of transmission = aerosols from rodent excreta, etc.

Lymphocytic Choriomeningitis Virus (LCMV) ssRNA --> - heliv --> enveloped --> B*A*DPROF

Live attenuated vaccines

Lyrics/*MYRICSS* MMR Yellow fever Rotavirus Influnza Chickenpox Smallpox Sabin polio virus

Member of Coronavirus fam. Found in camels. 65% males.

MERS / Middle Eastern Respiratory Virus

All viral gene products can be presented via

MHC I

Most common arthropod infectious disease

Malaria

Phosphotidylserine flips from inside the membrane to outside the membrane and serves as an "eat me" signal to macrophages. Engulf of apoptotic bodies improves antigen presentation and prevents unwarranted recognition of self antigens.

Membrane flipping

(TEST): Naegleria fowleri method of diagnosis

Microscopic exam of CSF

Diseases caused by Adenovirus

Military recruits' disease Infant diarrhea Enteritis and respiratory disease Keratoconjunctivitis Pharyngitis, conjunctivitis, pharyngealconjuctival fever 5% of acute URTI in children < 5 yr are due to adenovirus infections In military recruits, Ad4 and Ad7 have caused serious outbreaks (infection rates of 80%; hospitalization rates of 20 - 40%).

Rabies: Glycoprotein spikes attach to specific sites, such as the

NAR

downregulates CD4 and MHC class I from the cell surface

NEF - virus doesn't cause disease = vaccine strain possibly - knock out gene = live attenuated vaccine

Abs against HBsAg are

NEUTRALIZING - *basis of HBV vaccine* = made in yeast - Abs protective against virus in humans

Is Lyme disease prevalent in Mississippi?

NO - lyme disease in the South is controversial - not all erythema migrans diseases are lyme disease

Backbone of antiretroviral therapy

NRTIs = nucleotide analog - Zidovudine can be used for pregnant patients (start at 14 weeks gestation)

Where does Papovavirus replicate?

NUCLEUS - PApilloma - POlyoma = BK (kidney), JC (brain) - VAcuolating agent (SV40)

Friable cervix (bleeds when you touch it) with yellow discharge from cervical os (cervicitis), No tenderness on bimanual exam

Neisseria gonorrhea: Cervicitis (females)/Urethritis (men) - treatment = ceftriaxone

CxB and ECHO (EnB) Seen in children born to mothers who were infected within the last week of gestation...virus acquired during delivery...onset begins 3 - 7 days after birth *Principal presentation: Myocarditis or fulminant hepatitis...fatality rate ~ 50%* Management: Supportive, large doses IgIV, Pleconaril (compassionate use basis)

Neonatal Disease - deadly & little you can do

Sensitive test for Trichomonas vaginalis

Nucleic acid amplification test (*NAAT*) Also... - trophozoites (motile) on water mount - strawberry cervix

1st line drugs for HIV

Nucleoside and Nucleotide RT Inhibitors (NRTIs): *AZT (Zidovudine), 3TC (Lamivudine), tenofovir dioproxil fumarate/emtricitabine (TDF/FTC)* Non-nucleoside RT Inhibitors (NNRTIs): efavirenz Protease Inhibitors (PIs) + boost: *darunavir + ritonavir* Integrase Strand Transfer Inhibitors (ISTI) *Dolutegravir*

Acute infection of upper genital organs

PID Clinical clues: Female, age 15-44 Lower abdominal pain Fever (50% of cases) Cervical motion and adnexal tenderness

VA1 RNA (adenovirus) binds

PKR - *induced by interferon* - maintains viral protein synthesis by blocking the PKR-mediated inhibition of translation. - Viral Associated 1

Zoonotic diseases that can be transferred to human

Orf virus Pseudocowpox virus

(TEST): Treatment for acquired and congenital toxoplasmosis

PSF (pyrimeythamine, sulfadiazine, folinic acid)

Lentil-sized flat erythromatous papular eruptions on face, extremities Hepatomegaly, generalized lymphadenopathy Typically resolved in 15-20 days Associated with acute, anicteric hepatitis B (ayw subtype)

Papular acrodermatitis of childhood (Gianotti-Crosti syndrome)

Infection with this organism, acquired in the United States by eating raw or poorly cooked crayfish, is characterized by fever, hemoptysis, dyspnea, and chest pain.

Paragonimus kellicotti

2 groups of Paramyxoviruses

Paramyxovirinae Respirovirus: (Sendai Virus; HuPIV-1, - 3) Morbillivirus (Measles, rinderpest) Rubulavirus (Mumps, HuPIV-2, -4) Pneumovirinae Pneumovirus: RESPIRATORY SYNCYTIAL VIRUS (RSV) Metapneumovirus: Human Metapneumovirus (HMPV)

Administered after exposure to rabies

Passive immunization - killed vaccine --> active immunity

Topical applications for warts

Podophyllin Bi- or trichloroacetic acid (BCA/TCA) Sinecatechins

A 72-year-old man in good health presents to his family physician with fever and malaise that have lasted for several days. He also reports that he has developed an itchy, burning rash on the right side of his chest and back. All vital signs are within normal limits. Physical examination reveals an erythematous maculopapular rash with vesicles on the right side of the patient's back and chest wall. Based on history and physical examination, the patient is diagnosed with herpes zoster infection. Which of the following will this patient most likely experience as a result of herpes zoster infection?

Postherpetic neuralgia

Only DNA virus that completely replicates in *cytoplasm*

Poxvirus - makes its own envelope - has special DNA-dependent RNA polymerase = dumbbell shaped core

Largest known viruses infecting vertebrates

Poxvirus = *vaccinia virus genome is a covalently-closed, linear dsDNA molecule, = 200 proteins.* DNA: + icos --> enveloped --> pox = smallpox, cowpox, molluscum contagiosum

Treatment for Rabies

Pre-exposure: Vaccination postexposure: pre-made antibodies - thorough wound cleaning (can destroy enveloped virus) - rabies immunoglobulin (RIG) via IM - vaccinate site distant from site of RIG - 4 shots given on day 0 = on day of attack up to 7 days later Treatment: Milwaukee Protocol: induced coma; prolonged intensive care Milwaukee Protocol: Ketamine Amantadine Midazolam Phenobarbital Ribavirin

How is Hepatitis C transmitted?

Primarily *blood* (IVDU, post-transfusion) - especially 70s/80s - needle sharing or sticks HCV - enveloped icosahedral RNA virus in flavivirus fam - genotype 1 most common in US - transmitted parenterally, with primary means of infection being via injection drug use

Segments of tapeworms containing reproductive organs (male & female)

Proglottids

Severe, potentially fatal illness of smallpox that occurs in individuals with deficiencies in their cell-mediated immune system when vaccinated

Progressive vaccinia

HPV codes two proteins:

Proteolysis regulation: *E6 --> p53* - p53 = cell cycle checkpoint at G1S phase *E7 --> Rb* - Rb = tumor suppressor

Treatment goals of HIV

Pts should show a 1 log decrease in HIV RNA in 8 weeks and no detectable virus at 4 - 6 months.

Treatment of Enterobius vermicularis

Pyrantel pamoate Albendazole Mebendazole *PAM* has *P*inworms Enterobius vermicularis / Pinworm - simply life cycle = ingested --> mature in cecum & ascending large intestine --> female migrates to perianal area (at night) to lay eggs --> become infectious 4-6 hours later = perianal itching - diagnosis via scotch tape - change sheets daily!

"Regulatory" Proteins of HIV-1: promotes nuclear export of unspliced and partially spliced mRNAs.

REV - overrides splice sites --> transported messages to cytoplasm

What type of viruses make more mistakes?

RNA viruses

Tests for neutralizing antirabies antibody

Rapid Fluorescent Focus Inhibition Test

(TEST): The E7 genes of high-risk HPV types alter cell cycle regulation by binding, allowing E2F to induce transcription.

Rb

Patient heard that "on-demand" PrEP (that taken only in the context of sex) can also reduce HIV transmission and wants to stop daily use. What would you advise?

Recommend that he continue daily PrEP - increased chance of acquiring HIV

(TEST): Since no effective vaccine is currently available for this highly infectious disease of infancy, patients such as premature infants and infants with severe underlying respiratory conditions may be passively immunized using RespiGam or Palivizumab to prevent infection by

Respiratory Syncytial Virus (RSV)

AS OF DECEMBER 2015, this drug is licensed for combination HCV treatment

Ritonavir (HIV protease inhibitor)

HHV-6 (& 7)

Roseola Infantum (exanthum subitum) = *spiking fever over 2 days then rash* = possible co-factor for HIV-1 & HPV - co-infection with EBV

Difference between Salk and Sabin

Salk - IgG but no IgA or cytotoxic T cells - Abs in blood but not in mucus - inactivated = no local immunity = no CMR Sabin - IgA, IgG, cytotoxic T cell response - mimics natural infection - live vaccine = concurrent viruses may prevent functioning of this vaccine

Known as the Oriental blood fluke

Schistosoma japonicum

(TEST): Infection with each member of which of the following group of organisms can damage the liver?

Schistosoma mansoni, Fasciola hepatica, Echinococcus granulosus

Head or attachment portion of tapeworm. Attachment may be by suckers, hooks (armed), or both

Scolex

Most common presentation of neurocysticercosis

Seizures

HBV modes of transmission

Sexual Parenteral Perinatal

MRI of PML

Single or multiple confluent lesions without mass effects are seen most frequently in the parieto-occipital white matter. Occasional infratentorial lesions are usually asymmetrical. PML sometimes can resemble lymphoma, toxoplasmosis, or HIV encephalitis.

prolongation of the incubation time when prions from one species are transmitted to another species

Species barrier

Why is there not more Chagas Disease in the Southern United States

Species does not defecate when it bites, like those in South/Central America

Why is smallpox the perfect virus to eradicate?

Spread only by person-person contact, had no animal reservoir, possessed only a single serotype, and was readily identifiable.

HPV 6 & 11 like what epithelium?

Squamous epithelium

How do you confirm Strongyloides suspicion

Stool Ova & parasite --> *Larvae* not eggs --> look for track marks on agar Stool culture Serum ELISA - populations at risk = Population at risk for severe disease, hyperinfection & disseminated infection - children on steroids, children with malignancy, NOT HIV

A 3-year-old boy is brought to the physician because of a 2-day history of fever and an itchy rash. The rash began on his face and then spread to his trunk, arms, and legs. Several children at his day-care center have had similar symptoms. His temperature is 38.9°C (102°F), pulse is 100/min, respirations are 20/min, and blood pressure is 110/60 mm Hg. Physical examination shows multiple red papules and vesicles over the face, trunk, and upper and lower extremities. Some vesicles contain clear fluid, whereas others are crusted. Which of the following is the most likely causal virus?

Varicella-zoster virus

Entire chain of proglottids

Strobila

When does HBV vaccine have no effect with coinfection of HBV and HDV?

Superinfection on top of chronic HBV

Vitamin used to help reduce measle morbidity and mortality

Vitamin A

Cell fusion after measles virus infection

Synytium -unstable cells die

Pain of these genital ulcer diseases: Syphilis - Genital herpes - Chancroid - Lymphogranuloma venereum - Granuloma inguinale (donovanosis) -

Syphilis - painless Genital herpes - painful Chancroid - painful Lymphogranuloma venereum - painful Granuloma inguinale (donovanosis) - painless

Polyomavirus: suppresses early, enhances late transcription

T antigen

Endosomal Membrane TLRs that binds ds viral RNA

TLR3

Appropriate prophylaxis for Pneumocystis jerovicii (formerly carinii)

TMP-SMX (trimethoprim/sulfamethoxazole)

Infection with larval forms of this organism is the most common cause of seizures in Latin America.

Taenia solium

(TEST): A 29-year-old male who recently arrived from Mexico is brought to the UMC emergency room after suffering a seizure while working in the hot sun with a highway construction crew. On examination, he appeared to be healthy and his physical findings were all normal. Tests for infectious agents including stool ova and parasites were negative. The seizure responded to anti-convulsive therapy and he was released. Two weeks later he returned to the hospital after suffering another seizure. A CT scan showed two intraparenchymal ring-enhanced lesions measuring 8 mm by 1.5 cm and scattered punctuate calcifications. The results of serologic tests showed a strongly positive titer to antigens from which organism?

Taenia solium / Pork Tapeworm - humans via ingestion of undercooked pork infected with larvae Cysticerci in brain = Neurocysticercosis - 7-10 cysts in brain --> seizures, obstructive hydrocephalus, focal neurologic deficits - cysts grow slowly --> 5-10 yrs later = begin to die & leak fluid contents - endemic areas = Mexico, Center & South America, Philippines, SE Asia = most common cause of seizures there - Diagnosis via CAT scan or biopsy of infected tissue (brain or muscle) - treatment = albendazole or praziquantel - elevation of eosinophil level in blood

*TORCHeS* infections

Toxoplasma gondii Rubella CMV HIV HSV Syphilis

(TEST): Infection with each member of which of the following group of organisms can cause CNS pathology?

Toxoplasma gondii, Plasmodium falciparum, *Acanthamoeba spp.* Acanthamoeba = most common single-celled eukaryote in soil - found in fresh water = *keratitis & granulomatous amoebic encephalitis* (can cross BBB)

First intracellular step of replication of *negative-strand* RNA viruses

Transcription

First intracellular step of replication in positive-strand RNA viruses

Translation - *+RNA viruses DO NOT carry active viral RNA polymerase in the virions*

Strawberry cervix

Trichomonas vaginalis

Now used for immunization of smallpox

Vaccinia virus - more closely-related to camelpox, than to cowpox Smallpox vaccine (Dryvax) is administered by scarification with a bifurcated needle. It results in a localized infection characterized by a large, raised, vesicle that becomes pustular and eventually crusts over and falls off sometimes leaving a vaccination scar.

(TEST): Pre-exposure prophylaxis with this drug is recommended for sexually-active discordant heterosexual couples and men who have sex with men (MSM).

Truvada (a combination of two anti-HIV reverse transcription inhibitors)

Series of binding sites for transcription factors (like NFkB) in HIV

U3 - activate viral genome --> more viral particles = knock down CD4 cells

How to develop new vaccine...

Using Ebolavirus as model: *Identify target* - EboV surface protein (GP/glycoprotein) *Test in animal model* & in vitro *Phase I clinical trial* - small group studies - safety & dose *Phase II* - rarer side effects seen - further safety/efficacy *Phase III* - large population *at risk* of infection - need large control gropu *Approve/release* - data safe & efficacious *Phase IV* - sentinal phase = monitor outcomes in actual vaccinees for effectiveness, side effects = follow-up phase

Epidemiology of PML

Usually appears in hypergic adults Majority of patients between 40-70 yrs. old About half have had lymphoproliferative or myeloproliferative neoplasms (Hodgkin's disease, CLL) Carcinoma in various sites, sarcoid, TB, SLE AIDS patients (1-7%)

Kaposi's sarcoma causes dysregulation of

VEGF

Smallest herpes virus Largest herpes virus

VZV / HHV-3 CMV / HHV-5

Enhance replication or broaden host range of viruses

Viral efficiency genes

Impair host immunity in viruses

Viral immune evasion genes

Structure of Parvoviridae

Virions: Non-enveloped, icosahedral particles 18 - 26 nm in diameter. Genome: ssDNA, 5 kbp Erythrovirus: Human erythrovirus (a.k.a. B19V virus) DNA --> + icos --> naked --> *P*PAP --> ssDNA: Parvovirus = B19

A 34-year-old man comes to the physician because of a several month history of fever, chronic fatigue, weight loss, & night sweats. He has unprotected sexual intercourse with males & currently has more than 2 sexual partners. Lab studies show that he is HIV-positive by ELISA & Western blot. His CD4 cell count is 525/mm^3. He declines anti-retroviral therapy. What sets of findings is most likely to be present at his next visit? Virus, p24, RNA: CD4+: Anti-p24: Anti-env:

Virus, p24, RNA = increasing CD4+ = decreasing Anti-p24 = decreasing Anti-env = increasing slightly Asymptomatic phase of chronic HIV infection --> will soon enter the early symptomatic period = decline in immune function - As CD4 + cell declines further, ability to produce any isotype other than IgM will decline --> *Abs to capsid antigen (p24) will decline* - p24 is IgG in isotype = cannot be made without sufficient help from CD4 + cells - Abs to envelope Ags gp41 & gp120 will remain stable or increase slightly

Treatment of choice for *Aspergillus*

Voriconazole

Where do you see Coccidiomycoses?

West Coast

Member of Flavivirus fam. Worldwide distribution. Maintenance host = Culex species, birds. Amplifier hosts = birds. Incidental host = man. Mode of transmission = mosquito bite.

West Nile Virus - usually asymptomatic - paralysis - can have neuroinvasive diseases --> deaths - diagnosis via EIA or ELISA - no treatment but there is a vaccine for horses

Member of Togavirus fam. Western US, Canada. Maintenance host = Culex tarsalis mosquitos. Amplifier hosts = Culex & birds. Incidental hosts = man, horses. Mode of transmission = mosquito bite.

Western Equine Encephalitis Virus

vCJD Diagnosis

Western blot analysis Conformation Dependent Immunoassay - Monoclonal antibody specific for PrPSc - High sensitivity, unknown specificity MRI - Hypersensitivity in the pulvinar sign - Hypersensitivity in both pulvinar and dorsomedial thalamus (hockey stick sign)

(TEST): Flaviviruses with *intrauterine* infections

Zika, Dengue (rare)

(TEST): If vaccination with MMR were stopped today, it is likely there would be

a marked resurgence of measles, mumps, and rubella in the USA and the eventual return to periodic epidemics triggered by these viruses.

HBeAg present in

active infection! - resolved = none - acute or chronic = present

The potential for chronic liver disease following HBV infection is inversely proportional with the

age of infection - probability = over 90% with neonates

HSV-1 & HSV-2 are closely related

alphaherpes virus - both cause painful vesicles - both transmitted via close contact

HBV high in what fluids?

blood serum wound exudates

Initial findings of Paralytic Rabies (Dumb Rabies)

an ascending paralysis, resembling an acute polyneuropathy (GBS), or a symmetric quadriparesis - symmetric > asymmetric

4th generation tests for HIV diagnosis

anti-HIV IgM/IgG & detect p24

(TEST): An effective vaccine is not available to protect against HCV infection because

antibodies against HCV surface proteins are not capable of neutralizing HCV infection

(TEST): The number of individuals within the USA who are infected with HIV-1 but do not know it, is

approximately 200,000 people, or 20% of those infected.

(TEST): RT-PCR assays

are used to screen patient sera for the presence of HIV-1 and West Nile Virus.

Categories of HHV-6 & 7

betaherpesviruses - 6 = 6A and 6B

Smallpox efficiently spread by

bodily fluids

Enveloped viruses must ...

bud through membranes

Most common flee in this location

cat flee

Patient presents with *post-coital bleeding* = think:

cervical cancer

Anti-HBc present in

chronic = IgG acute = IgM - history of infection - not positive after vaccination

HAART increases the length of

clinical latency

Inner city asthma is often associated with

coackroaches

All RNA viruses, except orthomyxovirus, replicate in

cytoplasm

What happens to patients with EBV who are mistakenly given amoxicillin or ampicillin?

develop *maculopapular rash*

(TEST): The HIV-1 Rev gene is critical for successful virus replication because it

directs transport of incompletely spliced gag-pol & env mRNAs to cytoplasm

(TEST): Which of the following has components of herpesvirus virions litsted in the correct order from inside to outside?

dsDNA genome, Capsid, Tegument, Envelope

Sterile rash

exanthema

2 types of herpes gamma genes

gamma1 = transcribed before replication gamma2 = transcribed after replication gammaherpes viruses - HHV-4 = EBV - HHV-8 = Kaposi

Outer glycoprotein of envelop in HIV

gp120

Fuzeon/Enfuvirtide targets

gp41 - fusion inhibitor

Codes for transmembrane protein of envelope in HIV

gp41 = where CD4 binds

- stranded RNA viruses

helical --> enveloped --> BADPROF

(TEST): The enzyme responsible for the synthesis of HIV-1 mRNAs is

host cell DNA-dependent RNA polymerase II

B19 virus targets

human erythroid progenitor cells (BFU-E amd CFU-E) which are rapidly dividing cells capable of supporting virus replication.

(TEST): Classic Creutzfeldt-Jakob Disease (CJD) can be defines as inherited, sporadic, or infectious. Variant CJD is associated with bovine transmissible spongiform encephalopathies, and shares a number of features with classical CJD. Classical and variant CJD differ dramatically in the percentage of patients who develop ataxia and

in age of onset

(TEST): Up to 80% of antimicrobial use is...

inappropriate & may contribute to antibiotic resistance

(TEST): A naturalized American citizen from India recently participated in a church-sponsored mission trip to Peru. The 23-year-old woman developed a severe hemorrhagic fever with hemoconcentration and symptoms of shock. Ultimately, dengue fever virus was identified by PCR in the patient's serum and a diagnosis of Dengue Hemorrhagic Fever was made. This clinical picture typically occurs following

infection by a second, unrelated serotype in a patient previously infected by a heterologous serotype.

(TEST): A young man from Mississippi has just returned from his first trip outside the US where he worked for six months in Central America for a survey company. During this time, he developed classic Dengue Fever but had no hemorrhagic complications. Classic Dengue Fever typically occurs following

infection by any serotype of the virus in a previously uninfected individual.

(TEST): Cryptosporidium parvum mode of transission

ingesting the infective stage in fecally contaminated food or water

fCJD mutations

isolated families of Libyan Jews, Slovaks, and Chileans have *glutamate to lysine mutation at codon 200*

(TEST): Respiratory syncytial virus (RSV) is a common infection in both children and adults. Evidence of anti-RSV IgM antibodies in a 4-month-old child is

likely due to recent RSV infection

Immunity of Enteros

local IgA blocks infection; systemic IgG blocks paralysis due to poliovirus.

Monitoring active HBV infection

look for HBV *DNA*

Destruction of the LN occurs late in infection and may lead to an irreversible loss of immune function in HIV

lymph node architecture

A 23-year-old woman presents to a local emergency department in Rankin County with a fever, severe headache, and stiff neck. She has recently moved into a small trailer on her family farm and reports that she has had a "lot of trouble with mice" getting into her new home. A likely cause of this zoonosis is

lymphocytic choriomeningitis virus (LCMV).

Gender more likely to have HBV

males

Acute-phase proteins that activate the lectin pathway of complement

mannose-binding lectin (MBL) & filcolins

Appropriate therapy for Amebiasis and Giardiasis

metronidazole

Newer vaccines for smallpox

modified vaccinia Ankara (MVA)

(TEST): Toll-like receptors recognize pathogen associated molecular patterns and target viral

nucleic acid

Characteristics of viruses most definitive of viruses compared to to other pathogens

obligate intracellular parasite

Trichomoniasis, a sexually transmitted infection characterized by vaginal tenderness and a purulent foul-smelling vaginal discharge, is usually diagnosed by

observing motile trophozoites forms in a wet mount of a vaginal smear.

Ability of cell to support a productive viral infection

permissiveness

A 42-year-old man comes to the ED because of right upper quadrant pain & fever. He also has had a 2-month history of right upper quadrant pain & diarrhea with blood & pus in the stools. Physical exam shows a large, tender liver. Stool microscopy shows the presence of numerous cysts. Ultrasound shows an ovioid, hypoechoic lesion near the liver capsule. Exam of tissue obtained on biopsy of the liver wall will most likely show what?

pic = *Entamoeba histolytica* - intestinal amebic parasite - amebic dysentery = *bloody diarrhea with abdominal pain & dehydration, peritonitis, liver abscess formation* - cysts or trophozoites in stool = intestinal amebiasis - trophozoite of E. histolytica = *"cart-wheel" distribution* of chromatin in nucleus & evidence of ingested red blood cells - treatment = metronidazole

Codes for reverse transcriptase of HIV

pol

Largest known DNA virus

poxvirus

Set Point

progression marker for HIV want this as low as possible - high = progress faster than 8-10 years

(TEST): The nucleocapsid protein associated with the viral genome of influenza virus and measles virus

provide stability and protection to RNA genome

Acute-phase proteins that bind oligosaccharides on microbes, protein lung against infection

pulmonary surfactant proteins SP-A & SP-D

Treatment for toxoplamosis.

pyrimethamine + sulfadiazine

How to recognize *black widow*

red hour glass marking - bright - venom = *neurotoxin*

Bite from tick =

saliva --> hypersensitivity

Patients initially infected with HBeAg- mutant viruses more likely to have

severe (fulminant) hepatitis - high HBeAg correlates with chronic HBV

PID: pushing on cervix =

severe pain --> chandelier pain - tenderness on bimanual exam Gonococcal infection of cervix can progress to PID - infection of uterus/endometritis, fallopian tubes/salpingitis, ovaries/oophoritis - fever, lower abdominal pain, abnormal menstrual bleeding, *cervical motion tenderness (pain when cervix is moved by doctor's examining finger*) - menstruation allows bacteria to spread from cervix to upper genital tract - over 50% of cases of PID occur within 1 week of onset of menstruation

(TEST): Carol, a 23-year-old female former Peace Corps volunteer, received only inactivated poliovirus vaccine as a child. As part of a research study after returning from a two year rotation in Nigeria, she was found to have IgG antibodies for poliovirus types 1, 2, and 3, but both IgA antibodies and cytotoxic T cells specific for poliovirus type 3. The most likely explanation for this phenomenon is that

she was exposed to live poliovirus type 3 while serving in Nigeria.

(TEST): Healthcare workers (HCW) rates of HCV

similar to general population

HPV 16 & 18 = what epithelium?

squamous, columnar

PAMPS of *certain* viruses

ssRNA

The eclipse period of a one-step viral multiplication curve is defined as the period of time between the

start of the infection & the first appearance of intracellular virus

(TEST): A 10-year-old boy presents with vesicular lesions in his mouth, on the soles of his feet, and the palms of his hands. The appropriate treatment in most cases involves

supportive care only

(TEST): The HIV-1 protease cleaves

the viral polyprotein to yield structural & catalytic proteins

Poxviruses encode proteins that salvage DNA breakdown products, e.g. =

thymidine kinase (TK), deoxyuridine triphosphatase (dUTPase), ribonucleotide reductase (RR)

The insect vector responsible for the transmission of both Rocky Mountain Spotted Fever and Babesiosis is a

tick

Herpes: alpha genes mostly

transcription factors - immediate

PAMPS common in bacterial and viral DNA

unmethylated cytosine-guanine dinucleotides

violin spider

violin marking on back - usually nothing happens all other = rare - usually just *local necrosis* = brown recluse spider

(TEST): Integration of papillomavirus DNA into host DNA can cause unregulated expression of

viral E6 & E7 proteins

Prodrome of Rabies begins when...

virus enters CNS (spinal ganglia)