Micro

Which of the following patients is at highest risk for invasive aspergillosis, that is, invasion of Aspergillus hyphae into tissue and blood vessels and potential dissemination to other organs?

- A 16-year-old girl that has been neutropenic for one month during induction chemotherapy for acute myelogenous leukemia * - A 33-year-old man with asthma and a history of allergic bronchopulmonary aspergillosis - A 60-year-old woman that was treated for tuberculosis as a child and developed a pulmonary cavity that is now superinfected with an aspergillus fungal ball (aspergilloma) - A 70-year-old man that lives in a mold-ridden cinderblock house since the Katrina hurricane destroyed most of his neighborhood - A new born baby discovered in the morning after being abandoned on a mulch pile

A 40-year-old woman had an upper respiratory tract infection with cough and copious rhinorrhea but no fever two weeks ago. She recovered, however, 3 days later she began to have worsening nasal congestion, and developed low-grade fevers. It has been 12 days since these new symptoms began and she is worsening. She now has headache most of the day, fevers up to 38.5°C, and feels pressure and pain over her cheekbones when she bends forward. The most likely explanation for her symptoms is that:

- A viral infection triggered an inflammatory reaction that then resulted in a localized autoimmune response against commensal bacteria. - She acquired a contagious bacterial pathogen from some other infected human. This infection has a biphasic course first resembling a viral infection during colonization, then producing virulence factors that rapidly increase inflammatory responses and local swelling - She had viral rhinitis that caused inflammation and swelling of the nasal passages, and disruption of the local bacterial commensal flora. This resulted in trapping of both commensals and potential pathogens in her maxillary sinuses * - A viral infection caused an inflammatory response that induced commensal bacteria to produce toxins. These affected the sensory end of the trigeminal nerve and now she has a facial neuritis - She first had a minor viral or bacterial infection. However this allowed spores from an environmental mold to germinate in her nasal passages. She likely has has minimally invasive fungal sinusitis.

Despite the varied shapes, sizes, structural and genomic organization found in viruses they all share one common feature that makes them distinct from living cells:

- All viruses need host cell DNA polymerases to make the first copies of the viral genome - All viruses lack a protein synthesis machinery and therefore need to generate mRNA that can be translated into proteins by host ribosomes. * - All viruses can be organized into a phylogenetic tree with a common ancestor that gave rise to all viral families - All viruses protect their core by enclosing themselves in a lipid envelope derived from the host cell plasma membrane - All viruses have incomplete transcription machineries that need to be complemented by host derived transcription initiation factors

You are a star Medical Student that has discovered a new gram-negative bacterium, and isolated several of its virulence factors. Now you want to make a vaccine to prevent disease with this microbe. Of the following components you might add to your vaccine which do you think would make it most specific and effective in preventing infection without affecting the commensal microbiota or injuring the host:

- An active exotoxin that acts as a neurotoxin by blocking synaptic transmission - A bacterial ribosomal subunit responsible for protein production in the pathogen - A plasmid from your pathogen containing its antibiotic resistance cassette - Purified endotoxin from the outer membrane of your pathogen - A purified pilus tip protein involved in initial attachment to the host epithelium via a cell surface receptor *

A 14-year old male teenager that you saw last week in your primary care clinic for a skateboard injury told you that he has had multiple sexual partners this past year. You decide to test him for sexually transmitted infections and include a test for HIV. Which of the following HIV tests would be used for screening an asymptomatic teenager?

- An enzymatic test that detects the presence of reverse transcriptase by measuring the capacity of his serum to convert RNA into DNA - A skin test that detects the presence of T-cells reactive to HIV antigens - A flow cytometry test to measure the CD4 and CD8 T-cell counts in his blood - A western blot that detects antibodies to specific HIV proteins in the person's blood - An antigen detection test that looks for the presence of HIV capsid protein combined with a test that looks for the presence of antibodies against the virus *

Your patient's son is a healthy-appearing 24-year-old man, without a history of cough, fevers or weight loss. Since he has been exposed to his father with active pulmonary TB, you decide to test him and see if he has been infected himself. You find out that he was also born in India and received BCG at birth. You therefore choose to obtain an IGRA instead of placing a TST. The IGRA test is more specific than the TST because:

- Antigens used for IGRAs are not found in M. bovis which is more closely related to M. avium than to Mtb - PPD is a mixture of antigens from the BCG vaccine - IGRAs cannot detect reactivity to antigens in any nontuberculous mycobacterial species - Answer IGRAs utilize Mtb peptide antigens lost in the BCG vaccine strain during attenuation * - IGRAs measure interferon gamma, which is a more specific cytokine response to TB than the multiple cellular responses measured by the TST

Vincent is a 61-year-old man with a history of smoking one pack of cigarettes a day for the last 30 years. He also drinks a couple of glasses of whiskey each evening. He comes to your clinic with a high fever of 41°C and shortness of breath. His exam reveals crackles and decreased breath sounds in the right lower chest. A chest radiograph shows a lobar pneumonia. His sputum has many short Gram-negative bacilli as well as neutrophils. Which of the following is the most common mechanism that explains his clinical condition:

- Because of the effects of cigarette smoke on the eustachian tube, Vincent developed a purulent otitis media due to infection with Streptococcus pneumoniae. The bacterial IgA protease prevented opsonization and clearance by neutrophils, and Vincent became bacteremic. Bacteria from the bloodstream seeded the pulmonary vasculature initiating the pneumonia and causing his symptoms and clinical picture. - Vincent drank too much whiskey one night, which lead to nausea, retching and vomiting. His airway protection was impaired by alcohol allowing gastric juices contaminated with bacteria to reach the alveoli of his right lower lobe. E. coli, resident in the stomach, initiated an infection in the lung aided by the tissue destruction caused by the caustic gastric acid. - While sleeping, Vincent had episodes of microaspiration that brought resident bacteria from the nasopharynx into the lower airways. Cigarette smoke had injured his respiratory cilia and caused ectasia of small airways trapping and impairing the clearance of the bacteria. An encapsulated type of Haemophilus influenzae avoided phagocytosis by neutrophils and alveolar macrophages and began to grow in the alveoli, eliciting a strong neutrophilic response. * - Mycoplasma pneumoniae resident in Vincent's upper airway avoided clearance thanks to the toxic effects of cigarette smoke on the respiratory epithelium. These bacteria invaded the epithelium intracellularly and expanded, making their way into the lower airways where they initiated a pneumonia. - Fungal spores of Aspergillus niger are commonly found in tobacco. Because Vincent rolls his own cigarettes and they lack a filter, he inhaled the spores and bypassed the glottis. The spores germinated in the alveoli and produced hyphae which were too large to be engulfed by the resident macrophages. Hyphal obstruction of the airways and local inflammation produced his symptoms and radiographic picture.

Marta, a 30-year-old woman who recently completed a course of clindamycin for a soft tissue infection complains of watery diarrhea, abdominal pain, and cramping. She is subsequently diagnosed with Clostridium difficile infection. Which of the following explains the pathogenesis of this bacterial infection:

- C. difficile are Gram-positive cocci that compete with and displace commensal enterococci, short-circuiting an important pathway of nutrient flow in the microbiota and leading to malabsorptive diarrhea. - C. difficile produces toxins that disrupt the enterocyte cytoskeleton and break the intestinal barrier. * - C. difficile spores contain a tough capsule with sharp ridges that can produce micro-abrasions on the epithelial surface that lead to diarrhea and inflammation. - Since the bacteria are resistant to acid they colonize the stomach and irritate the vagus nerve leading to increased gastrointestinal peristalsis which produces diarrhea. - Because of its aerobic metabolism C. difficile spores steal oxygen from the epithelium causing anoxic epithelial cell death.

Another of your patients, a 60-year-old man with colon cancer has undergone a colectomy and has a central line in place. He develops low grade fevers and is started on broad spectrum antibiotics with vancomycin and ceftazidime. Two-days later, three separate blood cultures begin to grow a yeast. A day after that, the yeast is identified as Candida glabrata. He is otherwise well appearing with normal vital signs. In addition to starting antifungal medication, your team decides that the central line should be removed because:

- Candida forms biofilms that are more resistant to antifungals and will cause the infection to relapse after treatment * - Antifungal medication is not compatible with central catheters because of the proximity to the heart could cause QT elongation and arrhythmia. It should only be given through peripheral intravenous lines - Candida is a skin colonizer, so the best treatment will be topical and not intravenous. The central line is not needed - Antibiotics and antifungals should not be delivered through the same intravenous line. He will need multiple peripheral lines instead - He is well appearing with normal vital signs and a central line will just increase his risk of further infections. You will treat him with oral antifungal medications

Which of the following molecules is a lipid component of the fungal membrane and an important target of some antifungals?

- Chitin - Ergosterol * - Beta-glucans - Galactomannan - Lipomannan

A 23-year-old woman develops the sudden onset of fevers, productive cough, and chest pain. Her physician notes focal consolidation at the left lung base, and a likely pathogen is identified by Gram stain and routine bacterial culture of sputum. Etiologies of this "typical" bacterial pneumonia syndrome include which of the following?

- Chlamydophila pneumoniae - Haemophilus influenzae * - Pneumocystis jirovecii - Legionella pneumophila - Mycoplasma pneumoniae

Once inside red blood cells Plasmodium parasites depend on hemoglobin as an amino acid resource. Large quantities of hemoglobin are brought into a food vacuole where it is metabolized. Heme becomes a waste product that is detoxified by the formation of hemozoin crystals. How are some antimalarial drugs able to interfere with merozoite growth inside red blood cells:

- Chloroquine and its derivatives bind hemozoin molecules and interfere with hemozoin crystal formation thus generating buildup of toxic heme products that kill the parasites * - Artemisinins induce covalent cross-linking of heme to the hemoglobin blocking digestion of this molecule by the parasite - Atovaquone binds hemoglobin, stabilizing the molecule and preventing Plasmodium from utilizing it as a nutrient source - Mefloquine triggers the breakdown of heme into hemosiderin thus starving the parasites of iron - Primaquine changes the pH of the parasite vacuole causing heme to precipitate and form crystals inside the growing parasites

A 70-year-old woman is critically ill with respiratory failure from pneumonia and is intubated in the intensive care unit of your hospital. She requires frequent suctioning of the endotracheal tube to clear thick pulmonary secretions. Your resident is concerned that the patient's ventilatory status is worsening despite empiric treatment with broad spectrum antibiotics, and decides to use a sterile cotton-tip applicator to collect some of endotracheal tube secretions for culture. The swab is sent to the microbiology lab, with the hope of identifying a possible pathogen. Growth of which of the following is likely to represent a contaminant from the normal oropharyngeal microbiota rather than the cause of the pneumonia,

- Coccidiodes immitis - Aspergillus fumigatus - Candida albicans * - Mucor indicus - Sporothrix schenckii

A child in the local elementary school developed fever and a persistent cough three weeks after traveling to Disneyland by car across the California San Joaquin valley. Her astute pediatrician considered coccidiodomycosis and tuberculosis based on the exposure history and epidemiology and obtained a chest radiograph that revealed a focal infiltrate. Tests for tuberculosis are negative, while serologic tests for antibodies against Coccidioides immitis confirmed the diagnosis. You are asked by her elementary school teacher, whether the child can return to class or whether there is a risk of contagion to other students? You explain that:

- Endemic fungi are not transmitted person-to-person and are acquired only from environmental sources. There is no danger of transmission to other children. * - You will start her on high dose oral Fluconazole and thus the risk of transmission to others will be minimal. - She will not be able to attend school in the near future because there are no oral formulations to treat this infection and she would be putting others at high risk if she attends school while untreated. - Pulmonary coccidioidomycosis is a sentinel infection suggesting severe immunosuppression like AIDS, thus she will be at risk of acquiring other infections if she attends school. - She can attend school but should wear an N-95 protective mask for the first month until you repeat a chest radiograph to make sure the fungal pneumonia is treated.

A 35-year old healthy woman was treated with a course of antibiotics for presumed sinusitis. She now returns two weeks after stopping antibiotics complaining of an itchy rash in her vulvar area associated with some mild discomfort when urinating and a white discharge. In your primary practice, if you suspected vaginitis due to Candida albicans you would

- Examine of the vaginal discharge by microscopy wet mount looking for budding yeast and pseudohyphae * - Use a fluorescent antibody test against beta-d-glucan on the vaginal discharge - Send serology to detect IgM antibodies to Candida albicans - Order a fungal culture of the vaginal discharge in Sabouraud plates - Obtain a serum galactomannan level

Toxoplasma gondii has a very broad range of intermediate hosts that even includes marine mammals. In California, scientists have found an increase in sea otter deaths due to Toxoplasma gondii Which of the following is a likely mechanism by which Toxoplasma gondii is being transmitted to these endangered sea otters?

- Freshwater runoff containing cat feces is contaminating the bay costal water with T. gondii oocyst * - Otters kept as pets and fed animal meat have become infected with T. gondii tissue cysts and when released into the wild transmit the disease to their mates and offspring - T. gondii tachyzoites are a normal part of the coastal zooplankton and thus are ingested by otters from the sea water - Otters are eating birds infected with T. gondii tissue cysts - Human sewage is contaminating the bay water with T. gondii oocyst released by infected humans

Your 60-year-old aunt tells you that in the Dr. Oz TV show she heard that infection with pylori causes stomach cancer. She wants her doctor to test her for the infection and treat her because she "already has enough problems and doesn't need another one". She eats like a horse and has no symptoms. She asks you for your advice and you tell her that,

- Gastric cancer is the third leading cause of cancer death and those that have had another cancer, like breast cancer, are at higher risk if infected with H. pylori. - She should be tested and treated immediately with a proton pump inhibitor and two antibiotics, since about half of the people infected with H. pylori will end up developing cancer - H. pylori is only associated with peptic ulcers, not cancer, so there is no need to worry - If no one in her family has had stomach cancer, it may not be necessary to treat an H. pylori infection because most people do not develop disease * - About 15% of the people infected with H. pylori will develop peptic ulcers which puts those people at high risk of developing cancer

Most people that have stomach ulcers say that emotional stress and acid in their stomach worsens their pain, and anti-acids are effective in controlling the symptoms. In fact anti-acid medication has been the mainstay for the treatment of peptic ulcers for decades. Of the following, which is the best evidence that H. pylori is a causative agent in peptic ulcers and not just an innocent bystander?

- H. pylori is highly resistant to stomach acid - People without H. pylori infection do not get ulcers - Treatment of H. pylori infection with antibiotics cures most ulcers * - Barry Marshall drank a culture of H. pylori and developed an ulcer - H. pylori infection is statistically associated with ulcers

You are seeing a 40-year-old man that has had symptoms of gastritis for several months, and you just diagnosed him with Helicobacter pylori using a stool antigen test. He is very worried about how he caught this infection, and where H. pylori is hiding in the environment. "Should he get rid of his dog and cat? Should he install a new water filter? Should he sterilize all his bed linens?" Regarding the environmental reservoir of H. pylori you explain that:

- H. pylori spores shed in the stool contaminate drinking water sources, so he should avoid travel to underdeveloped countries. - H. pylori colonizes of the stomach of multiple domestic animal species including dogs and cats so pets spread it within households - Flies and other insects can serve as vectors and reservoirs of H. pylori. - Helminths can carry and transmit H. pylori that is why its prevalence is much higher in the developing world. - H. pylori does not survive in the environment and it is only transmitted through close human--to-human contact. *

The urea-breath test takes advantage of which evolutionary adaptation of H. pylori?

- H. pylori urease depletes the human body of urea and its reduction can be detected in the breath. - H. pylori urease breaks down urea to buffer acidic pH, and the CO2 generated is absorbed into the bloodstream and detected in the breath. * - H. pylori produces large amounts of a urease enzyme that is used to generate the proton-motive force that turns the flagellar motor. - H. pylori metabolism produces large amounts of urea, which causes burping, and halitosis that can be detected in people's breath. - H. pylori evolved the capacity to decrease gastric and esophageal motility which leads to buildup of urea in gastric contents that when refluxed into the mouth can be detected in the breath.

Everyone infected with H. pylori develops:

- Histological gastritis with inflammatory cells infiltrating the gastric mucosa * - Pre-malignant lesions known as intestinal metaplasia that can evolve into gastric cancer - Methane gas production in the stomach leading to uncomfortable distention and belching - Chronic abdominal pain because of stimulation of the gastric enteric plexus by H. pylori neuroactive toxins - Gastric erosions that usually grow into gastric ulcers.

Two week after the devastating Hurricane Mathew you traveled to provide medical assistance in Haiti. Your first patient was a 20 year-old man with profuse diarrhea. He appeared extremely dehydrated. He looked sleepy and barely responded during the exam. His capillary refill time was prolonged. He had tachycardia and his blood pressure was low. You quickly placed an intravenous line, gave him antibiotics and began rehydrating him with saline solution. Over a five hour period, he continued to produce 4 liters of watery diarrhea. You were told that many patients were arriving at the hospital with this clinical presentation. What was occurring on the molecular level in his enterocytes to drive this severe diarrhea?

- Increased sodium efflux through reversal of the sodium/glucose co-transporter - increased chloride efflux through paracellular opening to the epithelial tight junctions - movement of aquaporin molecules (water channels) from the basolateral to the apical membrane of enterocytes - increased calcium efflux inducing enterocyte apoptosis - increased efflux of chloride through a transmembrane channel followed by sodium efflux to maintain electrical neutrality *

A 3 month-old infant boy, born 12 weeks prematurely, presents with respiratory distress and fever. The pediatrician does a PCR test on the nasal secretions and tells the family that the child has been infected with the most common cause for bronchiolitis. What is the mechanism of pathogenesis of this clinical disease?

- Infection of the respiratory dendritic cells results in increased antigen presentation and recruitment of natural killer T-cells with subsequent sloughing of the epithelium and blockage of the airway - Viral infection of the respiratory epithelial cells elicits cytokine and chemokines that recruit inflammatory cells resulting in increased mucus and edema and swelling of the walls of the respiratory tract. * - Viral infection of respiratory epithelial cells resulting in formation of multinucleated giant cells, necrosis, and obstruction of small airways - Viral Infection of the vascular endothelial cells of the capillary bed for the small airways releases an exotoxin that results in loss of endothelial tight junctions and extravasation of capillary fluid, edema and constriction of the airways - Viral infection of the smooth muscle cells of the respiratory airways causes smooth muscle cell contraction and spasm of the airway walls resulting in narrowed air passages

Patients with HIV/AIDS are at risk for serious sequelae from Toxoplasma gondii infection because:

- Ingested oocytes are much more likely to migrate to the brain in patients with HIV because of a defective blood-brain barrier - Latent Toxoplasma gondii bradyzoites in the tissue can reactivate when immune responses are deficient * - Antiretroviral medication stimulates replication of Toxoplasma gondii - Persons with HIV/AIDS harbor highly infectious forms of Toxoplasma gondii spreading the infection within their community - HIV infection of cells harboring Toxoplasma gondii undergo apoptosis forcing the parasites to exit, reinvade and multiply the number of infected cells

The relative capacity of a microorganism to cause damage to the host is called "virulence". This is a property that:

- Is inherent in the genetic sequences of virulence genes in the pathogen - Is equivalent amongst different strains of a microorganism and thus can serve as a way of differentiating microbial species - Is dictated by both pathogen characteristics and the immune responses of the host * - Is strongly correlated with the infectivity of a microorganism - Is most highly apparent in the preferred host species

The bacterial cell envelope of Gram-negative bacteria differs from that of Gram-positive bacteria in that,

- It is impervious to antimicrobial peptides - The cell wall is much thicker thus making it difficult for beta-lactam antibiotics to penetrate - It has two membranes surrounding the peptidoglycan * - Its lipooligosaccharides are modified so that lysozyme cannot degrade them - The inner membrane contain porins that can actively pump antibiotics out of the periplasmic space

Together with over half a million deaths each year throughout the world, a number of famous people have died from complications Typhoid fever, including Leland Stanford Jr, Alexander the Great, Tad Lincoln (youngest son of president Lincoln), Cecile and Jeanne Pasteur (Louis Pasteur's daughters), and Ignacio Zaragoza (a general in the Mexican Army responsible for the Cinco de Mayo celebration). Typhoid fever has a fatality rate of 20-30% if untreated because:

- It is inherently resistant to antibiotic therapy - It colonizes the terminal ileum for prolonged periods and can reactivate at any moment causing serious relapses - It invades beyond the intestinal mucosa, surviving in the liver, spleen, bone marrow and lymph nodes and causes complications such as intestinal perforation, meningitis, and osteomyelitis * - It causes massive diarrhea and dehydration leading to rapid demise in places that have no access to proper rehydration therapy - Its lipopolysaccharide (LPS) is so immunogenic that it leads to septic shock syndrome if it gets into the bloodstream

Invasive bacterial pathogens evade the immune system using many strategies. One strategy is to avoid being engulfed by phagocytes. One prominent mechanism used by Streptococcus pyogenes to avoid phagocytosis is:

- It secretes a coagulase enzyme that encases the bacteria in thrombi thus making them inaccessible to phagocytes - The presence of white blood cells induces the production of flagella which allow the bacteria to move out of range of the phagocytes - It secretes a pore forming toxin, alpha-leukocidin, which kills phagocytes - It induces autoantibodies through M-protein that bind to phagocytes causing white blood cells to engulf each other rather than the microbes - It produces a hyaluronic acid capsule that mimics human connective tissue and hides surface antigens from opsonizing antibodies *

The pathogenesis of uropathogenic E. coli involves colonization of the bladder epithelium. The main colonization factor involved is thought to be:

- LPS in the bacterial outermembrane which activates TLR2 in the ureters causing relaxation and vesicoureteral reflux - flagellin which binds to the epithelial surface and activates TLR4 initiating a strong immune response - lipoteichoic acids in the peptidoglycan which bind strongly to mannosylated uroplakins - specialized type 1 pili that contain the adhesin and FimH, which binds glycoproteins on the uroepithelium* - beta-lactamases in the periplasmic space which inactivate naturally occurring antibiotics in the urine

During March 1998, twin infants aged 2 weeks were admitted to a hospital after 1 day of poor feeding, diarrhea, and fever. They were treated intravenously with ampicillin for 6 days. The infants' mother and a child aged 3 years in the home also had diarrhea. Stool specimens from one of the twins, the mother, and the older child yielded a gram-negative bacterial pathogen. The family recently had acquired an iguana, which was not allowed out of its cage. Only the mother handled the reptile and cleaned the cage. When the family learned that the iguana was the probable source of the infections, the iguana was euthanized. Culture of intestinal contents from the iguana yielded:

- Listeria monocytogenes - Salmonella enterica serovar Typhimurium * - Enteropathogenic E. coli - Campylobacter jejuni - Salmonella enterica serovar Typhi

After mosquitos deliver Plasmodium falciparum sporozoites into the bloodstream, the first cells to be invaded by the parasites are:

- Macrophages in the bone marrow - Red blood cells in the peripheral circulation - Keratinocytes in the skin - Hepatocytes in the liver * - Dendritic cells in the dermis

A 12-month-old baby boy contracted RSV infection in December. He required a brief hospitalization and resolved his infection without sequelae. A year later, at the end of January he comes to your office with similar symptoms of tachypnea and fever and is confirmed to have RSV infection again by PCR testing. The parents ask you, his primary pediatrician, why he is re-infected again. You explain that children can be re-infected with RSV because:

- Many people refuse the RSV vaccine for fear of autism, so heard immunity is low - Use of the monoclonal antibody palimuzimab (which is only directed against one epitope of the F-fusion protein), selects for escape mutants that can re-infect children - The antiviral he received last winter suppressed viral replication but also reduced the immune response to RSV, thus allowing reinfection - RSV has multiple serotypes that circulate simultaneously in the Winter and year-round, so an immune response to one serotype is not enough to protect against infection with another serotype. - RSV has evolved several strategies to evade immune responses, so RSV protective immunity is incomplete, although it helps reduce severity. *

You decide to treat Marta with metronidazole, an antibiotic that damages DNA. She is a student of genetics and is afraid that the metronidazole may cause DNA damage in her cells. You reassure her by saying that:

- Metronidazole only binds to Clostridial DNA, it has no effect on other bacteria or on human cells. - Metronidazole targets dihydrofolate reductase, which is an enzyme that is not found in human cells. - Metronidazole first binds to RNA polymerase before damaging DNA. Since RNA polymerase is outside of the nucleus in eukaryotic cells the drug is only toxic to bacteria. - Metronidazole is inactive in aerobic conditions, and activated by reduction in anaerobic conditions. Thus it damages DNA in anaerobic bacteria and hypoxic tissue. * - Metronidazole inhibits bacterial-specific enzymes involved in DNA super coiling.

Michael and John are 25 and 28-year old brothers. John needed a kidney transplant two years ago and Michael was able to donate one of his kidneys. They recently took a celebratory trip together and stayed in a resort where they swam in a chlorinated pool and drank only bottled water. At the end of their trip they both developed watery diarrhea and took oral antibiotics for traveller's diarrhea. Michael recovered after about 7 days of a mild illness, but John continued to have profuse watery stools without fever or blood. John is now hospitalized since his stool output increased to as much as 6 liters a day and he could no longer drink enough to stay hydrated and protect his transplanted kidney from hypovolemic injury. Stool O&P studies on John revealed Cryptosporidium oocysts. The main reason Michael recovered while John continues to have a life threatening illness is that:

- Michael's Cryptosporidium was susceptible to the antibiotics they took while John acquired a different, antibiotic-resistant strain, thus susceptibility testing should be carried out - John acquired C. difficile in addition to Cryptosporidium exacerbating the diarrhea, thus oral vancomycin therapy is warranted - The Cryptosporidium infection triggered an episode of rejection in John which is manifested by gut hypermotility explaining his diarrhea, thus steroids to block the rejection should be given immediately - John does not have good B-cell function due to his transplant immunosuppression and thus would benefit from intravenous gamma globulin - T-cell mediated immunity is most important in clearing Cryptosporidium, thus John's immunosuppressive drugs should be lowered with close monitoring for evidence of rejection *

One reason many Gram-negative bacteria are resistant to penicillin is that:

- Most Gram-negative bacteria have acquired a gene for the production of penicillin efflux pumps that rapidly secrete the antibiotic out of the bacterial cell cytoplasm - They have acquired mutations in the genes for LPS which no longer binds to penicillin - Their outer membrane restricts penetration of the antibiotic and many make beta-lactamases that concentrate in the periplasm * - The target of beta-lactam antibiotics is not essential in Gram-negative bacteria because they do not need to cross-link their thin peptidoglycan - The inner membrane porins have evolved mutations making them impermeable to penicillin

How would you characterize the pathogenic bacteria that cause infections in the spaces of the head and neck:

- Most of the pathogenic bacteria in the nasopharynx are zoonotic that is are acquired from animals and displace the normal human commensal counterparts - They are mostly commensals or normal flora living on the mucosal surfaces in the nasopharynx and cause disease when there is an environmental change associated with inflammation like a viral respiratory infection * - They enter when another ill person sneezes or coughs on you, rapidly cause inflammation and disease and are cleared from the nasopharynx once the infection resolves - The pathogenic bacteria are not detected by the immune system, thus one cannot make vaccines against them. - The pathogenic bacteria are almost never found in asymptomatic individuals

The patient described above is admitted to the hospital and started on empiric intravenous antibiotic therapy with vancomycin and ceftriaxone. You then decide to

- Obtain CSF through a lumbar puncture because given his headache and vision changes he could have meningitis - Wait for 24 hours on IV antibiotics before switching to an oral regimen with amoxicillin/clavulanate and finish a three week total course - Add an oral antihistamine and ophthalmic steroid drops to reduce the inflammation - Obtain a sinus and orbit CT-scan or MRI and consult ENT and Ophthalmology for possible surgery * - Culture his conjunctiva to be able to narrow empiric therapy to definitive therapy

A normal function of the spleen is to remove abnormal erythrocytes such as those containing infectious inclusions. P. falciparum-infected red blood cells (RBCs) are not efficiently phagocytosed and cleared in the spleen because:

- P. falciparum expresses adhesins on parasitized RBCs that cause the RBCs to adhere to vascular endothelium in the peripheral vessels * - P. falciparum produces a pore-forming toxin that kills macrophages in the spleen - parasitized RBCs express an antiphagocytic transmembrane protein similar to M-protein from Streptococcus pyogenes - parasitized RBCs are coated with a capsular polysaccharide which prevents phagocytosis - parasitized RBCs retain their compliance and elasticity and are not recognized by phagocytic cells in the spleen

You are evaluating a 5-year-old boy with cough, runny nose, fever, conjunctivitis and a sore throat. It is July and you wonder whether his symptoms are due to a seasonal allergy vs a viral infection. Of the following respiratory viruses, which is most likely to explain your patient symptoms:

- Parainfluenza virus - Rhinovirus - Respiratory syncytial virus (RSV) - Influenza virus - Adenovirus *

Which of the following best describes the pathogenesis of otitis media:

- Pathogenic bacteria colonizing the ear canal translocate into the middle ear across the tympanic membrane - Commensal bacteria of the middle ear become pathogenic and secrete toxins when the host restricts iron - Inflammation induced by a viral infection results in dysfunction and swelling of the eustachian tube allowing bacteria to avoid mucociliary clearance, become trapped and grow in the middle ear space. * - Viruses infect commensal bacteria in the middle ear and deliver DNA that codes for virulence factors allowing the bacteria to cause inflammation - Bacteria colonizing the mastoid air cells travel to the middle ear via the mastoid antrum where they can initiate an infection.

A two-year-old little girl is seen in the emergency room. Her parents are concerned that she is having trouble breathing and you hear an inspiratory stridor and prominent cough. You suspect that her symptoms are due to:

- Pneumonia from adenovirus infection - Laryngitis due to human metapneumovirus - Bronchiolitis due to respiratory syncytial virus (RSV) - Acute otitis media and rhinitis due to rhinovirus - Laryngotracheobronchitis due to parainfluenza virus*

You are the resident taking care of a 19-year-old adolescent young man with acute myelocytic leukemia (AML) who is experiencing prolonged neutropenia during an attempted hematopoietic stem cell transplantation. He develops fevers and a chest radiograph shows new pulmonary nodular infiltrates surrounded by "ground glass" opacity. You are concerned about an infection due to Aspergillus fumigatus. Which of the following established microbiological tests is most consistent with this diagnosis?

- Positive blood test for galactomannan * - Positive blood test for polysaccharide capsule antigen - Positive blood test for ergosterol - Blood cultures growing a yeast-like fungus - Positive urine antigen test for Aspergillus

Samantha, a previously healthy 2-year-old girl, is brought to your clinic because of the following rash (impetigo and bollous impetigo) on her left arm three weeks after starting daycare. The upper part of the rash has been present for several days. Today she also developed a 1 cm fluid-filled lesion shown below. She is afebrile and otherwise well appearing.

- Samantha will require intravenous antibiotics for treatment because topical antibiotics cannot reach the depth of the skin at which the infection begins - you will admit Samantha to the hospital and place her on intravenous antibiotics, since this rash can be a precursor of severe necrotizing skin infection - the blister is due to a bacterial toxin that cleaves intercellular junctions in keratinocytes and is made only by S. aureus. You will therefore prescribe a topical antibiotic ointment with activity against both MSSA and MRSA * - this rash is not due to a bacterial infection and most likely represents varicella zoster virus infection - this rash is very likely due to Streptococcus pyogenes which produces a toxin, streptolysin O, that causes skin blistering, so you will prescribe a course of penicillin

Sara is a 35-year-old woman from El Salvador who was healthy, working as a baby sitter in the Bay Area for ten years. A few weeks ago, she suddenly developed new onset generalized seizures. An MRI of her head showed a nodular lesion with surrounding edema in the subarachnoid space of the temporal lobe. She underwent a craniotomy for a diagnostic excisional biopsy. She recovered promptly from the surgery, and fortunately the pathologists did not report a brain tumor, but instead found evidence of degenerating juvenile worm scolex. Sara was infected with Taenia solium, a cestode helminth that can form tissue cysts in the brain and other tissues. Ova and parasite examinations of her stool did not find evidence that she is infected with Taenia in her gastrointestinal tract. Which of the following would be the most likely source of Sara's infection:

- Sara ingested food contaminated with human feces when she was living in El Salvador * - Sara ate food contaminated with pork feces in Mexico during the trip she took to enter the United States - Sara ate poorly cooked beef at the local Church during a Sunday community barbecue - Sara was bitten by a sand fly in the coastal region of La Palma in El Salvador where these parasites are endemic - Sara ate poorly cooked pork meat on a recent trip to El Salvador to visit her family

Most immunocompetent human hosts infected by Toxoplasma gondii will develop:

- Seizures - No symptoms or signs of disease * - Hydrocephalus - Chorioretinitis - Anemia

Referring to Sara from the previous question. The most likely mechanism by which Sara developed seizures is:

- She had larval cysticerci migrating through her brain tissue, thus disrupting normal electrical activity - The growing cyst stole blood flow from the surrounding brain tissue causing local ischemia - The newly acquired larval cyst secreted neuroactive peptides that triggered excitatory synapses resulting in seizures - Sara is likely immunocompromised, perhaps due to undiagnosed HIV, which allowed the cysticercal cysts to grow displacing brain tissue. - Her immune system responded to dying larval cysts which lead to inflammatory damage *

You have a patient with signs and symptoms consistent with atypical community acquired pneumonia. If his condition is due to Mycoplasma pneumoniae

- She will likely develop a lobar pneumonia because Mycoplasma produce pneumolysin which damages the epithelium and causes localized vascular leak - One choice for treatment would be azithromycin which inhibits protein synthesis. * - Antibiotics, such as fluoroquinolones, that inhibit DNA topoisomerases have no activity against this bacterial species - Penicillin would be a good treatment choice because of the high peptidoglycan content in its cell wall. - This organism cannot be cultured on artificial growth medium because it is an obligate intracellular pathogen that cannot grow without the host cell.

You decide to treat her with empiric antimicrobials that will cover the following microbes:

- Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis * - Neisseria meningitidis, Corynebacterium diphtheriae, and Mycoplasma pneumonia - Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli - Aspergillus fumigatus and Coccidioides immitis - Fusobacterium nucleatum, Arcanobacterium haemolyticum and Streptococcus pyogenes

The microbiology lab calls to tell you that the his sputum smears do show AFB-positive bacilli. Perhaps the cavitary lesion has tuberculous caseum irritating the airways. Caseum is made from:

- T-cell cytokines causing loss of blood vessels in the granuloma and thus making the avascular structure appear white in the microscope - The metabolism of Mtb inside the granulomas which ferments membranes in a similar process to cheese fermentation - Cellular and tissue necrosis formed by cell-mediated immune responses to Mtb * - Macrophages binding to each other and forming epithelioid structures that resemble crumbling cheese at autopsy - Dying Mtb bacilli which agglutinate into waxy cheese like aggregates

Taenia solium Sara again How does the formation of brain cysts in Sara's brain benefit Taenia solium?

- T. solium evolved at a time where infected humans were not properly buried and their carcasses contaminated the soil with Taenia cysts - T. solium becomes latent in the human brain in order to reactivate later when the immune system weakens - The weak immune response in the brain allows T. solium to replicate to high numbers in the brain tissue - T. solium brain cysts changes human behavior to make us less likely to undertake hygienic practices that curtail transmission - T. solium does not benefit from causing brain cysts in humans but it evolved to do so in pork to enhance its transmission into the human intestine *

You are counseling a patient that was diagnosed with HIV. She is in the clinically latent phase of the infection and has no symptoms. She has never taken medications for more than a day or two. The regimen involves taking several pills every day. You need to convince her that starting a drug regimen involving multiple antiretroviral medications is important. Which of the following arguments would be best to use?

- Taking all the medications as prescribed will likely eliminate the HIV virus and cure the infection - All the medications should be taken together since some prevent side effects from the others such as nausea - One medication is not sufficient because each targets a different part of the virus, but taking a different one each day is OK - Combining several medications prevents the virus from becoming resistant to the treatment * - One of the medications is for inhibiting virus replication but an equally important one is to stimulate the differentiation of CD4 T-cells in the bone marrow

You are taking care of a 6-year-old girl with a fever, sore throat and exudative tonsillitis. The rapid strep test was negative but the microbiology lab now says her throat culture is growing Gram-positive cocci. These bacteria could represent a pathogen causing her pharyngitis or a number of commensal bacteria that reside in the throat. Which of the following descriptions would be consistent with Streptococcus pyogenes?

- The Gram stain shows Gram-positive cocci in short chains. The blood agar plate shows no hemolysis around the colonies. - The Gram stain shows Gram-positive cocci in groups. The blood agar plate shows a zone of greenish hemolysis around the colonies. - The Gram stain shows Gram-positive cocci in short chains. The blood agar plate shows a zone of clear hemolysis around the colonies. * - The Gram stain shows Gram-positive cocci in groups. The blood agar plate shows no hemolysis around the colonies. - The Gram stain shows Gram-positive cocci in long chains. The blood agar plate shows a zone of greenish hemolysis around the colonies.

A 25-year-old young man presents with a headache and change in vision. On exam he has unilateral left-sided proptosis, ptosis and cannot move his left eye laterally. The rest of his exam is unremarkable. What is the likely source of microbes in this infection?

- The eye muscles became infected with a myotropic virus through the bloodstream - The conjunctiva became infected with a virus and then superinfected with skin bacteria - The ethmoid sinus became infected and bacteria eroded into the medial wall of the orbit * - The middle ear became infected with bacteria which extended through the ethmoid sinus into the orbit - The lacrimal duct became congested and superinfected by nasal bacterial colonizers

A 32-year-old man with community-acquired pneumonia chooses not to take antibiotic therapy since he wants to "train" his immune system to better fight off infection. After 7 days, he develops high fevers, worsening chest pain, and dyspnea, despite the fact that he now started taking the antibiotics. Physical examination and chest x-ray reveal a large amount of fluid in the pleural space near the region of the original pneumonia. Likely explanations include which of the following?

- The fluid could represent an infected empyema that may not respond to antibiotics alone and would likely need to be drained for cure. * - The presence of a pleural effusion in the presence of pneumonia strongly argues for a fungal etiology of infection. - The fluid likely represents pulmonary hemorrhage associated with an aspiration pneumonia syndrome. - The presence of fluid in the pleural space indicates that the original diagnosis of pneumonia was incorrect and that this syndrome represents pleuritis instead of pneumonia - This is a typical course for pneumonia due to influenza virus, a viral pleural effusion that should resolve as the underlying infection improves.

You are assigned by the Centers of Disease Control to help determine the source of recent outbreak of campylobacteriosis. A cluster of people developed bloody diarrhea and fever and their stool cultures grew Campylobacter jejuni in microaerophilic cultures at 42°C. The isolate was intrinsically resistant to cephalosporins. Which of the following transmission scenarios is most compatible with the biology of Campylobacters:

- The infected people had been on vacation in the same cruise ship where close contact rapidly spread the infection person-to-person. - The infected people ate a salad that was prepared next to a thawing turkey during Thanksgiving. Campylobacters are commensals in the gastrointestinal tract of birds and can easily contaminate food preparation. * - This cluster was linked to swimming in a local public swimming pool since Campylobacters are resistant to chlorine and only some swimming pools have adequate filters. - The infected people all drank tap water contaminated by an urban sewage system. The sewage was contaminated with Campylobacter shed by asymptomatic humans. - People contracted the bacteria from contact with infected hand rails at a local hospital. Most strains of Campylobacter are resistant to cephalosporins so they are able to survive and are transmitted in hospitals.

A 65-year-old woman with breast cancer is admitted to the hospital for chemotherapy and subsequently develops Clostridium difficile colitis. Which of the following is the most important risk factor that contributed to her C. difficile infection?

- The pre-formed C. difficile toxins are contaminants in medication solutions and difficult to eliminate during manufacture. - She was visited by a relative that works in the cafeteria and forgot to use the alcohol gel that is in the entrance to the room. - She has a genetic susceptibility to C. difficile carried by 25% of the Caucasian population. - She suffers from gastroesophageal acid reflux disease and her stomach acid stimulated C. difficile spore germination. - She received antibiotics for five days because of fever in the setting of neutropenia. *

You have been studying the life cycle of a new virus that spreads rapidly and kills 40% of those infected. You need to quickly choose a target to develop antivirals before the infection reaches epidemic proportions. Which of the following parts of the life cycle would be the most reasonable to target:

- The virus uses microtubules to transport its newly synthesized capsid proteins for self assembly. You will test a drug that is a powerful microtubule depolymerizer to block virus assembly. - The virus enters the cell by binding to a growth factor receptor that is essential for viability of alveolar cells. You decide to make a monoclonal antibody that will bind to this receptor and cause its internalization thus removing the ability of the virus to enter. - The virus uses clathrin-dependent endocytosis to become internalized into the host. You decide to use a clathrin inhibitor to block endocytosis of the virus. - The virus RNA is transcribed by the host cell ribosomes. You decide to use a drug that inhibits protein synthesis by binding to the ribosomes and thus prevent virus replication. - The virus codes for its own RNA-dependent RNA-polymerase. You decide to target the RNA polymerase enzyme with a drug that will bind covalently at the catalytic site. *

Which of the following statements is true about the 23-valent pneumococcal vaccine?

- This vaccine induces immunity to surface bacterial antigens normally hidden from immune recognition. - This vaccine induces immunity to surface protein antigens common to most penicillin-sensitive strains of Streptococcus pneumoniae. - This vaccine is recommended for all patients on an annual basis due to antigenic drift. - The vaccine covers all known serotypes of Streptococcus pneumoniae - The polysaccharide antigens included in this vaccine are normally present in the capsule of this microorganism. *

More than 100,000 fungal species are known and many secrete powerful enzymes that can digest plant and animal tissues. It is surprising that only a few dozen species can cause invasive disease in humans with normal immune systems. One major reason the number of fungal pathogens infecting humans is small is:

- Very few fungi can digest the tough keratinized layers that cover our epithelial surfaces - Human tissues are rich in iron, which is a toxic chemical for most fungi - Human body temperature is higher than the temperature at which most fungi thrive * - Most fungi require cellulose as part of their nutrition and this is a component of plants, not animals - Most fungi derive their energy from photosynthesis, only those that have lost this capacity are human pathogens

A 15-year-old adolescent comes to the emergency department complaining of worsening sore throat and fever. He looks unwell and speaks with a muffled voice. He whispers that it is painful to open his mouth. When you examine his throat you notice that the left tonsillar area is swollen and that his uvula is deviated to the right. You suspect a peritonsillar abscess and admit him to the ENT service. They place him on IV vancomycin and piperacillin/tazobactam perform an incision and drainage procedure in the operating room that drains pus. The Gram stain of the pus has gram-positive cocci in chains. The next morning he is afebrile and the culture is growing Streptococcus pyogenes. In terms of his antibiotic management you should:

- Wait until sensitivities are available for the Streptococcus pyogenes strain that grew from your patient and choose the antibiotic with the lowest MIC. - Add an antibiotic with a broader spectrum of activity because you want to make sure to cover any possible microbe that was present in the throat - Stop antibiotics since his symptoms have now resolved - Narrow your treatment to penicillin * - Stay on vancomycin and piperacillin/tazobactam since this treatment is already working and you don't want to breed resistance to a different drug

A 47-year-old man comes to your clinic with a symmetrically distributed rash consisting of non-pruritic macules on his trunk and limbs. He is HIV-negative and otherwise healthy, and was not on any medications. He had performed unprotected orogenital sex with a female partner about four months prior and recalls having had a painless "cold sore" on his lip for several weeks that healed on its own. On your examination his vital signs are normal, he has no fever, but has generalized non-tender lymphadenopathy and a grayish shallow ulcer on his tongue in addition to the rash. You suspect secondary syphilis. At this stage the spirochaetes:

- Would not be found in his tongue ulcer since secondary syphilis is not contagious - Are confined to the genital mucosal surfaces through which they transmit and would not be found in any of the skin lesions - Are no longer susceptible to penicillin since they have stopped replicating - Have spread to most organs and may have even reached the CNS * - Have been mostly eliminated by the immune system and the clinical findings are due to the inflammatory response

Several thermally dimorphic fungi can be serious pathogens in immunocompetent hosts. These fungi are characterized by having a different morphology in the environment vs inside the mammalian host. These fungi grow as

- Yeasts within tissues at mammalian body temperature but as molds at room temperature * - Molds at mammalian body temperatures from where they form conidia to disperse and are found as mucoid yeast biofilms in the soil - Pseudohyphae on the skin but as highly branching septate hyphae when they invade deeper tissues at higher body temperature - Invasive mycelia when they are in the high temperature and high oxygen content of the lung, but as small budding yeasts between keratinocytes in the skin - Large yeasts with a thick glucoronic acid capsule in the tissue which prevents phagocytosis, and as small yeasts covered in a thin layer of glycoprotein that serves to help extract nutrients from the soil in the environment

Five days later, you see Patrick, a 2-month-old boy that attended the same daycare as the Samantha. Patrick developed fever, a red rash throughout his body followed by large areas of shallow, fluid filled, blisters that easily break. No obvious sites of pus or infected skin are noted. You admit Patrick to the hospital. Are Samantha's and Patrick's diseases related?

- Yes, Patrick's skin is teeming with the same S. aureus that infected Samantha and a swab of fluid from one of the blisters will confirm the diagnosis - Yes, Patrick has staphylococcal scalded skin syndrome, a consequence of the same toxin that causes bullous impetigo * - No, Patrick was probably burned in a hot water bath and you should call child protective services - Yes, this represents a highly contagious form of varicella zoster virus - Yes, Patrick's rash is due to the S. pyogenes streptolysin O toxin and babies are more likely to develop diffuse blistering

Your patient with Candida glabrata bloodstream infection was started on Caspofungin, an echinocandin. Your colleague is concerned that the antifungal agent that you have recommended might have excessive toxicity due to inhibition of both the fungal protein targeted by this medication as well as the analogous human enzyme. Which is the most appropriate response?

- You acknowledge that folic acid synthesis is a common process in both fungi and humans, and you review the patient's medication list to ensure that there are no other medications inhibiting this process. - You indicate that beta-glucan synthesis is a fungal-specific process, and that there is no analogous mammalian enzyme. * - You indicate that ergosterol biosynthesis is a fungal-specific process, and that there is no analogous mammalian enzyme. - You choose an alternative antifungal agent since caspofungin has no activity against pathogenic yeasts. - You explain that the isoform of the human enzyme targeted by caspofungin is only present in certain ethnic populations that do not include your patient.

Many microbes have the capacity to cause disease but don't do so often. Thus we can think of infectious diseases as a spectrum of outcomes of the host-microbe interaction. Which of the following patients is most likely to have a severe infection:

- Your patient is colonized in the throat by a microbe that can produce a thick capsule - Your patient recently received a bone marrow transplant * - Your patient is infected with a microbe that can persist in the body for years - Your patient is colonized in the intestine by a bacterium carrying a plasmid for multi-drug resistance - Your patient is colonized in the oral cavity by a microbe that can form biofilms

Although Escherichia coli are normal enteric flora, several strains have acquired genes that turn them into enteropathogens. Enterotoxigenic E. coli (ETEC) strains, for example, acquired a plasmid that encodes virulence factors. These strains cause diarrhea in infants and children of developing countries and are responsible for most cases of traveler's diarrhea. Every year, approximately 380,000 children less than 5 years old die from illness caused by infection with ETEC. The main way that ETEC strains cause diarrhea is through:

- a neurotoxin of the enteric nervous system that causes intestinal hypermotility and the rapid intestinal transit time produces the diarrhea - long pili that insert themselves between cells causing loss of junctional integrity and diarrhea through paracellular flow of ions - a pair of distinct toxins, one of which is almost identical to cholera toxin, both of which induce secretory diarrhea * - a porin-type toxin that inserts into the host cell membrane acting as an ion channel that leaks intracellular electrolytes into the gut lumen - an AB toxin that ADP ribosylates the ribosomes of the host cell resulting in loss of protein synthesis and cell death followed by a strong inflammatory response

CagA is a virulence factor in H. pylori that is associated with cancer. It is:

- an immunodominant antigen that generates serum antibodies that are microbicidal against H. pylori. - a potent immunosuppressive molecule secreted by the microbe to avoid innate immune responses. - injected by the bacteria into the host cell cytoplasm via a molecular microsyringe. * - transferred via plasmids to the more virulent strains of H. pylori. - a cell surface molecule present in the outer membrane that functions as an adhesin for the gastric epithelium.

Viruses are called infectious particles rather than organisms because they cannot replicate on their own without invading a host cell. In their simplest form viruses are composed of:

- an outermembrane envelope studded with host derived glycoproteins surrounding a segmented RNA genome - a fragment of a bacterial cell - a protein coat surrounding mRNA and ribosomes - a pleomorphic cell membrane surrounding a small amount of cytosol and a circular plasmid - a nucleic acid genome surrounded by a protein capsid *

Viruses sometimes persist in reservoir hosts in which they cause minimal or no disease. Influenza A virus has a preferred animal host in which it persists and from which it can evolve into strains that can infect other animals and humans. This main reservoir animal host is:

- aquatic birds * - mosquitoes - dogs - humans - bats

When he became asymptomatically infected by Mtb, he formed some granulomas. Tuberculous granulomas:

- are composed of multiple cell types including lymphocytes, neutrophils, dendritic cells and even macrophages that resemble epithelial cells * - are made up of large numbers of granulocytes, white blood cells characterized by cytoplasms full of granules. - are made up of calcium and have the same density as bones on X-ray films - do not contain Mtb bacilli, rather they are follicular compartments with large numbers of Mtb-specific B-cells that produce opsonizing antibodies - rapidly trap and kill Mtb. Only those bacilli that avoid granulomas are able to survive to cause disease

Jock itch, ringworm, and athlete's foot all share which of the following?

- are conditions caused by filamentous fungi with the ability to digest, metabolize and survive on keratin * - are diseases caused by fungal spores from soil that germinate in the humid environment of public bathrooms and locker rooms - typically become superinfected with bacteria and thus require both antifungal and antibiotics for treatment - are rare and difficult to diagnose requiring a biopsy for accurate determination of etiology - when they cause symptoms of itching and pain they involve deep dermal structures of the skin

Many pathogenic microbes attach to host cells via specific adhesins to avoid host mechanisms of mechanical clearance, establish colonization, deliver toxins or invade. Several forms of bacterial adhesion have been described. Pili or fimbriae, for example are often involved in initial adhesion of pathogenic bacteria. These structures:

- are only found in pathogenic forms of a microbe - function like spears, impaling the cell surface for both adhesion and release of cytosolic nutrients - are polymerized protein tubes that have unique tips to bind to host cell glycoprotein or glycolipid receptors* - inject toxins directly into host cells to modify the host cell cytoskeleton under attached bacteria - wrap around epithelial cilia to avoid being cleared by mucociliary action

Biofilms are a form of inter-bacterial adhesion important in medicine because:

- biofilm polysaccharides are a good target for lysozyme-like antibiotics - biofilms allow some bacteria to form aggregates and colonize foreign bodies like intravenous catheters * - biofilms form nets that trap neutrophils preventing them from reaching the site of infection - biofilms allow intracellular bacteria to find each other in the cytosol of the host cell forming large aggregates that cannot be recognized by innate immune sensors - biofilms allow the bacteria to survive on autoclaved surgical instruments and cause most surgical site infections

Influenza virus can change quickly because it has a segmented RNA genome. The mechanism by which its genome undergoes major changes (antigenic shift) and gives rise to most pandemic strains is:

- by breaking the genome into smaller segments, shuffling the fragments and creating new genes at each replication cycle - by shuffling of RNA segments when a single cell is infected by multiple different viruses thus giving rise to reassortants. * - by multiple viruses fusing with each other and creating multicopy virions that acquire new properties - by rapid mutation due to the fact that its RNA polymerase has no proof reading mechanism - by being themselves infected by bacteriophages that can add new pathogenic determinants

How have most strains of MRSA become resistant to beta-lactam antibiotics?

- by horizontal gene transfer of a transpeptidase gene that, when expressed, binds poorly to beta-lactam antibiotics * - through the acquisition of an efflux pump that quickly removes beta-lactam antibiotics from the cytoplasmic space - by mutation of cell membrane porins that prevent influx of the antibiotic into the bacterial cell - through a point mutation in the peptidoglycan side chain that makes it resistant to penicillin binding proteins - through acquisition of a plasmid that codes for a broad spectrum beta-lactamase enzyme

STEC (Shiga toxin-producing Escherichia coli) also known as enterohemorrhagic E. coli (EHEC) is a commensal in cattle, but it is particularly dangerous to humans because it causes hemolytic uremic syndrome in up to 15% of people infected, and can result in renal failure. The disease:

- can be treated if one rapidly administers anti-Shiga-toxin immunoglobulin. - occurs when sufficient Shiga-toxin is absorbed into the circulation, causing endothelial cell damage, platelet aggregation, and glomerular microthrombi. * - only occurs after eating improperly cooked hamburger meat contaminated with cattle feces. - requires early intervention with antibiotics to reduce chances of developing HUS. - presents as massive watery diarrhea causing dehydration and acute tubular necrosis in the kidneys.

Enteric fever syndrome is:

- characterized by intracellular invasion of the colonic enterocytes accompanied by inflammation, high fevers, and bloody diarrhea - best diagnosed through blood cultures * - commonly caused by Salmonella enterica serovar Enteritidis in the U.S. - an auto-immune process that occurs after gastrointestinal infections - caused by Enteropathogenic E. coli In the developing world

A 50-year-old man develops shingles in the the lower abdomen. He has a new girlfriend that does not believe in vaccines. If he transmits the infection to his girlfriend who has never been immunized or had natural infection, you would expect that she will:

- develop fever and splenomegaly without a rash - develop shingles in multiple dermatomes - develop painful mouth ulcers - develop shingles in the same abdominal dermatome in the opposite side of the body - develop a generalized vesicular rash throughout her body *

Elena was admitted to the hospital three days ago and has received empiric broad spectrum antibiotics with vancomycin and ceftazidime, but she remains febrile. Her admission chest radiograph did not reveal a pneumonia and ECHO did not show evidence of endocarditis. Yesterday the microbiology lab reported that both pus from her arm lesion and her blood culture taken on admission were growing Gram-positive cocci in groups. Today the infecting organism was identified as MRSA. Her serum vancomycin levels have been within the therapeutic range. You discontinue ceftazidime since it has no activity against MRSA and continue intravenous vancomycin. On physical exam today she has normal blood pressure and respiratory rate, but she is tachycardic during febrile episodes (pulse 120-130, normal 60-100), and continues to have periods of high spiking fever to 40°C once-a-day. She has a normal cardiac exam without a murmur, clear lung fields on auscultation, and complains of mild tenderness on palpation of her right upper quadrant. The indurated red nodule on her left antecubital area has resolved. You obtain a CT scan of the abdomen and pelvis, which reveals the following abnormality: (Abscess on the liver)

- double the dose of vancomycin to increase antibiotic levels at the site of the abscess - restart ceftazidime and continue therapy with both antibiotics - change to clindamycin since her MRSA is likely to be resistant to vancomycin - obtain a consult from surgery or interventional radiology to drain the abscess since antibiotics may not penetrate well enough to sterilize * - increase the dosing frequency of vancomycin to maintain levels above the MIC

Penicillin-binding-proteins or PBPs are:

- enzymes that crosslink the stem-peptides in the nascent peptidoglycan chains * - bound and inactivated by vancomycin which is the reason this antibiotic is very broad spectrum - proteins made by fungi that have a high affinity for penicillins and thus can be used to purify the antibiotics in large quantities - secreted proteins that bind to penicillin and inactivate it thus making the bacteria resistant - only found in gram-positive bacteria and thus gram negatives are resistant to penicillins

The IGRA test you sent is also positive. You decide to start therapy with four anti-tuberculosis drugs while awaiting the sputum culture results, which will potentially take several weeks. You also inform the public health system of the case. An important role of the public health system in protecting the population from TB is to:

- give directly observed therapy (DOT) to reduce the emergence of resistant strains and improve cure rates * - distribute N-95 masks to close contacts of people with active TB in high risk settings like prisons and drug rehabilitation centers - test all Mtb isolates to determine their drug susceptibility patterns - enter all persons with LTBI into a registry so that they can be promptly identified if they develop active TB disease - quarantine every person with a positive TST or IGRA until active TB can be ruled out

The result of his IGRA is positive, consistent with prior infection by Mtb. To make sure he has only LTBI and not active TB disease, you perform a full physical exam and order a chest radiograph. The film shows a calcified nodule in the right middle lobe. This means:

- he may have lung cancer and you should consider a biopsy of the lesion - he has had a very recent infection less than 9 weeks since exposure - the calcified granuloma is consistent with LTBI and you should reassure him that he is not contagious or diseased * - you have now been exposed to TB and you have better get an IGRA test on yourself in the next week or two - he is likely immunocompromised and you should also test for HIV

A five-year-old girl is brought in with symptoms and signs of fever, tachypnea, crackles, and hypoxia. You suspect she may have pneumonia and obtain a chest radiograph. A finding in her radiograph that should make you suspect a bacterial over a viral pneumonia is:

- hyperinflation of the lungs visualized as flattening of the diaphragms - loss of visualization of the heart border - localized consolidation of a lobe of the lung parenchyma * - a steeple sign of the trachea due to subglottic edema - diffuse interstitial patchy opacification of both lungs

The outer membrane of gram-negative bacteria has an outer leaflet with specialized sugar-decorated lipid termed lipopolysaccharide (LPS). Our innate immune system can recognize the lipid portion of LPS at nanomolar amounts and this sometimes leads to:

- hypotension, capillary leak and fever * - production of large amounts of antimicrobial peptides which can injure not just bacteria but also the epithelium - severe constipation that can lead to intussusception - severe pain at the site of infection - non-specific activation of T-cell signaling via crosslinking of the T-cell receptor with MCH molecules

In which of the following scenarios should you consider prescribing a course of antibiotics for asymptomatic bacteriuria:

- in an elderly woman with a urinary catheter because advanced age is associated with poor immune function and she will be at risk of developing bacteremia - in a woman with a history of recurrent UTIs known to be colonized by uropathogenic E. coli - in a young woman that has recently had her first UTI and you want to make sure the infection has cleared completely to avoid recurrent infections - in a pregnant woman because mechanical changes increase the risk of urinary stasis and vesicoureteral reflux and increase the risk of developing pyelonephritis * - in any woman who has had a UTI with multi-drug resistant Gram-negative bacteria

A 19 y/o Stanford student returns from SWEAT camping trip in the Sierra Nevada mountains of California. He has had three weeks of intermittent diarrhea and describes that his stools have become very foul smelling and "kind of floats and sticks to the sides of the toilet bowl". You order ova and parasite microscopic examination of his stools and also a direct immunofluorescent assay (DFA) that uses fluorescein-tagged monoclonal antibodies to detect a specific pathogen. The micro lab calls to say they have detected protozoal cysts in his stools. What is the mechanism by which this pathogen causes diarrhea:

- invades enterocytes - covers the surface of intestinal microvilli, blocking absorption * - induces elongation and loss of enzymes in the intestinal microvilli - blunts the intestinal villi - secretes a toxin that causes apoptotic death of enterocytes

When you obtain a history, you find out that the man's mother died of pulmonary tuberculosis when he was a child in India. He was eight years old when she died. He helped take care of her until the end, and never became ill himself. However, he does remember that her symptoms are similar to the ones he has now. A likely reason he did not develop tuberculosis as a child is that:

- most people infected with Mtb will clear the infection once their T-cell mediated immunity is established - most people with a normal immune system infected with Mtb can control Mtb infection and keep it in an asymptomatic state throughout their lives * - it is rare for family members to transmit TB to each other because the constant exposure to small doses of Mtb induces protective immunity - most infected people shed and transmit tuberculosis asymptomatically thus never experiencing disease - he received the BCG vaccine as an infant which prevented him from becoming infected by his mother

You are volunteering your services as a doctor for low income families. You visit a household of Indian immigrants and are asked to see a 73-year-old man who has become cachectic and has been coughing for several months. He sometimes coughs blood-tinged sputum. Tuberculosis is on your differential diagnosis. Before entering his small room, you put on an N-95 mask. If he has active TB, the Mtb bacilli will circulate in the closed space and remain viable for several hours. Mtb are resistant to desiccation and survive being airborne in microscopic respiratory nuclei because:

- mycobacterial porins are regulated by osmosis and close if the mycobacteria become dehydrated - the cell envelope mycolic acids form a hydrophobic barrier that protects them from drying * - the mycobacterial thick peptidoglycan layer absorbs water molecules in its lattice - mycobacterial metabolism uses beta-oxidation to split long chain fatty acids into acetyl CoA and water thus maintaining hydration - mycobacteria naturally thrive in environments with low water content like dessert soils

If Gram-positive cocci were cultured from one of Samantha's lesions, which of the following tests distinguishes Staphylococcus from Streptococcus:

- penicillin sensitivity since all Staphylococci are penicillin resistant - catalase which allows Staphylococci to detoxify hydrogen peroxide * - beta-hemolysis which is only found in Streptococci due to their production of streptolysin O - gram stain morphology because Staphylococci usually grow as short chains while Streptococci grow as long chains - coagulase which allows Staphylococci to activate clot formation

One of the first steps in identifying the cause of a bacterial infection may be an analysis of a Gram-stain from a patient sample. This study will describe not just the result of the Gram-stain reaction (positive or negative), but also the shape (cocci, rods, spiral, etc) and the organization of the bacteria (groups, chains). Bacteria can have many shapes which can be an important clue to their identity. Which of the following components of bacterial structure is most important in determining cell shape:

- peptidoglycan * - biofilm exopolysacharides - capsular polysacharides - glycolipids of the outer membrane - flagellar motors

You are in the Emergency Room taking care of Elena, a 26 year-old woman (HIV-negative) with a history of intravenous drug abuse. On physical exam she is unkempt and thin, and appears mildly ill. She is febrile (39.1°C) but with otherwise normal vital signs. On physical exam, her heart and lung exam is normal and she complains of mild diffuse abdominal pain. On the antecubital area of her left arm she has a raised indurated red nodule of about 1 cm diameter. Part of it feels fluctuant. Her laboratories show an elevated WBC count (26,000 WBC [normal 5,000 - 11,000]), and elevated c-reactive protein (CRP- 7.2, normal < 1). Urinalysis is normal. Based on her risk factors for infection what would be your recommendation.

- perform an incision and drainage of the fluctuant lesion on her arm and send fluid for Gram stain and culture, refrain from giving antibiotics since subcutaneous infections are most often cured by drainage alone and antibiotics breed resistance and damage the microbiota - perform an incision and drainage of the fluctuant lesion on her arm, send fluid for Gram stain and culture, obtain blood cultures, and admit her to the hospital to receive empiric intravenous antibiotics and further workup * - prescribe a course of oral penicillin which will empirically treat most Staphylococcus aureus and Streptococcus pyogenes strains, send her home but have her follow up in two days if her symptoms have not resolved - repeat her HIV testing now since due to her risk factors her status may have changed and she would be very susceptible to infection. Have her follow up in clinic in a week to review the results - schedule an MRI of the arm for the next available time and have her follow up in clinic after this study to determine if there is a potential deep infection that could require surgery or empiric antibiotic therapy

Rima, a 3-month old baby girl, is brought to your clinic because of fever. On examination she is febrile to 38.6°C, with otherwise normal vital signs. She is irritable but consolable and has a normal physical exam. You obtain blood for CBC and blood culture and urine via a catheter for urinalysis and urine culture. Of the following urinalysis results which would be the most concerning for the possibility of a urinary tract infection:

- positive leukocyte esterase because it signifies pyuria * - positive ketones because it represents bacterial degradation of urinary lipids - negative glucose because it represents bacterial consumption of urinary glucose - specific gravity of 1.2 because it signifies severe dehydration and poor renal function - positive protein because it signifies bacterial growth in the urine

Given that he is not sick with active tuberculosis, he may have benefited from BCG vaccination, which is given in many countries in which TB is endemic. BCG is most effective at:

- preventing infants from developing miliary tuberculosis * - reducing the number of people that become infected with Mtb after exposure - preventing disease from M. bovis since it is an attenuated form of this mycobacterium - reducing the amount of time required to treat an infected person with antibiotics - preventing adults from progressing from LTBI to active TB disease

One way Mtb bacilli survive attack by professional phagocytes like macrophages is to:

- produce a thick waxy capsule that is anti-phagocytic because the macrophages cannot bind to it - use bioactive cell envelope lipids to block fusion of the phagosome with lysosomes and prevent acidification * - produce a decoy molecule that structurally resembles the TNF-alpha receptor, thus reducing signaling and macrophage activation via this pathway - Secrete IgA proteases that cleave the Fc portion of anti-mycobacterial antibodies and thus avoid opsonization - secrete bioactive surface lipids that paralyze the cytoskeleton of phagocytes preventing engulfment

The definitive host for Plasmodium falciparum is:

- rodents - humans - monkeys - snails - mosquitoes *

Samantha's mother asks whether Samantha is contagious and when she can return to daycare? You tell her that:

- she should not return to daycare for two weeks until her intravenous antibiotics are finished - Samantha should be treated with antibiotics for at least 24 hrs and the rash kept covered before returning to day care * - children are not contagious unless they pick their nose - these lesions are not infectious because they are only a superficial reaction to the toxin and do not contain bacteria - it really doesn't matter since all the daycare children are probably carriers

You are working in a local ED and are called by a family physician who just saw a 6-month-old ex-premature baby that tested positive by nasopharyngeal swab for RSV infection. He is sending the patient to you for evaluation. The main symptoms you would be concerned about include:

- tachypnea, subcostal retractions and wheezing due to inflammation of the bronchioles * - stridor due to inflammation of the laryngeal mucosa - ear pain due to swelling of the eustachian tube and fluid accumulation in the middle ear cavity - tachypnea, and snoring due to mucus plugging of the mainstem bronchi - copious nasal secretions due to inflammation of the nasopharynx

Most viruses cannot infect many cell types and have specific tropism of a particular tissue. This determines what kind of clinical manifestations can occur. An important determinant of viral tissue tropism is:

- the site and abundance of host receptors that bind specifically to viral adhesion proteins prior to internalization * - the type of internalization that a cell is capable of i.e. clathrin-mediated endocytosis vs caveolin-mediated endocytosis - the blood flow to a particular organ carrying the viral particle to those cells - the type of endosomal transport that a cell possesses such as microtubule vs microfilament based transport - the type of host cell ribosome that can transcribe viral mRNA

You examine the patient, draw blood to be sent for an Interferon Gamma Release Assay (IGRA), obtain sputum for AFB smears and culture, and also ask the family to bring him to the hospital for a chest radiograph and further evaluation. The next day you review the chest radiograph and find that he has a cavitary lesion in the right lung. If the cavitary lesion is due to tuberculosis:

- this explains why he only has low grade fever, since the liquefying caseum has anti-inflammatory metabolites - Mtb will thrive in the aerobic extracellular environment of the caseum and grow to high numbers * - transmission of TB will not occur unless the cavity erodes into a blood vessel causing hemoptysis - Mtb bacilli will be in a non-replicating state in the caseum of the cavity because of its acidic and avascular nature - the only option is to surgically remove the affected lung tissue since anti-tuberculous drugs will not penetrate the cavity

Once inside the host, pathogens hide from the host immune system in order to persist and replicate. One important way some bacteria avoid phagocytosis is:

- to avoid phagolysosome fusion in order to persist inside host cell vacuoles - to produce superantigens to overwhelm host immune responses and allow unchecked replication in the bloodstream - to produce polysaccharide capsules that can block phagocyte receptors from detecting bacterial surfaces and inhibit complement * - to secrete endotoxin which inhibits the phagocytic machinery of macrophages - to make neurotoxins, like botulinum toxin, which cause respiratory arrest thus completely disarming the immune response