BHL Week 4 Questions

The disease known as sleeping sickness is caused by Trypanosoma brucei and spread by the bite of the tsetse fly. After infection, the number of parasites in the blood fluctuates periodically; this cycle of parasitemia, remission, and recrudescence is due to destruction of trypanosomes by host antibody, followed by the emergence of parasites expressing different surface antigens or variant surface glycoproteins (VSGs). Which of the following is the best term to describe this method of host immune evasion?

Antigenic variation (Antigenic variation is the most striking example of successful adaptation by microbes and is exemplified by the ability of the trypanosome causing sleeping sickness to avoid destruction by the host's immune system. Each parasite is covered by hundreds of thousands of molecules of VSGs. Antibodies produced after each wave of parasitemia are specific for one VSG only. The parasite possesses a number of genes that code for its VSGs and can shed the old coat of VSGs and put on a new one not recognized by antibodies. The antibodies do not trigger the switch; it occurs spontaneously. Thus, by presenting an immunodominant antigen that it can vary, the parasite diverts its host's attention away from essential, constant elements on its surface. )

A 42-year-old patient presents with symptoms suggestive of pneumonia. He has just returned from a trip to California. Examination of bronchoalveolar lavage fluid shows the presence of large spherules. Which of the following is most likely responsible for the infectious property of this organism?

Arthroconidia that are aerosolized in the environment

A 50-year-old industrial worker engaged in handling animal products developed a painless papule on his right forearm where he had a minor abrasion 5 days earlier. The papule became a vesicle after 48 hours and ruptured, leaving an ulcer with a black necrotic area in the center and surrounding edema. Gram stain of smear from the skin lesion showed Gram- positive bacilli (1-1.5 x 3-5 microns) that appeared encapsulated. Aerobic culture done from the lesion on 5% sheep blood agar yielded pure growth of non-hemolytic colonies 2-5 mm diameter with wavy border and ground glass appearance after overnight incubation. The isolate was non-motile, produced spores, and was sensitive to penicillin. Which of the following is the most likely infectious agent?

Bacillus anthracis (Bacillus anthracis is the bacterium isolated. The skin lesion is likely to be acquired as a result of infection from animal products. The gram positive large encapsulated bacilli demonstrated in smear from the lesion, its rapid aerobic growth, characteristic appearance of the colonies, absence of motility, and sensitivity to penicillin support presumptive identification as Bacillus anthracis. The organism is an aerobic spore-bearer that produces a poly-gamma-d-glutamic acid capsule in vivo. The capsule is anti-phagocytic and protects the bacteria from complement-mediated lysis. Spores are highly resistant and are not produced in living tissue. Carbon dioxide levels within the body inhibit sporulation. Exposure to free oxygen is necessary for formation of spores. Absence of motility and absence of hemolysis in culture help to differentiate the organism from other bacillus species often encountered as contaminants in culture. Bacillus anthracis causes three clinical forms of anthrax, cutaneous, inhalational and gastrointestinal. Cutaneous form is the most common. Inhalational anthrax is the most severe form. Complications like septicemia and meningitis can occur. The development and appearance of the skin lesion in the patient is characteristic of cutaneous anthrax (malignant pustule). Anthrax vaccine for humans contains the protective antigen. B. anthracis considered an important agent of bioterrorism because of its virulence factors and physical properties. Bacillus cereus is an aerobic spore-forming bacillus related to B. anthracis and is a ubiquitous organism. It is motile and produces hemolysis on sheep blood agar. It produces beta lactamase and is therefore resistant to penicillin and other beta lactam antibiotics. It causes food poisoning: emetic type following consumption of preformed toxin in rice dishes and diarrheal type following consumption of contaminated meat or dairy products. B. cereus can also cause severe diseases when combined with predisposing factors in the patient, such as drug addiction, immunosuppression, and prosthetic implants. Endophthalmitis, osteomyelitis, pneumonia, and endocarditis are examples of severe infections. Clostridium perfringens is a large Gram-positive, nonmotile, anaerobic spore-bearing bacillus. It causes invasive infections, myonecrosis, and gas gangrene, often following wound contamination. C. tetani is also a large Gram-positive motile, anaerobic spore-bearing bacillus. It causes tetanus or lockjaw when the spores are injected into the skin. Listeria monocytogenes is a large, Gram-positive, non-spore-forming motile bacillus. It causes food poisoning and meningitis.)

A 10-year-old boy was diagnosed with a zoonotic infection endemic in the U.S. This small pleomorphic Gram-negative bacillus is recognized as a frequent cause of benign lymphadenopathy in children. Following a scratch from his pet cat, the boy had developed an erythematous papule on his arm and a few weeks later, regional lymphadenitis. Which of the following is the most likely infectious agent?

Bartonella henselae The boy's history of 'cat scratch', typical presentation with regional lymphadenitis, and the features of the zoonotic infection described are suggestive of Cat Scratch Disease (CSD). The infection is endemic in the U.S. and about 24,000 people have CSD annually, 80% of whom are children. The main agent of CSD is Bartonella henselae. B.henselae is a zoonotic pathogen capable of causing a broad range of clinical manifestations in humans. CSD is usually a self-limited infection in immunocompetent children. Other manifestations of B.henselae infection include bacillary angiomatosis-peliosis, bacteraemia, encephalitis, endocarditis, and neuroretinitis. Bacillary angiomatosis-peliosis is characterized by the formation of vasoproliferative tumors resulting from bacterial colonization and activation of human endothelial cells. Ability to induce endothelial cell proliferation is a common characteristic of Bartonella species pathogenic to humans. Systemic diseases mostly occur in immunocompromised persons. B.henselae is a very fastidious bacterium. Once isolated from the lymph nodes of CSD patients, it needs prolonged incubation in enriched blood media in the presence of carbon dioxide, so detection is often unsuccessful. The most common form of anthrax caused by Bacillus anthracis is cutaneous anthrax and the lesion on the skin is called a black eschar due to malignant pustules. This organism is a Gram-positive, spore-forming bacillus. Francisella tularensis is also a pleomorphic Gram-negative, pleomorphic coccobacillus that requires cystiene in the culture media in order to grow. It is typically acquired by humans by contact with infected rabbits or by tickes, lice, or mites. Infection with this organism causes ulcers to develop and eventually caseating granulomas and regional lymphadenopathy. Brucella melitensis is also a Gram-negative, pleomorphic coccobacillus but it is typically acquired by the ingestion of contaminated food products or direct skin contact. In the latter case, caseating granulomas and abscess formation can occur in the reticuloenthothelial system. However, the most common clinical presentation in humans is undulating fever. Borrelia borgdorferi is a spirochete that cannot be cultured in vitro. Infection with this organism can cause a spreading annular red lesion often termed a "bulls-eye" rash.)

A 25-year-old man living in Delaware comes to the primary care doctor with a rash on his left leg that appeared 1 week ago as a small red area and is getting bigger. He also experiences of muscle pain, joint stiffness, and fatigue, but he attributes this to being an avid hunter and he has been exercising more than usual due to hunting season. At physical exam, he has a flat circular lesion on his leg that is pale in the center and red at the periphery. The rest of the exam is normal. What is the agent causing this infection?

Borrelia burgdorferi

An outbreak of Epidemic louse borne typhus is favored by crowded living conditions with poor hygiene and is especially common in parts of central and northeastern Africa. Which of the following is the causative agent of this disease?

Rickettsia prowazekii (Epidemic typhus is louse borne and is caused by Rickettsia prowazekii. It has 10 to 14 days of incubation period. The infection is characterized by high fever and rash on trunk and extremities. It has a high mortality rate (40% for untreated patients). Myocardial and neurological involvement can lead to the death of the patient. Treatment includes tetracycline or chloramphenicol in combination with measures for louse control. Rickettsia prowazekii can reactivate and cause Brill-Zinsser disease (recrudescent typhus) in previously infected host. C. burnetii causes Q fever. Cattle, sheep, and goats are the primary reservoir and the organisms are excreted in milk, urine, and feces of infected animals. Infection of humans is usually by inhalation of these organisms from air that contains dust contaminated with the infective form. R. rickettsii is discussed on other slides. R. tsutsugamushi (now called Orientia tsutsugamushi) causes scrub typhus which is transmitted by mites, etc. This is a disease found primarily in SE Asia and Japan and was a major cause of mortality during WWII among troops that were stationed there. Bartonella quintana (formerly called Rochalimaea quintana) is a cause of bacillary angiomatosis (BA) and is spread by lice. BA typically occurs in immunocompromised patients (HIV) and is a vascular proliferative disease.)

A 10-year-old boy from Oklahoma City, who lives near the zoo, presented to the physician with a rash, fever and a severe headache that began three days ago. The rash was first seen on the palms of the hands and soles of the feet but has now spread centrally to his trunk. He just returned from boy scout camp and reports that he had ticks on his body following an all day hiking trip. He recovered after treatment with tetracycline. Which of the following organisms is the most likely cause of this infection? What would you use to confirm the diagnosis?

Rickettsia rickettsii

A 7-year-old boy is brought to the pediatrician with a rash that appeared 3 days ago. It began in the palms and soles and now covers most of his body. He also complains of fever, nausea, vomiting, sore throat, abdominal pain, and headache. At physical exam the patient has pink macules all over his body, which disappear with pressure. He also has some ulcers and ecchymosis. What is the agent causing this infection?

Rickettsia rickettsii (Rickettsia rickettsii is a rickettsia that causes Rocky Mountain spotted fever. It is transmitted to humans by the wood tick (Dermacentor andersoni) and the dog tick (Dermacentor variabilis.). Typical symptoms include flu appearing 5 to 7 days after the inoculation and a rash (pink macules) that begins in palms and soles, disseminating to the rest of the body and disappearing with pressure. Later on ulceration and ecchymosis can be seen. The neurologic and circulatory systems can also be involved. Treatment is with tetracycline, doxycycline, and chloramphenicol. Borrelia burgdorferi is a spirochete transmitted to humans by a deer tick (Ixodes scapularis). It causes Lyme disease. There are 3 stages of this disease: Stage 1 (early localized): usually the first 10 days after the bite. It is a localized erythematous macule or papule, pale in the center (erythema migrans), present at the site of the bite, accompanied by flu-like symptoms. Stage 2 (early disseminated): A few weeks later. Usually neurological symptoms such as facial nerve palsy or meningitis, and cardiac symptoms as arrhythmias or pericarditis are seen. Stage 3 (late chronic disease): Developing even years later with symptoms like arthritis, dermatitis, and cardiomegaly. The diagnosis is mainly clinical. The treatment depends on the severity and the stage of the disease. Doxycycline is used in early stages. Francisella tularensis is a Gram negative rod that causes tularemia (rabbit fever). It is transmitted to humans by ticks (A. americanum, D. variabilis, and D. Anderson) or flies but also by eating uncooked infected meat, contaminated water, or through skin lesions when skinning rabbits that are infected. The ulceroglandular manifestation is most common. Symptoms such as flu appear 3 to 5 days after the inoculation and depending on the source of infection the patient can also show skin ulcers, pneumonia, pericarditis, and regional lymphadenopathy. The diagnosis is done by serology, but a PCR of the ulcer is also available. Although a vaccine has been around for 50 years, its use has not yet been approved. The treatment is streptomycin and gentamicin. P. multocida typically does not cause a rash. Brucella is a group of bacteria found in animals such as dogs, goats, sheep, cattle, deer, or pigs. Humans get infected (Brucellosis) when they come in contact with the animals or their products (milk). Brucellosis can produce abscesses in many different organs such as liver and spleen. The treatment depends on the type of presentation.)

A sexually active adolescent male, 17 years of age, presents with a fever, weight loss, and generalized lymphadenopathy. An HIV ELISA test was positive, and subsequent western blot was positive for p24. CD4 positive lymphocyte levels were 300 CD4+ T-cells per ml while PCR analysis revealed a low level of circulating virus. No opportunistic infections or malignancies were found. Which of the following is most consistent with the clinical picture described above?

The patient has AIDS-related complex

The virus responsible for causing AIDS (HIV) is classified as a retrovirus. Many of the drugs used to treat HIV infection take advantage of a unique sequence of events involved in the replication of retroviruses. In order for HIV to replicate, which of the following steps must occur first?

The viral RNA must be converted to DNA

Which of the following is the most accurate statement about acute physiology scoring systems?

They can estimate mortality in newly admitted ICU patients

Last summer a group of 30 volunteers went to Nigeria to work in a free clinic and all of them took prophylaxis to prevent malaria. They claim that they took the medication as prescribed 2 weeks before, during their stay, and for 4 weeks after returning home. In October, one person developed malaria and by April of this year, 9 of the 30 volunteers had been treated for malaria. Which of the following is the least likely explanation for this apparent failure of prevention?

This could be P. falciparum that was not completely treated by the prophylaxis

An AIDS patient was brought to the emergency room after suffering a grand mal seizure. He informed the physician that he has had headaches that were persistent over the past few weeks. The doctor ordered a CT scan fearing that the patient had a brain tumor. The scan revealed the presence of calcifications and a brain biopsy revealed the presence of tachyzoites. Which of the following is the most likely infectious agent?

Toxoplasma gondii

A 50-year-old man presented with diffuse pain, stiffness and swelling of his right knee. His symptoms were of 3 weeks duration. He was living near a wooded area, and had history of tick-bite 7 months earlier. He had developed a local skin lesion at the site of the tick-bite, followed by flu-like symptoms, and had recovered without any specific treatment. Radiography of the knee joint showed evidence of fluid accumulation. Which of the following is recommended for confirming the diagnosis?

Treatment for serum antibodies (ELISA)

An East African man is asked to leave his job after repeatedly falling asleep. He visits the doctor hoping to cure his somnolence, as well as accompanying headache and dizziness. During the interview, the patient explains that he had suffered recurring bouts of fever and enlarged lymph nodes before the sleepiness started. The doctor decides to perform a lumbar puncture, and after finding a flagellated protozoan in the CSF, he plans to start the patient on melarsoprol. What is the infectious agent?

Trypanosoma brucei rhodesiense (bc of melarsoprol used for CNS infection.) (Gambiense occurs slowly. Rhodesiense occurs quickly.)

A Mexican man complains to his doctor of worsening constipation and stomach pains. On physical exam, the doctor is surprised to find an enlarged heart on auscultation and moderate arrythmia. Following an abdominal X-ray revealing megacolon, the doctor makes his diagnosis. Unfortunately, the treatments she offers are only symptomatic. What is the infectious agent?

Trypanosoma cruzi

An immigrant from South America sees her doctor because of complaints of chest palpitations and shortness of breath. It is found that her heart is dramatically increased in size. Electrocardiogram (EKG) results are consistant with a diagnosis of a vector-borne disease. Which of the following is the causative agent?

Trypanosoma cruzi (Chagas' disease is caused by the protozoa Trypanosoma cruzi. The included image is a micrograph of Trypanosoma cruzi in a blood smear using Giemsa staining technique. Image and description courtesy of CDC/Dr. Mae Melvin. Chagas' disease is also referred to as American trypanosomiasis. Chagas' disease is seen in the Western Hemisphere, primarily in South America, Central America, and Mexico. Transmission of Chagas' disease is by contact with the feces of an infected insect. There is an acute stage and a chronic stage. The chronic infection can lead to cardiomyopathy. The cardiac changes seen with Chagas' disease include enlarged heart and EKG findings as seen in this patient (right bundle branch block and premature ventricular contractions). The chronic infection can also lead to megaureter, megaesophagus, and megacolon)

A 42 year old woman who was complaining of shaking chills and fever went to the Salt Lake City Homeless clinic. She had enlarged lymph nodes in the right axilla. "Upstream" from the enlarged nodes was an ulcer on the top of the patient's right hand. When carefully questioned, the patient said she remembered being bitten there by an insect resembling a horsefly, but with yellow stripes on its abdomen; "It's what we used to call a deerfly," she added laconically. The patient denied any contact with rats or fleas. The patient's disease was most likely:

Ulcero-glandular tularemia ( A. Brucellosis (aka UNdulent fever) - from ingesting UNpasteurized animal products. B. Ulcero-glandular tularemia (F. tularensis) - carried primarily in rabbits, but transmitted by ticks, lice, mites C. Pneumonic plague - no fleas rules this out D. Relapsing fever - malaria E. Cutaneous anthrax - from goat, cow or other herbivore products)

You are an epidemiologist employed by the Public Health Service to investigate several outbreaks of disease. Which organism is most likely to cause an outbreak in children handling dead squirrels on a camping trip?

Yersinia pestis (Yersinia pestis belongs to the class of gram negative rods whose habitat is wild rodents, (e.g., prairie dogs and squirrels) and transmission is by flea bite. Pathogenesis depends on endotoxin, exotoxin, the v and W antigens, and an envelope antigen that protects against phagocytosis. Francisella tularensis is carried primarily in rabbits and transmitted to humans by ticks, lice, or mites, or contact with infected animal. Pasteurella multocida is usually transmitted by the bite of cats/dogs. Brucella abortus is found primarily in cattle. R. Prowazeki causes louse-borne epidemic typhus.

Persister cells are:

dormant. ( -found in both biofilm and planktonic cells -are metabolically hyperactive and therefore degrade antibiotics faster -are responsible for extracellular polymeric substance production -encode resistant genes against antibiotic treatment -are dormant)

A previously healthy 25-year-old-man comes to the physician because of a two-day history of fever, backache, headache, shivers, nausea and loss of appetite. He has vomited on several different occasions. His last episode produced dark brown vomitus. He has also had repeated nosebleeds. The patient and his girlfriend returned from a trip to Venezuela five days ago during which they swam in jungle waterfalls. His girlfriend is asymptomatic. Physical examination shows yellow discoloration of the sclera. Serum studies show an increased total serum bilirubin concentration and increased aspartate and alanine aminotransferase activities. This patient could have avoided this disease by

immunization with an attenuated organism. (This disease is Yellow Fever which is caused by a member of the Flaviviridae family. The vaccine was developed by Max Theiler in the 1930s and is still basically the same vaccine. The vaccine confers lifelong protection to 95% of recipients. A certification of vaccination is required for travel to endemic regions of Africa. Travelers should wear clothing to protect exposed areas, use DEET repellent spray and sleep under mosquito netting.)

Serologic testing before kidney transplantation reveals that the leukocytes of a prospective recipient are killed by the following anti-HLLA antibodies in the presence of complement: anti-B27, anti-A1, and anti-A3. Which of the following is the most likely conclusion?

that the prospective recipient expresses the B27, A1, and A3 HLA specificities

Herd immunity is the process by which...

the spread of communicable diseases within a population is prevented by high rates of immunity, despite individual susceptibility. (Herd immunity is a form of immunity that occurs when the vaccination of a significant portion of a population (or herd) provides a measure of protection for individuals who have not developed immunity. It arises when a high percentage of the population is protected through vaccination against a virus or bacteria, making it difficult for a disease to spread because there are so few susceptible people left to infect. This can effectively stop the spread of disease in the community. It is particularly crucial for protecting people who cannot be vaccinated. These include children who are too young to be vaccinated, people with immune system problems, and those who are too ill to receive vaccines (such as some cancer patients). The proportion of the population which must be immunized in order to achieve herd immunity varies for each disease but the underlying idea is simple: once enough people are protected, they help to protect vulnerable members of their communities by reducing the spread of the disease. However, when immunization rates fall, herd immunity can break down leading to an increase in the number of new cases. For example, measles outbreaks in the UK and pertussis outbreaks in the US have been attributed to declining herd immunity.)

A 43-year-old cattle rancher develops a severe headache, fever and chills. He has complaints of malaise and muscle pain as well. He sees his family doctor. On physical examination, he is found to have a temperature of 39.2°C. There is no rash present. His liver is slightly enlarged. Serology performed on acute and convalescent serum samples indicate a five-fold rise in titer of complement fixing antibodies. He is diagnosed with Q fever. What is the causative agent of Q fever?

Coxiella burnetii (Q fever is an acute illness that is caused by the Rickettsia Coxiella burnetii. It is transmitted to humans from exposure to infected livestock. The symptoms that this male experienced are consistent with Q fever: fever, chills, headache, muscle pain, and malaise. Endocarditis can be a complication of Q fever. Brucella is a non-motile gram-negative rod. They do not form spores. The disease caused by Brucella is called Brucellosis. Brucellosis can be caused by Brucella suis, Brucella abortus, Brucella melitensis, and Brucella canis. Malta is where Brucellosis infection was originally documented. Therefore, brucellosis is sometimes called Malta fever. Brucella abortus is not the cause of Q fever. Brucella abortus is one of the causes of brucellosis. Brucella abortus generally infects cattle and it can then be transmitted to humans. Brucella suis is not the cause of Q fever. Brucella suis is one of the causes of brucellosis. Brucella suis generally infects pigs and it can then be transmitted to humans. Borrelia burgdorferi is not the cause of Q fever. Borrelia burgdorferi is the cause of Lyme disease. This is transmitted to humans by a tick bite, specifically by deer ticks (Ixodes ticks). Borrelia burgdorferi is classified as a spirochete. Some of the symptoms that can be seen with Lyme disease include arthritis, bull's eye rash and fatigue, chills and fever, headache, and muscle pain. Rickettsia prowazekii is not the cause of Q fever. Rickettsia prowazekii is the cause of epidemic typhus. This is transmitted to humans by the human body louse. War, poverty, crowding, famine, and unsanitary conditions predispose to the occurrence of epidemic typhus. Some of the symptoms of epidemic typhus include rash, headache, chills, delirium, and high fever.)

Most of the population of West Africa is resistant to Plasmodium vivax infection due to

Absence of an antigen that acts as a receptor for Plasmodium vivax infection. (Most of the population of West Africa is resistant to Plasmodium vivax infection due to absence of an antigen that acts as a receptor for Plasmodium vivax infection and not due to prevalence of sickle cell disease, previous infection, or due to the presence of a specific antigen or antibody. )

A forest worker developed an ulcer on his leg at the site of a tick bite within 1 week after exposure. He complained of fever and chills and had painful inguinal lymphadenopathy. From the ulcer material, a small Gram-negative, weakly staining pleomorphic coccobacillus (0.2-0.5 x 0.7-1 microns) was isolated on chocolate agar medium at 37°C. The isolate was identified by conventional methods. It belonged to a bacterial species recognized as a Category A bioterrorism agent. Which of the following makes this pathogen a potential bioterrorism agent?

Aerosolized bacteria can be easily inhaled (The disease is tularemia caused by F. tularensis and the correct answer is 3. The bacterial agents considered Category A bioterrorism agents are the zoonotic pathogens Bacillus anthracis, Yersinia pestis, and Francisella tularensis. They cause anthrax, plague, and tularema, respectively. All possess high infectivity, and the infective dose is very low. 3) Inhalation of a very small number of aerosolized organisms by humans can result in fatal pneumonia and septicemia. Factors associated with pathogenicity of F.tularensis include its lipopolysaccharide (LPS), surface capsule, and genes in the Pathogenicity Island. 1) They are not spore formers. The unique features that account for increased virulence of F.tularensis subspecies tularensis (type A) are not well understood. Type A infections are predominant in North America and type B in Europe and Asia. F.tularensis does not possess the other properties listed. 4) Not only ticks, but other arthropods like biting flies and mosquitoes, are also vectors for the organism but vectors would not be employed for a bioterrorism attack. The bacterium does not require X and V factors for growth. 2) No secreted toxin has been detected for F.tularensis. 5) The organism is susceptible to aminoglycosides. Gentamicin and streptomycin are drugs of choice for treatment of tularemia, especially in severe illness. F.tularensis produces beta-lactamase. Beta-lactam antibiotics, including third generation cephalosporins, are not effective against the bacterium. Doxycycline and quinolones are useful in less serious disease. Clinical presentation of tularemia depends on the route of entry of the organisms. In addition to arthropod bite, transmission can occur also by direct contact with infected animals or animal tissue, inhalation of aerosols, or ingestion of contaminated food or water. Ulceroglandular, pulmonary, oculoglandular, oropharyngeal, gastrointestinal, and typhoidal are different clinical forms of tularemia. 3) Airborne and waterborne outbreaks and laboratory infections have been reported and aerosolization of the bacteria would be the mode of transmission in an attack of bioterrorism. Bacillus anthracis is a large Gram-positive bacterium and can be excluded by its morphology. Yersinia pestis may morphologically simulate Francisella tularensis, though its typical morphology shows bipolar staining. Bubonic plague caused by Y.pestis may clinically simulate ulceroglandular tularemia caused by F.tularensis. Y.pestis is transmited by rat flea, not by tick. Ticks are important vectors of F.tularensis. The patient's illness is related to tick bite, and the clinical presentation is in accordance with ulceroglandular tularemia. Therefore, it can be concluded that the isolate is a strain of Francisella tularensis.)

Which of the following explains why antiretroviral therapies are relatively ineffective in treating HTLV-1 induced tumors?

After infection is established, viral replication is not required for tumorgenesis. (-HTLV-1 causes malignant transformation of CD4 T cells so that they live longer. -Tax and HBZ are transcription factors that alter the cellular epigenetics. Tax activates IL-2 synthesis ↑prolif. of infected cells T-cell LL -Mediates infection through cell-cell contact (not virion)

The Weil-Felix test is used for detection of which of the following type of antibodies?

Anti-rickettsial (The Weil-Felix test is used for detection of anti-rickettsial antibodies. These are detected in the patient's serum by their ability to agglutinate Proteus bacteria. The specific rickettsial organism can be identified by the agglutination observed with the O antigen polysaccharide of one or another of three different strains (OX-2, OX-19 and OX-K) of Proteus vulgaris. However, the test is of limited value as there can be false positives following Proteus urinary tract infection and false negatives due to variable antibody response.)

A 28-year-old HIV-positive male is brought to the emergency room, as he is suffering from severe headache and vomiting. On examination, he is disoriented and has a stiff neck. Cerebral spinal fluid examination shows the following:  Glucose: 60 mg/dl (normal) Protein: 25 mg/dl (normal) Cell count: 10 cells/mm3 (slightly elevated) Cell type: Occasional lymphocytes only (normal) India ink preparation shows encapsulated mucoid yeast like structures. The patient dies despite the treatment. The autopsy shows the basal leptomeninges are opaque. The subarachnoid space is filled with gelatinous material. The parenchyma shows multiple small cysts. What is the most likely diagnosis in this case?

Cryptococcal meningitis (The patient in this case is immunocompromised due to the immunosuppressive therapy and is prone for opportunistic infections. Cryptococcal meningitis is caused by the fungus Cryptococcus neoformans. It occurs in increasing frequency in association with AIDS and may be fulminant and fatal in as little as 2 weeks or indolent, evolving over months or years. The mucoid encapsulated yeasts can be visualized in the C.S.F by India ink preparation. The brain shows chronic meningitis affecting the basal leptomeninges, which are opaque and thickened. Sections of the brain disclose a gelatinous material within the sub-arachnoid space and small cysts within the parenchyma. Parenchymal lesions consist of aggregates of organism within the expanded peri-vascular spaces associated with minimal or absent of inflammation or gliosis. The meningeal infiltrates consists of chronic inflammatory cells, fibroblasts admixed with cryptococci, which can be seen well with PAS, mucicarmine or silver stain. Cytomegalovirus causes typically sub-acute encephalitis in immunosuppressed patients. Although any type of cell in the CNS can be infected by CMV, there is a tendency for the virus to localize in the ependymal and sub-ependymal regions of the brain causing severe hemorrhagic necrotizing ventriculi-encephalitis and choroids plexitis. Prominent cytomegalic cells with intranuclear and intracytoplasmic inclusions can be readily identified by conventional light microscopy, immunocytochemistry, or in-situ hybridization. Fungal disease of the C.N.S is encountered primarily in immunocompromised patients. Aspergillosis and mucormycosis has marked predilection for invasion of blood vessel walls causing thrombosis producing hemorrhagic infarction with subsequent ingrowth of the fungus. Cerebrospinal fluid examination will not be of any diagnostic value. Numerous septate hyphae invading blood vessels with acute inflammatory reaction can be seen in tissue sections. Cerebral toxoplasmosis is caused by the protozoa Toxoplasma gondii. In immunocompetent patients, most infections are asymptomatic or self-limiting. Congential toxoplasmosis occurs following primary maternal infection early in the pregnancy causing cerebritis in the fetus with production of multi-focal cerebral necrotizing lesion that may calcify producing severe damage to the brain. Infection with T. gondii is one of the most common causes of neurological symptoms and morbidity in patients with AIDS. CT and MRI show multiple ring enhancing lesions. The brain shows multiple abscesses often involving the cerebral cortex. Acute lesions consist of central foci of necrosis with variable petechiae surrounded by acute and chronic inflammation, macrophage infiltration, and vascular proliferation. Both the tachyzoites and encysted bradyzoites may be found at the periphery of necrotic foci. The organisms are usually seen by routine H& E and Giemsa stains, but can be readily recognized by immunocytochemical methods.)

The anti-phagocytic capsule of Bacillus anthracis is composed of

D-glutamate (The anti-phagocytic capsule of Bacillus anthracis is unique in that it is composed of D-glutamate. Peptidoglycan is composed of peptides and sugars that are found in bacterial cell walls. Teichoic acids are polymers of glycerol phosphate or ribitol phosphate located in the outer layer of the cell wall of gram-positive bacteria. Lipopolysaccharides are present in the outer layer of the cell wall of gram-negative bacteria. Nucleoid or nucleus is part of a cell that contains DNA.)

A 30 year-old woman presented to the clinic with fever, backache, and headache of 2 days' duration. She complained bitterly about intense myalgias in the upper arms and pain on moving her eyes. She had just returned from a trip to El Salvador, where she had extensive exposure to mosquitoes. On physical exam, she appeared uncomfortable but not toxic. A blanching, erythematous rash was present on the face, arms, trunk, and thighs. There was no murmur or splenomegaly. Her WBC was 1,600/ul with a normal differential; platelet count was 140,000/ul and hemoglobin was 17.5 g/dl. Convalescent-phase antibodies to a mosquito-borne viral disease were diagnostic. What is this and which of the following best describes the infectious agent? (stranding, sense, env or naked, dna/rna)

Dengue virus. Single-stranded, positive-sense, enveloped RNA virus. (Dengue virus is a member of the Flavivirus family which also includes St. Louis encephalitis virus and West Nile virus, among others that are important pathogens worldwide. 2 refers to Picornaviruses and these are not transmitted by arthropod vectors. 3 refers to Togaviruses (Eastern equine encephalitis virus , Western equine encephalitis virus, Rubella) or Bunyaviruses (California encephalitis virus). 4 does not fit any known human pathogens. 5 refers to the Reoviridae which includes Rotavirus and Colorado tick fever virus.)

A 13-year-old male patient presents at the emergency room complaining of fatigue and severe abdominal pain. Other vital signs were normal with the exception of noticeable enlarged maxillary lymph nodes. The patient was placed in a room and monitored over several hours. By the third hour, routine evaluation of blood pressure found a precipitous loss. A transfusion was ordered, but even after 5 units of blood, the blood pressure could not be maintained. A laparotomy revealed a ruptured spleen which was subsequently removed. The patient was discharged three days later but continued to complain of fatigue. Which of the following is the most likely culprit based on the symptoms presented by this patient?

EBV

A 21-year old female nursing student developed low grade fever, sore throat, malaise, and fatigue that lasted several days. Physical examination revealed swollen lymph nodes and discomfort in the left upper quadrant of the abdomen. Examination of peripheral blood smear revealed 50% of atypical lymphocytes of the total white cells. The heterophile antibody test was positive. What is the most probable cause of infection?

EBV (Epstein-Barr virus elicits a large T-cell response, resulting in a mononucleosis-like syndrome. EBV infection is subclinical and milder in children than adolescents or adults. EBV initiates infection in the epithelial cells of the oropharynx and then spreads to the B lymphocytes in lymphatic tissue and blood. Classical lymphocytosis is associated with activation and proliferation of suppressor T cells and leads to infectious mononucleosis. The atypical lymphocyte also known as "Downey cells" increases in peripheral blood during the second week of infection. Major T-cell response causes swollen lymph glands, spleen, and liver. Fever, malaise, fatigue, pharyngitis, lymphadenopathy, and hepatosplenomegaly are the classical symptoms associated with infectious mononucleosis. Polyclonal B cell activation by EBV leads to production of heterophile antibodies which can be detected by the end of first week of infection and last for several months. CMV causes heterophile-negative mononucleosis. Coxsackie virus B, Streptococcus pyogenes, and varicella zoster virus are not associated with infectious mononucleosis.)

Which of the following antiviral agents is a guanosine analog that is effective in the treatment of CMV retinitis in AIDS patients?

Ganciclovir

The antiviral agent acyclovir can be used to promote the healing and relieve the pain of skin lesions caused by chickenpox in adults. Suppose you have an adult patient with chickenpox whose condition is not helped by acyclovir. You obtain a sample of the virus from the patient and discover a mutation in a gene required for acyclovir sensitivity. Which of the following genes is most likely to be mutated?

Guanylate Kinase

Blood banks in Southern California and Texas have done studies to evaluate how often blood containing Trypansoma cruzi is found in their blood donor pool. They have found that the incidence varies from 1:8,000 to 1:40,000 donors. If you were making up a list of questions to ask blood donors, which of the following questions would be least helpful in screening to exclude this organism from persons that have grown up in an endemic area?

Have you ever had a blood test positive for Chagas disease? (Because there are many false positives)

A 56-year-old man was admitted to a hospital in central Illinois with symptoms of high fever, chills, dry cough, headache, night sweats, and chest pain of 7 days duration. He was experiencing shortness of breath since the previous day. His previous medical history was not significant. More than a month ago he had moved to a small town in central Illinois. With his 3 sons, he was engaged in the repair work of an attic of an old building and had cleaned the accumulation of bird droppings and bat guano in the attic. Two of his sons also had developed flu-like illness, but had recovered without any specific treatment. The patient's chest radiography showed an accumulation of fluid in the lungs and enlarged regional lymph nodes. Among the investigations done, serology and urinary antigen tests done in the regional reference laboratory were positive for infection by a thermally dimorphic fungus endemic to the region. In infected tissues this fungus is known to occur as oval yeasts (2-4 microns) inside phagocytic cells. What fungi is most likely to be the causative agent of this patient's illness?

Histoplasma capsulatum (The patient's condition is most likely to be acute pulmonary histoplasmosis acquired by exposure to bat guano containing spores of Histoplasma capsulatum. In the U.S., infections by H.capsulatum are highly endemic in Ohio and Mississippi valleys and also in localized foci in mideastern states. Infection occurs due to inhalation of aerosols containing the fungal conidia (spores). Person to person transmission does not occur. Excreta of birds and bats are known to accelerate the growth of the mycelial forms and sporulation of the fungus. Bat guano can be a good source of the spores, as the fungus can colonize in the gastrointestinal tract of bats. Exposure may result in asymptomatic infection or symptomatic disease. The extent of disease depends on the number of conidia inhaled and the host's cellular immunity. Pulmonary infection is the primary manifestation of infection. It is often self-limited, with flu-like symptoms from which recovery occurs without any specific treatment. Inhalation of a large number of spores may result in severe pulmonary disease with acute respiratory distress syndrome. Thermally dimorphic fungi are fungi that occur in 2 morphological forms at different temperatures. Yeast forms are seen in tissues and when grown on enriched media at 37°C. Mycelial forms are seen in the soil and when grown on Sabouraud's or similar media at 25 to 30 degrees. Description of the tissue form given in the question is typical of H.capsulatum. Histoplasmosis is worldwide in distribution. It is more prevalent in North and Central America. Occupation and travel-associated outbreaks of acute histoplasmosis have been reported in U.S. Other than acute pulmonary infection, main clinical manifestations of the disease are chronic cavitary pulmonary histoplasmosis and disseminated histoplasmosis. Chronic cavitary pulmonary histoplasmosis simulates pulmonary tuberculosis and develops in people with pre-existing pulmonary conditions like emphysema or chronic obstructive pulmonary disease (COPD). Disseminated histoplasmosis occurs in people with impaired cell-mediated immunity, as in HIV positive individuals, immunosuppressed individuals, and the elderly. Dissemination affects the reticuloendothelial system and may involve other organs including skin and mucous membranes. Aspergillus fumigatus is a mold and Cryptococcus neoformans is yeast. Neither are dimorphic fungi. Coccidioides immitis is one of the thermally dimorphic fungi and causes coccidioidomycosis, endemic in the dry arid regions of Southwest U.S. The tissue form of the fungus does not resemble that of H.capsulatum and occurs as large spherules (10-80 microns) with a thick doubly refractile wall containing endospores. Blastomyces dermatitidis is similar to H. capsulatum in many respects. However, it appears in tissue as a broad-based yeast.)

A 35-year-old male received a renal transplant with the appropriate pre- and post-transplant immunosuppression. The patient exhibited no problems until two weeks later when serum creatinine levels dramatically increased. Leukocytes infiltrates, predominantly lymphocytes, were noted on a biopsy of the kidney. Which of the following most likely would account for the cellular infiltrate?

Host antibodies recognize C3a and C5a generated from grafted cells.

The human immunodeficiency virus (HIV) shows extensive genetic variation and undergoes rapid evolution. The rapid replication of HIV, coupled with genetic variability, leads to the generation of many variants of HIV in a single infected patient in the course of an infection. Thus HIV can rapidly develop resistance to antiviral drugs. When antiviral drugs are administered, variants of the virus that carry mutations conferring resistance to their effects emerge and expand until former levels of plasma virus are regained. Resistance to some of the protease inhibitors appears after only a few days. This remarkable variability was first recognized in HIV, has since proved to be common to the other lentiviruses. What is it caused by?

Hypermutability (The hypermutability of HIV, which mutates at a rate 1,000,000 times as great as that of eukaryotic DNA genomes, is important to the pathogenesis of HIV. The high error rate of HIV reverse transcriptase in vitro translates to approximately 5 to 10 errors per HIV genome per round of replication in vivo. This high error rate suggests that misincorporation by HIV reverse transcriptase is, at least in part, responsible for the hypermutability of the AIDS virus. Researchers hope that our understanding of the process may provide a basis for the systematic construction of antiviral nucleosides. In gene conversion, DNA segments are copied so that one sequence replaces sequences in another gene on the same chromosome. Studies of the sequences of different alleles have shown that the same sequences are found within several genes on the same chromosome, providing evidence for gene conversion. Gene duplication is the creation of an extra copy of a gene. This is a key mechanism in evolution. Once a gene is duplicated, the identical genes can undergo changes and diverge to create 2 different genes. Duplications typically arise from an event termed unequal crossing-over that occurs between misaligned homologous chromosomes during meiosis. Antigenic shift is the appearance of a new assortment of genes. This type of reassortment happens rarely and can be devastating, since shift produces a virus strain with a combination of surface antigen proteins to which the human population will have little or no immunity. Antigenic drift is caused by point mutations in the genes of microbes, such as the influenza virus. Every 2 to 3 years, a variant arises with mutations that allow the virus to evade neutralization by antibodies in the population. As new variants appear, they replace the previous variant so that within about 4 years, a given individual can be re-infected with an antigenic variant that has been gradually generated by infection of other individuals. This results in local epidemics.)

You wish to develop a retroviral inhibitor as part of your project at the Flumax Pharmaceutical Company. Of the many approaches that you might try, one that may have some success would be to target elements that are required for the life cycle of the viral particle. Name two possible targets for these drugs.

Integrase and reverse transcriptase, which are carried in the virion. (The retroviral life cycle begins when the virion lands on specific receptors and enters the cell, where the virion coat is removed in the cytosol. The virus particle contains two copies of an RNA molecule. One of the copies is designated the (+) strand. In addition to the (+) strand, the virion also carries into the host cell the enzyme reverse transcriptase and a non-covalently attached tRNA molecule. The enzyme reverse transcriptase has three major activities: RNA-directed DNA synthesis, DNA-directed DNA synthesis, and RNA hydrolysis. The RNA molecule that the virion brings into the cell must be duplicated for the viral life cycle to continue. The steps of this process are as follows: Using the tRNA that the virion brings into the cell, the transcriptase engages in DNA synthesis in the 5' to 3' direction. This gives a short segment of DNA that is attached to the tRNA. This DNA is termed (-) DNA. RNAase activity of the transcriptase removes RNA bases paired with the newly formed DNA. The (+) RNA strand contains repeated sequences at each of its termini. The newly formed DNA-tRNA hybrid molecule pairs with the other end of the (+) RNA strand and the RNA is reversed transcribed into DNA. Most of the (+) RNA strand that is now paired with the newly synthesized DNA is hydrolyzed by the RNAase activity of the transcriptase. The remaining small segment of RNA is used as a primer to replicate a (+) DNA strand from the (-) DNA strand used as template. Any residual RNA is hydrolyzed. The newly formed (+) DNA strand pairs with the opposite end of the (-) DNA strand and primes the synthesis of the remaining (+) DNA strand. Each end of the (-) DNA strand consists of long terminal repeat sequences termed long terminal repeats (LTR). For it to function, the formed linear DNA must travel to the nucleus and be integrated into the host genome. The integration reaction is catalyzed by the viral product integrase, which is carried in the virion along with the reverse transcriptase. The integration of the viral DNA occurs at random sites in the host genome. Integrated proviral DNA is transcribed by the host enzymes to make viral RNAs. These RNA molecules can function both as mRNA and as inserts to make more virion particles.)

An HIV-positive woman gives birth to a baby girl. The baby's PCR test for HIV is found positive after birth. Her Apgar score after the birth is 9 and the first general examination of the baby is completely normal except the positive PCR. Which of the following vaccinations will be contraindicated for this baby in her immunization schedule?

MMR

A student reports to his college clinic complaining of "the flu." He complains that he has been suffering from intermittent headaches, fever, and muscle aches. Assuming the flu, the physician sends the student home with acetaminophen. Now, days later, the student returns to the clinic EW with chills, extreme fever, and debilitating fatigue. Physical exam also reveals yellow sclera and sever splenomegaly. CBC reveals low hematocrit, and urinalysis shows hemoglobinuria. Alarmed, the EW doctor questions the student about recent travels and learns that he has just returned from a visit to India. A blood smear showing ring shapes confirms the diagnosis. What is the disease? What would possible treatments be?

Malaria. (-Mefloquine: for chloroquine-resistant P. falciparum. -Chloroquine. -Primaquine: for P.vivax/ovale dormant liver infections)

A healthy woman gave birth to a baby. The newborn infant was found to be HIV seropositive. Which of the following is the most likely explanation?

Maternal HIV-specific IgG was transferred across the placenta to the baby

Which of the following are the goals of resuscitation during the first 6 hours of management of severe sepsis?

Mean arterial pressure >65 mmHg, CVP 8-12 mmHg, SvO2 >70%, Urine output >0.5 ml/kg-1hr-1

A line of tumor cells was injected into a mouse that was syngeneic to the tumor line (i.e. shared MHC I and MHC II antigens). The tumor line was rapidly destroyed within the first two days. Analysis of the tumor line revealed that it did not express MHC class I molecules on its membrane. What it the most likely mechanism responsible for rejection of the tumor?

NK cells that are large and granular

To diagnose malaria, thick and thin blood smears are stained with Giemsa, Wright, or other stains. Which of the following statements best describes the appearance of red blood cells parasitized by Plasmodium falciparum on a stained blood smear?

Not enlarged with coarse stippling, invades cells regardless of their age. (When red blood cells infected by Plasmodium falciparum are stained, they appear not enlarged with coarse stippling and invade cells regardless of their age. Cells infected by Plasmodium vivax appear enlarged and pale with fine stippling and primarily invade reticulocytes. Cells infected by Plasmodium malariae appear not enlarged, with no stippling, and invade older cells. Those infected with Plasmodium ovale appear with enlarged pale Schuffner's dots, conspicuous cells that are often oval, fimbriated, or crenated; they do not appear normal. )

A 3-year-old female was brought to the pediatrician. She was bitten by a cat and had developed redness, heat, induration and tenderness at the site of the bite as well as lymphadenitis. Cultures revealed the presence of a Gram-negative rod with bipolar staining. The physician cleaned the wound but did not suture it. He treated the patient with penicillin and the condition resolved. Which of the following is the most likely cause of this infection?

Pasteurella multocida

A 75-year-old woman was bitten by her pet cat. On the third day she was hospitalized with a localized subcutaneous abscess at the site of the cat bite. Pus drained from the abscess was cultured in the microbiology laboratory. Colonies of small Gram-negative coccobacilli with bipolar staining grew on chocolate agar incubated at 37°C for 24 hours. The bacterium was non-motile, oxidase-positive, and catalase-positive. Which of the following is the most likely infectious agent?

Pasteurella multocida (Among the listed zoonotic pathogens , Pasteurella multocida is the only bacterium possessing the described characteristics of the isolate. The bacterium is part of the normal flora of cats, dogs, and other domestic and pet animals. Human infection often follows bite, scratches, or licks from these carrier animals. Increased carriage rates have been observed in cats. Infections following cat bites and scratches are more common. Majority of infections involves skin and subcutaneous tissue. Rapid onset of wound infection and development of cellulitis or abscess at the site of the bite is very characteristic. P.multocida can also cause bacteremia, meningitis, pneumonia, septic arthritis, and osteomyelitis, endocarditis, peritonitis, sinusitis, and urinary tract infection. Persons in extremes of age and immunocompromised individuals, including those with liver cirrhosis, renal disease, hematological malignancies, and post-transplant patients, are at the risk of more severe invasive disease by P.multocida. Bartonella henselae, the agent of 'cat scratch disease' (CSD), is a fastidious Gram-negative bacterium, and cultural isolation on chocolate agar requires a minimum of 3 weeks of incubation. It gives negative catalase, oxidase, and carbohydrate utilization tests. CSD is often self-limited. Typical clinical presentation is fever and lymphadenopathy developing about 2 weeks after contact with a cat. B.henselae is associated with bacillary angiomatosis also. Ehrlichia chaffeensis causes human monocyte ehrlichiosis and is transmitted by ticks. E.caffeensis and Coxiella burnetii, the organism of Q fever, are strictly intracellular and fail to grow on cell-free media. C.burnetii is transmitted among animals by ticks. Humans acquire infection mostly by inhalation of contaminated aerosols and also by drinking unpasteurized milk. Leptospira interrogans is a spirochete that is transmitted by contaminated water/soil and enters humns via mucosal abrasions. It enters the blood spread and causes flu-like symptoms and potophobia. It can develop into aseptic meningitis and in severe cases, vasculitis with hemorrhagic complications.)

A 9-year-old male presents with fever, headache, and vomiting. On examination, he is febrile and mildly icteric. There is mild splenomegaly. His biochemical investigations show serum total bilirubin: 4 mg/dl, Serum direct bilirubin: 1.8 mg/dl, and serum indirect bilirubin: 2.2 mg/dl. His blood test shows Hb 7 gm/dL, and Total WBC Count 6,200/mm3. Differential count: 62% neutrophils, 30% of lymphocytes, 6% of monocytes, and 2% eosinophils. Refer to the image for the peripheral blood smear. What is the most likely diagnosis? (It's a banana-shaped cell)

Plasmodium falciparum. (The banana-shaped gametocyte (red arrow) is pathognomonic for P. falciparum. Malaria is an acute and sometimes chronic infection of the blood stream caused by the parasite of the genus Plasmodium. The 4 species of plasmodium causing human malaria include: Plasmodium falciparum, P. vivax, P. ovale, and P. malariae. The common presenting symptoms of malaria include chills and fever, which are often associated with splenomegaly. In the early stages of the disease, the febrile episodes occur irregularly but eventually become more synchronous, assuming the usual tertian (P. vivax, P. Falciparum, P. ovale) and quartan (P. malariae) periodicity. Patients with malaria may develop anemia and other manifestations, including diarrhea, abdominal pain, headache, and muscle aches and pains. P. falciparum malaria can result in high parasitemias, which can lead to severe hemolysis with hemoglobinuria and profound anemia. Erythrocytes infected with growing trophozoites, schizonts of P. falciparum, become sequestrated in small vessels of the body, and they may lead to occlusion of these vessels, causing symptoms related to capillary obstruction and tissue anoxia. Involvement of the brain is known as cerebral malaria, in which the patient becomes disoriented, progressing to delirium, coma, and often death. Malarial parasites undergo sexual phase (sporogony) in anopheles mosquitoes and an asexual stage (schizogony) in humans that results in the production of schizonts and merozoites. In the blood stream, some merozoites eventually differentiate into gametocytes (gametogony), which when ingested by female anopheline mosquitoes, mature into male microgametes and female macrogametes. Fusion of a microgamete and a macrogamete results in the formation of the motile ookinete, which migrates to the outside of the stomach wall and forms an oocyst. Within the oocyst, numerous spindle-shaped sporozoites are formed. The mature oocyst ruptures into the body cavity, releasing the sporozoites, which then migrate through the tissues to the salivary glands, from which they are injected into the vertebral host as the mosquito feeds. The time required for the development in the mosquito ranges from 8 to 21 days. The sporozoites injected into the vertebrate host reaches the hepatic parenchymal cells within minutes and initiate the proliferative phase known as exoerythrocytic schizogony. Release of merozoites from ruptured hepatic schizonts initiates the blood stream infection or erythrocytic schizogony and eventually the clinical symptoms of malaria. P. vivax and P. ovale differs from P. falciparum and P. malariae in that true disease relapses of the former species may occur weeks to months following subsidence of previous attacks. This occurs because of renewed exoerythrocytic and eventually erythrocytic schizogony from latent hepatic sporozoites, which are known as hypnozoites. Recrudescences of disease due to P. falciparum or P. malariae called recrudescences arise from an increase in the number of persisting blood stage forms to clinically detectable levels, not from persisting liver stage forms. P. vivax and P. ovale parasites primarily infect young erythrocytes, whereas P. malariae affects older erythrocytes, and P. falciparum infects erythrocytes of all stages.)

A 33-year-old male presents to the emergency room with shortness of breath. The symptoms started a week ago and have gradually worsened. He has had a low-grade fever and dry cough. He has not been exposed to anyone with a respiratory tract infection. Past medical history is significant for being HIV positive, first diagnosed 4 years ago. He has had several opportunistic infections and reports that his CD4 T cell count was 220/mm3 a few months ago. He has never been hospitalized. He has not had any surgery. Current medications include two nucleoside analogues and a protease inhibitor, a regimen that he was placed on a month ago after his viral load was found to be 400,000 copies/ml. A chest x-ray is obtained and it shows diffuse fluid accumulation in both lungs (bilateral infiltrates) that have a ground glass appearance. There is no effusion (collection of fluid next to the lung). Cardiac silhouette is normal in width. The patient was treated with trimethoprim/sulfamethoxazole. Which of the following is the most likely infectious agent?

Pneumocystis jiroveci (Pneumocystic jiroveci (formerly called [P. carinii] pneumonia (PCP) is one of the leading causes of death in AIDS patients. The immunocompromised status in AIDS results in opportunistic infections like PCP. The patient presents with dry cough and shortness of breath. Chest X ray shows diffuse bilateral infiltrates extending from the perihilar region. Ground glass appearance is often used to describe chest x-rays in PCP. About 90% of HIV-infected patients with PCP have an elevated LDH. Bronchoalveolar lavage may also prove useful in diagnosis. Other organs may also be affected; hepatomegaly, cotton wool spots, thyromegaly, skin lesions, and bone marrow necrosis have been reported. Treatment is effected with Trimethoprim and Sulfmethoxazole (TMP-SMX). Pentamidine is used in cases with TMP-SMX toxicity. However, relapses are common. Toxoplasma gondii is an intracellular parasite with predominant nervous system manifestations. Patients usually present with convulsions, disorientation, and dementia. Cryptosporidium parvum is a diarrhea-causing protozoan in HIV infected patients. Patients present with 20 to 40 episodes of watery stools per day and abdominal cramps. Coccidioides immitis is endemic to the Lower Sonoran Life valley (SW USA) and is an opportunistic fungal pathogen, particularly for HIV-positive individuals. This organism causes a pneumonia after inhalation of the infective arthrospore. The radiograph results are not consistent with C. immitis. Histoplasma capsulatum is a dimorphic fungus that is often found in patients with HIV. It has an endemic area in the Ohio and Mississippi River Valley. Usually, biopsy indicates the presence of small, intracellular yeasts.)

What clinical condition is associated with the Dengue fever virus?

Breakbone fever (Dengue fever virus and Powassan virus are members of the family Flaviviridae. Flaviviruses are enveloped viruses with icosahedral symmetry. The genome consists of a linear single stranded RNA molecule and replication occurs in the cytoplasm. Dengue fever virus is transmitted by the mosquito and is associated with bone break fever and dengue shock syndrome. Bone break fever is characterized by headache, myalgia, arthralgia, and rash. Secondary exposure can result in dengue shock syndrome and is characterized by gastrointestinal hemorrhage. Powassan virus is associated with tick-borne virus encephalitis. Ixodes tick is the vector for Powassan virus. Domestic animals can play a role in the spread of the disease, as the tick can bite the domestic and farm animals and humans can be infected by the ingestion of raw milk or tick bite. Coxsackievirus type A and coxsackievirus type B are members of the Picornaviridae family. Picornaviruses are naked viruses with an icosahedral nucleocapsid. The genome consists of single molecule of single stranded RNA. Coxsackievirus type A is associated with herpangina, which is commonly seen in children. Herpangina is a severe febrile pharyngitis characterized by vesicles or nodules primarily on the soft palate. Coxsackievirus type B is associated with Bornholm disease seen mainly in older children and young adults. Bornholm disease is myositis and is also called Pleurodynia. It is characterized by paroxysms of stabbing pain in the chest muscles and abdomen muscles. Variola virus is a brick-shaped virus with a single linear molecule of double stranded DNA and is a member of the Poxviridae family. Variola virus was the causative agent of smallpox that multiplied in the lymph nodes. Smallpox is an ancient disease that is eradicated.)

A 33-year-old woman started experiencing a severe, intermittent fever, which continued for at least 11 days. No other symptoms or complications were revealed. Her husband was experiencing mild flu-like symptoms for the past week. The couple had returned two weeks ago from a vacation in Acapulco, Mexico. A blood specimen was collected and cultured, which revealed a small, Gram-negative coccobacilus after 5 days of incubation. Which of the following organisms is the most likely cause of this infection?

Brucella melitensis

Which of the following organisms is most likely to be transmitted by ingestion of contaminated milk?

Brucella melitensis (Brucella melitensis is spread by ingestion of contaminated dairy products or contaminated animal tissues. Yersinia pestis is spread by flea bites. Francisella tularensis is spread by contact with infected animal tissues and ticks. Pasteurella multocida is spread by cat or dog bites. Vibrio cholerae is spread by fecal contamination of water and food.)

Human immunodeficiency virus, or HIV, is an enveloped human retrovirus of the lentivirus family. There is also a significant number of HIV-infected individuals who never become sick, never experience a decline in their CD4 counts, and never develop high plasma loads of viral RNA. The reason for this seems to be the presence of host genetic mutations that render them resistant. Mutations in which of the following genes might provide resistance to HIV infection?

CCR5 (CCR5 is a chemokine receptor that binds to several chemokines including MIP-1alpha, MIP-1beta and RANTES. CCR5 is necessary for HIV entry into the host cell. CCR5 is expressed by macrophages, dendritic cells, and CD4 T cells. It is thought to be the major co-receptor for establishing primary infection, since individuals who are homozygous for a mutation in CCR5 appear to be resistant to infection by HIV. For example, the CCR5-Delta32 deletion mutation seems to confer resistance against HIV-1 by blocking its attachment to CCR5 so that HIV cannot gain entry to the cell. Development of drugs directed at chemokine receptors is thus an active area of research. CXCR4 is the other major co-receptor for HIV. Lymphotropic HIV uses CXCR4 found on T cells and requires a high density of CD4 on the cell surface. CXCR4 also binds the CXC-chemokine stromal-derived factor-1 (SDF-1) as a co-receptor. Both co-receptors are G-coupled proteins with 7 transmembrane spanning domains. Mac-1, also called CD11b/CD18, is stored in specific granules that are shuttled to the granulocyte surface. It exists as a chemoattractant activation-dependent molecule that undergoes a conformational change upon stimulation. Until stimulation occurs, it remains in a resting, non-adhesive state. Mac-1 is a β2 integrin. SDF-1 is a small chemokine of the CXC subfamily that is produced constitutively by bone marrow stromal cells and has an important role in early stages of B cell development. It is a growth factor for B cell progenitors and a chemotactic factor for T cells, monocytes, CD34+ hematopoietic progenitor cells, mature megakaryocytes, and dendritic cells. Interleukin-8 or IL-8, a CXC chemokine, is an 11-kDa homodimer of 99 amino acids that is also known as monocyte-derived neutrophil chemotactic factor (MDNCF). It is an important mediator of neutrophil, lymphocyte, and basophil chemotaxis and activation. It is released from several cell types in response to an inflammatory response.)

An infant was born with manifestations of intrauterine retarded growth, jaundice, hepatosplenomegaly, microcephaly, thrombocytopenia, and retinitis. Urine and blood samples were collected and tested for agents causing congenital infections. Result of polymerase chain reaction test was diagnostic of infection by a virus that belongs to beta Herpes viruses. Which of the following is the most likely infectious agent?

CMV (The clinical features described are typical of congenital cytomegalic inclusion disease caused by cytomegalovirus (CMV). Among the beta-herpes viruses, CMV is the one associated with congenital infection. CMV when grown on human fibroblastic cells produces a characteristic cytopathic effect. Many affected cells become enlarged. Giant cells with large intranuclear acidophilic inclusions (owl eye inclusions) and perinuclear cytoplasmic inclusions are seen. Virus replicates very slowly and infection spreads from cell to cell. It may take several days for the entire monolayer to be infected. Inclusion-bearing cytomegalic cells can be demonstrated in centrifuged deposit of urine and in other clinical samples from infected tissues. In the US, up to 80% of adults show antibodies to the virus indicating high prevalence of the infection. CMV is the most frequent congenitally transmitted virus in the country. Each year about 40,000 children are born with congenital cytomegalovirus infection. Congenital CMV disease causes estimated 400 deaths each year and leaves approximately 8,000 with permanent disabilities like mental retardation, hearing loss, and ocular impairment. Fetal death or generalized cytomegalic inclusion disease results when the mother acquires and transmits primary CMV infection to the fetus during the first trimester of pregnancy. Reactivated maternal infections may not cause fetal damage. Perinatal infection of the new born can occur from the mother's birth canal or breast milk. Spread of the virus is predominantly by close contact and through oral and respiratoy routes. In immunocompetent persons usually the infection is subclinical. The virus sometimes causes heterophile antibody negative mononucleosis. This most commonly follows transfusion of CMV infected blood (post-transfusion mononucleosis). CMV is an important pathogen in patients with AIDS. The already weakened immune response is further damaged by the nonspecific CMI-inhibiting effect of CMV. Disseminated and often fatal infections are produced with manifestations such as chorioretinitis, gastroenteritis and pneumonia. Immunosuppressed individuals like organ transplant recipients are also at high risk of developing severe CMV disease. Often development of illness may be due to reactivation of their own latent virus.)

A 30-year-old patient with advanced HIV infection comes into clinic complaining that food is sticking in the back of his throat and in his chest when he tries to swallow. You look in his mouth and see patches of whitish material on the surface that can easily be removed and leaves a red base. Which of the following is the most likely infectious agent?

Candida Albicans

A 40-year-old male attends the clinic, as he is suffering from a severe headache with vomiting and myalgia for 2 days. His history reveals that he had renal transplantation for which he takes cyclosporine, azathioprine, and prednisone. He has been doing well for the past year and has been coming regularly for his checkup. The patient's wife reveals that he has become very forgetful these days. After a thorough examination, a provisional diagnosis of meningoencephalitis is made. His CT scan reveals multiple ring enhancing lesions. His cerebrospinal fluid examination findings are as follows: glucose 50 mg/dL, protein 20 mg/dL, and cell count of 4 lymphocytes/mm3, all of which are within normal range. India ink and acid-fast stains are negative. A tissue section that is taken from a brain biopsy shows necrotic tissue, surrounded by acute and chronic inflammatory cells. There are cyst-like spherical structures measuring 30 microns in diameter, which contains oval shaped structures. What is the most likely diagnosis in this patient?

Cerebral toxoplasmosis (The patient in this case is immunocompromised due to the immunosuppressive therapy and is prone for opportunistic infections. Cerebral toxoplasmosis is caused by the protozoa Toxoplasma gondii. In immunocompetent patients, most infections are asymptomatic or self-limiting. Congential toxoplasmosis occurs following primary maternal infection early in the pregnancy causing cerebritis in the fetus with production of multi-focal cerebral necrotizing lesion that may calcify producing severe damage to the brain. Infection with T. gondii is one of the most common causes of neurological symptoms and morbidity in patients with AIDS. CT and MRI show multiple ring enhancing lesions. The brain shows multiple abscesses often involving the cerebral cortex. Acute lesions consist of central foci of necrosis with variable petechiae surrounded by acute and chronic inflammation, macrophage infiltration, and vascular proliferation. Both the tachyzoites and encysted bradyzoites may be found at the periphery of necrotic foci. The organisms are usually seen by routine H& E and Giemsa stains, but can be readily recognized by immunocytochemical methods. Cytomegalovirus causes typically sub-acute encephalitis in immunosuppressed patients. Although any type of cell in the CNS can be infected by CMV, there is a tendency for the virus to localize in the ependymal and sub-ependymal regions of the brain causing severe hemorrhagic necrotizing ventriculi-encephalitis and choroids plexitis. Prominent cytomegalic cells with intranuclear and intracytoplasmic inclusions can be readily identified by conventional light microscopy, immunocytochemistry, or in-situ hybridization. Cryptococcal meningitis is caused by the fungus Cryptococcus neoformans. It occurs in increasing frequency in association with AIDS and may be fulminant and fatal in as little as 2 weeks or indolent, evolving over months or years. The mucoid encapsulated yeasts can be visualized in the C.S.F by India ink preparation. The brain shows chronic meningitis affecting the basal leptomeninges, which are opaque and thickened. Sections of the brain disclose a gelatinous material within the sub-arachnoid space and small cysts within the parenchyma. Parenchymal lesions consist of aggregates of organism within the expanded peri-vascular spaces associated with minimal or absent of inflammation or gliosis. The meningeal infiltrates consists of chronic inflammatory cells, fibroblasts admixed with cryptococci, which can be seen well with PAS, mucicarmine or silver stain. Fungal disease of the C.N.S is encountered primarily in immunocompromised patients. Aspergillosis and mucormycosis has marked predilection for invasion of blood vessel walls causing thrombosis producing hemorrhagic infarction with subsequent ingrowth of the fungus. Cerebrospinal fluid examination will not be of any diagnostic value. Numerous septate hyphae invading blood vessels with acute inflammatory reaction can be seen in tissue sections. HSV encephalitis can cause necrosis of the left temporal lobe but does not exhibit ring-enhancing lesions.)

A 44-year-old veterinarian in San Diego, California who specializes in exotic birds developed a fever and myalgia. Within days it progressed to a constant, nonproductive cough. Radiologic examination of the chest suggested bronchopneumonia. No pathogenic microorganisms grew after culture of sputum on a blood agar plate. Which of the following organisms is most likely the cause of this patient's disease?

Chlamydia psittaci

A 24-year-old pigeon fancier presents with fever of 40°C, severe, diffuse headache, malaise, dry hacking cough and muscle aches. A chest x-ray exam reveals pneumonia and hepatosplenomegaly is found on the physical exam. Which of the following is the most likely infectious agent?

Chlamydia psittaci (The disease is acquired by inhaling dried secretions from infected birds. The bacteria bind to respiratory epithelium, enter the bloodstream and infect cells of the reticulendothelial system before infecting the lungs. Pet birds are most commonly involved in human transmission. The rest of the organisms would be included on a differential diagnosis. Further work-up would be required to identify the infectious agent. In vignettes such as this, the contact with a pigeon is the main clue as to the disease.)

A 30-year-old Asian man develops fever, cough and expectoration. Two days later, finding red tender nodules on his shins, he comes to the clinic. He reveals that he returned ten days ago from a holiday in California, where he went exploring the desert with his friends. He has no known allergies. An X-ray film of the chest shows a left pleural effusion. A dimorphic fungal infection endemic in the state of California is suspected as the cause of the patient's illness. What is the most likely agent and diagnosis?

Coccidiodes immitis - Coccidiodomycosis? (Endemic mycoses: 1) Coccidiodomycosis - SW U.S. 2) Histoplasmosis - Mississippi/Ohio River Valleys, SE U.S., river basisns 3) Blastomycosis - east of Mississippi River, Central America)

Methicillin resistant Staphylococcus aureus, vancomycin resistant enterococci, resistant Gram-negative bacilli, zoster, scabies, uncontained abscesses, impetigo, herpes simplex virus, Clostridum difficile, diarrheal pathogens, and SARS require which type of infection control precaution?

Contact precautions