Heme / Onc 1

The answer is A: Creatine kinase serum level. The most reliable diagnosis is trichinellosis (trichinosis), specifically Trichina nativa—a close relative of the pig species Trichinella spiralis. Infected patients are usually positive for creatine kinase, probably because Trichina larvae invade striated muscle cells inducing myositis. Creatinine clearance pertains to the renal function (i.e., filtering capacity), which is not relevant to this particular case. At this point in the disease process, seroconversion has not occurred, and, therefore, ELISA results would be inconclusive. Larvae are almost never recovered in a fecal preparation or visualized in a stained blood slide.

1 Within 2 weeks of eating jerky that is made from a mountain lion, a Montana man develops intense vomiting and diarrhea, followed shortly by a fever of 103°F, throbbing headache, and achy muscles. After a few more days of these unrelenting symptoms, he seeks medical attention. His white blood cell count at presentation is 16,100/mm3, with 22% eosinophils. Which of the following laboratory tests would be most helpful to make the correct diagnosis? Creatine kinase serum level Creatinine clearance level Examination of a wet mount of fresh stool Enzyme-linked immunosorbent assay (ELISA) Inspection of a Giemsa-stained blood smear

TB (107 The answer is C: Mycobacteria overwhelming alveolar macrophages. The case suggests that the man was suffering from progressive primary tuberculosis or a fulminant pulmonary infection. The TB bacillus is described as an intracellular parasite that, in this case, has successfully multiplied to exponential numbers within the phagosomes of macrophages. A virulence determinant of Mycobacterium tuberculosis prevents phagosome-lysosome fusion and, in so doing, escapes the killing effects of the lysosomal enzymes. A major clue with this question is the fact that the organisms here are acid-fast bacilli. This would immediately eliminate all the other choices. In addition, there is no evidence in the visual of consolidation or intracellular inclusions. Although patients with AIDS are at risk for Legionella pneumophila, the clinical findings in this case are not reflective of legionellosis. Lastly, Pseudomonas aeruginosa certainly produces isolated areas of limited growth, especially in burn patients, but huge numbers of bacilli present in the tissue section are beyond the microcolony level._

107 A homeless man who is known to be HIV positive unexpectedly dies in a dormitory of a congregate nighttime shelter. A roommate states that during the night, he complained of periods of shaking chills and fever and appeared to be coughing up blood. An acid-fast stain slide of tissue from the lungs is shown in the photograph. Which statement best describes the disease process that is visible in the stained slide? Cytoplasmic inclusions associated with Chlamydia Legionella within alveoli indicating atypical pneumonia Mycobacteria overwhelming alveolar macrophages Pseudomonas microcolonies within lung parenchyma Signs of consolidation linked to typical pneumonia

The answer is A: Heterosexual sex. The majority of HIV infections globally result from heterosexual sex. In contrast, only 33% of newly diagnosed cases of HIV/AIDS in the United States in 2006 were attributed to heterosexual sex; whereas 50% were attributed to men having sex with men.

63 What is the most common route of transmission of HIV around the world? Heterosexual sex Homosexual sex IV drug use Perinatal Transfusion

The answer is D: Activated cells express transcription factors and polymerases required for transcription of HIV genes. While reduction of cell surface viral receptors might reduce virus retention from infected host cell surface (choice A), activated CD4 T cells increase in surface expression of CD4, CCR5, and CXCR4. Activated cells are not likely to be impaired in the potential to induce the antiviral state (choice B). While TLR can bind viral RNA (including HIV), this binding does not induce the antiviral degradation of integrated DNA (choice C). HIV is not limited to infection of activated cells due to a lack of coreceptors on resting cells (choice E). HIV requires host factors, in particular, transcription factors in order to optimize gene expression for viral replication to occur. In fact, HIV produces a protein, negative factor, which promotes the activation of macrophages (M-tropic disease).

11 HIV can infect any cell expressing the appropriate coreceptors but a productive infection occurs only in activated cells. What is the most likely reason for this observation? Activated cells decrease their cell surface expression of the coreceptors, so budding virions can easily escape to infect new host cells Activated cells do not have the capacity to induce the antiviral state Resting cells have sensitive TLR molecules which bind HIV RNA molecules and activate the antiviral state, resulting in degradation of the integrated HIV DNA Activated cells express transcription factors and polymerases required for transcription of HIV genes Resting cells are resistant to HIV attachment and penetration due to low expression of the HIV coreceptors

117 The answer is A: Clarithromycin plus ethambutol plus rifabutin. The patient in the case has disseminated Mycobacterium avium complex. This organism is an acid-fast bacillus that causes multiorgan system disease in AIDS patients with CD4 counts of less than 50/cmm. With the advent of highly active antiretroviral therapy, the incidence of the disease among AIDS patients has markedly declined. The above triple drug regimen is recommended for treatment of this disease in AIDS patients as well as pulmonary disease in immune competent individuals. AIDS patients with CD4 counts of less than 50/cmm should receive prophylactic clarithromycin or azithromycin to prevent infection with this organism.

117 A 54-year-old HIV-infected male with a CD4 cell count of 45/cmm presents with fever, shortness of breath, diarrhea, fatigue, night sweats, weight loss, and right upper quadrant abdominal pain of 2 weeks duration. He has refused antiretroviral therapy for the past 2 years due to debilitating side effects. Physical examination reveals a pale, ill appearing, cachectic male with hepatosplenomegaly. Lab tests reveal elevated transaminase and alkaline phosphatase levels. Blood cultures grew acid-fast bacilli. With which antibiotic regimen should this patient be treated? Clarithromycin plus ethambutol plus rifabutin Isoniazid plus rifampin Piperacillin plus tazobactam Trimathoprim plus sulfamethaxazole Vancomycin plus dalfopristin

The answer is C: Macrophages. An M-tropic HIV isolate binds to CD4 and the coreceptor CCR5 which are both expressed on macrophages, monocytes, and dendritic cells. These cells carry the virus to draining lymph nodes, where the virus infects other cells. Activated T cells express CCR5 as well as CD4 and are infected as they pass through the lymph nodes. As the disease progresses, the virus mutates to a T-trophic strain, infecting T cells expressing CD4 and a different coreceptor, CXCR4. HIV has been shown to infect mucosal epithelial cells and mast cells; however, these cells are not the primary cellular targets for virus replication and systemic spread.

13 A prophylactic drug is being developed to prevent infection of cells by M-tropic HIV strains following exposure at mucosal sites (vagina, colon). M-tropic HIV strains primarily infect which of the following cell types? Colonic mucosal cells Intestinal M cells Macrophages Mast cells Vaginal mucosal cells

The answer is D: HIV peptides have alterations which do not permit efficient CTL TCR interactions. The CTL response to HIV is quite robust; however, HIV employs a number of evasion maneuvers to avoid clearance, including downregulation of class I MHC molecules and upregulation of FasL on target infected cells. Also, infection of dendritic cells results in inhibited maturation and limited professional Ag presentation. These infected dendritic cells can also serve as taxis for the virus to invade monocytes and T cells. HIV cannot infect CTL (choices A and B) due to a lack of the appropriate viral receptors (CD4 and chemokine receptor). Since CTLs recognize antigens presented only by class I MHC molecules, any impact on class II MHC is irrelevant (choice C). One of the reasons HIV is so elusive is that the high error rate of the reverse transcriptase produces differences in the virus during the course of infection within the same patient (choice E). In many cases, these mutations alter HIV proteins to the point that either they do not bind to the class I MHC properly or cannot be recognized by the responding CTL.

14 The CTL response to HIV infection is quite robust; however, these activated CD8+ T cells have little impact on viral clearance or inhibition of AIDS progression. Which one of the following offers an explanation for this observation? HIV can directly infect CTL causing their lysis upon viral replication HIV infection of CTL results in insertion of viral DNA into areas of the host genome critical for cell function, thus, infected CTL are functionally impaired HIV peptides generated in infected cells do not fit into the grooves of the host cell class II MHC molecules, thereby, inhibiting CTL recognition and killing HIV peptides have alterations which do not permit efficient CTL TCR interactions HIV reverse transcriptase is highly efficient (not error prone) and thus protein mutation is a rare event

15 The answer is E: Pneumocystis jiroveci. All of the organisms listed are opportunistic infections that may occur in AIDS patients. Prophylaxis for P. jiroveci is recommended to begin when CD4 cell levels decline to less than 200/cmm. No chemoprophylaxis is recommended to prevent infections with C. neoformans due to its relative infrequency. Nitazoxanide is approved for treatment of C. parvum; however, no drug has been recommended for prophylaxis. Persons with AIDS and CD4 cell counts of <150/cmm and who live in areas hyperendemic for H. capsulatum can be protected from disease with prophylactic itraconazole. Azithromycin or clarithromycin can be used in AIDS patients with CD4 cell counts of <50/cmm to prevent infections due to M. avium complex.

15 A 42-year-old man with HIV, presenting for his regular checkup, is found to have a CD4 cell count of 180/cmm. He is given a prescription for TMP-SMZ for the prevention of which opportunistic pathogen? Cryptococcus neoformans Cryptosporidium parvum Histoplasma capsulatum Mycobacterium avium complex Pneumocystis jiroveci

The answer is C: Cutaneous larva migrans. Sometimes referred to as creeping eruptions, this is solely a dermal disease in people. The person becomes infected when the filariform larva, which is found in moist soil or sand, penetrates bare skin. Individuals who go barefoot in a tropical setting are prime targets. The linear or serpiginous lesion is primarily an inflammatory response to the microscopic larval worm wandering through the skin. Ancylostoma braziliense, a hookworm that infects dogs and cats, is believed to be the most frequently encountered species, and the human is an unsuitable host for this particular hookworm species. Recommended therapy includes topical thiabendazole, albendazole, or ivermectin. Cercarial dermatitis or swimmer's itch is produced by an avian schistosome and the rash is widespread and produces pruritic papules. Chiggers and the Demodex mites both are capable of producing dermatitis, but the rash will usually not appear serpiginous. Dracunculus medinensis, a nematode that can cause skin lesions, is not found in the United States.

19 A mother becomes alarmed when she discovers a serpiginous reddish rash on the foot of her child who just returned from a 2-week summer camp on a beach in South Florida. The child reports that the lesion "itches a lot." Their family physician prescribes a topical preparation of thiabendazole and, within 2 weeks, the condition resolved. What is the most likely diagnosis? Cercarial dermatitis Chigger dermatitis Cutaneous larva migrans Demodex follicularis infesation Dracunculus medinensis infection

The answer is B: Albendazole plus a corticosteroid. Albendazole therapy is most effective in a patient who is experiencing the intestinal phase of the disease. Usually, this patient will have significant relief within a few weeks following completion of the anthelminthic drug. Patients with encapsulated disease could possibly experience residual myalgia, at least until the larvae are calcified. Corticosteroid will help the person cope with the adverse hypersensitivity reactions that invariably occur when the larvae are killed.

2 What is the best therapeutic option available for the with trichinellosis? Mebendazole Albendazole plus a corticosteroid Corticosteroid alone Metronidazole Praziquantel plus a hydrochlorothiazide

The answer is E: HIV Vpr stops cell cycling in G2. Based upon the HIV replication cycle, the virus buds from the infected cell and does not lyse it for release (choice A). Rev or regulator of viral gene expression (choice B) is a protein which serves to enhance translation by facilitating transfer of viral mRNA across the nuclear pore complex into the cytoplasm (or ER). Thus, Rev does not impact host cell mitosis. Nef can promote apoptosis of cells but generally it accomplishes this task by upregulating FasL on infected cell surface providing a type of immune privilege. Nef has many other functions but does not upregulate Bax expression (proapoptotic molecule) (choice C). HIV promotes activation of host cells to utilize host transcription factors for viral gene expression, and employs Vpr to arrest the infected cells in the G2 stage. The infected host cell does not detect the integrated HIV DNA at least according to our current understanding (choice D).

20 Active HIV infection requires susceptible host cells to be in an activated state; however, once they are infected, these host cells rarely undergo mitosis. Which one of the following is most likely an explanation for this observation? The infected host cell is rapidly lysed by exiting HIV virion HIV Rev prevents first stages of mitotic division HIV Nef promotes Bax expression and host cell apoptosis Infected host cell detects inserted HIV DNA and stops cell cycling to activate DNA polymerase in order to remove the viral genome HIV Vpr stops cell cycling in G2

The answer is C: Flucytosine. Cryptococcosis is caused by Cryptococcus neoformans, an opportunistic pathogen. It is the most common cause of fungal meningitis and AIDS patients are at high risk of developing this disease. In addition, cryptococcosis can present initially as pneumonia that may quickly disseminate depending upon the immune status of the patient. Neurological infection is 100% fatal if left untreated. In this setting, amphotericin B is the most appropriate treatment. Flucytosine appears to be highly effective against this fungus, however, resistance can develop when this drug is used alone for therapy. Therefore, treatment of cryptococcal meningitis initially involves 2 weeks of amphotericin B in combination with flucytosine. Following this, an 8-week treatment with an azole is recommended. Amphotericin B can also be administered for other fungal infections without the aid of another antifungal. Itraconazole, TMP-SMZ, and ketoconazole can be used alone against susceptible fungi.

22 Which one of the following antifungals is specifically employed in the treatment of cryptococcosis and is always used in combination with other antifungals? Itraconazole Amphotericin B Flucytosine Ketoconazole Trimethoprim-sulfamethoxazole

The answer is D: Toxocara canis. Although several nematode species have been linked to ocular parasitic infections in humans, T. canis is the most common cause of ocular toxocariasis or ocular larva migrans—a variety of visceral larva migrans. Children who suffer from pica, especially geophagy, are the ones at most risk. Dogs and cats naturally harbor the parasitic worm. Embryonated eggs are infective to children, even though the human is an unsuitable host for parasite maturation. Retinal involvement is simply a matter of chance as the worm has the potential to migrate to any visceral organ. Unfortunately, due to the inflammatory response, visually distinguishing the condition in situ from a retinoblastoma is difficult. Enucleation and subsequent histopathogenic examination might be required for an accurate diagnosis. Trichuris trichiura matures in the intestinal tract; A. caninum is an agent of cutaneous larva migrans; and, O. volvulus and L. loa are tropical filarial worms that are transmitted by an arthropod vector.

23 A 6-year-old boy, who has a history of eating dirt while playing in a New York City park, develops a vision problem in one eye. An opaqueness of pupil or leukokoria is readily discernable by the parents, and this prompts a visit to the ophthalmologist. Funduscopic examination reveals a single granulomatous lesion of the retina. Assuming that his ocular condition is caused by a parasitic worm, what is most likely the etiologic agent? Ancylostoma caninum Loa loa Onchocerca volvulus Toxocara canis Trichuris trichiura

28 The answer is D: Fever, headache, confusion, motor weakness. Toxoplasmosis is a neurologic disease in AIDS patients and other severely immune compromised patients. Neurological disease in this patient population typically represents reactivation of an old infection. Individuals become infected with Toxoplasma gondii either through ingestion of oocysts shed in cat feces, or ingestion of cysts in undercooked meat. Serologic evidence suggests that about 15% of adults in the United States harbor the parasite. Most infections are asymptomatic, although some people experience a mononucleosislike illness. The organism replicates as tachyzoites in muscle and brain tissue. Eventually, cysts containing bradyzoites are formed in these tissues and the organism can remain viable for years without causing harm to the infected individual. Reactivation of the parasite can occur in infected persons who become severely immune suppressed due to AIDS or organ transplantation. The parasite can also cause serious congenital neurological disease if a woman becomes infected during pregnancy.

28 A 43-year-old AIDS patient with a CD4 cell count of 15/cmm develops toxoplasmosis. Which of the following describe his likely symptoms? Abdominal pain, anorexia, nausea, vomiting Fever, malaise, nonproductive cough, dyspnea Fever, weight loss, night sweats Fever, headache, confusion, motor weakness Profuse, watery diarrhea occasionally streaked with blood

29 The answer is C: Human immunodeficiency virus. While the bacteria and fungus listed cause pulmonary disease, the clinical manifestations and acid-fast sputum results are consistent with pulmonary TB. In immune competent individuals without identifiable risk factors for TB, an area of induration of ≥15 mm is considered positive. In contrast, a ≥10 mm area of induration is considered positive for at-risk individuals including immigrants from endemic countries, intravenous drug abusers, or children. Persons infected with HIV or who have other causes of severe immune suppression are considered to have a positive TB skin test if they develop an area of induration of ≥5 mm in diameter. Thus, the patient in this case, with a positive sputum and symptoms of pulmonary TB who developed a 5 mm area of induration may be infected with HIV. In addition, the patient is in a well-documented risk group for both infections. The CDC recommends HIV screening for all TB patients.

29 A 32-year-old prison inmate presented with fever of 38.5°C, unexplained weight loss of 12 pounds, and a cough of 3 weeks duration. The cough was productive of bloody sputum. A sputum Gram stain failed to reveal any predominant organisms. An acid-fast stain of the sputum is shown in the figure. Chest radiographs showed cavitary lesions in the right upper lobe; however, an intradermal skin test showed a 5 mm area of induration after 72 h. In addition to the organism causing the respiratory symptoms, for which other organism should he be tested? Aspergillus fumigatus Histoplasma capsulatum Human immunodeficiency virus Klebsiella pneumoniae Streptococcus pneumoniae

The answer is C: Nurse cell. Even though limited clinical information was given, the apparent diagnosis for these patients is trichinellosis (trichinosis) or a Trichinella spiralis infection. Certain groups of people who come to the United States are not always aware of the dangers of eating raw pork that has been raised in the family farm setting—especially one that allows the pigs to wander freely in the yard. Of course it is illegal to feed uncooked refuse to pigs, but on a small farm, these animals may acquire the infection by feeding on rat carcasses. Rats often harbor trichina larvae in this way. More to the question: When the larval stage of T. spiralis penetrates a striated muscle fiber, it promotes the development of a protective collagenous capsule often called the nurse cell. Referencing the correct name of a parasite stage will avoid frustrating moments with the pathologist in the hospital setting. The cysticercus is a tapeworm stage (e.g., Taenia solium); an onchocercoma is a fibrous growth common to an Onchocerca volvulus infection, and metacercaria is the infective stage for certain flukes.

3 Public health officials investigate an onset of febrile gastrointestinal illness in a member of a family who recently emigrated from a Southeast Asian country. A raw pork dish is implicated, and the meat was purchased from an owner of a small farm. A micrograph of stained tissue from the meat is shown in the image. What is the correct term that properly describes the encysted larval stage? Encapsulated cysticercus Metacercaria Nurse cell Onchocercoma Pseudocyst

The answer is E: Western blot for HIV. Several rapid screening tests for antibodies to HIV have been approved by the FDA with the intent of offering HIV testing in more medical sites as well as community sites where persons who do not regularly seek medical care may be tested. The CDC estimates that as many as 25% of persons infected with HIV are unaware of their infection status. Thus, offering testing in more sites is an essential part of an overall prevention strategy by making people aware of their infection and offering counseling on medical care and ways to prevent transmission to others. These rapid screening tests can use saliva, blood, or plasma and can give results in 20 min. The results of all positive HIV screening tests must be confirmed with western blot, regardless of whether the test was done by conventional laboratory based methods or by point-of-care rapid tests.

30 A 37-year-old man presents to your office in a panic, stating that he tested positive for HIV based on the results from a saliva-based rapid test offered at a health fair. The man reports no risk factors for HIV. Which of the following tests should be ordered right away? CBC and differential Lipid profile Serologies for hepatitis viruses Viral load and resistance testing Western blot for HIV

The answer is E: Inhalation of yeast-like cells from soil contaminated with pigeon droppings. C. neoformans is an opportunistic fungus that is found worldwide as a saprophyte in soil enriched with bird droppings. Although immune competent persons can be infected, the result is often a flulike illness with complete recovery. The organism is not walled off in the lung as is the case with Histoplasma capsulatum or Mycobacterium tuberculosis. Infection of persons with T cell immune suppression, such as AIDS patients or patients with hematological malignancies, most commonly leads to meningoencephalitis.

31 A 56-year-old AIDS patient presents with fever and signs of meningitis. Antigens of Cryptococcus neoformans are found in his cerebral spinal fluid by latex agglutination. How did this patient most likely acquire this infection? Consumption of spores in contaminated food or water Immune suppression-induced reactivation of previously acquired organisms contained within lung granulomas Inhalation of infectious particles in respiratory secretions from a person with similar symptoms Inhalation of oocysts from the cat feces while cleaning a litter box Inhalation of yeast-like cells from soil contaminated with pigeon droppings

The answer is E: Wuchereria bancrofti. Hydroceles are perhaps the most common presentation of W. bancrofti, a filarial worm that is endemic to Brazil. The diagnostic microfilaria is described as being sheathed but is often not visible in Giemsa-stained material. Chyluria is an associated sign. Scrotal elephantiasis is successfully managed through surgery. The other nematodes listed are not associated with this presentation.

31 A Brazilian man presents with an enlarged scrotum (shown in the first photograph). The man reports that his scrotum is gradually "getting bigger." During the medical history, he also expresses alarm that his urine appears milky—giving the physician the impression that he is also suffering from chylous urine. A thick blood film stained with Giemsa is shown in the second image. With which organism is he most likely infected? Ancylostoma brasiliense Loa loa Onchocerca volvulus Trichinella spiralis Wuchereria bancrofti

33 The answer is C: Epstein-Barr virus. The mass described is Burkitt lymphoma. This B-cell lymphoma occurs on the face or jaw of children in malaria-endemic areas of Africa. The virus induces a translocation of the c-myc oncogene from chromosome 8 to chromosome 14 near the promoter for the immunoglobulin heavy chain genes. Relocation of c-myc to this transcriptionally active area allows for the aberrant expression of the oncogene protein, and subsequent transformation of the cell. Additional evidence of the role of EBV in tumorigenesis is provided by the finding of EBV DNA and Epstein-Barr nuclear antigen-1 in tumor cells.

33 A 12-year-old boy in central Africa presents to a medical mission with a noticeable mass on the left side of his face at the jaw line. His bottom teeth on the left side are loosened and cervical lymph nodes are enlarged. His parents report that the swelling appeared about 2 weeks ago and has grown very rapidly in size. A biopsy of the mass subsequently reveals cells of fairly uniform size and shape, with round to oval nuclei containing multiple nucleoli. Many mitotic figures are seen suggesting that the mass is a cancer. With which microorganism is this cancer causally associated? Actinomyces israelii Blastomyces dermatitidis Epstein-Barr virus Plasmodium falciparum Trypanosoma brucei

The answer is D: Epstein-Barr virus. All the choices listed can cause pharyngitis; however, only Epstein-Barr virus (EBV) fits the entire picture presented in the case. HIV can cause a similar clinical presentation as well as atypical lymphocytes. Only EBV induces heterophil antibodies. Heterophil antibodies are usually of the IgM class and bind to red blood cells of other mammals. They are detectable during the acute phase of infectious mononucleosis caused by EBV. Following the acute illness, heterophil antibodies rapidly decline in titer. Not all patients with EBV-associated mononucleosis develop heterophil antibodies, and for those cases, definitive diagnosis is made by demonstrating IgM to viral capsid antigen.

34 A 16-year-old boy presented with a 1-week history of sore throat, fever, and profound fatigue. Physical exam revealed a fever of 39.5°C, cervical lymphadenopathy, exudative pharyngitis, and mild hepatosplenomegaly. His white blood cell count was 12,500/μL with 20% neutrophils, 24% monocytes, 42% lymphocytes, and 12% atypical lymphocytes. A rapid serologic test performed at the physician's office revealed the presence of heterophil antibodies. What is the cause of this boy's illness? Adenovirus Cytomegalovirus Enterovirus Epstein-Barr virus Human immunodeficiency virus

34 The answer is A: Cryptococcus neoformans. This is a typical presentation of C. neoformans-induced meningitis. It occurs most commonly in T-cell immune suppressed individuals such as those with AIDS. Its onset is typically insidious rather than sudden, and it can wax and wane in severity delaying time of diagnosis by several weeks. The most common presenting symptom is headache, although changes in mental status such as confusion may occur as well, especially as the disease progresses. Papilledema is a common sign of meningeal inflammation. Stiff neck is another common indicator if meningitis is often absent in patients with C. neoformans meningitis. The CSF analysis is typical of nonbacterial meningitis (mononuclear pleocytosis, mildly increased protein, and moderately decreased glucose). India ink staining of the CSF shows encapsulated budding yeasts in 25% to 50% of patients; thus a negative India ink smear should not be considered conclusive. Tests to detect polysaccharide capsular antigens are positive in about 90% of patients. Alternatively, diagnosis can be made by culture of the organism on routine fungal medias. Haemophilus and Listeria are ruled out as possibilities, even though Haemophilus has a polysaccharide capsule, because both would elicit a neutrophilic pleocytosis. M. tuberculosis can present with meningitis and can cause mononuclear pleocytosis; however it lacks a polysaccharide capsule and is not diagnosed by antigen detection in the CSF. Instead, an acid-fast stain of centrifuged CSF may detect the organism. More typically, cultures and/or PCR provide diagnosis of M. tuberculosis meningeal infections.

34 A 47-year-old AIDS patient with a CD4 cell count of 95/cmm presents with an insidious onset of severe headache and fever for the past 3 weeks. In the past few days, he had become mildly confused and developed diplopia. Papilledema is seen on physical exam. Ring-enhancing lesions are seen on MRI. Cerebral spinal fluid (CSF) showed 150 mononuclear cells/cmm, mild elevation of protein, and decreased glucose. An India ink stain of the CSF was negative; however, capsular polysaccharide antigens, found in the CSF, allowed for a definitive diagnosis. What is the etiology of this man's infection? Cryptococcus neoformans Haemophilus influenzae b Listeria monocytogenes Mycobacterium tuberculosis Neisseria meningitidis

The answer is D: Nasopharyngeal epithelial cells and B cells, respectively. EBV infects cells expressing CD21, also known as complement receptor 2. B cells and epithelial cells of the upper respiratory tract and parotid gland epithelial cells express CD21. The virus produces a lytic infection with virus production in epithelial cells, but is only semipermissive in B cells. Semipermissive means that the virus can replicate in only a small percentage of infected B cells. B cells in which viral proteins are produced but replication is not complete may be stimulated to proliferate, and viral proteins may upregulate expression of cellular genes involved in cytokine secretion and prevention of apoptosis. These B cells may become transformed. EBV is associated with B cell lymphomas including those occurring in the central nervous system of immune suppressed individuals, as well as Burkitt lymphoma and at least some Hodgkin lymphomas.

35 Which cells infected by EBV allow full virus replication and which may become transformed by the virus? Lymph node dendritic cells and T cells, respectively Monocytes and cells of the oropharynx, respectively Monocytes and hepatocytes, respectively Nasopharyngeal epithelial cells and B cells, respectively T cells and splenic macrophages, respectively

The answer is C: Gag. HIV protease serves to make cuts in the polyprotein, group-specific antigen or Gag, in three areas releasing the matrix, capsid, and nucleocapsid proteins. This release allows proper formation of the virion for infection (maturation). Without these splices, the virion would have limited ability to infect new cells. Env or envelope proteins (choice A), pol or polymerase (choice B), and Nef or negative factor (choice E) are spliced by other enzymes. Matrix (choice D) is spliced by protease but is only one of the proteins released during maturation as discussed above.

88 Protease inhibitors are useful drugs against HIV by preventing maturation of the budding virion. This maturation process involves proteolytic cleavage of which HIV protein? Env Pol Gag Matrix Nef

The answer is E: Trimethroprim-sulfamethoxazole (TMP/SMZ). This case is descriptive of pneumocystis pneumonia. Pneumocystis jiroveci (formally carinii) is the causative agent of this condition. The micrograph depicts the cystic stage of the organism. It is found in the respiratory tracts of healthy individuals where its growth is controlled by macrophages. Without sufficient CD4+ cells that secrete γ-interferon to activate macrophages, these phagocytic cells will have difficulty in killing the microbe. Pneumocystis infection can be prevented by TMP/SMZ given prophylactically to HIV-infected individuals with CD4 counts of less than 200/cmm. The patient in this case was noncompliant with medication, thereby increasing his risk for this and other opportunistic infections. P. jiroveci was once thought to be a protozoan; however, genetic evidence supports its categorization as a fungus. Nevertheless, antifungal drugs are not effective either as chemoprophylactic agents or in treating a full-blown infection. TMP/SMZ is the preferred choice, assuming of course that the AIDS patient can tolerate the drug. Pentamidine, clindamycin plus primaquine, atovaquone, and dapsone have also been shown to have activity against this organism.

38 A 49-year-old patient with advanced HIV disease presents with fever, dyspnea, nonproductive cough, and moderate chest pain. His history includes noncompliance with medication. His CD4 count is 120/cmm. Chest radiographs reveal diffuse bilateral infiltrates. Lactate dehydrogenase levels are elevated. Cystlike structures are recovered in the bronchoalveolar lavage fluid (shown in the image). Which of the following antimicrobial agents represents the best treatment option for this patient? Amphotericin B Diethylcarbamazine Itraconazole Ketoconazole Trimethoprim-sulfamethoxazole (TMP/SMZ)

40 The answer is E: Ulceroglandular tularemia. This is the most common form of tularemia diagnosed in the United States. Tularemia, caused by Francisella tularensis, is endemic to the Midwest and some Western States. This patient most likely acquired the disease through the tick bite, although deer flies can also transmit the infection. Infection can also result from contact with the tissues of infected animals such as rabbits. After seroconversion, an immunodiagnosis is possible, but sufficient time probably has not passed in this case. F. tularensis has an extremely low infective dose, and, therefore, a high potent for accidental transmission in the hospital laboratory. Isolation and identification of the Gram-negative coccobacillus requires a facility rated for a biosafety level three category. In this case, diagnosis and treatment based on the clinical presentation is appropriate. Streptomycin therapy is considered the standard of care. Other aminoglycosides may also prove to be efficacious, however. For Lyme disease, erythema migrans at the bite site would be more likely. Endemic typhus is a fleaborne rickettsial disease that is produces a rash. Human granulocytotropic anaplasmosis and human monocytic ehrlichiosis are not commonly found in Utah.

40 A college student who has a summer job clearing brush from hiking trails in Utah has an abrupt onset of fever and chills. He seeks medical help after a day of illness, when he becomes keenly aware of a painful lymph node in his groin area near an ulcerated and infected tick bite. After evaluation and subsequent consultation with an infectious disease specialist, streptomycin therapy is recommended. What is the most likely diagnosis? Endemic typhus Human granulocytotropic anaplasmosis Human monocytic ehrlichiosis Lyme disease Ulceroglandular tularemia

The answer is C: His CD4 cells cannot activate CD8 cells. The pictures show herpes zoster or shingles due to a recurrence of varicella-zoster virus (VZV). This virus is latent in ganglia, and prevented from recurring by a strong antiviral T-cell immune response. As CD4 cells decline in number, the ratio of CD4:CD8 cells decreases. In addition, the functional capacity of noninfected CD4 cells also declines in HIV-infected patients; thus, immune responses dependent on these cells decline. Latent herpes viruses tend to recur because cytotoxic T cells cannot be adequately activated by CD4-positive cells. B cells play no role in the control of viral latency. The patient's ability to make antibodies to HIV or to VZV, or the ability to activate complement are not affected in HIV nor do they have a role in the occurrence of shingles. Shingles can occur in immune compromised patients regardless of their levels of antibody or complement.

42 An HIV-infected man with a CD4 cell count of 400/cmm develops a painful, vesicular rash as seen in the accompanying photograph. What does this skin rash indicate about his immune system? He can no longer produce anti-HIV antibodies His B cells can no longer control the agent causing the skin infection His CD4 cells cannot activate CD8 cells His CD4 to CD8 ratio is increased His complement C5 to C9 is depleted

The answer is B: Enfuvirtide. This drug represents a novel treatment modality that blocks the ability of HIV to enter cells following binding of the viral gp120 with host cell CD4 molecules. Normally, a conformational change in the viral gp41 allows the viral envelope to fuse with the host cell plasma membrane. Enfuvirtide (Fuzeon) blocks the conformational change in gp41, thereby inhibiting the virus from entering the cell. Enfuvirtide was approved in 2003 for use in adults and children with advanced HIV disease resistant to several reverse transcriptase inhibitors and protease inhibitors, and for whom there are limited treatment options. It is still used in combination with other classes of antiretroviral drugs. No HIV medication is used as monotherapy due to the rapid appearance of resistant mutants.

43 A 58-year-old AIDS patient has failed several antiretroviral regimens due to viral drug resistance. Which of the following drugs blocks the entry of HIV into cells and is used in combination therapy after other regimens have failed? Efavirenz Enfuvirtide Fosamprenavir Lamivudine Ritonavir

45 The answer is D: Leptospira interrogans. The most plausible diagnosis is Weil disease, caused by L. interrogans. Leptospirosis is a zoonotic disease transmitted to people by rodents (including synanthropic rats of the inner city). Individuals who handle these animals or other types of wild animals are the most likely candidates to contract the infection, especially if mucous membranes or broken skin is contaminated with positive urine. Leptospira organisms can be identified from the patient's urine or tissue via darkfield microscopy or direct fluorescent-antibody staining, although these techniques are insensitive. Culture of the organism on specialized medium may take 2 weeks or longer. The finding of antibodies in the patient's serum to the organism is the preferred method of diagnosis. Like syphilitic spirochetes, leptospires are sensitive to β-lactam and tetracycline antibiotics. B. microti, arenaviruses, and hantaviruses are zoonotic infections with rodent hosts. Babesiosis does not present as described in the case, and the organism is restricted to the coastal regions of the northeast United States. Lymphocytic choriomeningitis virus, an Arenavirus, most commonly causes a self-limiting flulike illness, although meningitis can also occur. Other arenaviruses are found in South America or Africa. Hantavirus in the United States is associated with rapidly progressive respiratory distress. T. gondii infection is most commonly associated with contact with oocysts in cat feces, or transplacental transmission. If infected as an adult, it is often asymptomatic, or may result in a mononucleosislike syndrome.

45 A masters-level zoology student, who is researching the behavior of rats in urban St Louis, Missouri, develops a febrile illness, marked with headaches, conjunctival hemorrhages, and signs consistent with renal failure. He is hospitalized for 2 weeks before the etiologic agent is found in blood, CSF, and urine samples. Confirmatory serologic tests are positive. What is the most likely etiological agent? Arenavirus Babesia microti Hantavirus Leptospira interrogans Toxoplasma gondii

46 The answer is D: Ehrlichiosis. The case is most descriptive of human monocytic ehrlichiosis (Ehrlichia chaffeensis), an emerging disease that attacks the hematopoietic system. It has been reported from the Eastern and Midwestern United States. A primary risk factor is contact with ticks (e.g., Dermacentor variabilis, Amblyomma americanum), especially during the warm-weather months when tick infestations are most likely. In most cases, an empirical diagnosis is not feasible; however, a history of a tick bite in an endemic area, a CBC that is remarkable for leucopenia and possibly thrombocytopenia, monocytes with morulae (characteristic clusters of the cocci within a cytoplasmic vacuole), and an indirect fluorescent antibody test of greater than 1:128 is sufficient evidence for a firm diagnosis. Middle-aged individuals are more likely to present with symptoms. Headaches, myalgia, malaise, and gastrointestinal disturbances further characterize the disease. Ehrlichiosis can be fatal, especially in the elderly. The drug of choice is doxycycline, and treatment should be initiated early for favorable prognosis, definitely before laboratory confirmatory results are available.

46 In early July, a 45-year-old man from rural eastern Tennessee is taken to the emergency department with a high fever and episodes of delirium which appear to be connected to the high fever. History reveals that he has been sick for more than 10 days—his condition began about a week following a fishing trip. Positive tick exposure is verified; the hospital laboratory reports a WBC count of 3.1 (th/μL); and, the illness responds favorably to doxycycline treatment. Later, a reference laboratory confirms the suspected diagnosis with a type-specific antibody titer of 1:256 and granulocytic morulae. Which of the following is most the compatible diagnosis? Babesiosis Brucellosis Endemic typhus Ehrlichiosis Lyme disease

The answer is C: Ingesting soil contaminated with embryonated eggs. The thick shell of the egg stage identifies the disease as ascariasis or an infection of Ascaris lumbricoides. The parasitic helminth is often described as a geohelminth (i.e., to be infective to people, the egg must first develop or embryonate in soil). Ingestion of the contaminated soil results in an infection. The egg stage is remarkably resistant to the environmental pressures and remains viable for years in the soil. Drinking polluted water is the vehicle of transmission for protozoans like the diarrheogenic organisms of Giardia and Entamoeba. Meat is the vehicle for a taeniid tapeworm infection, wading in water best describes the means of acquiring schistosomiasis, and barefoot exposure pertains to the transmission of hookworms.

48 A young Haitian boy is brought to an aide station by his mother. She is seeking vitamins for her son. She indicates that her son "does not eat" and sometimes complains of nausea. He apparently has no diarrhea and no significant gastrointestinal pain. A fecal concentration is positive for parasite ova (shown in the image). How did this child become infected? Drinking water polluted with the cystic forms Eating insufficiently cooked meat infected with cysticerci Ingesting soil contaminated with embryonated eggs Wading in streams that harbor snails and cercariae Walking barefoot, thus allowing larvae to penetrate the skin

54 The answer is E: Symptomatically. The case is descriptive of infectious mononucleosis due to Epstein-Barr virus infection. There is no antimicrobial treatment available for this infection and it is generally treated symptomatically to reduce fever and pain. Acyclovir is used to treat herpes simplex virus and varicella-zoster virus. Amphotericin is used to treat serious fugal infections. Corticosteroids are not used in uncomplicated cases of infectious mononucleosis such as the one described here. They may be required in cases involving hematologic complications such as hemolytic anemia or thrombocytopenia or if enlarged tonsils or cervical lymph nodes threaten closure of the airways. Penicillin is an antibiotic that can be used for streptococcal pharyngitis; however, although some of the symptoms are similar (exudative pharyngitis, cervical lymphadenopathy, and fever), it is not the patient's diagnosis.

54 A 16-year-old girl presents with fever, exudative pharyngitis, profound fatigue, and cervical lymphadenopathy of 2-days duration. Palpation revealed mild splenomegaly. A blood test revealed 10% atypical lymphocytes and lymphocytosis, and a heterophil antibody test was positive. How should this patient be treated? Acyclovir Amphotericin Corticosteroids Penicillin Symptomatically

The answer is D: CXCR4 or CCR5. These molecules are chemokine receptors. Attachment and entry of HIV into infected cells involves the initial binding of viral gp120 to CD4 and then to one of the chemokine receptors. This binding induces a conformational change in the viral gp120/gp41 complex which brings gp41 (also called the fusion protein) in contact with the host cell plasma membrane, and allows the viral envelope to fuse with the cell membrane. CCR5 is the coreceptor for strains of HIV which infect macrophages; whereas CXCR-4 is the coreceptor for strains of the virus which infect T cells. HIV also binds to the dendritic cell membrane molecule DC-SIGN, which may enable dendritic cells to carry the virus into secondary lymphoid tissues to infect T cells. Binding of HIV to DC-SIGN does not appear to facilitate infection of dendritic cells. The other molecules listed are not involved in the attachment or entry of HIV into target cells. Both CD3 and CD25 are found on T cells, whereas CD80/86 is an essential costimulatory molecule on antigen presenting cells.

55 A researcher wanted to induce the replication of HIV in a cell culture line because it was easier than culturing human T cells. What molecule, in addition to CD4, would she have to transfect into the cultured cell line in order to make the cells susceptible to HIV infection? CD3 CD25 (γ chain of IL-2 receptor) CD80/81 CXCR4 or CCR5 DC-SIGN

The answer is B: Hookworm. The consumption and the oozing of blood from the intestinal site where the worm attaches explains the iron-deficiency anemia. Heavy infections of Trichuris trichiura or the human whipworm (not a choice in this question) has also been linked to anemia. Diphyllobothrium latum or the broad fish tapeworm has been noted to produce a type of pernicious or megaloblastic anemia.

56 A child with a helminth parasite is found to be anemic. Which parasitic worm is linked to microcytic anemia in children? Broad fish tapeworm Hookworm Pinworm Pork tapeworm Schistosome blood fluke

The answer is D: Strongyloidiasis. The identification of a Strongyloides stercoralis infection is determined in part because of the presence of rhabditiform larvae in a fecal sample. On the other hand, the laboratory diagnosis of hookworms, Ascaris, Enterobius, and Trichuria are based on the recovery of parasite eggs in the feces. Once in a while, however, a pinworm egg will hatch on the perianeum and a larva may be seen in a stool sample. The presence of pinworm larvae in a stool sample, which has been properly stored and processed, is a very rare occurrence. A key word in the stem, therefore, is "abundance" and indicates the presence of numerous larvae in the stool. Strongyloides is a common parasite in children who reside in developing nations, especially children who are confined to an orphanage. A pulmonary phase of the Strongyloides life cycle has been linked with pneumonitis and also asthmalike manifestations. Enteritis is also a possibility. More than not, intestinal involvement will produce a benign infection. From time to time, this nematode is identified from patients in the United States.

58 A young child, who was adopted from an orphanage in Asia, routinely experiences loose stools. An abundance of microscopic worms (shown in the image) are noted in a fecal preparation smear. What is the correct diagnosis? Ascariasis Enterobiasis Hookworm disease Strongyloidiasis Trichuriasis

capsule (6 The answer is A: Capsule. Robust bacterial rods (bacilli) are clearly visible in the tissue section, and based on the shape of these bacterial cells and the overall clinical picture (death of the steer), a laboratory diagnosis of Bacillus anthracis seems plausible. B. anthracis is epizootic in certain areas of the United States and is described as a disease agent of cattle and sheep in the North Dakota region. The unwitting rancher exposed to the infected livestock could potentially develop cutaneous anthrax. Herbivores are believed to acquire the infection by ingesting endospores while grazing on the contaminated pastures. A foremost virulence determinant for B. anthracis is the polyglutamic acid capsule. If lacking, the potential for the microbe to be pathogenic and generate disease is effectively zero. As with other bacteria, this particular capsular type plays a role in protecting the bacterium against phagocytosis and bactericidal components of the immune system.)

6 A steer dies on a ranch in North Dakota and a veterinarian is consulted. Histological sections of the spleen from the deceased animal show evidence of a bacterial causative agent (shown in the photograph). The bacterium was also cultured aerobically on blood agar. Which of the following substances is associated with increased virulence of this isolate, and if detected, would alarm the state health officials and result in a more extensive investigation at the national level? Capsule H antigen Hemolysin Lipid A Lipoteichoic acid

The answer is A: Ascariasis with biliary involvement. More than 1 billion people worldwide are infected with Ascaris lumbricoides. Children are more likely candidates than adults to be infected. The worms commonly reside in the small intestine, but migration into the biliary tract is fairly common. Based on the exquisite radiating pain in this case, biliary involvement should be ruled out, probably though radiographic findings. It is not unusual for a child to spit up a worm upon being treated. Children in Latin America will harbor multiple worms—sometimes hundreds—and intestinal obstruction is a potential complicating factor. Usually, however, abdominal symptoms are vague with nothing more than a loss of appetite and occasional episodes of diarrhea.

60 An 8-year-old child, who recently emigrated with the family from Central America, is taken to the emergency department because of a stomach ache that has persisted for about 24 hours. In fact, the mother indicates that the pain did not lessen even after the child vomited up two worms (shown in the image) the night before. The mother further indicates that for the past several weeks the child has had little desire to eat and often complains of diarrhea. Physical examination reveals that the pain is more pronounced in the right upper quadrant region and directly radiates to the scapular area of the back. Based on these findings, what is the most likely diagnosis? Ascariasis with biliary involvement Disseminated strongyloidiasis Hemolytic uremic syndrome Intestinal and hepatic amebiasis Salmonella enterocolitis

The answer is E: 2.5 million. The World Health Organization estimates that 2.5 million people became infected with HIV in 2007. It is important for physicians to recognize the global impact of this virus.

60 You are a physician working for a public health agency charged with reducing the incidence of HIV infection. To understand the impact of the disease, you ask many questions about the epidemiology of the disease in the United States and around the world. According to recent statistics, approximately how many new infections with HIV occur yearly around the world? 2,500 25,000 40,000 400,000 2.5 million

The answer is C: 40,000. It is important for physicians to recognize the impact of this virus in the United States. The CDC estimates that the number of new infections with HIV in the United States has remained stable at 40,000 for a number of years. In 2006, 35,180 newly diagnosed cases were reported from 33 states with long-term, confidential name-based HIV reporting.

61 Approximately how many new infections with HIV occur yearly in the United States? 2,500 25,000 40,000 400,000 2.5 million

The answer is C: Ingestion of contaminated soil or water. Ascaris lumbricoides is a geohelminth, meaning that the eggs that are passed in the stool must first embryonate in the soil or the environment. The parasite is not commonly transmitted person-to-person via feces. Consequently, the embryonated egg—not the unembryonated egg in fresh feces (choice A)—is the infective stage. Ingesting food and drink contaminated with these embryonated eggs would be the most likely way for humans to become infected. Lack of proper hand washing before eating only compounds the problem. Choice C has reference to hookworm disease, D refers to schistosomiasis, and E hemorrhagic Escherichia coli.

61 With reference to ascaris how did the child most likely become infected? Direct fecal contamination from a sibling Eating raw or insufficiently cooked hamburger Ingestion of contaminated soil or water Swimming in cercariae-infested lake water Walking barefoot on moist soil or grass

The answer is D: Sub-Saharan Africa. According to the World Health Organization, almost 70% of people currently living with HIV/AIDS reside in Sub-Saharan Africa. In this area, about 5% of adults are infected. By comparison, the estimated prevalence of infection in 2007 in the other regions included in the question is as follows: South and Southeast Asia—0.3% Eastern Europe and Central Asia—0.9% North America—0.6%

62 Which area in the world has the highest prevalence of HIV/AIDS? Indian subcontinent Southeast Asia States of the former Soviet Union Sub-Saharan Africa The United States

The answer is A: Acute Chagas' disease. Chagas' disease is endemic to many countries in Central and South America. The acute phase is defined when motile trypanosomes are detected in the anticoagulated blood or the buffy coat (layer of white blood cells and platelets just above the erythrocyte zone). The trypomastigote stage, often C-shaped (see micrograph), is readily visualized in a fixed Giemsa-stained blood smear. The clinical manifestations in this case clearly pertain to the acute phase of the disease. Sleeping sickness is endemic to Africa and not South America, blackwater fever is linked to falciparum malaria. Malaria is an intraerythrocytic life cycle, and leishmaniasis is characterized with amastigotes and not tryptomastigotes.

63 While completing a public health rotation in an urban clinic in Peru, a US medical student is given an academic assignment to study a cluster of acute febrile cases in young children. Incident to each case is an acute regional lymphadenitis, myalgia, and a characteristic bloodborne parasite (shown in the image). Which of the following diseases is the most reasonable diagnosis? Acute Chagas' disease Benign tertian malaria Blackwater fever Chronic sleeping sickness Disseminated leishmaniasis

The answer is C: He inoculated himself by rubbing infected reduviid feces into the bite site. The reduviid bug, Triatoma infestans, is responsible for transmitting most of the infections of Chagas' disease. The parasite (Trypanosoma cruzi) is passed in the feces of the bug, a process described as posterior station. A pseudocyst or a pocket of amastigotes, is clearly depicted in the micrograph and is characteristic of T. cruzi infection. Cardiac disease, including sudden death, is connected with chronic Chagas' disease. Toxoplasma is associated with litter boxes of cats. Tickborne diseases include Rocky Mountain spotted fever, Lyme disease, and babesiosis. Malaria is transmitted by anopheline mosquitoes, and sand fly species are vectors for leishmaniasis.

64 A middle-aged man who emigrated from South America unexpectedly dies of cardiac failure. A histological section of myocardial tissue reveals numerous bodies as shown in the image. How did the man most likely become infected with this disease? A sand fly injected the parasite into the blood stream while feeding An infected anopheline mosquito introduced the parasite during a blood meal He inoculated himself by rubbing infected reduviid feces into the bite site The man inadvertently ingested infected feces from a house cat The parasite was transmitted to the man during a tick bite

The answer is D: Male-to-male sexual contact. Of the new infections among adults and adolescents diagnosed in 2006, 50% occurred in male homosexuals; 33% occurred in people who engage in high-risk heterosexual sex; and 13% occurred in intravenous drug users. Less than 1% of infections diagnosed in 2006 occurred in persons less than 13 years of age.

64 Persons in which transmission category in the United States currently have the highest number of newly diagnosed cases of HIV/AIDS? High risk heterosexual contact Intravenous drug use Medically related Male-to-male sexual contact Perinatal

The answer is C: Increase in CD4 cells, decrease in viral load. Acute retroviral syndrome refers to the clinical manifestations that may develop within weeks of infection with HIV. The virus during this time is replicating rapidly in T cells and a decreased number of T cells is seen along with a peak in plasma viral load. Following recovery from acute retroviral syndrome, virus is sequestered in lymph nodes; thus the viral load typically declines. In addition, T-cell proliferation is thought to raise T-cell numbers in order to maintain homeostasis.

65 A 23-year-old heterosexual male was diagnosed with acute retroviral syndrome. His CD4 count and viral load at the time of diagnosis were 450/μL (normal 500 to 1,500) and 80,000 copies, respectively. He returns in 6 weeks, and is asymptomatic. What changes in the CD4 count and viral load are typically expected at this time in the infection? Decrease in CD4 cells, decrease in viral load Decrease in CD4 cells, increase in viral load Increase in CD4 cells, decrease in viral load Increase in CD4 cells, increase in viral load No significant change would be expected

66 The answer is B: Invasive cervical carcinoma. This cancer is considered an AIDS defining condition. The other options listed are indicative of progression of disease, and/or poor control of virus replication but are not included in the case definition of AIDS.

66 A 27-year-old female is diagnosed with acute retroviral syndrome and is placed under the management of infectious disease specialists. Which of the following, if it occurred in this patient, would indicate that she has progressed from HIV infection to AIDS? CD4 cell count 50% of normal Invasive cervical carcinoma Shingles Thrush Viral load >100,000/cmm

The answer is B: Invasive cervical cancer. Of the options listed, only invasive cervical cancer is considered an AIDS-defining illness. Zoster; pelvic inflammatory disease; recurrent fever, night sweats, and generalized lymphadenopathy; and recurrent, severe vaginal yeast infections are conditions that indicate diminished T-cell immunity and/or are complicated by the presence of HIV; however, they do not fit the case definition of AIDS as defined by the CDC.

66 A 43-year-old woman has been infected with human immunodeficiency virus for the past 12 years. Which of the following, if it occurs, will indicate that the woman's disease has progressed to fit the case definition of AIDS? Herpes zoster Invasive cervical cancer Pelvic inflammatory disease Recurrent fever, night sweats, and generalized lymphadenopathy Recurrent, severe vaginal yeast infections

The answer is B: Hookworm disease. Distinctive clues with this case include the geographic location, socioeconomic conditions, the anemia, and most importantly the fragile nature of the egg. Ancylostoma and Necator hookworms are transmitted when the filariform larvae penetrate bare skin. Parasite eggs are passed in the stool and, under austere sanitary conditions, will contaminate soil. The warm moist soil of the South favors development of the infective stage or the filariform larva. Protein deficiency and mental dullness are clinical manifestations of severe disease.

68 A nurse who works part time in an elementary school in rural southern Mississippi notes loss of appetite, weakness, and poor school performance in a boy. The child's weight is below the second percentile, and a low hemoglobin level is noted in the laboratory findings. Of note, the child lives in a rural setting without adequate toilet or latrine facilities and customarily goes barefoot. Parasite eggs are observed in the stool sample (shown in the image). What is the diagnosis? Ascariasis Hookworm disease Intestinal amebiasis Strongyloidiasis Taeniasis

The answer is C: Glycoprotein switching. The diagnosis is African sleeping sickness—caused by the acute form of Trypanosoma brucei rhodesiense. The trypomastigote stage, seen in the micrograph, is able to hide from host defenses by regularly changing or switching its glycoprotein surface molecules. Cysteine proteinases, phospholipases, and lectin are virulence factors of the diarrheogenic ameba, Entamoeba histolytica. Schistosome blood flukes disguise themselves with a coating of host blood product (i.e., host antigenic mimicry). The occurrence of African sleeping sickness in the United States is extremely rare, but arguably, the real significance of this disease gives insight into a critical microbial mechanism that leads to successful invasion of the human host.

69 A wildlife photographer travels to a big game park in East Africa and returns home with intermittent fever and a painless chancrelike sore on his neck. A Giemsa-stained blood smear is positive for a flagellated microbe (shown in the image). Which of the following mechanisms gives the microbe the ability to evade humoral defense responses? Cysteine proteinase production Host antigenic mimicry Glycoprotein switching Lectin adhesion Phospholipase activity

The answer is C: Flow cytometry. In this method, mononuclear cells are separated from the blood and incubated with fluorescence-conjugated anti-CD4 antibodies. CD4+ cells are stained and the number of fluorescing cells is determined as the cells are passed singly in a fluid stream by a series of detectors in the flow cytometer. The direct fluorescent antibody test utilizes fluorescent-tagged monoclonal antibodies to detect specific pathogen antigens in patient tissues. Enzyme immunoassay is a technique whereby antibodies are utilized to detect antibodies or antigens from patient samples—detection made possible by coupling an enzymatic reaction to a detection antibody. Immunoprecipitation is a procedure using antibodies to bind antigens for extraction from tissue samples. Quantitative polymerase chain reaction is a method used to measure the amount of pathogen DNA in patient samples. It is used to determine viral load in HIV-infected individuals, and is part of an initial evaluation to determine if a patient should be placed on antiretroviral drugs.

7 A newly diagnosed HIV-infected male is being evaluated prior to being placed on antiretroviral therapy. What technique is used to determine the number of CD4+ cells in his peripheral blood? Direct fluorescent antibody test Enzyme-linked immunoassay Flow cytometry Immunoprecipitation Quantitative polymerase chain reaction

The answer is A: Adsorption. The first step in virus replication is adsorption, in which a specific viral protein binds to a specific protein on the membrane of the host cell. In the case of HIV, the viral protein is gp120. Neutralizing antibodies are defined as those which bind to the specific viral protein involved in adsorption, thereby directly preventing the virus from entering the cell. The other options are steps in the replication cycle of viruses, and certainly would not occur if the virus does not enter the cell.

70 A patient with HIV is shown to have neutralizing antibodies against HIV gp120. Which aspect of the virus's replication cycle is directly blocked by these antibodies? Adsorption Assembly Genome replication Reverse transcription Uncoating

The answer is B: Cytomegalovirus. This virus causes retinitis in AIDS patients with CD4 cell counts below 100/cmm. Of the other viruses listed, only adenoviruses cause eye infections; however, these viruses are associated with conjunctivitis. Human herpes virus type 8 is associated with Kaposi sarcoma. Lymphocytic choriomeningitis virus causes a febrile meningitis. Metapneumovirus causes respiratory illness ranging from pneumonia and bronchiolitis to colds and croup.

71 A 57-year-old AIDS patient with a CD4 cell count of 75/cmm develops vision problems in the right eye. Fundoscopic examination of the eye reveals widespread necrosis and hemorrhage as shown in the accompanying photograph. A viral cause for these findings is suspected. What is the most likely etiology of this man's visual loss? Adenovirus Cytomegalovirus Human herpes virus type 8 Lymphocytic choriomeningitis virus Metapneumovirus

73 The answer is B: Epstein-Barr virus. Causes of ring-enhancing lesions in the brain of AIDS patients include EBV-associated lymphomas, toxoplasmosis, and cryptococcosis. The neurological disease described in this case is due to CNS lymphoma. The diagnosis of CNS lymphoma is aided by the finding of EBV DNA by PCR of the CSF. EBV is an oncogenic virus which is causally related to primary CNS lymphomas in AIDS patients. This disease arises in AIDS patients with CD4 counts of less than 100/μL. Its incidence has dropped dramatically since the introduction of highly active antiretroviral therapy. Cytomegalovirus causes encephalitis in AIDS patients, and the occurrence of herpes simplex encephalitis is not increased in patients with immune suppression. The diagnosis of CMV and HSV encephalitis is aided by the demonstration of viral DNA by PCR, and a lymphocytic pleocytosis can be seen; however, the cells are not malignant appearing. St Louis encephalitis virus causes encephalitis especially in the elderly, and is diagnosed by demonstration of antiviral IgM in the cerebral spinal fluid. JC virus is the cause of progressive multifocal leukoencephalopathy which often presents with focal neurologic signs including hemiparesis, ataxia, aphasia, or cortical blindness. Both JC virus and St Louis encephalitis virus are RNA viruses.

73 A 43-year-old AIDS patient with a CD4 cell count of less than 50/μL was brought by a friend to the emergency department after suffering a seizure. The friend reported that the patient had been lethargic, confused, and forgetful for the past week. Physical exam revealed a confused, afebrile man with focal neurological signs. A ring enhancing lesion was seen on CT and MRI of the brain. Cytology of the CSF showed malignant appearing lymphocytes. A PCR of the cerebral spinal fluid revealed viral DNA. Which virus is most likely involved in the etiology of this man's neurological signs? Cytomegalovirus Epstein-Barr virus Herpes simplex virus type 1 JC virus St Louis encephalitis virus

The answer is C: pol. The pol gene codes for reverse transcriptase. This enzyme has a high error rate, and rapidly generates mutant viruses which can be selected for resistance to antiviral medications. The env gene codes for the envelope glycoproteins gp120/gp41. Nef, tat, and vpu are viral regulatory proteins.

74 A 56-year-old AIDS patient fails his third regimen of antiretroviral drugs despite being very compliant about taking his medications properly. His failure reflects the development of resistance in his population of viruses to various antiretroviral drugs. The protein product of which gene of HIV is responsible for the rapid production of mutations that leads to antiretroviral drug resistance? env nef pol tat vpu

The answer is C: Human herpes virus type 8. The lesions in the case fit the description of Kaposi sarcoma, a vascular tumor caused by human herpes virus type 8 (HHV-8). This virus was first described in 1994. It affects about 5% of the general population but 30% to 60% of male homosexuals. It has been shown to be transmitted by sexual contact, shared needles, and transfusion. Kaposi sarcoma in the United States is most frequently associated with AIDS. The man in the case is at high risk for HIV infection due to his homosexuality and IV drug use and his lymphopenia is suggestive of AIDS. More rarely, KS can occur in patients with immune suppression due to other causes, such as transplantation. Although associated with lymphoproliferative diseases which may manifest in the skin, Epstein-Barr virus does not typically cause skin lesions. Chronic hepatitis C virus is associated with numerous skin lesions, many of which are due to immune complex-mediated vasculitis. The skin lesions of molluscum contagiosum are flesh-colored, umbilicated papules. Papillomaviruses cause warts.

75 A 45-year-old homeless Caucasian male presents with multiple 3 to 5 cm erythematous macular lesions on his back, arms, chest, and face. His history is significant for homosexuality and IV drug use. Physical exam reveals an afebrile male in no acute distress with no organomegaly and no edema. A 1-cm diameter, reddish nodular lesion was seen on the palate. A white blood cell count reveals marked lymphopenia, but normal neutrophil, red cell, and platelet numbers. What is the most likely virus that could be identified within the lesions? Epstein-Barr virus Hepatitis C virus Human herpes virus type 8 Molluscum contagiosum virus Papillomavirus

inhalation of aerosolized bacteria (he answer is D: Inhalation of aerosolized bacteria. Plague is a zoonotic infection of rodents caused by Yersinia pestis. It is transmitted among rodents and rarely to people by fleas. Human infection resulting from the bite of an infected flea results in bubonic plague characterized by high fever and painful, enlarged lymph nodes or bubos. Bubonic plague is not transmitted person-to-person. Bacteremia can occur in untreated individuals with bubonic plague, leading to lung infection or pneumonic plague. This form of plague is transmissible person-to-person through respiratory aerosols.)

77 An outbreak of pneumonic plague occurs in the Democratic Republic of the Congo killing over half of the affected individuals. How is this form of plague transmitted? Bite of infected flea Direct skin contact with bubos Ingestion of contaminated water Inhalation of aerosolized bacteria Introduction of bacteria into wounds while butchering infected animals

leptospira (78 The answer is C: Leptospira interrogans. This organism is the cause of Weil disease. Bartonella quintana causes trench fever, an emerging disease among urban homeless individuals in developed nations. Chlamydia psittaci is an avian pathogen that can cause fever and respiratory illness in persons with pet birds. M. leprae is the cause of leprosy. U. urealyticum is a bacterium that colonizes the urogenital tract and can occasionally cause nongonococcal urethritis.)

78 A 35-year-old man developed a flu-like illness that lasted 3 days and was followed by apparent recovery. Within days, he suffered a recurrence of illness with symptoms of meningitis and oliguria. He was hospitalized and diagnosed with Weil disease. Which of the following organisms is the cause? Bartonella quintana Chlamydia psittaci Leptospira interrogans Mycobacterium leprae Ureaplasma urealyticum

78 The answer is E: Trypanosoma cruzi. The case is descriptive of myocarditis in chronic Chagas disease. T. cruzi is a flagellated protozoan parasite transmitted by reduviid bugs and endemic to areas of South and central America. None of the other organisms listed are transmitted by this vector, although some are or can be vectorborne. With the exception of R. akari all can cause cardiac manifestations. B. burgdorferi, the causative agent of Lyme disease, is transmitted by ticks. Myocarditis can occur in patients with Lyme disease. C. hominis is a member of the HACEK group of Gram-negative bacilli found as mouth flora and cause culture-negative endocarditis. C. burnetii is the cause of Q fever, a disease characterized as a flulike illness which can progress to mild pneumonia. Human infection with this organism is usually acquired by inhalation of the organism in soil contaminated with livestock feces, birth fluids, or dried placental material; however, ticks transmit the organism among livestock. Chronic infections can lead to endocarditis. R. akari causes rickettsialpox, a mite-borne disease characterized by high fever, chills, myalgia, and a generalized rash. No cardiac disease occurs in rickettsialpox.

78 A 65-year-old man, a South American immigrant, presents with biventricular heart failure with peripheral edema, hepatosplenomegaly, and pulmonary congestion. Global heart enlargement is seen on chest radiography. Electrocardiography reveals right bundle-branch block and left anterior fascicular block. Serum collected from the patient and run on ELISA detects antibodies to an agent transmitted by the bite of reduviid bugs. What is the etiology of this man's disease? Borrelia burgdorferi Cardiobacterium hominis Coxiella burnetii Rickettsia akari Trypanosoma cruzi

The answer is E: JC virus. Progressive multifocal leukoencephalopathy (PML) is caused by JC virus, a ubiquitous human polyomavirus. Most people carry this virus latently in the kidney, from which it is periodically reactivated. Seroprevalence of this viral infection is about 90% among adults. Initial infection is not linked to any particular disease. In severely T cell-immune compromised individuals, the virus is reactivated and enters the brain where it replicates and damages glial cells. Damage to oligodendrocytes leads to areas of demyelination within the brain and subsequent clinical manifestations of neurologic disease. No specific treatments exist for PML. The disease is addressed by attempting to improve the immune status of the patient. In AIDS patients, suppression of virus replication with antiretroviral therapy has reduced mortality from PML from about 90% to about 50% by improving the patient's T-cell immunity. Cytomegalovirus and human herpes virus type 6 can cause encephalitis in AIDS patients. Human immunodeficiency virus also causes neurologic disease in AIDS. Endogenous retroviruses are found in the DNA of all cells in the body, but have not to date been linked with any disease.

82 A 37-year-old AIDS patient develops an insidious onset of cognitive, motor, and visual problems and is diagnosed with progressive multifocal leukoencephalopathy. What is the viral etiology of this condition? Cytomegalovirus Endogenous retrovirus Human herpes virus type 6 Human immunodeficiency virus JC virus

94 The answer is E: Prevent maturation of the virus by blocking formation of essential structural and nonstructural proteins. This drug combination is a preferred regimen according to the 2008 treatment guidelines developed by the Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. The drugs atazanavir and ritonavir are both protease inhibitors. The HIV protease cleaves the polypeptide into individual structural proteins essential for the formation of infectious virions.

94 A 23-year-old newly diagnosed HIV-infected male has a CD4 cell count of 150/cmm and a viral load of 10,000 copies per mL. He is placed on an antiretroviral drug regimen that includes efavirenz, atazanavir + ritonavir and abacavir/lamivudine. What is the mechanism of action of the drugs atazanavir and ritonavir? Block entry of HIV into the cell by inhibiting conformational change in gp41 Block budding from the cell by preventing cleavage of sialic acid residues Block the formation of the provirus by inhibiting reverse transcription Prevent incorporation of the provirus into host cell chromosomes Prevent maturation of the virus by blocking formation of essential structural and nonstructural proteins

95 The answer is C: Efavirenz. The recommended regimen for a treatment of naïve HIV-infected patient is a combination of drugs consisting of either one non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside reverse transcriptase inhibitors (NRTI) or a protease inhibitor (PI) combination plus two NRTIs. It is important to know which drugs belong to those categories. Abacavir and lamivudine are NRTIs. Atazanavir and ritonavir are PIs.

95 Which drug being taken by the patient in the above question is a non-nucleoside reverse transcriptase inhibitor? Abacavir Atazanavir Efavirenz Lamivudine Ritonavir

96 The answer is B: Atazanavir + ritonavir. The patient has developed a problematic side-effect of many protease inhibitors. Atazanavir and ritonavir are both protease inhibitors. Abacavir and lamivudine are nucleoside reverse transcriptase (RT) inhibitors and efavirenz is a non-nucleoside reverse transcriptase inhibitor.

96 After several months on the drug regimen, the individual in the above case develops a buffalo hump, central obesity, and dyslipidemia. Which of the following drugs could account for these findings? Abacavir/lamivudine Atazanavir + ritonavir Efavirenz Lamivudine alone

The answer is B: Antiretroviral therapy. The form of Kaposi sarcoma seen in the United States occurs primarily in AIDS patients not receiving or not responding adequately to antiretroviral therapy. Kaposi sarcoma in AIDS patients may respond to antiretroviral therapy (ART) alone. Other treatment modalities depend on the extent of disease and include surgery, chemotherapy, and radiation therapy. The other antiviral therapies listed are not effective against the tumor or its viral cause. Acyclovir is used for diseases caused by herpes simplex viruses and varicella-zoster virus. Imiquimode is used to treat genital warts. Lamivudine is an inhibitor of reverse transcriptase used in some ART regimens and used for chronic hepatitis B virus infections. Ribavirin is used most frequently in combination with α-interferon to treat chronic hepatitis C virus infections.

Which antiviral therapy is most frequently recommended as a first step in treating kaposi sarcoma? Acyclovir Antiretroviral therapy Imiquimode Lamivudine Ribavirin