Microbiology and Immunology 2 Flashcards
1
Q
Under what conditions does the causative microorganism grow?
A
Both lepromatous and tuberculoid leprosy are caused by Mycobacterium leprae, an acid-fast bacillus that cannot be grown in vitro. M leprae is an obligate intracellular bacillus that, like other mycobacteria, contains mycolic acid in its cell wall. M leprae grows best in cooler temperatures (eg, skin, peripheral nerves, testes, upper respiratory tract).
2
Q
How does this patient’s condition differ from a more severe form?
A
This patient has tuberculoid leprosy, which is largely confined to the skin (hypopigmented macules) and peripheral nerves. Cell-mediated immunity is intact, and patients’ T cells recognize M leprae (positive lepromin skin test). Lepromatous leprosy holds a much worse prognosis because patients have ineffective cell-mediated immunity (negative lepromin skin test). Skin lesions and nerve involvement are much more extensive than in the tuberculoid form, and there may be involvement of the testes, upper respiratory tract, and anterior chamber of the eye.
3
Q
What is the appropriate treatment for tuberculoid and lepromatous leprosy?
A
Both tuberculoid and lepromatous leprosy can be treated with a course of oral dapsone. The tuberculoid form is reliably cured by a short course of this medication. Patients with lepromatous leprosy have an exceptionally high bacterial load and may require an extended or even lifelong course of chemotherapy. Alternate therapies for leprosy include rifampin or a combination of clofazimine and dapsone.
4
Q
What are the side effects of treatment for tuberculoid and lepromatous leprosy?
A
Dapsone can cause agranulocytosis, so patients should be monitored initially with weekly or biweekly complete blood counts. Rifampin can turn body fluids such as sweat, tears, and urine a red-orange color. Rifampin therefore can be remembered as the “Gatorade drug,” referring to commercials that showed athletes with colored sweat from drinking Gatorade. This can startle patients (and rightly so) if they are not counseled before commencing therapy.
5
Q
What is the most likely diagnosis?
A
Meningitis due to Listeria monocytogenes infection. This microorganism, identifiable by its classical tumbling motility, is a gram-positive rod and a common cause of meningitis in newborns and the elderly (Table 3-2).
6
Q
How is Listeria monocytogenes transmitted?
A
L monocytogenes is transmitted through ingestion of unpasteurized dairy products such as milk, cheese, and ice cream.
7
Q
What microorganisms should empiric antibiotic therapy target for this patient?
A
Group B streptococcus, Escherichia coli, and L monocytogenes are the most common causes of sepsis and bacterial meningitis in infants younger than 1 month of age. Therefore, empiric therapy should be aminopenicillin or vancomycin for gram-positive infection and aminoglycosides, antipseudomonal penicillins, or third- or fourth-generation cephalosporins for gram-negative infection.
8
Q
How does Listeria monocytogenes evade the host immune response?
A
L monocytogenes is a facultative intracellular bacterium able to survive in the macrophages of neonates and immunosuppressed patients. In an immunocompetent host, activation of macrophages destroys phagocytosed Listeria.
9
Q
What other population is at particular risk for developing Listeria monocytogenes infection?
A
Pregnant patients are at increased risk of developing a serious illness from Listeria known as granulomatosis infantiseptica. It can cause various complications to the mother and baby from premature rupture of membranes and intrauterine fetal demise. The elderly and immunocompromised are also at increased risk for this infection.
10
Q
What is the most likely diagnosis?
A
The patient most likely has a hydatid cyst, which is a liver cyst due to Echinococcus infection.
11
Q
How is Echinococcus transmitted?
A
Echinococcus is a tapeworm that is transmitted by food or water contaminated with feces containing eggs from the tapeworm. Infection is not endemic to the United States and so is most commonly seen in immigrants or those with a travel history to endemic areas.
12
Q
What is the typical presentation of Echinococcus infection?
A
Echinococcus causes slow-growing cysts in the liver. As a result, symptoms are often gradual in onset and include abdominal pain, cough, low-grade fever, a sense of abdominal fullness, hepatomegaly, and obstructive jaundice. Leakage of cysts can cause flushing and urticaria, whereas rupture can cause anaphylaxis and death. Other organs that can be involved include the lungs and the brain. In the lungs, the presentation includes chronic cough, dyspnea, hemoptysis, and pleuritic chest pain. In the brain, presentation includes headache, dizziness, increased intracranial pressure, and hydrocephalus.
13
Q
How is this condition (a hydatid cyst, which is a liver cyst due to Echinococcus infection) diagnosed?
A
On x-ray of the abdomen, a rim of calcification around the cyst is able to distinguish hydatid cyst from amebic and pyogenic cysts. However, the diagnosis usually cannot be made with radiology alone and requires an enzyme-linked immunosorbent assay (ELISA). In addition, 25% of patients have eosinophilia.
14
Q
What is the treatment for Echinococcus infection?
A
The treatment for Echinococcus infection is usually surgical and involves aspiration of cyst contents followed by excision. However, during drainage, the interventional radiologist or surgeon must be careful not to rupture the cyst as this can lead to anaphylaxis. Therefore, many physicians prefer to inject formalin or ethanol into the cyst to kill the organism before aspirating. In some cases, therapy with a combination of albendazole and mebendazole is sufficient.
15
Q
What other organisms are classified as cestodes?
A
Diphyllobothrium latum is a cestode transmitted by ingestion from freshwater fish that causes vitamin B12–deficient macrocytic anemia. D latum is treated with praziquantel. Taenia solium larvae are ingested from undercooked pork and can cause calcified cysts in various organs including the brain (cysticercosis or neurocysticercosis). Cysticercosis is treated with praziquantel, whereas neurocysticercosis is treated with albendazole.
16
Q
What is the most likely diagnosis?
A
Malaria due to Plasmodium falciparum. The symptoms give a clue as to the species. The patient’s altered mental status is consistent with a diagnosis of P falciparum malaria, since this is the only strain that commonly has cerebral involvement. This patient’s continuous fever and irregular chills and sweats are also characteristic of P falciparum malaria. Early in infection, irregular fevers are common in all types of malaria, but the fever can become periodic in well-established cases of non-falciparum disease. For example, P vivax and P ovale cause episodes of fever, chills, and sweats every 48 hours. With P malariae, these episodes occur every 72 hours. Splenomegaly is a common finding in malaria due to work hypertrophy from increased RBC breakdown.
17
Q
What phase of thePlasmodium falciparum life cycle results in the development of anemia?
A
RBC lysis occurs during the erythrocytic cycle, when the products of asexual replication inside the RBCs (the merozoite form) are released. The immune response to the merozoites, and resulting cytokine release, is responsible for the fever, chills, and sweats.
18
Q
What are the likely peripheral blood smear (PBS) findings in Malaria due to Plasmodium falciparum?
A
A PBS is likely to show ring-shaped trophozoites inside the RBCs (see Figure 3-25), and there may be several trophozoites per RBC. Schizonts, the large, multinucleated cells formed from the trophozoite by multiple cycles of nuclear division, may be visible in the erythrocytes in non- falciparum malaria, but are very rarely seen in falciparum disease. Outside the RBCs, oblong gametocytes, diagnostic for P falciparum, may also be visible.
19
Q
What is the treatment of choice for Malaria due to Plasmodium falciparum?
A
Chloroquine is the drug of choice in the few areas where there is no resistance. Its major mode of action against Plasmodium is inhibition of the enzyme responsible for polymerizing heme. This results in the accumulation of free heme, which is toxic to the protozoan. Quinidine in combination with doxycycline or pyrimethamine /sulfadoxine is commonly used as first-line treatment for chloroquine-resistant P falciparum. Other effective drugs include mefloquine and atovaquone-proguanil.
20
Q
What 2 conditions provide protection against malaria?
A
Sickle cell trait and glucose-6-phosphate dehydrogenase (G6PD) deficiency both protect against malaria. The hypothesis is that increased fragility of the erythrocytes in these diseases does not allow for Plasmodium species to effectively replicate.
21
Q
What is the most likely diagnosis?
A
Third-degree atrioventricular (AV) block secondary to Lyme disease. This condition is caused by Borrelia burgdorferi, a gram-negative spirochete that is poorly grown in culture and too small to be seen under regular light microscopy. Fluorescence may be used to visualize the corkscrew-shaped bacterium. However, the diagnosis is usually made clinically, supported by serology. Early local infection may present with a bull’s-eye rash (erythema chronicum migrans) after several days. The early disseminated stage may develop as early as a few days later and presents with cardiac conduction abnormalities (Lyme carditis), cranial nerve palsies (especially cranial nerve VII), and meningitis. Up to 43% of patients with Lyme carditis develop complete heart block.
22
Q
What other conditions can cause Third-degree atrioventricular (AV) block?
A
Damage to the heart’s conduction system by fibrosis, ischemia, cardiomyopathy, myocarditis, or iatrogenic damage (eg, after valve replacement) may cause complete heart block. Digitalis, calcium channel blockers, and β-blockers may produce a temporary conduction abnormality.
23
Q
What is the route of infection in Lyme disease?
A
Lyme disease is an arthropod-borne infection. The Ixodes tick transmits B burgdorferi. Mice and deer are reservoirs for the disease.
24
Q
What is the prognosis for a patient with Lyme disease?
A
The prognosis is good. The conduction abnormalities secondary to Lyme carditis are self-limited and short lived and often resolve within days to weeks. It is uncommon for residual conduction abnormalities to persist after the infection has been cleared.
25
What is the appropriate immediate treatment for a patient with Lyme disease?
The patient’s ECG demonstrates bradycardia at a rate of 40/min. The episode of syncope indicates that cerebral perfusion is inadequate at this heart rate. Consequently, transvenous pacing may be initiated, but a permanent pacemaker is not needed. Antibiotic treatment for Lyme carditis consists of intravenous ceftriaxone until the PR interval is < 300 ms, at which point oral antibiotics may be initiated. The same regimen applies to Lyme disease with neurological features. Doxycycline or amoxicillin is used for primary infection and Lyme arthritis only.
26
What is the most likely diagnosis?
This child has measles, one of the most transmissible viral infections. Measles is caused by an RNA virus that is a member of the genus Morbillivirus and the family Paramyxoviridae. Transmission occurs by respiratory droplets and the incubation period is approximately 10 days. Two of this patient’s symptoms are typical of measles: Koplik spots and blanching rash with cephalocaudal spread.
27
What should be considered in the differential diagnosis other than measles?
Flulike symptoms may also be caused by infection with rhinoviruses, parainfluenza or influenza, adenovirus, or respiratory syncytial virus. Common causes of rash include Mycoplasma pneumoniae, human herpesvirus-6, rubella, Rocky Mountain spotted fever, scarlet fever, or a drug reaction. However, none of these rashes have cephalocaudal spread and none feature Koplik spots.
28
What are potential neurologic sequelae of measles?
Approximately 1:1000 patients with measles develop encephalitis, which is rapidly fatal in 15% of cases and leads to permanent neurological damage in 25% of patients. Infection with Morbillivirus can trigger acute disseminating encephalomyelitis, an autoimmune attack on the central nervous system, which is lethal in up to 20% of cases. Survivors often suffer mental retardation and epilepsy. Approximately 7–10 years after a measles infection, subacute sclerosing panencephalitis may develop; this infection, although rare, is almost always fatal.
29
What tests can confirm the diagnosis of measles?
Anti-measles IgM is seen in patient serum approximately 48 hours after the onset of the rash. A mucosal biopsy may demonstrate Warthin-Finkeldey cells (multinucleated giant cells with inclusion bodies in the nucleus and cytoplasm).
30
What is the appropriate treatment for measles?
There is no treatment for active infection; care is limited to supportive measures. Measles is a reportable disease and the patient must be placed in isolation. If other children in the family have not received the measles-mumps-rubella vaccine, it is likely that they will develop measles as this virus is highly transmissible.
31
What is the most likely diagnosis?
Infectious mononucleosis is most frequently caused by Epstein-Barr virus (EBV), a member of the Herpesviridae family.
32
Other than infectious mononucleosis, What should be considered in the differential diagnosis?
Several diseases present with symptoms similar to mononucleosis. However, streptococcal infection of the oropharynx is usually not associated with splenomegaly, and cytomegalovirus pharyngitis tends to be mild if clinically apparent at all. Low-grade fever, lymphadenopathy, and splenomegaly may also be seen in lymphoma. Lymphoproliferative disorders generally do not present with tonsillar exudate.
33
What are the peripheral blood smear (PBS) findings in infectious mononucleosis?
Infectious mononucleosis leads to lymphocytosis. The WBC count is often elevated (12,000–18,000/ mm3) with more than 50% lymphocytes. Up to 10% “atypical” lymphocytes containing large amounts of cytoplasm may be seen. However, these findings may also be seen in other infections (eg, cytomegalovirus, rubella, and toxoplasmosis), in some malignancies, and as a result of drug reactions.
34
Which malignancies are associated with EBV infection?
Burkitt lymphoma is endemic to Africa and primarily affects children. The disease is a B-cell lymphoma and often presents with a tumor of the jaw. This tumor often has a “starry sky” appearance under light microscope. Nasopharyngeal carcinoma is one of the most common cancers in southern China, and evidence supports EBV as its primary causative agent.
35
What treatments are available for Infectious mononucleosis?
Symptomatic treatment, usually with nonsteroidal anti-inflammatory drugs, is usually used. Although EBV might be expected to be susceptible to acyclovir since it is a herpesvirus, studies have shown that acyclovir produces reduction of oral shedding of the virus but no other significant clinical benefit. Ampicillin should be avoided, not just because it is ineffective against viruses but because it can precipitate a rash.
36
What is the most likely diagnosis?
Mucormycosis.
37
What is the microscopic appearance of the fungus involved in Mucormycosis?
The zygomycetes are nonseptate, branching fungi, with wide (> 90-degree) branch angles and large hyphae. By contrast, Aspergillus tends to have narrow, septated hyphae and branches in acute angles.
38
What patient populations are at increased risk for Mucormycosis?
The fungus is ubiquitous in nature and spores can be transmitted in air. Most patients are exposed to these spores several times per year, but an intact immune system is usually sufficient protection. Therefore, mucormycosis is typically seen in diabetic patients with poor glucose control or those with ketoacidosis. Neutropenic patients, burn victims, and patients treated with iron-chelating drugs are also at risk.
39
What patient populations are at increased risk for Mucormycosis?
The fungus is ubiquitous in nature and spores can be transmitted in air. Most patients are exposed to these spores several times per year, but an intact immune system is usually sufficient protection. Therefore, mucormycosis is typically seen in diabetic patients with poor glucose control or those with ketoacidosis. Neutropenic patients, burn victims, and patients treated with iron-chelating drugs are also at risk.
40
What is the pathogenesis of Mucormycosis?
The fungi grow along blood vessels and invade their walls. Protruding hyphae are highly thrombogenic, resulting in ischemia and necrosis of distal tissues, which, in turn, provide nutrients for continued fungal growth. Necrosis compromises the integrity of the bony walls of the sinuses and the cribriform plate, allowing fungal growth into paranasal sinuses, the bony orbit around the eye, or the brain. This rhinocephalic form of infection is rapidly progressive and carries a high mortality rate. Other forms include pulmonary, gastrointestinal, cutaneous, and disseminated infection.
41
What is the appropriate management for Mucormycosis?
Surgical debridement of infected and necrotic tissue is paramount. Reversal of the permissive condition (in this case ketoacidosis) should be initiated in conjunction with potent antifungal therapy with amphotericin B. However, despite optimal management, this condition still carries a high mortality rate.
42
What is the most likely diagnosis?
Orchitis secondary to mumps. In rare instances, orchitis can affect both testes and lead to sterility.
43
How is the mumps virus transmitted?
The mumps virus is a member of the Paramyxoviridae family of single-stranded RNA viruses. It is not stable enough to be aerosolized but can be transmitted by droplets (eg, sneeze). The virus has a 2- to 3-week incubation period, after which the infection results in painful inflammation and edema of glandular tissues including the parotid gland, testes, and ovaries.
44
What other clinical syndrome can result from infection with the mumps virus?
45
How is mumps diagnosed?
For the most part, the diagnosis of mumps can be made clinically. Supportive laboratory values include elevated amylase due to infection in the parotid glands. In uncertain cases, viral polymerase chain reaction assay may also be used.
46
What is the appropriate treatment for mumps?
The treatment is supportive and directed at reducing pain. Analgesics, compression, and icing of the parotid gland can be useful. In children, aspirin should be avoided as it has been linked to Reye syndrome. Vaccination with live attenuated mumps virus as part of the measles-mumps-rubella vaccine is used to prevent disease.
47
What is the most likely diagnosis?
This patient likely has Neisseria meningitidis meningitis, a gram-negative, kidney-shaped diplococci infection.
48
What test can confirm the diagnosis of Neisseria meningitidis meningitis?
Culture of meningococcus from cerebrospinal fluid (CSF) or blood. Lumbar puncture shows an elevated WBC count (with mainly polymorphonuclear cells), decreased glucose levels, and normal to high protein levels. Bacteria are visible on Gram stain. This pathogen can also be cultured on Thayer-Martin media (chocolate agar with antibiotics to kill competing bacteria). N meningitidis is oxidase positive and ferments both maltose and glucose.
49
What are Kernig and Brudzinski signs?
Kernig sign is considered positive when the patient resists straightening of the knee joint while the hip is flexed. Brudzinski sign is considered positive when the patient, while supine, lifts his legs when the neck is flexed by the examiner. Neither test is very sensitive, but a positive result is suggestive of meningeal irritation either by blood or inflammation.
50
What are the most important virulence factors and toxins of Neisseria meningitidis?
N meningitidis has thin protrusions called pili that help it attach to nasopharyngeal epithelial cells. Once attached to the nasopharynx, the pathogen secretes IgA protease to neutralize the predominant antibody idiotype found on mucous membranes. N meningitidis also features a capsule that protects it from other host defenses such as complement and phagocytosis. As with all gram-negative bacteria, N meningitidis has lipopolysaccharide, a potent endotoxin, in its cell wall.
51
What is the appropriate treatment for Neisseria meningitidis meningitis?
Intravenous penicillin G or ceftriaxone must be administered immediately. Bacterial meningitis can be fatal within hours, so empiric antimicrobial treatment must be started before culture results or other confirmatory tests become available. Rifampin is recommended as prophylactic treatment for contacts of the patient, especially if they are immunocompromised or have not been vaccinated.
52
What is the most likely diagnosis?
Onchocerciasis (river blindness) is caused by Onchocerca volvulus, a nematode (roundworm) found near rivers. Onchocerciasis is the leading cause of blindness in the developing world. Of the 18 million people infected worldwide, 99% of cases are in Zaire and Nigeria.
53
How is Onchocerca volvulus transmitted?
The bite of a female black fly transmits larvae (microfilariae) into the host’s skin. Humans are the only known definitive host of this parasite.
54
What is the pathogenesis of the Onchocerca volvulus?
The larvae become adults within 6–12 months, and subsequent fibrosis around the adult worms results in subcutaneous nodules, which protect the parasite from the host’s immune system. The parasites mate in the tissue, releasing microfilariae that can migrate to the eye where they cause keratitis and subsequent sclerosis.
55
What tests can help confirm the diagnosis of Onchocerciasis?
A skin biopsy may show larvae under the microscope, whereas nodules contain the adult filariae. The microfilariae in the eye may be visible on slit-lamp examination. Serologic tests such as enzyme-linked immunosorbent assay, polymerase chain reaction assay, and direct antigen testing are also available but require a laboratory, which is often not available to physicians treating the primary patient population.
56
What are the appropriate treatments for Onchocerciasis?
Ivermectin is effective against the larvae (microfilariae). It must be given every 6–12 months until the patient is asymptomatic. The subcutaneous nodules containing adult worms can be surgically removed.
57
What is the most likely diagnosis?
Osteomyelitis. Staphylococcus aureus is responsible for approximately 90% of pyogenic osteomyelitis cases. S aureus expresses receptors for the bone matrix, thus allowing it to adhere to bone and produce a focus of infection. Many affected adults have a history of compound fracture or surgery.
58
What patient populations are susceptible to osteomyelitis?
Osteomyelitis can be a sequela of trauma, as is the case in this patient, but is also often found in intravenous drug abusers (direct injection of bacteria) and patients with diabetes who have poorly controlled blood glucose. Bacteremic patients (typically children) may develop osteomyelitis as a consequence of hematogenous spread.
59
How does a subperiosteal abscess lead to accelerated bone necrosis?
A subperiosteal abscess separates the bone from its blood supply in the periosteum, leading to ischemic injury and necrosis.
60
A history of sickle cell disease would increase a patient with osteomyelitis’s risk of infection from which pathogen?
Patients with sickle cell disease have an increased risk of developing Salmonella osteomyelitis because of the reduced immune clearance of this pathogen.
61
What are the typical imaging findings in osteomyeltitis?
Periosteal elevation is often found on plain film radiography. This finding, however, can lag up to 2 weeks behind the onset of the infection. MRI is sensitive but not specific as it cannot distinguish osteomyelitis from other causes of marrow edema, such as normal postsurgical changes. Negative MRI findings essentially exclude osteomyelitis.
62
What is the most likely diagnosis?
Pinworm infection caused by Enterobius vermicularis, a nematode (roundworm).
63
What is the life cycle of the roundworm Enterobius vermicularis?
After fecal-oral transmission, the eggs hatch in the small intestine. Adults mature in the ileum and large intestine and mate in the colon. Females exit the rectum at night to lay eggs in the perianal area. This irritates the perianal area, inducing the host to scratch. Scratching transfers eggs onto hands, greatly increasing the likelihood of transmission to another host.
64
What sequelae may a Pinworm infection caused by Enterobius vermicularis, a nematode (roundworm) have?
Intense scratching may compromise the integrity of the perianal skin, predisposing the patient to dermatitis or folliculitis due to dermal invasion of fecal bacteria.
65
What test can help confirm the diagnosis of Pinworm infection caused by Enterobius vermicularis, a nematode (roundworm)?
Adhesive tape test: The physician places adhesive tape over the perianal area and then removes and examines the tape. The presence of eggs under light microscopy indicates pinworm infection.
66
What are the appropriate treatments for Pinworm infection caused by Enterobius vermicularis, a nematode (roundworm)?
Mebendazole or albendazole is first-line therapy. Pyrantel pamoate can also be helpful. Individual cases are easily treated, but institutional outbreaks (eg, in preschool) are more difficult to treat because undertreated patients quickly reinfect others who had already been cured.
67
What is the most likely diagnosis?
Pneumocystis jiroveci (formerly carinii) pneumonia causes interstitial pneumonia in certain patient populations. Once thought to be a protozoan, P jiroveci is now recognized as a fungus (yeast).
68
What patients are most at risk for developing a clinical infection with Pneumocystis jiroveci?
Most individuals are exposed to P jiroveci during childhood but develop no symptoms. However, immunocompromised patients (including patients with AIDS who have low CD4+ cell counts) and malnourished infants may develop severe clinical disease. Pneumocystis pneumonia in steroid-treated immunocompromised patients is most often seen as steroids are being withdrawn.
69
What are the likely x-ray findings in Pneumocystis jiroveci pneumonia?
“Ground-glass” bilateral infiltrates are commonly seen on x-ray of the chest (see Figure 3-31). In these patients, hypoxia is often out of proportion to the radiographic findings.
70
What tests can help confirm the diagnosis of Pneumocystis jiroveci (formerly carinii) pneumonia?
Sputum samples, bronchoalveolar lavage, or lung biopsy treated with silver stain demonstrate cysts and dark oval bodies contained within the cyst (sporozoites).
71
What is the appropriate treatment for Pneumocystis jiroveci pneumonia?
Treatment is primarily with trimethoprim-sulfamethoxazole (bactrim). In immunocompromised patients, trimethoprim- sulfamethoxazole or dapsone may be used as prophylaxis when CD4+ cell counts fall below 200 cells/ mm3. In patients with severe hypoxia, steroids should be given as adjunctive therapy to prevent worsening respiratory status due to the inflammatory response induced by treatment.
72
What is the most likely diagnosis?
Phytodermatitis secondary to poison ivy. This rash is characterized by vesicles < 5 mm in diameter. However, vesicles often coalesce in severe rashes.
73
Which type of hypersensitivity reaction is occurring in phytodermatitis secondary to poison ivy?
Was this the patient’s first exposure to poison ivy?
Type IV hypersensitivity reactions (delayed or cell-mediated) include contact hypersensitivity from poison ivy, transplant rejection, hypersensitivity pneumonitis, granulomatous hypersensitivity reactions, and the tuberculosis skin test (Table 3-3). Type IV reactions are also important in the control of mycobacterial and fungal infections. A key feature of type IV hypersensitivity is that the patient must be sensitized to the antigen before development of hypersensitivity on subsequent exposure. The tuberculin skin test relies on the principle of prior sensitization to assess for previous exposure to tuberculosis.
74
What is the most likely diagnosis?
Poliovirus, a picornavirus, can cause subclinical gastrointestinal infection, aseptic meningitis, or poliomyelitis. Poliomyelitis results in the classic flaccid paralysis (fasciculations, areflexia, and muscle wasting) secondary to destruction of the lower motor neurons in the anterior horn cells of the spinal cord. Similar symptoms may be seen in cauda equina syndrome, botulism, and Guillain-Barré syndrome.
75
What is the morphology of the Poliovirus?
Poliovirus is a single-stranded, positive-sense RNA virus with an icosahedral coat. Like other viruses that infect the gastrointestinal tract, it lacks an envelope.
76
How is the poliovirus transmitted?
Poliovirus is spread by the fecal-oral route. The virus can attach to and infect host cells in the pharynx and ileum. It can then disseminate hematogenously to lymphoid tissue during a primary “minor” viremia, which is typically asymptomatic. In a minority of patients, there is a secondary or “major” viremia that likely allows the virus to spread to the central nervous system (CNS). During the second viremia, patients experience mild symptoms and low-grade fever. Subsequent CNS disease typically occurs 11–17 days after exposure.
77
What treatments are available to prevent polio?
Two vaccines are available to prevent this condition. The Salk vaccine consists of formalin-killed virus and elicits an IgG response. This is the form used in the United States. The Sabin vaccine is a live attenuated virus. Its major disadvantage is that it may revert to its natural form on rare occasions, leading to illness. However, its major advantage is that the recipient sheds attenuated viruses, thereby vaccinating household contacts secondarily. The attempt to eradicate polio failed because of the fear among some populations that the vaccine had been designed by colonial powers to sterilize the African people. Since then, poliomyelitis has resurged in several African countries.
78
What is the most likely diagnosis?
Pseudomonas aeruginosa infection. P aeruginosa is a gram-negative, aerobic, oxidase-positive, rod- shaped bacterium with a single flagellum. As an opportunistic pathogen, it causes infection in patients with impaired defence mechanisms, especially immunocompromised individuals and burn victims. It commonly lives in water or wet environments and can be particularly problematic for patients on ventilators. It is a major cause of respiratory failure in patients with CF.
79
What other infections does Pseudomonas aeruginosa cause?
Community-acquired infections include otitis externa (“swimmer’s ear”), endocarditis (seen in intravenous drug users), osteomyelitis, and pneumonia. Nosocomial infections may present as bacteremia, leading to sepsis in burn victims and neonates. Ventilator-associated pneumonia and infections secondary to Foley catheter placement may also be due to P aeruginosa.
80
What is the pathology of chronic respiratory infection with Pseudomonas in patients with CF?
Pseudomonas can colonize the lungs of patients with CF. These patients cannot effectively clear the pathogen as the thickened mucous is not easily expectorated. The patient’s immune response causes a chronic inflammatory state that eventually results in progressive loss of pulmonary function.
81
What virulence factors contribute to acute infection with Pseudomonas?
Pseudomonas has a host of virulence factors that contribute to pathology in acute infection. These include pili and a flagellum for host invasion; lipopolysaccharide (endotoxin); exotoxins A, S, and U; elastase; and various cytotoxins.
82
What are the appropriate treatments for Pseudomonas aeruginosa?
Pseudomonas is frequently resistant to multiple-drug regimens, so therapy guided by antimicrobial susceptibility testing is essential. In addition to its intrinsic resistance to many antibiotics, it is able to acquire resistance rapidly during treatment. Potentially useful antibiotics include ceftazidime, cefepime, ciprofloxacin, aztreonam, imipenem, piperacillin-tazobactam, and the aminoglycosides. These drugs are usually employed in combinations of two drugs of different classes. Topical (eg, inhaled) as well as systemic antibiotic therapy are utilized in CF patients. Colistin is a drug of last resort for severe cases of multidrug- resistant Pseudomonas infection.
83
What condition is this boy at risk of contracting?
Rabies. If left untreated, rabies results in a nearly 100% mortality rate. Rabies causes only a few deaths per year in the United States but is significantly more dangerous in countries with unvaccinated domestic animals. For example, rabies-infected dog bites cause tens of thousands of deaths each year in India.
84
What is the morphology of the pathogen that causes Rabies?
Rabies is caused by a rhabdovirus, a single-stranded RNA virus enveloped by a bullet-shaped capsid, covered by glycoprotein “spikes.” The spikes bind to acetylcholine receptors, a property that may contribute to virulence.
85
What is the pathogenesis of Rabies?
Animals transfer the virus to humans through bites that inoculate the host. The virus remains local for a period of days to months, then binds to acetylcholine receptors on neurons and travels to the central nervous system (CNS), utilizing axonal retrograde transport mechanisms. In the CNS, the virus infects neurons, including Ammon horn cells of the hippocampus. Rabies carries a significant person-to-person transmission risk through bites or mucous membrane exposure.
86
What signs and symptoms are associated with Rabies?
Spasms of the pharyngeal muscles cause dysphagia, which leads to painful swallowing and accidental aspiration. This often leads to hydrophobia, a fear of water. Excess autonomic stimulation can cause hypersalivation. The buildup of saliva accounts for the apparent “foaming at the mouth.” As rabies multiplies in the CNS, nonfocal neurological symptoms result, including confusion, agitation, hallucinations, and sensitivity to bright light (photophobia). Focal neurological deficits include cranial nerve palsies. Encephalitis can give rise to seizures, and inflammatory edema eventually leads to coma, then death.
87
How is rabies diagnosed and treated?
Identifying cytoplasmic inclusions called Negri bodies in tissues obtained from brain biopsy, polymerase chain reaction for viral RNA, and serology are diagnostic. In the event of a bite by an infected animal, the human diploid cell vaccine (a live attenuated virus) is administered. Additionally, human rabies immune globulin (IgG) is used to confer passive immunity to the patient. Both treatments are effective only in the lag period between the bite and onset of symptoms. Once symptoms appear, there is no effective treatment.
88
What is the most likely diagnosis?
Ringworm (tinea pedis) infection. Although caused by the same group of fungi, each dermatophytosis is named after the region of the body that it infects: tinea cruris (perineum and creases of inner thigh; “jock itch”), tinea pedis (“athlete’s foot”), tinea capitis (scalp), tinea unguium (nails), and tinea corporis (body).
89
What three microorganisms are often responsible for this presentation?
Microsporum, Trichophyton, and Epidermophyton are three filamentous fungi that cause dermatophytosis.
90
How is Ringworm (tinea pedis) transmitted?
After contact with an infected host, the keratinized epithelium of warm, moist skin is colonized. The infection expands radially and is characterized by curvy (wormlike) circular borders. Thus, it is termed “ringworm,” despite the fact that the causative microorganism is actually a fungus.
91
What tests can help confirm the diagnosis of Ringworm (tinea pedis)?
Branched hyphae are observed on potassium hydroxide preparation (KOH mount). This fungus is not dimorphic. A sample from the lesions on the patient’s feet will likely demonstrate the organism.
92
What is the appropriate treatment for Ringworm (tinea pedis)?
Topical azoles (eg, fluconazole), butenafine, terbinafine, or griseofulvin is used for treatment.
93
What infections frequently cause a rash on the palms and soles?
Infections with:
1. Rickettsia rickettsii
2. Treponema pallidum
3. Coxsackievirus A can all cause a rash in this distribution.
94
What is the most likely infectious agent in this case?
This patient is most likely infected with R rickettsii. The clinical course is typical for Rocky Mountain spotted fever, which is characterized by fever with abrupt onset and a rash that spreads from the extremities toward the trunk. Palpable purpura is a poor prognostic sign, as it indicates active vasculitis and leakage of blood into the skin. The rash in syphilis and coxsackievirus is typically more gradual in onset. However, syphilis should never be excluded because of the patient’s age, as it is occasionally seen in sexually abused children.
95
How is R rickettsii transmitted to humans?
R rickettsii is acquired from Dermacentor tick bites.
96
What other diseases are caused by Rickettsia organisms?
Endemic typhus (also known as murine typhus) is caused by R typhi. This illness presents with vasculitis leading to headache, fever, chills, and myalgia. Epidemic typhus is caused by R prowazekii and often presents with high fevers, hypotension, and delirium. It often occurs in conditions of crowding and after disasters (eg, refugee camps). Both diseases are caused by arthropod-borne agents: endemic typhus is transmitted by fleas, whereas epidemic typhus is transmitted by the human body louse.
97
What laboratory technique can be used to identify the cause of this patient’s illness - Rickettsia rickettsii?
Diagnosis is made clinically. Direct fluorescent antibody or polymerase chain reaction testing of a skin biopsy of one of the petechial lesions will confirm the diagnosis, but not early enough to guide therapy. Rocky Mountain spotted fever antibody testing can also be used to confirm the diagnosis after recovery.
98
What is the appropriate treatment for choice for organisms of the Rickettsia class?
Tetracyclines are most frequently used in rickettsial infections. The rickettsiae are obligate intracellular organisms, as they require coenzyme A and nicotinamide adenine dinucleotide from the host cell; they also lack the peptidoglycan cell wall targeted by many antibiotic classes. Tetracyclines can enter cells and act on ribosomal targets.
99
What is the most likely diagnosis?
Rotavirus infection is the most common infectious cause of diarrhea in infants and young children and a major cause of acute diarrhea in the United States during the winter. It is also the most common cause of gastroenteritis in infants globally.
100
What is the pathogenesis of Rotavirus?
Rotavirus is transmitted via the fecal-oral route and infects villus cells of the proximal small intestine. The virus replicates intracellularly and eventually causes lysis in host cell. Cell destruction results in a significant decrease in intestinal surface area and consequently absorption from the intestinal lumen, thus causing watery diarrhea. Rotavirus does not cause inflammation and the stool is nonbloody.
101
What is the appropriate treatment for Rotavirus?
Treatment is supportive through rehydration. Suspected rotavirus can be confirmed by enzyme-linked immunosorbent assay of a stool specimen. In practice, this is generally reserved for epidemiological investigations. Stool ova and parasite examinations and bacterial cultures are sometimes obtained to exclude more serious causes of diarrhea that might require antibiotic treatment.
102
In what age group is Rotavirus usually seen?
Infection is not commonly seen before 6 months of age, as children have passive immunity from IgA from the mother’s breast milk. By 3 years of age, most children worldwide have developed lifelong immunity from prior infection. Therefore, it is most common between these two ages.
103
What is the most likely diagnosis? What other species are intermediate hosts of this pathogen?
The patient likely acquired schistosomiasis, caused by a type of trematode (fluke), from contact with contaminated water. The three main flukes are Schistosoma japonicum (in East Asia), S mansoni (in South America and Africa), and S haematobium (in Africa).
Snails are the intermediate host for all trematodes. Reservoirs include primates (S mansoni and S haematobium) and domesticated animals (S japonicum).
104
In which human organs are the schistosomiasis organisms found?
S japonicum and S mansoni reside in the intestines, where organisms mate in the mesenteric veins and release eggs into the feces as well as the portal circulation. S haematobium resides in the bladder, where organisms mate in the vesicular (bladder) veins and release eggs into the urine.
105
How is schistosomiasis diagnosed?
Examination of the urine (S haematobium) and stool (all three species) reveals eggs.
106
What are the chronic manifestations of schistosomiasis?
After the initial “swimmer’s itch,” which is a dermatitis that occurs as the organism initially penetrates the skin; there is a lag period of 4–8 weeks. Katayama fever occurs as the adult organisms lay eggs. The eggs trigger a granulomatous immune response, fibrosis, and inflammation. For example, eggs that pass into the portal system become foci for granulomatous inflammation of the liver, eventually leading to fibrosis. Complications include portal hypertension (S japonicum and S mansoni), pulmonary artery hypertension, chronic abdominal pain, and central nervous system injury. S haematobium can increase the risk for developing squamous cell bladder cancer.
107
What is the appropriate treatment for schistosomiasis?
Praziquantel is the treatment of choice.
108
What is the most likely causative organism?
Enterohemorrhagic Escherichia coli (EHEC) serotype O157:H7. Infection with this organism most commonly occurs through consumption of undercooked meat or contaminated vegetables.
109
What is the mechanism of action of Shiga toxin and Shiga-like toxin?
These toxins are similar. One is produced by Shigella and the other by E coli O157:H7. They bind to host ribosomes and cleave a particular glycosidic bond, which inhibits ribosome function. The reduction in cellular translation triggers events that lead to apoptosis.
110
What is the cause of the blood in the patient’s urine?
The patient has developed hemolytic-uremic syndrome. This is a complication of infection with Shigella and EHEC in which the toxin damages the renal vascular endothelium, compromising vascular integrity. Several schistocytes are apparent on the PBS and the kidney biopsy shows a fibrin thrombus (Figure 3-35B).
111
What is the classic triad of findings associated with hemolytic-uremic syndrome?
In hemolytic-uremic syndrome the triad of findings is renal damage, hemolytic anemia, and thrombocytopenia.
112
What other conditions could feature a similar Peripheral blood smear to Enterohemorrhagic Escherichia coli (EHEC)?
The PBS shows schistocytes (Figure 3-35A). When RBCs are forced past a partial microvascular obstruction, they become damaged and assume the characteristic schistocyte shape. Other conditions in which schistocytosis may be seen are thrombotic thrombocytopenic purpura (TTP) and disseminated intravascular coagulation (DIC). In TTP, an autoantibody destroys ADAMST13, an enzyme responsible for cleaving large multimers of von Willebrand factor (vWF), which is more prone to cause coagulation of blood. By contrast, DIC is caused by an overabundance of tissue factor in the blood, triggering the coagulation cascade. Increased levels of tissue factor may be seen in severe trauma, cancers, or sepsis. DIC has a mortality rate of up to 55%.
113
What serum markers should be measured to follow the progression or recovery of this patient?
The platelet count is a useful marker for this syndrome. In addition, the blood urea nitrogen and creatinine levels should be measured to follow renal recovery. The hemoglobin and hematocrit should be followed to assess the need for transfusion.
114
Which nerve relays the painful sensation in this patient? What infectious agent may be responsible for this woman’s pain?
Sensory information from the face is relayed by the trigeminal nerve to the ventral posterolateral nucleus of the thalamus. Specifically, the area described by the patient is the left V1 dermatome.
This woman is suffering from herpes zoster, or “shingles,” a late complication of prior infection with varicella zoster virus, one of the herpesviruses.
115
What are the characteristic distribution patterns of shingles?
The virus remains latent in the ganglia of sensory nerves after the primary infection. When reactivation occurs, virions are transported to the dermatome innervated by this sensory nerve using axonal transport mechanisms. Therefore, the characteristic shingles rash is always confined to a dermatome and does not cross the midline.
116
What are the likely findings on histologic examination of vesicles found in shingles?
A Tzanck smear may demonstrate multinucleate giant cells, which are typical for infection with varicella and herpes simplex viruses. This test is rarely used for diagnosis, having been superseded by more specific molecular tests such as polymerase chain reaction.
117
What are the appropriate treatments for shingles?
Acyclovir is activated by viral thymidine kinase to inhibit viral DNA polymerase. Valacyclovir and famciclovir have a similar mechanism and longer half-lives. These drugs target herpesviruses and may provide relief, speed recovery, and prevent postherpetic neuralgia. The drug doses for varicella are substantially higher than for herpes simplex virus. Primary infection with varicella and zoster can be prevented by vaccination. A zoster vaccine is available for the elderly population; however, its use remains controversial.
118
What are the advantages of a live attenuated vaccine?
Three general types of vaccinations are available: live attenuated, killed, or passive. Passive vaccination is the transfer of antibodies and is limited by antibody half-life in the bloodstream. A killed vaccine can stimulate only a humoral response as the virus cannot replicate within cells; therefore, no viral proteins can be displayed on major histocompatibility complex receptors. Live attenuated virus vaccine stimulates both arms of the immune system (humoral and cell mediated) as it leads to limited viral replication. Live attenuated vaccines should be avoided in pregnancy as only the humoral arm of the mother’s immune system can protect the fetus across the placental barrier.
119
What is the most likely diagnosis?
Strongyloidiasis, caused by Strongyloides stercoralis, a nematode (roundworm).
120
What is the life cycle of the Strongyloides stercoralis parasite?
Larvae in the soil penetrate the skin, usually the sole of the foot (fecal-cutaneous transmission). Local itching at the entry site promotes scratching, which aids larval entry into the bloodstream. Once in the blood, the larvae settle in the respiratory tree and travel up the trachea into the pharynx to be swallowed. They enter the small intestine, where the larvae mature into adults. Female adults invade the intestinal wall and lay eggs. During passage through the gastrointestinal tract, the eggs hatch into larvae. Most of these larvae pass with the stool and can continue the life cycle in the soil; some, however, directly penetrate the colonic wall or perianal skin and, uniquely, continue the life cycle within the original host. These continually migrating parasites are responsible for the eosinophilia commonly seen in chronic Strongyloides infections.
121
What other two organisms demonstrate the same route of transmission in humans as Strongyloides stercoralis?
Necator americanus (New World hookworm), and Ancylostoma duodenale (Old World hookworm).
122
What is the pathogenesis of hyperinfection syndrome?
Hyperinfection syndrome, caused by uncontrolled autoinfection, can increase parasitic burden and widely disseminated disease. This is more common in individuals with defective eosinophil function, such as patients treated with steroids or cytotoxic chemotherapeutic agents that cause granulocytopenia.
123
What tests can help confirm the diagnosis of Strongyloidiasis?
Stool sample reveals larvae (not eggs as in hookworm infection). Blood samples reveal eosinophilia. Strongyloides antibody testing can also be valuable in patients with unexplained eosinophilia, as larvae are not always detectable in the stool.
124
What are the appropriate treatments for Strongyloidiasis?
Ivermectin or thiabendazole.
125
What is the most likely diagnosis?
Blastomycosis, one of the systemic mycoses.
126
To what areas are the systemic mycoses endemic?
Three forms of systemic mycoses are endemic to the United States. Coccidioidomycosis (also called desert bumps, San Joaquin Valley bumps, or valley fever) is specific to the southwestern United States. Histoplasmosis is endemic to the Mississippi and Ohio River Valleys and is found in bird and bat droppings. Blastomycosis is found east of the Mississippi River (and in Central America). Paracoccidioidomycosis is found in rural Latin America.
127
Which diagnostic tests can differentiate between the mycoses?
Systemic mycoses are caused by dimorphic fungi, which grow as molds in the cold (eg, in the soil) and as yeast at higher temperatures (eg, in tissues at 37°C [98.6°F]). The exception is coccidioidomycosis, which is a spherule in tissue. Therefore, growing cultures on Sabouraud’s agar at multiple temperatures aids in the diagnosis. In addition, a tissue biopsy revealing broad-based budding yeast is diagnostic for blastomycosis. Tissue biopsy demonstrating yeast cells within macrophages is diagnostic of histoplasmosis. A biopsy showing “captain’s wheel” morphology of budding yeast is diagnostic of paracoccidioidomycosis. Serologic testing for antifungal antibodies is also useful in some patients, and a histoplasma antigen test is the diagnostic test of choice for systemic (but not localized) Histoplasma infections.
128
What are the typical x-ray findings of systemic mycoses?
These diseases can mimic tuberculosis, forming granulomas, which appear as small calcium deposits on x-ray.
129
What is the appropriate treatment for systemic mycoses?
Systemic infection is treated with itraconazole or amphotericin B.
130
What is the most likely diagnosis?
Toxic shock syndrome (TSS).
131
What microorganism is the most likely cause of this condition?
Staphylococcus aureus is the most common cause, although β-hemolytic group A streptococci can cause a similar presentation. The most common nidi of infection are high-absorbency tampons worn for a prolonged period of time and cutaneous wounds.
132
What are the distinguishing characteristics of the Staphylococcus aureus microorganism?
S aureus is a gram-positive coccus. It is catalase-positive and coagulase-positive and may produce an enterotoxin. Figure 3-37 provides a useful laboratory algorithm for differentiating the gram-positive bacteria.
133
What is the pathophysiology of Toxic Shock Syndrome?
The exotoxin (TSST-1) acts as a “superantigen” and is responsible for this presentation. Superantigens activate large numbers of T cells at once by simultaneously binding directly to T-cell receptors and major histocompatibility complex (MHC) molecules, regardless of the peptide presented by MHC. Activated T cells then release large amounts of inflammatory cytokines, which are responsible for the manifestations of TSS.
134
What other conditions should be considered in the differential diagnosis of Toxic Shock Syndrome?
The differential for desquamating disease is limited. Toxic epidermal necrolysis should be suspected; this is an exacerbation of Stevens-Johnson syndrome that may be a serious adverse reaction to certain medication. Additionally, scalded skin syndrome leads to desquamation of the skin. In this condition, an infection with S aureus producing exotoxin A and B causes detachment of the epidermal layer from the dermis. Lastly, pemphigus vulgaris features autoantibodies against desmosomes, leading to flaccid blister formation that may look like desquamation in severe cases.
135
What is the appropriate treatment for Toxic Shock Syndrome?
Removal of the infected wound dressing or tampon is the first step, followed by supportive care. Antibiotics that cover both Staphylococcus and Streptococcus will kill these bacteria and stop the production of additional exotoxin. However, it is the toxin, not the bacteria, that is responsible for the symptoms. In severe cases, intravenous immunoglobulin is also given.
136
What is the most likely cause of this patient’s seizure? How did this patient likely become infected with this microorganism?
Toxoplasma gondii infection.
It is likely that this man (like most individuals) has been latently infected with this protozoan for many years. However, his immunocompromised status has resulted in disease reactivation. Humans are most often infected by ingestion of cysts in undercooked meat or by fecal-oral transmission of cat feces. Cats may shed the protozoan and pregnant women are discouraged from cleaning the litter box as inhaled aerosolized particles are sufficient to cause infection.
137
Why is Toxoplasma gondii infection dangerous in pregnancy?
Primary infection with T gondii in a pregnant woman can allow parasites to cross the placenta. This leads to congenital problems in the newborn, including mental retardation, microcephaly, chorioretinitis, intracerebral calcifications, and blindness. It is one of the ToRCHeS infections (Toxoplasmosis, other infections, Rubella, Cytomegalovirus, Herpes simplex virus, Syphilis).
138
Given this patient’s ring-enhancing lesions on CT scan, what other conditions should be included in the differential diagnosis?
This patient is also at an increased risk of lymphoma, cryptococcosis, and tuberculosis, all of which appear as ring-enhancing lesions on CT scan (although less likely to cause multiple lesions) and can also cause seizures.
139
What is the appropriate treatment for Toxoplasma gondii infection?
First-line treatment is a regimen of pyrimethamine and sulfadiazine.
140
What caused the transplanted organ to fail?
Hyperacute rejection occurs within minutes of the transplantation. Rejection is due to preformed antibodies that recognize graft antigens. The patient’s serum must be tested for antibodies that bind to a biopsy of the graft tissue before transplantation. There are three types of graft rejection (Table 3-4).
141
What would histology show in a kidney that had undergone Hyperacute transplant rejection?
The kidney would show fibrinoid necrosis of the small vessels and thromboses.
142
What would histology show in a kidney that had undergone acute or chronic transplant rejection?
Acute rejection is primarily cell mediated, although antibodies can also cause damage to graft tissue. A biopsy reveals T-cell and macrophage infiltrates as well as blood vessel and parenchymal damage. Chronic rejection is characterized by vascular damage. Damage to graft blood vessels can be due to antibody binding, complement activation, T-cell activation, and cytokines. The result is intimal proliferation, causing narrowing of the vessel lumen and tissue ischemia. Examination of the graft shows a small, scarred kidney.
143
Patients who undergo bone marrow or hematopoietic cell transplantation are at risk of another potential complication, graft-versus-host disease (GVHD). What is the mechanism of GVHD?
During bone marrow transplantation, the donor’s immune system is essentially introduced into the host’s body. As donor-derived T cells have not become immunotolerant toward host antigens, GVHD can occur when grafted T cells bind to host antigen and become activated, damaging host tissue. The most frequent sites of injury are the skin, liver, and gastrointestinal tract. By contrast, GVHD can be exploited in the treatment of certain haematological malignancies. For example, the host’s immune system is tolerant toward the malignant plasma cells in multiple myeloma. Allogenic bone marrow transplantation may cause an immune reaction against the cancerous cells.
144
What is the most likely diagnosis?
Yellow fever is endemic in South America and parts of Africa. It is characterized by an initial febrile illness, during which time serum aspartate aminotransferase and alanine aminotransferase levels begin to rise, followed by a remission of symptoms. Approximately 15% of infected patients experience a return of symptoms 2–3 days later, developing further liver dysfunction (resulting in jaundice and coagulopathy), renal damage, and myocardial damage.
145
What type of virus is responsible for yellow fever?
The yellow fever virus is a flavivirus. These viruses have positive, single-stranded RNA genomes and icosahedral, enveloped capsids.
146
What are the most likely liver biopsy findings in yellow fever?
The characteristic finding on liver biopsy is midzone hepatocellular death, with sparing of cells bordering the central vein and portal tracts. Councilman bodies are found in the affected hepatocytes. These are eosinophilic inclusions that represent condensed chromatin. Typically, there is no inflammatory response. Liver biopsies are usually not done because of their concomitant coagulopathy.
147
Enzyme-linked immunosorbent assay (ELISA) may be useful in confirming the diagnosis of yellow fever by detecting antibody to the virus. How does ELISA work?
ELISA is a technique often used for serologic testing. It involves coating the surface with the desired antigen (in this case, yellow fever viral particles) and then placing the patient’s serum on the surface, followed by a secondary antibody (antihuman antibody) that is linked to an enzyme. If the patient’s serum has antibody to the antigen, the secondary antibody will bind. The linked enzyme can be detected by a reaction that produces an alteration in color with a colorimetric agent (eg, horseradish peroxidise). The color change can be quantified by spectroscopy. Detection of antibody to yellow fever virus in a patient with exposure can support a clinical diagnosis of the disease.
148
What is the most likely diagnosis?
This patient’s symptoms and x-ray of the chest suggest primary tuberculosis (TB). Associated findings include a positive purified protein derivative (PPD) test, positive culture, and/or positive acid-fast staining of bacteria from sputum samples. Primary TB is often seen in the lower lobes of the lung with enlargement of the associated lymph node, whereas reactivation TB tends to cause cavitation in the apices.
149
What type of lesion does the x-ray show?
Primary lesions are usually found in the lower lobes as Ghon foci. If there is lymph node involvement, the lesions are termed Ghon complexes (see arrow in Figure 3-38). Reactivation (secondary) TB lesions are usually seen in the apical and posterior portions of the upper lobes.
150
How is the microorganism that causes TB cultured and stained?
Mycobacterium tuberculosis is cultured on Lowenstein-Jensen agar. It is an acid-fast bacterium and therefore stains with Ziehl-Neelsen stain.
151
What is the appropriate treatment for TB?
The standard treatment lasts for 6 months. Rifampin, Isoniazid, Pyrazinamide, and Ethambutol (RIPE) are used for the initial phase of therapy (usually 2 months), followed by rifampin and isoniazid for an additional 4 months. Susceptibility testing is necessary to guide the choice of agents. More drugs may need to be used in multidrug-resistant TB. Because emergent drug resistance is often due to medication nonadherence, the United States has installed “observed therapy” programs in which TB patients take their medication in the presence of a healthcare provider. Prophylactic treatment is with isoniazid.
152
What are the main side effects of treatment for TB?
Rifampin colors urine, feces, sweat, and tears a reddish-orange color. It also upregulates the cytochrome P450 isoenzyme system, increasing the metabolism of many drugs, including oral contraceptives. If the patient stays on her current dose of birth control pills and remains sexually active, she is more likely to become pregnant while taking rifampin. Isoniazid causes peripheral neuropathies; vitamin B6 reduces this adverse event. Rifampin, isoniazid, and pyrazinamide are associated with liver toxicity. Ethambutol can cause retrobulbar optic neuritis, which impairs visual acuity and color vision; patients should receive frequent ophthalmologic examinations during the treatment period.
