Case 1: Sudden fever, headache
A 24-year-old woman develops sudden onset of fever, severe headache, myalgias, arthralgias, and nausea that become debilitating within several hours. Ten days ago, she returned from Puerto Rico, where she stayed at a first-class resort, swam only in the ocean or the hotel pool, ate only at the hotel restaurant, and had no sexual contacts. Medical history is unremarkable. One other person in her group of five traveling companions has similar, but less severe, symptoms that began one day ago.
On physical examination, the patient is awake and alert but is very uncomfortable because of the headache. Temperature is 39.3°C (102.7°F), pulse rate is 118 beats/min, respiration rate is 18 breaths/min, and blood pressure is 112/68 mm Hg. The skin is clear, and optic fundi are normal. Flexion of the neck induces slight to moderate pain without nuchal rigidity.
Cardiopulmonary examination is normal except for tachycardia. Abdominal examination discloses reduced bowel sounds and slight tenderness to palpation in all quadrants. Palpation of the arm and leg muscles induces mild tenderness. There is no peripheral edema. Cranial nerves are intact. Sensation and muscle strength are normal. All reflexes are slightly hyperactive symmetrically.
Laboratory studies show the following: hemoglobin level, 12.9 g/dL (129 g/L); hematocrit, 38%; leukocyte count, 2,100 cells/µL (2.1 × 109 cells/L); platelet count, 124,000 cells/µL (124 × 109 cells/L); blood urea nitrogen, 16 mg/dL (5.71 mmol/L); serum creatinine concentration, 0.8 mg/dL (70.74 µmol/L); serum sodium, 122 mEq/L (122 mmol/L); serum potassium, 3.9 mEq/L (3.9 mmol/L); serum chloride, 101 mEq/L (101 mmol/L); serum bicarbonate, 24 mEq/L (24 mmol/L); serum aspartate aminotransferase, 210 U/L; serum alanine aminotransferase, 360 U/L; serum amylase, 38 U/L; and serum lipase, 44 U/L.
Lumbar puncture is performed; examination of cerebrospinal fluid shows the following: leukocyte count, 22 cells/µL (22 × 106 cells/L) (all lymphocytes); erythrocyte count, 2 cells/µL (2 × 106 cells/L); protein, 37 mg/dL (370 mg/L); and glucose, 74 mg/dL (4.11 mmol/L).
Radiographs of the chest and abdomen are normal.
Which of the following is the most likely diagnosis?
A. Dengue fever
B. Dengue hemorrhagic fever
C. Herpes virus encephalitis
Case 2: Rash, fever after safari
A 34-year-old man is evaluated because of fever, mild headache, and malaise that began while on a flight to the U.S. from South Africa. One day later, he developed a slight rash and swelling in the right axilla. The patient had been on a hunting safari. His group lived in tents and often walked through fields with low scrub. He had taken appropriate antimalarial prophylaxis and did not skin the animals or dress the meat. Medical history is unremarkable.
On physical examination, temperature is 38°C (100.4°F), pulse rate is 82 beats/min, respiration rate is 16 breaths/min, and blood pressure is 132/88 mm Hg. There is a firm swelling in the right axilla without fluctuance or erythema. No edema is noted. Approximately 15 to 20 small pruritic vesicles on erythematous bases are seen on the anterior chest and upper arms, and one vesicle appears on the left cheek. A 1-cm red-brown eschar is present over the right lateral clavicle. Neurologic examination is normal.
Laboratory studies show the following: hemoglobin, 14.9 g/dL (149 g/L); hematocrit, 44%; leukocyte count, 6,500 cells/µL (6.5 × 109 cells/L); and platelet count, 270,000 cells/µL (270 × 109 cells/L). Blood urea nitrogen, serum creatinine, serum electrolytes, liver chemistry studies and urinalysis are all normal.
Which of the following is the most likely diagnosis?
A. Herpes zoster virus
B. Dengue fever
C. African tick-bite fever
D. Cutaneous leishmaniasis
Case 3: Illness after trip to India
A 63-year-old woman is evaluated because of increasing nausea, malaise, and decreased appetite. The patient has just returned from her second trip to rural areas of southern India, and her symptoms developed two days before returning to the U.S. She developed Plasmodium falciparum malaria following her first trip to India, when she had not taken antimalarial prophylaxis. She took mefloquine for this current trip. None of her traveling companions have become ill.
On physical examination, she is awake and oriented but is in moderate distress because of nausea and malaise. Temperature is 38°C (100.4°F), pulse rate is 116 beats/min and regular, respiration rate is 28 breaths/min, and blood pressure is 98/60 mm Hg. Crackles are heard at the pulmonary bases bilaterally, and a grade 2/6 systolic murmur is auscultated.
The abdomen is obese with decreased bowel sounds and moderate tenderness in the right upper quadrant. The liver is palpated 4 cm below the right costal margin and is very tender. There are no other masses or organomegaly. The extremities and neurologic examination are normal.
Laboratory studies show the following: hemoglobin, 10.9 g/dL (109 g/L); hematocrit, 31%; leukocyte count, 6,100 cells/µL (6.1 × 109 cells/L); platelet count, 98,000 cells/µL (98 × 109 cells/L); blood urea nitrogen, 24 mg/dL (8.57 mmol/L); serum creatinine, 1.9 mg/dL (168 µmol/L); serum electrolytes, normal; serum aspartate aminotransferase, 6,200 U/L; serum alanine aminotransferase, 8,500 U/L; serum alkaline phosphatase, 720 U/L; and serum total bilirubin, 6.9 mg/dL (117.99 µmol/L).
Plain radiographs of the abdomen are normal. The patient is hospitalized for rehydration. She becomes increasingly icteric, her condition deteriorates rapidly, and she develops multi-system organ failure.
Which of the following prophylactic measures may have prevented this patient's illness if given before her current trip?
A. Malarial prophylaxis with a drug other than mefloquine
B. Hepatitis A immunization
C. Hepatitis B immunization
D. Typhoid immunization
Case 4: Symptoms after Mexico stay
A 27-year-old man has a three-week history of fever, headache, malaise, decreased appetite, a dry cough, and a 1.3-kg (3-lb) weight loss. His symptoms began one week after a one-month trip to help construct homes in rural Mexico. Seven or eight members of the construction group have developed similar symptoms. The patient's medical history is unremarkable.
On physical examination, temperature is 37.4°C (99.3°F), pulse rate is 74 beats/min, respiration rate is 20 breaths/min, and blood pressure is 142/88 mm Hg. The head, eyes, ears, nose, and throat are normal. Diffuse crackles are heard throughout all lung fields. Cardiac, abdominal, and neurologic examinations are normal. The extremities are normal.
Laboratory studies show the following: hemoglobin, 14.5 g/dL (145 g/L); hematocrit, 44%; leukocyte count, 9,200 cells/µL (9.2 × 109 cells/L); platelet count, 325,000 cells/µL (325 × 109 cells/L); blood urea nitrogen, 18 mg/dL (6.43 mmol/L); serum creatinine, 1.0 mg/dL (88.42 µmol/L); serum electrolytes, normal; serum aspartate aminotransferase, 71 U/L; serum alanine aminotransferase, 95 U/L; serum total bilirubin, 0.9 mg/dL (15.39 µmol/L); and urinalysis, normal.
A chest radiograph shows diffuse reticulonodular infiltrates throughout both lung fields with enlarged mediastinal lymph nodes. CT-guided lung biopsy samples demonstrate early granulomatous inflammation; stains for bacteria, mycobacteria, and fungi are negative.
Which of the following pathogens is most likely causing this patient's findings?
A. Mycobacterium tuberculosis
B. Aspergillus fumigatus
C. Staphylococcus aureus
D. Histoplasma capsulatum
Case 5: Persistent headache, nausea
A 26-year-old man comes to the emergency department because of a five-day history of headache, stiff neck, fatigue, nausea, vomiting, myalgias, and generalized weakness. He has just returned from a vacation in Jamaica, where he spent most of each day on the beach and much of each evening socializing in bars. He did not have any sexual contact on the trip. Medical history is unremarkable.
On physical examination, temperature is 38°C (100.4°F), pulse rate is 78 beats/min, respiration rate is 18 breaths/min, and blood pressure is 118/72 mm Hg. There is marked pain on flexion of the neck and moderate nuchal rigidity. Cardiopulmonary and abdominal examinations are normal. The extremities are also normal. There is moderate photophobia. The cranial nerves are intact. Motor strength appears to be unimpaired symmetrically, but the patient develops muscle pain during strenuous activity. Reflexes are symmetric and slightly hyperactive.
Laboratory studies show the following: hemoglobin, 15.1 g/dL (151 g/L); hematocrit, 47%; leukocyte count, 9,800 cells/µL (9.8 × 109 cells/L) with 72% neutrophils, 11% lymphocytes, 13% eosinophils, and 4% monocytes; platelet count, 288,000 cells/µL (288 × 109 cells/L); blood urea nitrogen, 14 mg/dL (5 mmol/L); and serum creatinine, 0.8 mg/dL (70.74 µmol/L). Serum electrolytes and liver chemistry studies are normal.
Lumbar puncture is performed. Opening pressure is 240 mm H2O. Cerebrospinal fluid leukocyte count is 290 cells/µL (290 × 106 cells/L) with 70% lymphocytes, 21% eosinophils, and 9% monocytes.
Which of the following pathogens is most likely causing this patient's current findings?
A. Angiostrongylus cantonensis
B. Trichinella spiralis
C. Strongyloides stercoralis
D. Entamoeba histolytica
E. Treponema pallidum
Case 6: Diarrhea for three weeks
A previously healthy 28-year-old man has a three-week history of diarrhea, intermittent nausea, mild abdominal pain, and a 2.2-kg (5-lb) weight loss. He has 5 to 10 small to moderate-sized watery bowel movements daily. Symptoms began one week after returning from a 10-day nature tour to rural Guatemala. One of the 15 other tour members has developed less severe diarrhea.
On physical examination, temperature is 37°C (98.6°F), pulse rate is 78 beats/min, respiration rate is 16 breaths/min, and blood pressure is 128/72 mm Hg. Abdominal examination discloses increased bowel sounds and slight tenderness to palpation throughout the abdomen. The liver edge is palpated just below the right costal margin on deep inspiration. The remainder of the examination, including a rectal examination, is normal. A stool sample is negative for occult blood.
Laboratory studies show the following: hemoglobin, 15.3 g/dL (153 g/L); hematocrit, 48%; leukocyte count, 6,900 cells/µL (6.9 × 109 cells/L); platelet count, 255,000 cells/µL (225 × 109 cells/L); blood urea nitrogen, 13 mg/dL (4.64 mmol/L); serum creatinine, 0.7 mg/dL (61.89 µmol/L); serum sodium, 136 mEq/L (136 mmol/L); serum potassium, 3.8 mEq/L (3.8 mmol/L); serum chloride, 104 mEq/L (104 mmol/L); serum bicarbonate, 28 mEq/L (28 mmol/L); serum amylase, 78 U/L; and serum lipase, 66 U/L.
Liver chemistry studies and urinalysis are normal. Microscopic examination of a stool specimen shows no leukocytes. An acid-fast stain of a fixed dried stool specimen is positive. Results of stool cultures for bacteria are pending.
Which of the following pathogens is most likely causing this patient's current findings?
A. Entamoeba histolytica
B. Salmonella typhi
C. Cyclospora cayetanensis
D. Campylobacter intestinalis
E. Mycobacterium kansasii
Answers and commentary
Correct answer: A. Dengue fever.
The epidemiology and clinical presentation (fever, myalgias, arthralgias, severe headache, leukopenia, and thrombocytopenia) are classic for dengue fever, which is spread by mosquitoes in endemic areas in the Caribbean and Central and South America. The diagnosis cannot be confirmed early in the course of illness, when other more serious diseases need to be ruled out. The usual diagnostic method is finding a rise in dengue virus antibodies in convalescent sera, although viral culture or polymerase chain reaction is available in some institutions. Treatment is supportive.
Dengue hemorrhagic fever is incorrect because the patient has no signs or symptoms of hemorrhage or capillary fragility, such as a petechial rash, pleural effusion, or peripheral edema. Although herpes virus encephalitis should be included in the differential diagnosis, the patient has no findings suggestive of temporal lobe or other parenchymal central nervous system lesions. The patient has not traveled to areas endemic for babesiosis, and her findings are much too abrupt and severe for a diagnosis of this infection.
- Dengue fever is characterized by the abrupt onset of severe headache, high fever, myalgias, arthralgias, leukopenia, and thrombocytopenia.
- Dengue hemorrhagic fever is associated with hemorrhage and capillary fragility.
Correct answer: C. African tick-bite fever.
The patient has characteristic features of African tick-bite fever, which is probably the most common rickettsial infection in humans. He has just returned from a highly endemic area, and his signs and symptoms developed within the known incubation period for the disease. The relatively mild symptoms and vesicular rash with one or two inoculation eschars (presumed to be in the area of the original tick bite) are also characteristic. A definitive diagnosis is made by serologic studies or, if available, by polymerase chain reaction. Without treatment, the disease is self-limited.
The patient's mild symptoms, speed of onset of infection, presence of a rash, and normal laboratory findings preclude dengue fever. Leishmaniasis does not occur in South Africa, and the clinical presentation of cutaneous leishmaniasis is typically that of slowly progressing cutaneous ulcers rather than vesicles.
- African tick-bite fever is the most common rickettsial infection in humans.
- Symptoms of African tick-bite fever are relatively mild and are characterized by a vesicular rash with an inoculation eschar.
Correct answer: B. Hepatitis A immunization.
This patient's presentation is most typical of fulminant hepatitis A or hepatitis E and could be either infection. A highly effective vaccine is available for hepatitis A, which must be administered at least two weeks before a potential exposure. If this is not possible, standard pooled gamma globulin provides effective prophylaxis. There is no vaccine for hepatitis E, and gamma globulin is not protective against this virus.
The patient's findings are not consistent with malaria. In addition, mefloquine is very unlikely to cause significant hepatotoxicity, so giving a different antimalarial agent would not have prevented her illness. Although an effective vaccine is available for hepatitis B, patients with this infection tend to be asymptomatic and have a more chronic course. Typhoid fever is typically associated with mild hepatic findings and would also not have a fulminant course.
- A highly effective vaccine is available for hepatitis A, which must be administered at least two weeks before a potential exposure.
Correct answer: D. Histoplasma capsulatum.
This patient's epidemiologic data, clinical presentation, and laboratory findings are most consistent with histoplasmosis from exposure to a high inoculum. This type of histoplasmosis has occurred in the midwestern United States for some time, and similar point-source epidemics have been identified more recently in Central America. The construction sites that the patient and his colleagues worked on presumably contained areas where bird or bat droppings promoted the growth of Histoplasma capsulatum in the soil.
Although Mycobacterium tuberculosis can cause miliary disease, it is unlikely that multiple persons would become infected at the same time. Aspergillus fumigatus is unlikely to cause these findings in an immunocompetent person. Staphylococcus aureus would have caused a much more acute and severe disease, especially when the pulmonary disease is this extensive.
- Deep fungal infections such as histoplasmosis are a risk to travelers to endemic areas.
Correct answer: A. Angiostrongylus cantonensis.
The patient is most likely infected with Angiostrongylus cantonensis (the rat lungworm), which is the most common cause of eosinophilic meningitis. It is endemic in many tropical areas throughout the world and can infect humans when poorly cooked or uncooked intermediate hosts such as snails are ingested or vegetables contaminated with the larvae are consumed. The meningitis is self-limited, and the diagnosis is established by serologic studies demonstrating antibodies to the parasite.
Trichinella spiralis is an etiologic agent of encephalitis but would not be expected to cause meningitis. Strongyloides stercoralis also does not cause meningitis. Although some ameba are rare causes of meningitis, Entamoeba histolytica is not known to be associated with this infection. Treponema pallidum may cause meningoencephalitis, but this infection is associated with a more severe clinical presentation than that manifested by the patient. In addition, syphilis is not associated with eosinophilic meningitis.
- Angiostrongylus cantonensis (the rat lungworm) is the most common cause of eosinophilic meningitis worldwide.
Correct answer: C. Cyclospora cayetanensis.
This patient has Cyclospora infection based on the geographic site of acquisition, the clinical syndrome (copious diarrhea without fever), and a positive acid-fast smear of stool. Although cyclosporiasis is usually self-limited in immunocompetent patients, it may cause debilitating symptoms, significant weight loss, and an extended period of diarrhea. The treatment of choice is trimethoprim–sulfamethoxazole.
Entamoeba histolytica infection is an uncommon but well-recognized disease of travelers. Patients with E. histolytica infection generally appear more ill than the patient described here and have fever, small-volume diarrhea, blood in the stool, and negative acid-fast–stained specimens. Salmonella typhi causes typhoid fever, which occurs in many developing countries. However, patients with early typhoid infection have fever, which this patient does not have. Patients may also have diarrhea, but this is usually not copious. In addition, acid-fast–stained stool specimens are negative.
Campylobacter infections commonly cause fever and are more invasive than infections due to Cyclospora (as manifested by the presence of fecal leukocytes in Campylobacter infections). Acid-fast–stained stool specimens are also negative. Although acid-fast stains for Mycobacterium kansasii are positive, this infection does not cause diarrhea and is not a disease of travelers.
- Cyclosporiasis is associated with positive acid-fast–stained stool specimens and copious diarrhea without fever.
- The treatment of choice for cyclosporiasis is trimethoprim–sulfamethoxazole.