Family physicians are increasingly called on to evaluate patients before and after they travel outside the United States. Because of heightened interest in excursions to exotic locations, diseases that are uncommon in this country may have to be considered in patients who have recently returned from travel abroad. Among these illnesses are malaria, amebiasis and cutaneous larva migrans.
A 46-year-old man returned from the Peruvian city of Iquitos and the upper Amazon basin, where he had become ill with a fever and an unproductive cough associated with chest pain. His symptoms had waxed and waned for two weeks. The patient had received no pretravel immunizations or malaria prophylaxis. After he returned to the United States, he was seen at another hospital and treated empirically with azithromycin for cough. His symptoms did not improve.
On presentation at our hospital, the patient had a temperature of 38.6°C (101.5°F). On auscultation and percussion, his lungs were clear. No skin rash was evident. Notable laboratory findings were as follows: white blood cell count, 1,800 per mm3 (1.8 × 109 per L), with decreased neutrophils, lymphocytes and eosinophils; platelet count, 104,000 per mm3 (104 × 109 per L); and blood smears that were positive for Plasmodium vivax (less than 1 percent parasitemia). A chest radiograph revealed no unusual findings.
The patient's symptoms resolved promptly with oral chloroquine and primaquine. Repeat blood smears were negative.
Malaria is a major infectious cause of death in travelers to developing nations, particularly tropical and subtropical countries. Most Western travelers are not immune to this disease. Because the clinical manifestations of malaria can be varied, the correct diagnosis may be delayed. Plasmodium falciparum infections can be rapidly fatal.
Almost all malaria infections in tropical and subtropical areas are acquired through the bite of female Anopheles mosquitoes, which characteristically feed between dusk and dawn. Malaria can also be transmitted congenitally, as well as through blood transfusions and by contaminated needles. Rarely, the disease is contracted by persons who have never left the developed world. In these instances, malaria is acquired through the bite of infected Anopheles mosquitoes that were accidentally imported or the bite of domestic Anopheles species that have fed on an infected person. (Species of Anopheles mosquitoes are present in parts of the United States.)
Rapid diagnosis of malaria requires suspicion of its presence. Fever is the key clinical finding. Other manifestations can be protean, and the disease may mimic influenza or gastroenteritis. Leukopenia, thrombocytopenia and anemia may be noted. Most patients develop symptoms within six weeks after they return from a malarious area. In some patients, however, symptoms may not manifest until two to three years after the infection is acquired.
Malaria is diagnosed by the demonstration of Plasmodium organisms on specially prepared blood films. If malaria is suspected, these blood smears should be obtained repeatedly for several days. Thick blood films are more useful in demonstrating parasites, whereas thin films are helpful in determining the Plasmodium species. Blood smears should be obtained from febrile returning travelers, even if these patients took anti-malarial drugs and used insect repellent.
Because different Plasmodium species require different antimicrobial drugs, the species and intensity of parasitemia should be determined on a rapid basis before treatment is initiated. A rapid antigen-detection dipstick test using monoclonal antibody to the histidine-rich protein 2 of P. falciparum is available, but it is not helpful in diagnosing malaria caused by other Plasmodium species.
Assistance in identifying Plasmodium organisms may be obtained from state health departments or the Centers for Disease Control and Prevention (malaria treatment: 770-488-7788; malaria prophylaxis: 888-232-3228; Web site: www.cdc.gov). A list of tropical medicine specialists can be obtained from the American Society for Tropical Medicine and Hygiene (847-480-9592).
Because of the emergence of drug-resistant Plasmodium strains, family physicians should obtain updated treatment recommendations when they encounter a patient with malaria. In most areas, orally administered chloroquine (Aralen) is currently given for infections caused by Plasmodium malariae. Malaria caused by P. vivax or Plasmodium ovale is treated with chloroquine followed by primaquine. A course of oral quinine is effective in most patients with P. falciparum infection; however, seriously ill patients are given intravenous quinine or quinidine in an intensive care unit. Tetracycline, doxycycline (Vibramycin) and clindamycin (Cleocin) are also used to treat P. falciparum infections.
Patients with severe variants of glucose-6-phosphate deficiency should not be treated with primaquine. Neither primaquine nor tetracycline should be used in pregnant women. Because of their increased risk of severe complications and fetal death secondary to malaria, pregnant patients should be promptly hospitalized and treated with chloroquine or quinine.1–3
Patients should be hospitalized if more than 1 percent of their red blood cells show evidence of malarial parasites. Treatment in an intensive care unit is necessary for patients who have parasitemia of 3 percent or greater, hypoglycemia, cerebral malaria or respiratory distress, or are unable to take medications orally.
Blood smear results, serum glucose levels, kidney function and clinical status should be monitored during treatment. If blood smears continue to be positive, the laboratory should be asked to determine whether the smears contain trophozoites (asexual form of the parasite infective to humans) or gametocytes (sexual form infective only to mosquitoes). If only gametocytes are identified, additional treatment is not usually required.
A 42-year-old woman developed a temperature of 38.9°C (102°F), sweats, shaking chills, headache and slight constipation two days after returning from rural Indonesia. She had not taken malaria prophylaxis during her 10-week stay in that country.
The patient was found to have a white blood cell count of 28,000 per mm3 (28 × 109 per L) with a left shift (increased polymorphonuclear and band forms) and toxic granulations, but no eosinophilia. Serum electrolyte and transaminase levels were unremarkable. A chest radiograph showed minimal blunting of the right costophrenic angle.
On the night the patient was admitted to the hospital, her temperature became elevated to 39.4°C (103°F), and she reported increasing tenderness in the right upper quadrant. Ultrasound examination of the right upper quadrant and computed tomographic (CT) scanning of the abdomen revealed three large abscesses in the right lobe of the patient's liver. The two largest abscesses were each 5 cm in diameter. Serologic tests were positive for Entamoeba histolytica and negative for Echinococcus species.
Despite treatment with metronidazole, the patient continued to have a fever, and the liver abscesses became progressively larger. Consequently, CT-guided catheter drainage was undertaken. Thick, nonmalodorous, brown culture-negative fluid was withdrawn. After 18 days of metronidazole therapy, the patient was treated with iodoquinol, 650 mg taken orally three times daily for 20 days. By the end of the iodoquinol course, the patient no longer had a fever and was gaining weight. Serial ultrasound studies showed gradual resolution of the liver abscesses.
E. histolytica has a worldwide distribution, but amebiasis is more prevalent in tropical areas. Humans acquire the infection when they ingest E. histolytica cysts.
Amebic dysentery presents with liquid stools containing bloody mucus, abdominal cramps, chills, fever, prostration, nausea, headache and tenesmus. Complications of intestinal amebiasis can include perforation and peritonitis, appendicitis, ameboma, amebic stricture, cutaneous amebiasis, amebic liver abscess, pleuropulmonary amebiasis, amebic pericarditis and amebic brain abscess.
Extraintestinal amebic diseases, such as amebic liver abscess, can occur in the presence or absence of current or past intestinal symptoms. They can also occur with or without E. histolytica–positive stools. Amebic liver abscess may develop acutely or gradually, and the right lobe of the liver is usually affected. The patient may have referred pain to the right shoulder, non-productive cough, chills, sweats and leukocytosis with a left shift. Pus aspirated from an amebic abscess is usually brown in color because of a mixture of blood and necrotic material. The pus is not foul-smelling unless the patient has developed a secondary bacterial infection.
Amebiasis is diagnosed based on the demonstration of E. histolytica cysts or trophozoites in the stool. Serologic tests are useful in differentiating a liver abscess caused by E. histolytica from one caused by Echinococcus species (the source of serious larval cestode infection in humans).
Invasive E. histolytica disease must be treated first with a tissue-active drug. In the United States, the drug of choice is metronidazole (Flagyl), which can be given orally if the patient is able to swallow. To prevent relapses from intestinal cysts, metronidazole therapy should be followed by use of a drug that acts in the intestinal lumen, such as iodoquinol (Yodoxin) or paromomycin (Humatin). Therapeutic aspiration is reserved for use in patients with amebic liver abscesses that are at risk for immediate rupture or that do not respond to medical therapy.1
Cutaneous Larva Migrans
A 28-year-old medical resident and a companion returned from hiking in Central America with pruritic, erythematous, single-track linear and serpiginous lesions located predominantly on their lower extremities. Cutaneous larva migrans was diagnosed. Both patients were afebrile, and both responded to treatment with oral ivermectin.
Cutaneous larva migrans is caused by various animal hookworm species (e.g., Ancylostoma braziliense). The infection is acquired through skin contact with hookworm larvae in soil contaminated with dog and cat feces. Cutaneous larva migrans is common in tropical and subtropical areas, particularly areas with sandy soil.
Because cutaneous larva migrans is acquired by direct contact between skin and contaminated soil, preventive measures may be effective. In most instances, this infection can be avoided by wearing shoes and using towels to provide a barrier when sitting or lying on the ground.
In patients with cutaneous larva migrans, itchy papules develop at the sites where ground-dwelling larvae enter the skin (usually on the lower extremities or trunk). Serpiginous or linear single-track streaks later mark the course of the larvae as they migrate through the epidermis. Lesions may spread rapidly, and may disappear or appear at multiple sites. The diagnosis of cutaneous larva migrans is usually based on the clinical presentation.
Cutaneous larva migrans usually responds to a single dose of oral ivermectin (Strombectol), although the drug is not labeled for this purpose in the United States. Albendazole (Albenza) and thiabendazole (Mintezol) are alternative treatments. Biopsy, with or without cryosurgery of the lesions, is not helpful because of the consequent development of local inflammation.4–6
In the author's experience, ivermectin may be helpful as empiric treatment for chronic, raised, erythematous, pruritic lesions on the trunk or lower extremities of some refugee patients (e.g., former political prisoners), even if the lesions appear atypical. A 2 percent mupirocin ointment (Bactroban) may be useful in managing secondary infection with gram-positive bacteria.