malaria

Malaria

Primary Distribution: Tropical Africa, Asia, South and Central Americas; East China, Middle East. The range of distribution is increasing as is the incidence of "airport malaria," i.e., malaria contracted from mosquitos arriving on international flights from endemic areas to non-endemic areas such as Europe and North America (Nation's Health, 2000). Approximately 2.7 million people die each year from malaria and there are 300-500 million new cases/year (Malaria Foundation International, 2000).

Agent and Vector: The obligate intracellular protozoa Plasmodium falciporum, P. vivax, P. ovale, and P. malariae are transmitted by female Anopheles mosquitos. Transmission may also occur via parenteral injection or congenitally.

Incubation: Usually one to four weeks, but sometimes more than a year. Relapse may occur as many as 10 years after first episode. P. vivax and P. ovale may remain dormant in the liver and cause relapses. P. falciporum, the most virulent form, does not lie dormant, nor does P. malariae.

Clinical Findings and Treatment

Signs and Symptoms: Malaria is usually characterized by sudden onset of high fever, sweating, chills, uncontrollable shaking, headache, and splenomegaly. Fever tends to wax and wane in 48-72 hour cycles, though cycles may be irregular, especially with infection by P. falciporum. Onset may also be insidious, with less dramatic symptoms such as fever, headache, dyspnea, abdominal pain, nausea, diarrhea, myalgias, and splenomegaly. P. falciporum may cause parasitemia resulting in a life-threatening condition characterized by hemolysis, jaundice, anemia, acute renal failure, and hemoglobinuria. Cerebral malaria, also life-threatening, is characterized by gradual onset of severe headache, drowsiness, delerium, and coma. Seizures may also occur and are most common in children.

Complications: P. faciporum causes death in as many as 25% of untreated cases. Cerebral malaria primarily affects children and nonimmune patients. Other complications include splenic rupture, hypoglycemia, renal failure, anemia, pulmonary failure, and/or algid malaria (cold skin, profuse diarrhea, and profound weakness).

Laboratory Findings: Anemia, leukopenia, and thromboctopenia are common. Hyponatremia and hypoglycemia may be found in patients with P. falciporum infection. Diagnosis: Recurring fever, chills, anemia, and splenomegaly + geographic exposure lead to suspicion of malaria. Microscopic examination of Giemsa stained thick (detection of organisms) and thin (identification of species) blood smears is the standard for diagnosis. However, this technique requires specific expertise, and other commercially available techniques may yield more accurate (albeit more expensive) tests in areas with inexperienced labs, especially areas where malaria is imported. Sensitive alternatives to microscopy of Giemsa-stained films include:

Fluorescent microscopy after centrifugation (QBC).
Dipstick antigen detection of HRP2 and pLDH (Parasight-F, ICT Malaria Pf, OptiMAL).
Polymerase chain reaction assays.
Some automated blood cell analyzers.

See Hanscheid (1999) for in-depth review of these and other alternatives.

Differential Diagnosis: Influenza, visceral leishmaniasis, leptospirosis, relapsing fever, typhoid fever, dengue fever, brucellosis, trypanosomiasis, gastroenteritis, urinary tract infection, amebic liver abscess, hepatitis, tuberculosis; and other causes of fever, splenomegaly, hepatomegaly, and anemia.

Treatment: A variety of antimalarial drugs are in use, including the traditional quinine given orally or parenterally. Treatment depends on the organism, immune status of the patient, and severity of the attack. Oral chloroquine is a mainstay of treatment except for infection with chloroquine-resistant P. falciporum. P. falciporum presents the greatest challenge because of severity of attacks as well as the existence of multidrug (especially chloroquine)-resistant strains. Combination drug treatment is common, e.g., mefloquine combined with artesunate for multidrug-resistant strains. The following is taken from Rosenblatt (1999)

Treatment Specific to Parasite

P. vivax, P. ovale, P. malariae, and chloroquinine-sensitive strains of P. falciporum (only in Latin America and parts of the Middle east): Treatment of choice is chloroquine phosphate 1 g po (600 mg base), then 500 mg (300 mg base) in 6 hours, then 500 mg at 24 hours and again at 48 hours. Other treatment is primaquine phosphate 26.3 mg/day po (15 mg base) for 14 days for P. vivax or P. ovale to prevent relapse.
Chloroquinine-sensitive strains of P. falciporum: Quinine 650 mg po tid for 7 days + doxycycline 100 mg po bid for 7 days (or in place of doxycycline, clindamycin 900 mg po tid) OR mefloquine 750 mg po, then 500 mg po in 24 hours (avoid in pregnancy) OR halofantrine 500 mg po qid for 3 days; then repeat in one week. Consult inserts.
Complicated/cerebral malaria may be treated with IV quinidine.

Outside the U.S., other medications are availble. Readers are referred to the World Health Organization, U.S. Centers for Disease Control, and the other references given below for further specifics of treatment.

Prevention: Despite concerns about efficacy and side effects of agents to prevent malaria, persons traveling to endemic areas (especially relief workers and others living in difficult circumstances) should take preventive measures, including using bed netting (preferably sprayed with insect repellent), wearing protective clothing, using insect repellent containing N,N-diethylmeta-toluamide, and taking prophylactic medication unless contraindicated. Prophylactic medications currently include mefloquine, doxycycline, and proguanil + chloroquine. Primaquine phosphate provides terminal prophylaxis and thus prevents an asymptomatic carrier state. Readers are again referred to the WHO and CDC.

Top

References

Centers for Disease Control and Prevention. (1999). Online: http://www.cdc.gov/ (Search Journal of Emerging Infectious Diseases).

Chin, J. (Ed.) (2000). Control of communicable diseases manual (17th ed.). Washington, DC: American Public Health Association.

Hanscheid, T. (1999). Diagnosis of malaria: A review of alternatives to conventional microscopy. Clinical Laboratory Haematology. 21(40), 235-245.

Juckett, G. (1999). Malaria prevention in travelers. American Family Physician. 59(9), 2523-2530.

Karbwang, J. & Harinasuta, T. (1992). Overview: Clinical pharmacology of antimalarials. Southeast Asian Journal of Tropical Medicine and Public Health. 23(Supplement 4), 95-109.

Malaria Foundation International. (2000). Accessed on the World Wide Web, October 15, 2000 at http://www.malaria.org/

Nation's Health (2000). World health leaders fear spread of 'airport malaria.' Nation's Health, October, 2000, 14.

Price, R., Simpson, J.A., Teja-Isavatharm, P., Than, M.M., Luxemberger, C., Heppner, D.G., Chongsuphajaisiddhi, T., Nosten, F., & White, N.J. (1999). Pharmacokinetics of mefloquine combined with artesunate in children with acute falciporum malaria. Antimicrobial Agents and Chemotherapy. 43(2), 341-346.

Rosenblatt, J.E. (1999). Antiparasitic agents. Mayo Clinic Proceedings. 74(11), 1161-1175.

Strickland, G.T. (1991). Malaria. In G.T. Strickland (Ed.), Hunter's Tropical Medicine (7th ed.) (pp. 586-617). Philadelphia: W.B. Saunders Company. World Health Organization. (1999)Online: http://www.who.int/ (Search Health Topics).