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Part 1: Reporting § Epidemiology § Evaluation and Diagnosis

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Reporting | Epidemiology | Evaluation and Diagnosis | References

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Reporting

We encourage clinicians to report all cases of laboratory-confirmed malaria to help CDC's surveillance efforts. Refer to our information on the Malaria Case Surveillance Report Form.

To report an adverse event to an antimalarial drug

If your patient has experienced an adverse event while taking an antimalarial drug, you can report that side effect to MedWatch, the FDA Safety Information and Adverse Event Reporting Program. Reporting an event is voluntary. However, your participation is encouraged in order to keep safe and effective drugs and devices available on the market.

To submit your voluntary report, do one of the following:

• Complete the voluntary form 3500 online at www.accessdata.fda.gov/scripts/medwatch/ *
• Call 1-800-FDA-1088 to report by telephone
• Download a copy of the form and either fax it to 1-800-FDA-0178 or mail it using the postage-paid addressed form.

Epidemiology

Malaria continues to be one of the most important and devastating infectious diseases in developing areas of the world. Worldwide, over 40% of the population lives in areas where malaria transmission occurs (i.e., parts of Africa, Asia, the Middle East, Central and South America, Hispaniola, and Oceania).¹ It is estimated that 300-500 million cases of malaria occur each year resulting in 750,000-2 million deaths.²

While malaria transmission was successfully interrupted in the United States during the late 1940s, malaria remains a constant health threat for U.S. travelers to malarious areas and immigrants arriving from malarious areas. With approximately 27 million U.S. residents traveling each year to malarious areas, it is important for clinicians to provide pre-travel advice on malaria prevention, to remain alert to the possibility of malaria in persons returning from these areas, and to treat malaria cases promptly and effectively. While the vast majority of malaria cases diagnosed in the U.S. are imported (i.e., acquired outside of the United States and its territories), congenital infections, infections through exposure to infected blood or blood products, and infections through local mosquito-borne transmission still occur.^3-6

In 2004, 1,324 cases of malaria were reported in the United States.³ Plasmodium falciparum, the most severe and life-threatening form of the disease was identified in 50% of the cases. Malaria cases were reported from all 50 states with New York City (214), California (130), and New Jersey (75) reporting the highest number. Of the 1,324 malaria cases, 775 occurred in U.S. civilians, all of which were imported.³ Of the civilian patients with imported malaria, 65% did not take any chemoprophylaxis and only 20% were compliant with a chemoprophylactic regimen recommended by the Centers for Disease Control and Prevention (CDC) for the area in which they traveled. Eighty-eight percent of patients with imported malaria reported symptom onset after arriving back in the United States and, for patients with P. falciparum infections, 81% experienced symptom onset within one month after arrival back in the United States. Four patients died. Risk factors for fatal malaria include failure to take recommended chemoprophylaxis, refusal of or delay in seeking medical care, and misdiagnosis.⁷

Evaluation and Diagnosis

Because malaria cases are seen relatively rarely in North America, misdiagnosis by clinicians and laboratorians has been a commonly documented problem in case series.^8-12 However, malaria is a common illness in areas where it is transmitted, and therefore the diagnosis of malaria should routinely be considered for anyone who has traveled to an area with known malaria transmission in the past several months preceding symptom onset. Symptoms of malaria are generally non-specific and most commonly consist of fever, malaise, weakness, gastrointestinal complaints (nausea, vomiting, diarrhea), neurologic complaints (dizziness, confusion, disorientation, coma), headache, back pain, myalgia, chills, and/or cough.^{7, 13} The diagnosis of malaria should also be considered in any person with fever of unknown origin regardless of travel history. Patients suspected of having malaria infection should be urgently evaluated. Treatment for malaria should not be initiated until the diagnosis has been confirmed by laboratory investigations. "Presumptive treatment" without the benefit of laboratory confirmation should be reserved for extreme circumstances (strong clinical suspicion, severe disease, impossibility of obtaining prompt laboratory confirmation).

Laboratory diagnosis of malaria can be made through microscopic examination of thick and thin blood smears.³ Thick blood smears are more sensitive in detecting malaria parasites because the blood is more concentrated allowing for a greater volume of blood to be examined; however, thick smears are more difficult to read. Laboratories that have limited experience may prefer to use thin smears, which can aid in parasitic species identification. Blood films need to be read immediately; off-hours, qualified personnel who can perform this function should be on-call. A negative blood smear makes the diagnosis of malaria unlikely. However, because non-immune individuals may be symptomatic at very low parasite densities that initially may be undetectable by blood smear, blood smears should be repeated every 12-24 hours for a total of 48-72 hours.

After the presence of malaria parasites on a blood smear is detected, the parasite density should then be estimated. The parasite density can be estimated by looking at a monolayer of red blood cells (RBCs) on the thin smear using the oil immersion objective at 100x. The slide should be examined where the RBCs are more or less touching (approximately 400 RBCs per field). The parasite density can then be estimated from the percentage of infected RBCs.¹⁴

In addition to microscopy, other laboratory diagnostic tests are available. Several antigen detection tests using a “dipstick” format exist but are not yet approved for general diagnostic use in the United States. Parasite nucleic acid detection using polymerase chain reaction (PCR) are more sensitive and specific than microscopy but can be performed only in reference laboratories and should be reserved for specific instances (e.g., back up or confirmation of microscopy). Serologic tests, also performed in reference laboratories, can be used to assess past malaria experience but not current infection by malaria parasites. Your state health department or the CDC can be contacted for more information on utilizing one of these tests.

References

1. World malaria situation in 1994. Part I. Population at risk. Wkly Epidemiol Rec, 1997. 72(36): p. 269-74.
2. Breman, J.G., The ears of the hippopotamus: manifestations, determinants, and estimates of the malaria burden. Am J Trop Med Hyg, 2001. 64(1-2 Suppl): p. 1-11.
3. CDC, Malaria surveillance – United States, 2004. MMWR Surveill Summ, 2006. 66(No. SS-04): p. 23-37.
4. CDC, Congenital malaria as a result of Plasmodium malariae--North Carolina, 2000. MMWR Morb Mortal Wkly Rep, 2002. 51(8): p. 164-5.
5. CDC, Probable transfusion-transmitted malaria--Houston, Texas, 2003. MMWR Morb Mortal Wkly Rep, 2003. 52(44): p. 1075-6.
6. CDC, Local transmission of Plasmodium vivax malaria--Palm Beach County, Florida, 2003. MMWR Morb Mortal Wkly Rep, 2003. 52(38): p. 908-11.
7. Greenberg, A.E. and H.O. Lobel, Mortality from Plasmodium falciparum malaria in travelers from the United States, 1959 to 1987. Ann Intern Med, 1990. 113(4): p. 326-7.
8. Moore, T.A., et al., Imported malaria in the 1990s. A report of 59 cases from Houston, Tex. Arch Fam Med, 1994. 3(2): p. 130-6.
9. Kain, K.C., et al., Imported malaria: prospective analysis of problems in diagnosis and management. Clin Infect Dis, 1998. 27(1): p. 142-9.
10. Kain, K.C., et al., Malaria deaths in visitors to Canada and in Canadian travellers: a case series. Cmaj, 2001. 164(5): p. 654-9.
11. Svenson, J.E., et al., Imported malaria. Clinical presentation and examination of symptomatic travelers. Arch Intern Med, 1995. 155(8): p. 861-8.
12. Kyriacou, D.N., et al., Emergency department presentation and misdiagnosis of imported falciparum malaria. Ann Emerg Med, 1996. 27(6): p. 696-9.
13. White, N.J., The treatment of malaria. N Engl J Med, 1996. 335(11): p. 800-6.
14. Zucker, J.R. and C.C. Campbell, Malaria. Principles of prevention and treatment. Infect Dis Clin North Am, 1993. 7(3): p. 547-67.
15. Severe falciparum malaria. World Health Organization, Communicable Diseases Cluster. Trans R Soc Trop Med Hyg, 2000. 94 Suppl 1: p. S1-90.
16. CDC, Availability and use of parenteral quinidine gluconate for severe or complicated malaria. MMWR Morb Mortal Wkly Rep, 2000. 49(50): p. 1138-40.
17. Miller, K.D., A.E. Greenberg, and C.C. Campbell, Treatment of severe malaria in the United States with a continuous infusion of quinidine gluconate and exchange transfusion. N Engl J Med, 1989. 321(2): p. 65-70.
18. Powell, V.I. and K. Grima, Exchange transfusion for malaria and Babesia infection. Transfus Med Rev, 2002. 16(3): p. 239-50.
19. Luxemburger, C., et al., The epidemiology of severe malaria in an area of low transmission in Thailand. Trans R Soc Trop Med Hyg, 1997. 91(3): p. 256-62.
20. Nosten, F., et al., The effects of mefloquine treatment in pregnancy. Clin Infect Dis, 1999. 28(4): p. 808-15.