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Malaria is an acute and chronic disease caused by obligate, intracellular protozoa of the genus Plasmodium. In 2005, CDC received reports of 1528 cases of malaria in the United States; of these, patient age was known for 1460, and 276 (18.9%) occurred in persons aged <18 years (505Thwing J, Skarbinski J, Newman RD, et al. Malaria surveillance- United States, 2005. In: Surveillance Summaries, June 8, 2007.). For 220 pediatric patients aged <18 years for whom malarial species was known, most infections were caused by P. falciparum (70.9%) and P. vivax (19.5%) (505Thwing J, Skarbinski J, Newman RD, et al. Malaria surveillance- United States, 2005. In: Surveillance Summaries, June 8, 2007.). Of 231 children for whom country of exposure was known, 76% of malarial infections were acquired in Africa, 16% in Asia and the Middle East, and 6.1% in the Americas (505Thwing J, Skarbinski J, Newman RD, et al. Malaria surveillance- United States, 2005. In: Surveillance Summaries, June 8, 2007.).

Most (82%) malaria becomes symptomatic within 30 days after arrival in the United States; 99% of malaria cases become symptomatic within 1 year. Typically, 75% of U.S. travel-associated malaria occurs in persons who have not taken appropriate malaria chemoprophylaxis. Approximately 50% of infections among U.S. citizens are acquired during visits to friends and relatives in malaria-endemic regions (505Thwing J, Skarbinski J, Newman RD, et al. Malaria surveillance- United States, 2005. In: Surveillance Summaries, June 8, 2007.). U.S.- born children of immigrants returning to visit family are at highest risk for malaria-associated death. In 2005, refugees or immigrants accounted for 28.3% of U.S. pediatric malaria cases, and the proportion of malaria among refugees and immigrants has not changed in the past decade (505Thwing J, Skarbinski J, Newman RD, et al. Malaria surveillance- United States, 2005. In: Surveillance Summaries, June 8, 2007., 506Rivera-Matos IR, Atkins JT, Doerr CA, et al. Pediatric malaria in Houston, Texas. Am J Trop Med Hyg 1997;57:560-3., 507Emanuel B, Aronson N, Shulman S. Malaria in children in Chicago. Pediatrics 1993;92:83-5., 509Whitworth J, Morgan D, Quigley M, et al. Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study. Lancet 2000; 356:1051-6., 510Patnaik P, Jere CS, Miller WC, et al. Effects of HIV-1 serostatus, HIV-1 RNA concentration, and CD4 cell count on the incidence of malaria infection in a cohort of adults in rural Malawi. J Infect Dis 2005;192:984-91.).

No reliable data exist on the prevalence of HIV infection among immigrant and refugee children resettling in the United States because children aged <15 years are exempt from mandatory screening. Underlying HIV prevalence rates in children relocating to the United States are assumed to reflect the overall rates of HIV in the migrating population. For example, Somali refugees have very low rates of HIV, whereas rates in Central and West Africa are substantially higher. Presumably, children at risk for coinfection with HIV and malaria, particularly asymptomatic children or those with unrecognized disease, would be highest in populations where the underlying prevalence of both HIV and malaria are excessive (i.e., West, Central, and portions of East Africa).

In contrast to data suggesting increased frequency of both parasitemia and clinical malaria in HIV-infected adults (509Whitworth J, Morgan D, Quigley M, et al. Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study. Lancet 2000; 356:1051-6., 510Patnaik P, Jere CS, Miller WC, et al. Effects of HIV-1 serostatus, HIV-1 RNA concentration, and CD4 cell count on the incidence of malaria infection in a cohort of adults in rural Malawi. J Infect Dis 2005;192:984-91.), studies in young HIV-infected children in malaria-endemic areas usually have not found increased frequency or density of parasitemia with HIV coinfection (511Greenberg AE, Nsa W, Ryder RW, et al. Plasmodium falciparum malaria and perinatally acquired human immunodeficiency virus type 1 infection in Kinshasa, Zaire. A prospective, longitudinal cohort study of 587 children. N Engl J Med 1991;325:105-9., 512Taha TE, Canner JK, Dallabetta GA, et al. Childhood malaria parasitaemia and human immunodeficiency virus infection in Malawi. Trans R Soc Trop Med Hyg 1994;88:164-5., 513Kalyesubula I, Musoke-Mudido P, Marum L, et al. Effects of malaria infection in human immunodeficiency virus type 1-infected Ugandan children. Pediatr Infect Dis J 1997;16:876-81., 514Villamor E, Fataki MR, Mbise RL, et al. Malaria parasitaemia in relation to HIV status and vitamin A supplementation among preschool children. Trop Med Int Health 2003;8:1051-61., 515Rogerson SR, Gladstone M, Callaghan M, et al. HIV infection among paediatric in-patients in Blantyre, Malawi. Trans R Soc Trop Med Hyg 2004;98:544-52., 516Grimwade K, French N, Mbatha DD, et al. Childhood malaria in a region of unstable transmission and high human immunodeficiency virus prevalence. Pediatr Infect Dis J 2003;22:1057-63., 517Otieno RO, Ouma C, Ong'echa JM, et al. Increased severe anemia in HIV-1-exposed and HIV-1-positive infants and children during acute malaria. AIDS 2006;20:275-80.) with one exception. Parasite density in children aged <5 years was higher in those with HIV infection than in those without HIV infection in Uganda (518Mermin J, Lule J, Ekwaru JP, et al. Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda. Lancet 2004;364:1428-34.). Additionally, most studies have not found malarial episodes to be more frequent or to present differently in HIV-infected than uninfected children (511Greenberg AE, Nsa W, Ryder RW, et al. Plasmodium falciparum malaria and perinatally acquired human immunodeficiency virus type 1 infection in Kinshasa, Zaire. A prospective, longitudinal cohort study of 587 children. N Engl J Med 1991;325:105-9., 513Kalyesubula I, Musoke-Mudido P, Marum L, et al. Effects of malaria infection in human immunodeficiency virus type 1-infected Ugandan children. Pediatr Infect Dis J 1997;16:876-81.). However, one study found that HIV-infected children aged >1 year may be more likely to have severe or complicated malaria (516Grimwade K, French N, Mbatha DD, et al. Childhood malaria in a region of unstable transmission and high human immunodeficiency virus prevalence. Pediatr Infect Dis J 2003;22:1057-63.). A study in Kenya suggested that HIV-exposed children aged <2 years (regardless of their infection status) were more likely than children without HIV exposure to have severe anemia with malarial episodes (517Otieno RO, Ouma C, Ong'echa JM, et al. Increased severe anemia in HIV-1-exposed and HIV-1-positive infants and children during acute malaria. AIDS 2006;20:275-80.). Published studies on HIV/malaria coinfection have focused on adults and younger HIV-infected children; whether data from such studies applies to older HIV-infected children is uncertain. In a study in Uganda, HIV-infected persons aged ≥5 years with lower CD4 counts (<200 cells/mm³) had higher parasite counts during clinical malaria (518Mermin J, Lule J, Ekwaru JP, et al. Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda. Lancet 2004;364:1428-34.).

Signs and symptoms of malaria vary and depend on previous exposure (partial immunity), age of onset, and species of infecting organism but do not differ by HIV infection status in children. Fever is the most common symptom. In children, nonspecific symptoms predominate and may include chills, sweating, headache, myalgia, malaise, nausea, vomiting, diarrhea, and cough (519Skarbinski J, James EM, Causer LM, et al. Malaria surveillance-United States, 2004. In: Surveillance Summaries, May 26, 2006. MMWR 2006;55(No. SS-4):23-37., 520Shingadia D, Shulman ST. Recognition and management of imported malaria in children Seminars in Pediatr Infect Dis 2000;11:172-7.). These symptoms might increase the potential for misdiagnosis as a viral syndrome, upper respiratory tract infection, or gastroenteritis. Two thirds of all malaria in children in an area where malaria is nonendemic was misdiagnosed; children had two to four clinical visits before malaria was diagnosed (508Miller KK, Banerji A. Epidemiology of malaria presenting at British Columbia's Children's Hospital, 1984-2001: lessons for prevention. Can J Public Health 2004;95:245-8.).

Non-P. falciparum will be responsible for 75% of malaria diagnoses in nonimmune persons >30 days after they return to or travel to the United States from regions with malaria.

In contrast, the epidemiology in partially immune children may vary considerably. In one study, 60% of children migrating from malaria-holoendemic regions were smear-positive for P. falciparum 1 month after arrival in the United States (521Stauffer WM, Maroushek S, Kamat D. Medical screening of immigrant children. Clin Pediatr (Phila) 2003;42:763-73.). Since these data were collected, CDC has issued guidance to organizations resettling refugees to the United States to presumptively treat all refugees from sub-Saharan Africa, except under special circumstances, before they depart for the United States. This treatment should decrease malaria rates among refugees but does not completely eliminate risk because predeparture treatment with drugs effective against blood-stage parasites do not eliminate liver-stage parasites. However, nonrefugee immigrants from similar areas do not receive this presumptive therapy and are at greater risk for clinical manifestations of malaria after arrival in the United States. Therefore, children who have recently migrated from regions where malaria is highly endemic should be either presumptively treated for malaria or tested postarrival for malaria infection. CDC guidance can be found at http://www.cdc.gov/ncidod/dq/health.com.

Chronic symptoms of splenomegaly, fever, and thrombocytopenia are highly specific for malaria in immigrant children and need appropriate evaluation (519Skarbinski J, James EM, Causer LM, et al. Malaria surveillance-United States, 2004. In: Surveillance Summaries, May 26, 2006. MMWR 2006;55(No. SS-4):23-37., 522Maroushek SR, Aguilar EF, Stauffer W, et al. Malaria among refugee children at arrival in the United States. Pediatr Infect Dis J 2005;24:450-2.). Congenital malaria is rare but should be considered in febrile neonates whose mothers migrated from areas where malaria is endemic; however, empiric therapy should not be administered without a diagnosis to febrile neonates of recent immigrants (519Skarbinski J, James EM, Causer LM, et al. Malaria surveillance-United States, 2004. In: Surveillance Summaries, May 26, 2006. MMWR 2006;55(No. SS-4):23-37.).

Malaria is diagnosed by microscopic examination of a patient,s blood. A Giemsa-stained thick blood smear is the most sensitive smear technique for detecting infection, with a thin blood smear used for accurate parasite speciation. In nonimmune persons, because symptoms may develop before parasitemia is detectable, several blood-smear examinations taken at 12- to 24-hour intervals may be needed to positively rule out malaria in symptomatic patients. The sensitivity and specificity of blood smear depends substantially on the laboratorian,s skills. Assistance with microscopic diagnosis of malaria is available through state public health departments and the CDC Division of Parasitic Diseases diagnostic service http://www.dpd.cdc.gov/dpdx.com.

Although blood smear examination remains the gold standard for laboratory confirmation of malaria, FDA has approved the Binax Now^® Malaria Test, a rapid malaria antigen-capture assay, for use in clinical diagnosis of symptomatic malaria in children and adults. This test, which uses a monoclonal antibody to histidine-rich protein 2 to detect P. falciparum, and a monocloncal antibody aldolase to detect all malaria species, can be performed within 15 minutes. The studies presented to FDA show specificity approaching 100% for all malaria and a sensitivity of >95% for P. falciparumand 85%-95% for P. vivax. However, sensitivity for P. ovale, a less common form of human malaria, probably does not exceed 70%. Although this test performs well in symptomatic persons, preliminary data suggest poor performance of rapid diagnostic tests, including the Binax Now^® Malaria Test for screening asymptomatic persons for malaria (523Ndao M, Bandyayera E, Kokoskin E, et al. Comparison of blood smear, antigen detection, and nested-PCR methods for screening refugees from regions where malaria is endemic after a malaria outbreak in Quebec, Canada. J Clin Microbiol 2004;42:2694-700., 524Stauffer WM, Newberry AM, Cartwright CP, et al. Evaluation of malaria screening in newly arrived refugees to the United States by microscopy and rapid antigen capture enzyme assay. Pediatr Infect Dis J 2006;25:948-50.). Similarly, among asymptomatic immigrants, the sensitivity of a single blood smear is relatively poor (<50%) (523Ndao M, Bandyayera E, Kokoskin E, et al. Comparison of blood smear, antigen detection, and nested-PCR methods for screening refugees from regions where malaria is endemic after a malaria outbreak in Quebec, Canada. J Clin Microbiol 2004;42:2694-700., 524Stauffer WM, Newberry AM, Cartwright CP, et al. Evaluation of malaria screening in newly arrived refugees to the United States by microscopy and rapid antigen capture enzyme assay. Pediatr Infect Dis J 2006;25:948-50.). Specific guidelines for laboratory diagnosis are summarized elsewhere and are available at the CDC malaria website http://www.cdc.gov/malaria.com.

Severe malaria commonly induces hypoglycemia in children, especially when treated with IV quinine/quinidine because of the inhibition of gluconeogenesis and induction of endogenous insulin production. Therefore, use of a crystalloid solution containing glucose for fluid maintenance is prudent while closely monitoring glucose levels until IV quinine/quinidine therapy has been completed. Monitoring glucose is especially important for infants and for persons with altered mental status. Cardiac and intensive-care monitoring is recommended because quinine/quinidine can cause hypotension and may widen the QRS interval. Another common (50%-75%) adverse reaction to quinine is tinnitus, although this usually resolves after treatment. HIV-infected children may have more hematologic side effects, particularly neutropenia and anemia, following antimalarial therapy. IRIS caused by malaria has not been reported.

Treatment failure with P. falciparum among children receiving a full course of appropriate antimalarial therapy occurs uncommonly. Patients should be monitored for clinical response and for signs of recrudescence after therapy completion. Published studies do not have the power to detect a difference in treatment outcomes between HIV-infected and HIV-uninfected children (529Kamya MR, Gasasira AF, Yeka A, et al. Effect of HIV-1 infection on antimalarial treatment outcomes in Uganda: a population-based study. J Infect Dis 2006;193:9-15., 530Byakika-Kibwika P, Ddumba E, Kamya M. Effect of HIV-1 infection on malaria treatment outcome in Ugandan patients. Afr Health Sci 2007;7:86-92.). Relapse of P. vivax and P. ovale can occur from the dormant (hypnozoite) liver form but is less common with primaquine treatment. Malaria medications purchased in sub-Saharan Africa or Southeast Asia may be counterfeit (533Newton PN, McGready R, Fernandez F, et al. Manslaughter by fake artesunate in Asia- will Africa be next? PLoS Med 2006;3:e197.). When treatment failure occurs, malaria speciation should be confirmed, as should the geography of where the malaria was acquired. Retreatment with an appropriate first-line regimen should be given. Discussion with a tropical medicine expert or a call to the CDC malaria hotline is appropriate when complex situations arise.

Except for reactivation of P. vivax and P. ovale hypnozoites, malaria, once successfully treated, does not recur. Malaria infection does not infer protective immunity and continued exposure to malaria parasites can result in repeated infection.

Not applicable.