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Human malaria is a parasitic disease transmitted through the bite of an infected female Anopheles mosquito. Most malaria cases in the United States occur in travelers who recently visited areas where malaria is endemic without taking adequate chemoprophylaxis.1 This report describes five cases of Plasmodium falciparum malaria that occurred in a family residing near Chicago, Illinois, during 2006. These cases underscore the importance of malaria-prevention measures (e.g., avoidance of mosquito bites and appropriate chemoprophylaxis) for travelers to malaria-endemic areas.
In February 2006, three boys aged 10, 6, and 4 years (patients 1, 2, and 3, respectively) were hospitalized for complicated P. falciparum malaria (i.e., malaria with potentially life-threatening manifestations). They were members of a family of seven, including the two parents, the three male patients, and two girls aged 11 and 2 years (patients 4 and 5, respectively), all of whom had traveled in 2005 and early 2006 to Nigeria, the native country of the parents and their oldest daughter. The four youngest children, including the three boys and the girl aged 2 years, were born in the United States, where the family had lived for 10 years.
Before the trip to Nigeria, the parents had asked their local health department about malaria medications. They were told that antimalarial drugs were available. However, they assumed incorrectly that the drugs were to be taken for treatment only and did not realize that the drugs could also be used for chemoprophylaxis; therefore, they did not request a prescription. The mother and the three youngest children spent 3 months in Nigeria; the father and the two oldest children stayed 5 weeks. The family visited friends and relatives in various locations of Nigeria (e.g., Abuja, Ilorin, Kano, and Lagos) without taking malaria chemoprophylaxis. During their travel, three of the children (patients 2, 3, and 5) had onset of separate febrile episodes that were treated uneventfully with antibiotics, ibuprofen, and sulfadoxine-pyrimethamine (Fansidar®), all recommended by a local physician. All family members returned to the United States in January 2006.
Two weeks after their return, the four oldest children (the three boys and the girl aged 11 years) had onset of influenza-like symptoms, including fever and headaches, and were treated at a local clinic with antipyretics and amoxicillin. Three days later, the parents noticed that the eyes of the three boys (patients 1, 2, and 3) had yellow scleras and took them to the hospital. On examination, all three were febrile and jaundiced, and the boy aged 10 years (patient 1) appeared ill and had pallor and severe back pain. Blood smears confirmed the diagnosis of P. falciparum malaria in all three patients; the boy aged 4 years (patient 3) had a high parasitemia at 4.8%. Other abnormal laboratory findings for all three patients included anemia, thrombocytopenia, hyperbilirubinemia, and elevated aminotransferase levels. The boy aged 10 years (patient 1) had severe metabolic acidosis and hypoglycemia (glucose: 25 mg/dL; blood pH: 7.1; base excess: -15 mEq/L).
Because patients 1, 2, and 3 each had at least one manifestation of complicated malaria (e.g., acidosis, hypoglycemia, severe anemia, or jaundice),2 all three were admitted to the pediatric intensive care unit and treated with intravenous quinidine combined with doxycycline (patient 1) or clindamycin (patients 2 and 3, in whom doxycycline was contraindicated because they were aged <8 years).3 The boy aged 10 years (patient 1) had a hyperhemolytic syndrome with markedly decreased hemoglobin concentration, severe metabolic acidosis, and hypoglycemia and therefore required intubation, dextrose infusion, transfusions of red blood cells and fresh frozen plasma, erythrophoresis (exchange transfusion), and plasmapheresis. The boy aged 4 years (patient 3) required packed red blood cell transfusions for anemia. The boys aged 6 and 4 years (patients 2 and 3, respectively) had prolonged QT intervals on electrocardiogram, which resolved after discontinuation of the intravenous quinidine. Parasitemia in all three patients had resolved by the third day of hospitalization, and all three children were discharged in good condition after 1 week.
The day after hospitalization of the three boys, their two sisters also were tested by blood smear and determined to be infected with P. falciparum, albeit at lower parasite densities. The girl aged 11 years (patient 4) had fever and headache; her sister aged 2 years (patient 5) was asymptomatic. Both were hospitalized in a general pediatric unit and treated successfully with oral quinine combined with either doxycycline or clindamycin; parasitemia resolved by the third day of hospitalization.
The parents reported that patients 1 and 5 had sickle cell disease. Subsequent hemoglobin electrophoresis indicated that all five children had either sickle cell disease (SS) or sickle cell trait (SA).
Infection with P. falciparum was confirmed by polymerase chain reaction (PCR) performed at CDC on the pretreatment blood specimens of patients 1, 2, 3, and 4.4 No pretreatment blood sample was available for patient 5; PCR results for a posttreatment specimen (obtained 1 day after completion of quinine therapy) were negative.
Both parents were asymptomatic. They consulted their primary physician, who treated them presumptively with mefloquine, without taking a blood smear.
D Glikman, MD, JF Marcinak, MD, RS Daum, MD, Section of Infectious Diseases, CP Montgomery, MD, KS Hoehn, MD, Section of Critical Care Medicine, Dept of Pediatrics, J Anastasi, MD, Dept of Pathology, Univ of Chicago, Chicago, Illinois. HS Bishop, P Nguyen-Dinh, MD, Div of Parasitic Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases (proposed), CDC.
The high attack rate reported in the family described in this report illustrates the elevated risk for malaria in travelers to sub-Saharan Africa. Among 1,190 imported cases of malaria reported in the United States during 2004 for which the region of acquisition was known, 68% were acquired in Africa, with the majority of cases attributed to P. falciparum,1 the species that most typically causes severe malaria in humans. Three of the five infected children described in this report had complicated malaria and required treatment in the intensive care unit.
All five children had the sickle cell gene; two were SS homozygotes, and three were heterozygotes. The sickle cell gene is found more commonly in persons of African descent because the sickle cell trait confers a selective advantage, resistance to severe malaria.5 In a recent large cohort study of Kenyan children, the sickle cell trait was found to be approximately 50% protective against mild clinical malaria, 75% protective against admission to the hospital for malaria, and 90% protective against severe or complicated malaria.6 However, two of the three patients with sickle cell trait described in this report (patients 2 and 3) still had complicated malaria. Patient 1 had a low parasitemia but was severely ill, probably because of hyperhemolysis related to sickle cell disease. In a study from Nigeria, malaria was found to be an important risk factor for hyperhemolytic crisis in children with sickle cell disease.7
These five cases underscore the importance of preventive measures, including avoidance of mosquito bites and appropriate chemoprophylaxis, for travelers to malaria-endemic areas.8 The majority of cases of imported malaria occur in travelers who have not taken appropriate prophylaxis. Among U.S. civilians with imported malaria reported in 2004, approximately 76% had not taken any prophylaxis or had taken prophylaxis that did not conform to CDC recommendations.1 Failure to take prophylaxis is a major contributing factor to malaria cases and deaths in U.S. travelers.9 Especially low compliance rates are reported among U.S. residents born in malaria-endemic areas who return to their country of origin to visit friends and relatives, a situation derived from various cultural and economic factors, such as misperception that malaria is not a serious illness or lack of adequate insurance coverage.10 Acquired immunity to malaria is never complete and persists only through continual reexposure to malaria. Persons born in a malaria-endemic country who move to a nonendemic area are at risk for symptomatic and severe malaria upon return to their native country, unless they take preventive measures. Travelers who have onset of malaria while visiting a malaria-endemic country might receive a treatment that does not adhere to CDC guidelines; for example, the drug used to treat presumed malaria in three of the children during their travel (sulfadoxine-pyrimethamine) is no longer recommended by CDC because of drug resistance and adverse drug effects.3
Prophylaxis recommendations should be based on risk for malaria acquisition, occurrence of drug resistance in the areas to be visited, and traveler characteristics (e.g., age, reproductive status, and medical history). For example, chloroquine-resistant malaria is widespread in sub-Saharan Africa, including Nigeria, and resistance to sulfadoxine-pyrimethamine also occurs in this region. Malaria can affect both adults and children. Among 732 cases of malaria in U.S. civilians of known age reported in the United States during 2004, approximately 11% were in children aged <15 years. Detailed recommendations for preventing malaria in traveling infants and children are available from CDC.* In addition, recommendations for prevention of malaria in travelers of all ages are available.† Finally, CDC biannually publishes recommendations in Health Information for International Travel (i.e., “The Yellow Book”),8 which is available for purchase (telephone, 800-545-2522) and available and updated more frequently on the CDC website.‡
*Available at http://www.cdc.gov/travel/mal_kids_hc.htm.
†Available at http://www.cdc.gov/travel/diseases.htm#malaria and http://www.cdc.gov/malaria/travel/index.htm.
‡Available at http://www.cdc.gov/travel.
Malaria in Multiple Family Members—Chicago, Illinois, 2006. JAMA. 2007;297(20):2191–2193. doi:10.1001/jama.297.20.2191