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Congenital Malaria as a Result of Plasmodium malariae --- North Carolina, 2000

Congenitally acquired malaria is rare in the United States; <10 cases are reported each year (1). Congenital infection with Plasmodium malariae is particularly uncommon because distribution of this parasite is focal and sparse in areas where P. falciparum is endemic (2). The last case of congenital P. malariae infection in the United States was reported in 1992 (3). This report describes the investigation of a case of P. malariae in an infant with no travel history outside of the United States and suggests that health-care providers suspect malaria when treating a neonate or young infant with fever if the mother has traveled or lived in a malarious area.

In September 2000, a previously healthy female infant aged 10 weeks who resided in Raleigh, North Carolina, developed fever and dark urine. A pediatrician examined the infant and found a temperature of 103.7 F (39.8 C) but no other abnormalities. Laboratory evaluation included a white blood cell count of 4,600 µ/L (normal range: 9,000--30,000 µ/L]) and hemoglobin of 8.7 g/dL (normal range: 10.0--14.0 g/dL). The same day, she was admitted to a local hospital for treatment and further evaluation. Laboratory studies were performed, including cultures of blood, urine, and cerebrospinal fluid (CSF). A repeated complete blood count (CBC) demonstrated hemoglobin (6.6 g/dL) and platelets (109,000 µ/L). Intra-venous antibiotic therapy was begun with ampicillin and cefotaxime.

Two days after admission, blood films for malaria obtained the previous day were reported to contain Plasmodium malariae parasites; treatment with chloroquine was initiated. Over the next 2 days, the infant received two transfusions of packed red blood cells for anemia. Bacterial cultures of urine, blood, and CSF obtained on admission remained negative.The infant's clinical status improved, and she was discharged home after having completed chloroquine treatment. She had a negative malaria smear on specimens obtained 2 days and 15 days post-therapy.

In July 2000, approximately 42 days before admission, the infant was seen at a local hospital emergency department because her parents were concerned about her breathing pattern; however, physical exam and chest radiograph were normal and no treatment or follow-up was required. The infant had not traveled outside the city or received any blood products before hospitalization.

Both parents had emigrated to the United States from the Democratic Republic of the Congo; the father arrived in 1995 and the mother in 1996. The mother reported being treated for malaria with chloroquine shortly before leaving the Congo and presumptively completed a full course of therapy. Both parents denied any episodes of malaria, febrile illness, foreign travel, or blood transfusion following arrival in the United States. The family lived in a screened apartment in Raleigh, although some mosquitoes were noted indoors during August 2000. A friend from Kinshasa, Congo, stayed with the family during August; he reportedly was well during the visit.

Pretreatment malaria testing of the mother with thick and thin blood films prepared four times over a 2-week period was negative for malaria parasites. Subsequent serologic testing revealed positive IgG titers against P. falciparum and P. malariae (1:16,384), and against P. vivax and P. ovale (1:1,024). Polymerase chain reaction (PCR) analysis on pretreatment blood collected September 22 was negative for these four Plasmodium species. However, the mother was presumptively treated with chloroquine.

Reported by: NJ D'Avanzo, MD, Blue Ridge Pediatrics; VM Morris, MD, Raleigh Infectious Diseases Associates; TR Carter, MD, Rex Hospital; J-M Maillard, MD, PM Scanlon, MPH, General Communicable Disease Control Br, Div of Public Health, Raleigh, North Carolina. GM Stennies, MD, M Wilson, MS, Div of Parasitic Diseases, National Center for Infectious Diseases; and PDM MacDonald, PhD, RD Newman, MD, EIS Officers, CDC.

Editorial Note:

Although the infant in this report could have been infected by the bite of a mosquito that had bitten a P. malariae-infected person (e.g., one of the parents or the visitor from Kinshasa), congenital transmission is a much more likely source of infection. P. malariae can persist in humans as an asymptomatic erythrocytic disease for many years following an untreated or incompletely treated primary infection. Symptomatic recrudescence has been reported for up to 70 years following primary infection (4). Unlike P. vivax and P. ovale, no dormant form exists in the liver. Recrudescence should not occur following completed treatment with chloroquine; therefore, additional treatment with primaquine as is required for radical cure of P. vivax and P. ovale is not necessary.

Pregnancy can make women more susceptible to infection with malaria and might allow a sufficient increase in the density of parasitemia for passage of parasites through the placenta to the fetus (5). Suspected malaria in the neonate should be confirmed using Giemsa-stained thick and thin blood smears. If the infant's smear is positive for malaria parasites, the mother's smears also should be examined for malaria parasites. If the mother's smears are negative, then serologic analysis of her blood for Plasmodium-specific antibodies should be conducted. Negative results demonstrate an absence of current or previous malaria infection and would rule out maternal transmission of malaria. Positive results indicate infection at some time but cannot be used to differentiate current from previous infection or to determine the infecting Plasmodium species. In persons with negative blood films and positive serology, PCR might be useful to detect low-level parasitemia and to determine the infecting species.

In this case, the mother's serology demonstrates previous infection with malaria parasites at some time. The pattern of elevated titers to P. falciparumand P. malariae commonly is seen in persons who have had long-term exposure to malaria in areas of Africa where the disease is endemic. The failure to detect P. malariae in the mother by smear or the more sensitive PCR is expected because most women spontaneously clear parasitemia in the hours following delivery (6). The mother in this report was not tested until 10 weeks after delivery, well past the expected period for detecting parasitemia.

U.S. health-care providers should be alert to the diagnosis of malaria in ill neonates and young infants, particularly those with fever. During evaluation, health-care providers should obtain a complete and accurate travel and residency history on the patient and close relatives. Patients should be asked about transfusion of blood products. However, the absence of recent foreign travel or a long interval between immigration of the mother and the birth of the infant being examined should not dissuade clinicians from obtaining blood films on the patient to rule out a potentially life-threatening but easily treatable infection.

Additional information about malaria and its distribution is available from CDC at http://www.cdc.gov/travel. Information about the diagnosis of malaria and the preparation of blood films is available at http://www.dpd.cdc.gov/dpdx.

References

  1. Hubert TV. Congenital malaria in the United States: report of a case and review. Clin Infect Dis 1992;14:922--6.
  2. Gilles HM, Warrel DA. Bruce-Chwatt's Essential Malariology, 3rd ed. London: Arnold, 1996.
  3. Zucker JR, Barber AM, Paxton, LA, et al. Malaria Surveillance---United States, 1992. In: CDC Surveillance summaries. MMWR 1995;44(No. SS-5).
  4. Vinetz JM, Li J, McCutchan TF, et al. Plasmodium malariae infection in an asymptomatic 74-year-old Greek woman with splenomegaly. N Eng J Med 1998;2:367--71.
  5. Brabin BJ. An analysis of malaria in pregnancy in Africa. Bull World Health Organ 1983;61:1005--16.
  6. Nguyen-Dinh P, Steketee RW, Greenberg AE, et al. Rapid spontaneous postpartum clearance of Plasmodium falciparum parasitaemia in African women. Lancet 1988;2:751--2.

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