In countries without indigenous malaria, medical education stresses the peril of febrile Plasmodium falciparum malaria. While this is the case in non-immune persons, such as travelers, P falciparum infection presents in semi-immune persons mostly as a chronic disease with only rare bouts of fever, if any. Women immigrating from endemic to non-endemic countries with no malaria transmission are no longer considered to be at risk for the disease. The fact that they may still have persistent parasitemia after departing from their native country is not widely recognized. This report presents four afebrile pregnant women with P falciparum malaria who had emigrated from endemic countries 3 to 13 months earlier. We believe they represent only the tip of the iceberg, and the diagnoses are often missed in pregnant immigrants: in our patients the only sign was anemia found in a routine check-up.
We report four cases of asymptomatic Plasmodium falciparum malaria in pregnant African women. They had immigrated to Finland 3 to 13 months earlier. The disease was revealed only by anemia. The diagnosis relied on blood smear which showed a parasitemia <0.2% in three cases. Medical personnel should be informed about the possibility of afebrile forms of malaria in pregnant women even months after immigration. Very low levels of parasitemia may call for a more sensitive diagnostic approach such as polymerase chain reaction.
The first patient was a 32-year-old woman from Cameroon who had not traveled abroad since moving to Finland in July 2002. While in Cameroon, she had had malaria several times, most recently 1 year before immigration. Early in her pregnancy, in June 2003, she was found to be anemic (Hb 93 g/L) and started taking iron supplements. Despite the treatment, her hemoglobin decreased to 84 g/L, and she was referred to a hematologist. Her blood smear, obtained 13 months after arrival, was positive for P falciparum ring forms with a parasitemia of <0.1%. After 7 days of oral treatment with quinine, the anemia subsided.
The second patient was a 23-year-old woman who had immigrated to Finland in September 2007 from the Democratic Republic of the Congo, and had not traveled abroad since then. She had been treated for malaria about 1 year before emigrating. After living in Finland for 6 months, in week 29 of her pregnancy, she was referred to a maternity hospital owing to anemia with Hb 72 g/L. Microscopy was positive for P falciparum with a parasitemia of <0.1%. The patient was treated with oral quinine for 10 days and her anemia subsided.
The third patient, a 25-year-old woman from Nigeria, had not traveled abroad since immigrating to Finland early in her pregnancy in May 2010. After 6 months she was referred to the maternity hospital because of treatment-resistant anemia (Hb 72 g/L). Tests for hemolysis were positive with Hb 68 g/L at its lowest. A rapid diagnostic test was positive for P falciparum, and the laboratory reported a parasitemia of <0.2% in blood smear (pregnancy week 25+). The diagnosis was also confirmed by polymerase chain reaction (PCR). The patient was treated with a combination of oral quinine and clindamycin for 10 days after which her anemia subsided.
The fourth patient was a 26-year-old woman who had immigrated to Finland in April 2011 from Kenya, where she had been treated for malaria in January the same year. Three months after immigration, with pregnancy week 22+, she was admitted to the maternity hospital because of high C-reactive protein and abdominal discomfort. A diagnosis of anemia (Hb 101 g/L) was established, a rapid test for malaria proved positive, and a smear revealed a parasitemia of 1.6%. The patient was treated with a combination of oral quinine and clindamycin for 10 days, and remained well after that.
In areas where malaria is highly endemic, particularly in sub-Saharan Africa, constant exposure to the parasite results in a gradual development of immunity starting from early childhood. While severe malaria mostly occurs in children, adults usually get a mild or asymptomatic disease and parasitemia may persist for long periods of time, often unnoticed. In areas where malaria is mainly present during epidemics, such as India, the exposure to malaria parasites is not frequent enough to elicit similar immunity, and all age-groups are at risk of severe malaria.
Pregnant women differ from other patient groups. Even in highly endemic areas, immunity fails to protect women during pregnancy, as P falciparum parasites sequestering in the placenta start to express novel types of antigenic structures not covered by the pre-existing immunity. Moreover, high numbers of parasites may be present in the placenta even when the peripheral blood malaria smear remains negative or shows only low numbers of parasites.[4, 5] This implies that pregnant women, particularly during their first pregnancy, are at increased risk. During subsequent pregnancies, the immune system will have adapted to the new types of antigens associated with placental sequestration, which will reduce the risk of severe disease.
Asymptomatic malaria is quite common among immigrants from highly endemic areas.[8-10] According to various reports, the prevalence of persistent parasitemia among refugees varies from 3% to >60%. While the majority remains asymptomatic, the parasitemia may last for years. There is also a risk of symptomatic malaria in pregnant women; cases have been reported over 3 years after immigration.
Persistent parasitemia poses a health risk for both the mother and the unborn child. Subclinical malaria may become acute at any time, and the child runs a risk of congenital malaria. Anemia is found more commonly in parasitemic women. All our patients had hemolytic anemia, as judged on the basis of undetectable haptoglobin and elevated lactate dehydrogenase levels, and increased reticulocyte count. The parasites cause anemia in the mother in a number of ways: erythrocyte destruction, splenic sequestration of non-parasitized erythrocytes, and bone marrow dysfunction. The oxygen transport to the unborn child becomes impaired. Placental malaria contributes to premature deliveries, low birth weight, and increased risk of infant death. The prevention of malaria will reduce all these risks to a substantial degree. Accordingly, WHO recommends intermittent preventive treatment in pregnancy (IPTp) to all pregnant women at risk of P falciparum infection in countries in sub-Saharan Africa with stable malaria transmission given at the first and second scheduled antenatal care visits after the first noted movement of the fetus. The US Centers for Disease Control and Prevention (CDC) recommend pre-departure presumptive treatment without malaria tests to all refugees (not all immigrants) from highly endemic countries, excluding pregnant or lactating women—in these groups only confirmed malaria is treated. However, conventional thick films have been reported to significantly underestimate placental malaria,[4, 5] which leads to a failure to identify malaria as a cause of fetal impairment. Rapid diagnostic tests are considered more sensitive than conventional thick films.[4, 5] PCR, the most sensitive diagnostic tool,[4, 5] is rarely available.
After immigrating to non-endemic areas, pregnant women from regions with high malaria endemicity no longer benefit from the IPTp programs carried out in their native country. In the new home, their malaria tends to be neglected, as both the possibility of asymptomatic malaria and the persistence of parasites in semi-immune individuals are poorly known. Most Western countries have no recommendations on screening for malaria in pregnant immigrants, even though persistent parasitemia is a health risk for unborn children. A negative blood smear does not rule out the disease, which should be emphasized when training health care personnel. They should also be aware of the possibility of malaria in anemic pregnant immigrants from areas with high endemicity even years after the immigration. Diagnostic tests including rapid tests or, when possible, PCR should be made, and, if positive, treatment should be started without delay. Obviously, all immigrants from high malaria endemicity areas would benefit from screening.
The authors thank Elisabet Tyyni, HUSLAB, Helsinki University Central Hospital, Finland, for her contribution in laboratory work.
Declaration of Interests
The authors state they have no conflicts of interest to declare.