Pregnancy and malaria
Pregnancy is associated with an increased susceptibility to clinical malaria and severe infection in semi-immune women in areas of high malarial endemicity (see pp.657-74). The prevalence of malaria is highest during the second trimester of pregnancy and primi-gravidae are at greatest risk. 21 There is evidence of sup-pression of antibody formation and desup-pression of cell-mediated immunity to explain this increase in malaria infection in pregnant women. Severe anaemia results from the destruction of sensitized red cells and the depression of erythropoiesis. Malaria in pregnancy may cause abortions and an increase in premature labour. Heavy infections of the placenta with Plasmodium falciparum occur in immune mothers, particularly primiparous women. Microscopic examination of the infected placentae show large intervillous accumulations of parasitized erythrocytes together with monocytes containing ingested pigment.
In addition, the trophoblastic basement membrane shows irregular thickening with protrusion of syncytio-trophoblast into the basement membrane. These patho-logical changes prove that P. falciparum damages the placenta and interferes with the blood supply to the
fetus. Therefore, malaria in pregnancy leads to intra-uterine growth retardation and a high frequency of small-for-gestational-dates infants; mean singleton birth weights being depressed by about 170 g.
The incidence of congenital malaria is low in infants of immune mothers but is more frequent in babies born to non-immune women. The factors protecting the neonate against malaria include the placenta which acts as an effective filter of parasites, passively acquired maternal antimalarial IgG antibodies, fetal haemo-globin and a diet of milk. A cross-sectional survey in the Gambia showed that there was a seasonal fluctuation in antimalarial IgG in cord blood but this did not follow the pattern in pregnant women. During the wet season when parasitaemia and antibody levels rose steeply in pregnant women, antibody levels in cord blood fell.
The authors suggested that the placenta infected with malaria acted paradoxically as a barrier to the passage of antimalarial IgG from mother to fetus.
Malarial parasites experience retardation of growth in erythrocytes containing fetal haemoglobin. These findings suggest an explanation for high gene fre-quencies of thalassaemias in malaria-endemic areas because of the protection against malarial parasitaemia offered by fetal haemoglobin. An exclusive milk diet has been shown to suppress malarial infection in infants and experimental animals by depriving the parasite of para-aminobenzoic acid required for its growth in the erythrocyte.
Congenital malaria
Congenital malaria may occur with infections of P.
falciparum, P. vivax and P. malariae. Keitel et al.22 described a case of congenital quartan malaria which presented with the nephrotic syndrome at 21 months of age. The drug-addicted mother had acquired her infection by syringe inoculation in a non-malarious area. Complete remission of the nephrotic syndrome occurred following antimalarial treatment.
Factors responsible for the transplacental trans-mission of malaria are not fully understood but placental damage, either overt or occult, has been suggested as a probable route. The role of placental damage was probably crucial in the transmission of P. vivax malaria to one non-identical twin born in Birmingham. The first twin of a primigravid woman from India, delivered as a vertex presentation assisted by Wrigley's forceps, showed no evidence of malaria on repeated blood film examination. The second twin was a transverse lie who was delivered by breech extraction after an internal version under general anaesthesia.
This infant became febrile when 42 days old, developed
splenomegaly, anaemia (Hb 6g/dl) and had P. vwax In
the blood.
Clinical features
Infants with congenital malaria are usually well at birth but develop symptoms of fever, jaundice, abdominal distension and pallor from 5 to 20 days of age. Severe anaemia and massive splenomegaly are found in most infants. Clinical presentation is similar irrespective of the type of malarial infection. Women living in areas of unstable malaria may transmit the infection to their fetuses in spite of treatment. In South East Asia, a region of unstable malaria, untreated P. falciparum infection in a teenage primigravid Malay mother during the last trimester of pregnancy resulted in a neonate developing congenital malaria on the third day of life presenting with jaundice and parasitaemia.
Serological tests showed specific IgM antibodies against P. falciparum at titre 1 :64 in maternal blood, cord blood and in the baby during the first fortnight of life. Since maternal IgM antibodies do not cross the placental barrier, P. Jalciparum-specific IgM antibody in the neonate was probably a primary antibody response and confirmed intrauterine infection.
Treatment
Chloroquine is the drug of choice in the treatment of congenital malaria. An initial dose of chloroquine (10 mg/kg) is followed by a similar dose six hours later.
Two further doses of chloroquine (5 mg/kg) are given on the second and third day of treatment.
The widespread development of chloroquine-resistant P. falciparum infection has led to the use of quinine as the drug of choice in regions of unstable malaria; in Papua New Guinea, East Africa and parts of Central and West Africa. Quinine in a dose of 10 mg/kg every eight hours for seven days, may be given by mouth; intravenous infusion in 30 ml of 5 percent dextrose per dose of quinine over eight hours, may also be used. Cardiac arrhythmias (prolonged QT and T -wave flattening), hypotension and hypo-glycaemia may follow rapid intravenous infusion.
To ensure eradication of exoerythrocytic forms of P.
vivax, a 14 day course of primaquine (0.5 mg/kg daily) is given after the chloroquine. Primaquine should not be given to infants with glucose-6-phosphate dehydrogenase (G6PD) deficiency.
Protection of pregnant women
Pregnant women are at risk of severe malaria during
References 1 73 the second and third trimester. Semi-immune women become anaemic with malaria and their offspring are subject to intrauterine growth retardation because of placental damage by Plasmodia. Non-immune mothers are likely to transmit the malarial parasite to their infants. Therefore, it is prudent to protect all pregnant women living in endemic areas against malaria by chemoprophylaxis using pyrimethamine (25 mg weekly), proguanil (100 mg daily) or chloroquine (200 mg weekly). Visitors who leave a malarious country must remember to continue chemoprophylaxis for at least four weeks. In chloroquine-sensitive regions of stable P. Jalciparum malaria I recommend 200 mg of chloroquine once a week; in regions of unstable malaria where the P. Jalciparum is resistant to chloroquine, a combination of chloroquine (200 mg weekly) and proguanil (100 mg daily) is currently recommended by the World Health Organization.
Chloroquine-resistant P. falciparum malaria in South East Asia has spread to Latin America and East Africa and necessitated the use of combinations of pyrimethamine with dapsone (Maloprim) or pyri-methamine with sulphadoxine (Fansidar). But the use of these drugs in pregnant women is controversial because of the alleged embryopathic action of pyrimethamine or possible effects of long-acting sulphonamides on the haemopoietic organ of the fetus, and the reports of agranulocytosis associated with Maloprim. The search for new antimalarials has identified Mefloquine, a drug structurally related to quinine and Qinghaosu, a compound extracted from the herb Artemisia annua and used in China for 2000 years. Both compounds are being developed and evaluated under the auspices of the WHO.
Neonates who require blood transfusions or exchange transfusion in malaria endemic areas might be at risk of transfusion-acquired malaria. It is recommended that these infants receive a curative course of chloroquine following their transfusion. In areas now known to have chloroquine-resistant malaria, the new antimalarial compounds should be used.
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