Susceptibility of the mother
Complex physiologic changes happening during pregnancy, including hormonal and immunologic alterations, make both pregnant woman and the fetus more susceptible to malaria infection and its complications.
Both P.vivax and P.falciparum malaria can pose problems, although P.falciparum is much more dangerous in causing serious sequalae.
Pregnancy is naturally accompanied by generalized immunosuppression, which may cause the loss of acquired immunity to malaria. Finding the pathologic mechanisms explaining the dramatic course malaria in pregnancy, is a hot scientific topic nowadays. It has been hypothesized that pregnancy creates the "hole" in our physiologic barrier. This will expose a pregnant woman to the strain of the parasite never seen before by her immune system. This time the parasite will snick in through the "antibody hole" (Fig1.). According to this hypothesis the pregnant women in malaria endemic areas who used to be partially immune to malaria, suddenly become non-immune and thus strong candidates for severe and complicated infection.

Fig1. "Antibody hole" in pregnancy

Pregnancy Associated Malaria
In reality what is happening in pregnant woman with P.falciparum malaria is much worse than just downgrading to non-immune susceptible individual. As it has turned to be, placenta is one of the most preferable sequestration sites in human organism for P.falciparum (Fig2.).
Heavy placental sequestration may interfere with oxygen and nutrient transport to the fetus. High maternal susceptibility to malaria is responsible for high parasitemia in pregnancy (10 fold increase). Real hyperparasitemia in pregnancy may be often offset by high parasite burden in placenta. This has to be always kept in mind even if the peripheral parasite counts are low. In previously immune individuals first (primigravidae) and second pregnancies carry highest risk for both mother and infant. Subsequent pregnancies have usually milder forms of infection and carry lower risk. In non-immune mothers all pregnancies are dangerous.

Clinical features
Clinical features are often atypical especially in the second half of pregnancy. Severe anemia is an often complication, since besides the hemolysis of the infected blood cells, there is a background increased demands of iron and folate in pregnancy. Anemia increases perinatal mortality and maternal morbidity and mortality. Significant anemia (Hb < 7-8 g%) may have to be treated with blood transfusion. In view of the increased fluid volume in pregnancy, it is better to transfuse packed cells than whole blood. Rapid transfusion, particularly whole blood, may cause pulmonary edema.
Pulmonary edema is also an often complication, which carries a very high mortality. Patients should be managed in ICU with careful fluid management, oxygen, diuretics, and ventilation if needed. Hypoglacemia is another important complication. If untreated, it can easily cause fetal distress. In all pregnant women with falciparum malaria, particularly those receiving quinine, blood sugar should be monitored every 4-6 hours.
P.vivax malaria is much milder in pregnancy, although it still causes slight anemia and slight reduction in birth weight.

Effect on child
Malaria is very dangerous for the fetus. Placental insufficiency, hypoglycemia, anemia and other complications can all be detrimental for the child. Rates of abortion, premature birth, intrauterine growth retardation, low birth weight etc. are significantly higher during pregnancy. Both P.vivax and P.falciparum can dramatically increase infant mortality (see Fig3.), although the effect of P.falciparum remains most serious.

Fig3. P.falciparum effect on child

In rare cases (< 5%) malaria can be transmitted to the child. All four species can cause congenital malaria, but it is proportionately more with P.malariae.

Malaria in pregnancy should be treated immediately. One should always remember that malaria is more harmful for the fetus than any anti-malarial drug. However, using drugs that are acceptable in pregnancy should be always a priority.

Drugs felt to be safe: Chloroquine, Amodiaquine, Clindamycin, Quinine (careful administration - high dose may cause abortion), Sulfadoxine/Pyrimethamine (Fansidar®, avoid last month because of kernicterus risk), Proguanil, Dapson-Pyrimethamine (Maloprim), Pyrimethamine, Mefloquine, Artemisinins
Drugs with limited or no data: Malarone, Chlorproquanil-Dapsone (Lapdap), Combination of Artemisins with others
Drugs to be avoided: Tetracycline, Doxycycline, Primaquine, Tafenoquine, Halofantrine

When treating a pregnant woman with P.vivax, the administration of primaquine should be delayed untill after delivery or, if it is impossible to reveal the G6PD status of child, then untill the end of lactation period. Ssuppressive chemoprophylaxis with chloroquine is recommended during this period (500 mg weekly). Whenever safe, a complete treatment with full therapeutic dose of chloroquine and primaquine should be administered.

Prophylaxis to pregnant and pregnant travelers
Prophylaxis of all pregnant women in malaria endemic areas is an essential task of any antenatal care. Chloroquine with or without proguanil should be the first choice. The supplement of folate (5mg daily) is also recommended. 500 mg of chloroquine should be administered once every week. However, poor compliance and wide spread of chloroquine resistance limit this regimen. Alternative medications to consider include amodiaquine, Sulfadoxine/Pyrimethamine (SP), and mefloquine.
WHO recently changed their policy to recommend Intermittent Presumptive Therapy (IPT) with SP for women in high transmission areas. IPT with 2 to 3 doses of Sulfadoxine/Pyrimethamine in the 2nd and 3rd trimesters of pregnancy has been shown to decrease the prevalence of placental malaria in areas in East Africa with high rates of chloroquine resistance. IPT is thought to be an attractive alternative to weekly chloroquine as it should improve compliance.
All pregnant women should be advised against traveling to malarious areas, especially to multi-drug resistant regions, in which case woman should be strongly discouraged to travel. However, if woman persists on traveling, she should be very thoroughly educated about the mosquito bite prevention. Malaria prophylaxis (chloroquine +/- proguanil) should be started 1 week before travel and continued weekly for the duration of travel and for 4 weeks after leaving the malarious region. Woman should be also advised to seek care immediately once contracted malaria.


© 2002. Malaria in Armenia.
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