Monthly sulfadoxine-pyrimethamine might protect HIV-positive African pregnant women against placental malaria

Monthly treatment with sulfadoxine-pyrimethamine (SP) is significantly more effective in preventing malaria in pregnant women than the current practice of giving two doses of SP during pregnancy, according to a US-sponsored study carried out in Malawi, published in the August 1^st edition of the Journal of Infectious Diseases.

About twelve million pregnant women in sub-Saharan Africa suffered malaria attacks (caused by mosquito-borne Plasmodium falciparum) in 2005. Young women getting pregnant for the first time are at a greater risk of suffering severe placental malaria.

The severe consequences of placental malaria include anaemia, still-births, miscarriages, abortions, low birth weight infants, and maternal death. Low birth weight infants are vulnerable to the many childhood diseases which are rampant in Africa.

This problem is compounded by the fact that HIV infections are common in countries in which malaria is entrenched. Thus an HIV-positive pregnant woman will get one or two malaria attacks during the year. Since HIV compromises the immunity needed to control malaria, HIV-positive adult Ugandans have more frequent malaria attacks and more HIV-positive pregnant women than HIV-negative pregnant women have malaria parasites in their blood.

The HIV-positive pregnant woman also suffers the brunt of a malaria attack in a more direct way; malaria increases HIV viral loads and increases the risk of mother-to-child transmission of HIV and disease progression.

There is a conspicuous lack of a clear treatment policy for protecting pregnant women and their unborn infants from both HIV and malaria.

Early studies in Malawi and Kenya reported that giving two doses of sulfadoxine-pyrimethamine (SP) during pregnancy prevented malaria, anaemia and low birth weight deliveries. The two-dose SP regimen has since become the national treatment policy for the prevention of malaria in pregnancy in many African countries.

However, the effectiveness of two-dose SP in HIV-positive women has been questioned. Therefore investigators from Malawi and the US Centers for Disease Control investigated the usefulness of a two-dose SP versus monthly SP in preventing placental malaria.

The study took place at the Machinga District Hospital in Malawi and involved 266 HIV-positive and 432 HIV-negative pregnant women who were pregnant for the first or second time. Midwives saw the women monthly till delivery to record side-effects and malaria attacks. At delivery maternal, placental, and cord blood samples were examined for malaria parasites. HIV-positive women received a single dose of nevirapine during labour and their newborn infants received the drug within 72 hours of birth. After delivery, the infants were weighed and observed for one month.

Monthly SP significantly reduced placental malaria in both HIV-positive and HIV- negative women when compared to two-dose SP, although the effect was more striking in the HIV-positive group. HIV-positive women were almost 70% less likely to have placental malaria at the time of delivery if they received monthly SP (relative risk 0.31, 95% confidence interval 0.17-0.79).

In both groups of women, monthly SP resulted in significantly fewer malaria attacks by comparison with the 2-dose SP. There was no effect on infant birth weights.

SP contains sulfonamide and there is fear that HIV-positive patients on SP treatment are at an increased risk for sulfonamide-related side-effects. This was not the case in the Malawian study. Both the monthly and two-dose SP produced no serious side-effects in mothers and infants.

These results are exciting and provide important insights for a policy of controlling malaria in HIV-positive pregnant women. However, this enthousiasm must be tempered with caution, researchers from the United States, Malawi and Australia point out in an accompanying editorial.

First, the validity of the efficacy observed with the monthly SP in the Malawian HIV-positive pregnant women needs to be confirmed in other African countries. A recent study in Zambia suggested that there was no difference between the two-dosing regimens in HIV-positive people, the editorial authors note.

Second, SP resistance is increasing in many African countries. A policy based on SP might soon become obsolete.

Third, cotrimoxazole (CTX), another sulfonamide-containing drug, is recommended by World Health Organization (WHO) for controlling opportunistic infections in HIV-positive patients. There is evidence that CTX also controls malaria. There are also serious concerns about the side-effects of CTX use during pregnancy, for both mother and the child. The Malawian study did not assess the impact of CTX prophylaxis on the usefulness of once monthly SP.

Finally, there are concerted international and local efforts to make access to antiretroviral drugs (ART) available to all HIV/AIDS patients in Africa. However, the interaction between ART, CTX, and SP in these patients remains unknown.

Nevertheless, they say, the implementation of a policy which involves the integrated management of HIV and malaria in HIV-positive pregnant African women is an urgent imperative.