In Malawi, the standard of care to prevent malaria during pregnancy at the time of the study was a two dose sulfadoxine-pyrimethamine intermittent protective treatment (SP IPT) regimen administered in the second and third trimester of pregnancy. In this investigation, this two dose strategy was compared to a monthly SP regimen. The objective for the study was to determine the efficacy of the different regimens for HIV positive and HIV negative women in the prevention of placental malaria.

Condition	Intervention
Malaria, Falciparum HIV Infections	Drug: Monthly sulfadoxine/pyrimethamine  Drug: 2-dose sulfadoxine/pyrimethamine

Further Study Details: 

Primary Outcomes: Placental malaria parasitemia rates measured at time of delivery, stratified by HIV status
Secondary Outcomes: Proportion of newborns with low birth weight, stratified by HIV status; Proportion of women with third trimester anemia, stratified by HIV status; Proportion of pregnancies that suffer fetal loss, stratified by HIV status
Expected Total Enrollment:  700

In this protocol the researchers wish to elaborate prior investigations on factors which may affect prevalence and malarial parasite density in pregnant women in Malawi. Primarily, this investigation will evaluate the efficacy of the current Malawian national policy, sulfadoxine-pyrimethamine (SP) 2-dose intermittent protective treatment (IPT) strategy, and compare it to a monthly SP strategy for use in preventing malaria during pregnancy. Previous investigations in Malawi have demonstrated that: prevention of malaria during pregnancy is most important during the first and second pregnancies, particularly during the rainy season when malaria transmission is highest; and an efficacious antimalarial regimen which clears parasitemia and placental infection will result in a reduction in the incidence of low birth weight, the single greatest risk factor for neonatal and early infant mortality. There appears to be an interaction between HIV infection and placental malaria, with HIV-positive pregnant women having higher prevalences and densities of peripheral and placental parasitemia compared with HIV-negative pregnant women. This finding requires closer examination, in light of the high prevalence and incidence of HIV infection in Malawi and other African countries. Previously in Malawi, a 2-dose IPT regimen of SP administered during the second and third trimester of pregnancy was effective at clearing placental malaria infection at delivery More recent studies in both Malawi and Kenya show that 2 doses may not be adequate in clearing placental parasitemia especially in women who are HIV infected. In the Kenya study, HIV-positive women required 3 doses of SP (that were delivered in a monthly dosing scheme) to achieve similar reductions in placental parasitemia that were seen in HIV-negative women at 2 doses. There remains a need to identify the optimal dosing schedule for an intermittent treatment regimen; the Kenya findings need to be confirmed before decisions are made on national and global levels. This is especially important given the possibility of increasing SP resistance in Malawi. The question of HIV infection and its role in malaria during pregnancy, both in terms of impact on regimen effectiveness and on the incidence of adverse sulfa reactions needs to be examined. This study proposes to determine the efficacy of the current regimen of 2-dose SP intermittent protective treatment (IPT) and to compare it to monthly SP dosing in clearing placental parasitemia at delivery in Machinga district in Malawi where there is a high level of malaria transmission and an HIV seropositivity rate of nearly 20% in reproductive age woman. This study will also explore the effect of HIV seropositivity on the safety and efficacy of intermittent preventive treatment during pregnancy.

Ages Eligible for Study:  15 Years and above,  Genders Eligible for Study:  Female

Criteria

Inclusion Criteria:

• First or second pregnancy
• Greater than 16 weeks gestation
• Less than 28 weeks gestation
• Consent for HIV testing

Exclusion Criteria:

• Less than 15 years old

Malawi
      Machinga District Hospital, Liwonde,  Malawi

Study chairs or principal investigators

Scott J Filler, MD, DTM&H,  Principal Investigator,  Centers for Disease Control and Prevention   

Study ID Numbers:  CDC-NCID-3429
Last Updated:  August 22, 2005
Record first received:  August 3, 2005
ClinicalTrials.gov Identifier:  NCT00126906
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-08-23