1. Co-trimoxazole prophylaxis, antiretroviral therapy and ITNs can substantially reduce the incidence of malaria in women living with HIV.

A meta-analysis of studies assessing the impact of use of insecticide treated bednets (ITNs) on pregnant women found that use of ITNs compared to no use reduced placental parasitemia (malaria parasites in the placenta) by 23% and miscarriages and stillbirths by 33%. Three cluster-randomized and two individually randomized trials, four from Africa with 6,418 pregnant women and one from Thailand with 223 pregnant women, were included in the meta-analysis. Some women in the cluster-randomized trials became pregnant after ITNs were distributed and were therefore protected throughout pregnancy, when the risk of malaria parasitemia is greatest. ITNs used by the whole community results in area-wide reductions in malaria transmission.

A randomized nested case-control study of 836 HIV-infected persons on ART in Uganda from 2007 to 2008 examining the effects of discontinuing cotrimoxazole therapy for patients with CD4 counts over 200 cells/μl found that patients discontinuing daily cotrimoxazole therapy were at an increased risk for malaria and diarrhea compared to patients taking daily cotrimoxazole therapy. Ugandan national guidelines recommend all patients living with HIV take daily cotrimoxazole regardless of CD4 count. Participants were recruited from the Home Based AIDS Care program in Uganda, which provided HIV care and drug distribution primarily at home. On average, participants had been taking ART for over three years and CD4 cell count was 489 cells/μl. Seventy-five percent of study participants were women, yet sex-disaggregated data was not analyzed. Within four months of beginning the study, 315 cases of fever had been reported, 72% of which were among patients who had stopped taking cotrimoxazole. Patients who stopped taking cotrimoxazole had 32.5 times the risk of having malaria, 2.7 times the risk of having at least one febrile fever episode, and 1.8 times the risk of having diarrhea than patients taking cotrimoxazole. Patients that stopped taking cotrimoxazole were also more likely to have upper or lower respiratory infections. In the four years prior to the study, there had been no more than five cases of malaria reported within the Home Based AIDS Care program. However, in one month there were over 20 episodes of malaria in the group that had stopped taking cotrimoxazole. As a result of the increased risks to patients, the study was stopped four months after beginning so all patients could resume taking daily co-trimoxazole.

A prospective cohort study in Uganda funded by PEPFAR found that co-trimoxazole prophylaxis, antiretroviral therapy and insecticide treated bednets substantially reduced the frequency of malaria in adults with HIV. Of 466 people living with HIV aged 18 and over, 75% were women, of whom 56 died and 11 were lost to follow-up. Of those who died or were lost to follow up, none had received the intervention. Of the 399 remaining who started co-trimoxazole, 138 survived and were clinically eligible for antiretroviral therapy and received both co-trimoxazole and antiretroviral therapy. In addition to these 138 who received both co-trimoxazole and antiretroviral therapy, an additional 897 additional people also received both co-trimoxazole and antiretroviral therapy. Of these 1,035 people who received co-trimoxazole and antiretroviral therapy, 45 died and five moved or were lost to follow-up. The remaining 985 people also received insecticide treated bednets, including four people who started co-trimoxazole, antiretroviral therapy and received ITNs simultaneously. CD4 counts were taken when first enrolled and at regular intervals. Antiretroviral therapy was delivered to homes in prepackaged pillboxes and pills were counted at each visit. According to pill counts, 98% took at least 95% of the prescribed antiretroviral therapy. Two insecticide treated bednets were given to all households with instructions for use. Median follow up before co-trimoxazole was 154 days; during co-trimoxazole and antiretroviral therapy 126 days; and during co-trimoxazole, antiretroviral therapy and ITNs, 560 days. 120,750 home visits were done. Compared with no intervention, co-trimoxazole prophylaxis was associated with a 76% lower malaria rate (9.0 versus 50.8 episodes per 100 person-years); antiretroviral therapy and co-trimoxazole with a 92% lower malaria rate; and co-trimoxazole, antiretroviral therapy and ITNs with a 95% lower malaria rate (50.8 episodes per 100 person years to 2.1 episodes per 100 person years among people living with HIV) than during the time with no intervention of co-trimoxazole.

Starting in 2006, the government of Rwanda scaled up preventive and curative malaria interventions, increasing access to Artemisinin Combination Therapies (ACT) and delivering 1.6 million ITNs in one week with an additional 1.6 million ITNs distributed by April 2009 through ANC and community health workers, reducing deaths from malaria by 60%. Because everyone in the household received an ITN, pregnant women were ensured access to ITNs. Approximately 60% of pregnant women in 2007 slept under ITNs. Nine of ten private pharmacies now carry ACT. Between 2001 and 2005 only a few hundred thousand ITNs were distributed with negligible impact.

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2. Intermittent preventive treatment of malaria with sulfadoxine-pyrimethamine (SP) is effective in preventing malaria and decreasing prevalence of anemia among pregnant women with HIV.

A Cochrane review of two randomized controlled trials (Filler et al., 2006; Hamer et al., 2007) of 722 HIV-positive pregnant women found that the monthly regimen of sulfadoxine-pyrimethamine (SP) was associated with less placental parasitemia and less peripheral parasitemia than a two-dose regimen in the second and third trimesters among women in their first pregnancies (primigravidae) and women in their second pregnancies (secundigravida). Women who were pregnant for at least a third time (multigravidae) who took the monthly dose had significantly higher levels of haemoglobin compared to women taking the two-dose regimen. Also, babies born to primigravidae and secundigravida women taking the monthly dose had higher mean birth weight compared to babies born to women in the two-dose group. Using three or more doses of sulfadoxine-pyrimethamine (SP) was more effective than using the standard two-dose regimen among HIV-positive pregnant women.

A study of 302 pregnant women from Mozambique between August 2003 to November 2006, 88 HIV-positive, 177 HIV-negative, and 37 of unknown HIV status, randomized into a placebo-control trial found that two doses of intermittent preventative treatment (IPT) with sulfadoxine-pyrimethamine (SP) did not enhance the risk of malaria associated morbidity in mothers. Presence of maternal malaria was determined by collection of maternal placental tissue immediately following birth and a maternal blood sample eight weeks following delivery. At time of delivery or postpartum, 32% of HIV-positive mothers and 15% of HIV-negative mothers were infected with malaria. Results showed a lower level of antibodies among HIV-positive pregnant women receiving treatment compared to those receiving the placebo.

A randomized, double-blind, placebo-controlled trial of 1030 pregnant women in Mozambique from 2003 to 2005 found that two-dose SP reduced the incidence of maternal malaria during pregnancy and reduced the prevalence of peripheral parasitemia, regardless of HIV status. Women in the intervention group received two-doses of SP, three tablets twice during the second trimester, one month apart. All women in the study were given long-lasting insecticide treated bed nets and offered an HIV test. Eighty-five percent of women had an HIV test and 23.6% were HIV-positive. The risk of fetal anemia decreased by 50% in the SP group compared to the placebo group. Use of SP also decreased maternal malaria by 40%. Among the women with HIV, the SP group had significantly less parasite infected placentas (6%) than the placebo group (24%).

A study in Malawi from 2002 to 2005 compared monthly doses of Sulfadoxine-Pyrimethamine (SP) Intermittent Preventive Treatment (IPTp) from initiation to delivery with a 2-dose treatment of SP, at initiation and 28 weeks, to prevent placental malaria in 195 HIV-positive and in 303 HIV-negative pregnant women. The study found that monthly dosage proved more effective for HIV-positive women with only 7.8% having placental malaria at delivery compared to 21.5% of women who underwent the 2-dose regimen. Reduction in relative risk was similar for HIV-positive and HIV-negative women: for HIV-negative women, 2.3% receiving monthly SP and 6.3% receiving 2-dose SP had placental malaria, though the difference was not significant. Adverse drug reactions were reported in less than 1% of women. During the study combination antiretroviral therapy was not routinely available in Malawi.

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3. PCR has a higher sensitivity than blood-smear microscopy to detect malaria co-infection in HIV-positive and HIV-negative pregnant women.

A longitudinal cohort study of 182 pregnant women in the Democratic Republic of Congo from 2005 to 2006 found that real-time polymerase chain reaction (PCR) had a higher sensitivity and specificity for detecting malaria when compared with blood-smear microscopy. Sensitivity for PCR was 61.9%, more than 20% higher than blood-smear microscopy at 42.0%. Specificity for PCR was also higher at 91.4% than blood-smear microscopy at 83.4%. PCR detected 35 positive cases of malaria that blood-smear microscopy categorized as negative. In order to detect these 35 cases with microscopy the samples would need to be retested, costing over $3,000. The PCR strategy saved $1,553 by correctly detecting the 35 cases as positive, a 51% cost savings. Of the 182 women enrolled in the study 2.7% were HIV-positive and 31% had parasitic malaria either during pregnancy or at delivery.

A hospital-based study in Kenya followed 157 women ages 15-40 with vaginal deliveries and found placental malaria in 17.2% of infants and congenital malaria in 0% of infants by microscopy, while PCR detected 33.1% and 10.8%, respectively.

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