Intermittent preventive treatment of malaria during pregnancy in central Mozambique

PROBLEM: New WHO strategies for control of malaria in pregnancy (MiP) recommend intermittent preventive treatment (IPTp), bednet use and improved case management. APPROACH: A pilot MiP programme in Mozambique was designed to determine requirements for scale-up. LOCAL SETTING: The Ministry of Health worked with a nongovernmental organization and an academic institution to establish and monitor a pilot programme in two impoverished malaria-endemic districts. RELEVANT CHANGES: Implementing the pilot programme required provision of additional sulfadoxine-pyrimethamine (SP), materials for directly observed SP administration, bednets and a modified antenatal card. National-level formulary restrictions on SP needed to be waived. The original protocol required modification because imprecision in estimation of gestational age led to missed SP doses. Multiple incompatibilities with other health initiatives (including programmes for control of syphilis, anaemia and HIV) were discovered and overcome. Key outputs and impacts were measured; 92.5% of 7911 women received at least 1 dose of SP, with the mean number of SP doses received being 2.2. At the second antenatal visit, 13.5% of women used bednets. In subgroups (1167 for laboratory analyses; 2600 births), SP use was significantly associated with higher haemoglobin levels (10.9 g/dL if 3 doses, 10.3 if none), less malaria parasitaemia (prevalence 7.5% if 3 doses, 39.3% if none), and fewer low-birth-weight infants (7.3% if 3 doses, 12.5% if none). LESSONS LEARNED: National-level scale-up will require attention to staffing, supplies, bednet availability, drug policy, gestational-age estimation and harmonization of vertical initiatives.     

Effect of a community-based delivery of intermittent preventive treatment of malaria in pregnancy on treatment seeking for malaria at health units in Uganda

BACKGROUND: The impact of intermittent preventive treatment (IPTp) on malaria in pregnancy is well known. However, in countries where this policy is implemented, poor access and low compliance have been widely reported. Novel approaches are needed to deliver this intervention. OBJECTIVE: To assess whether traditional birth attendants, drug-shop vendors, community reproductive health workers and adolescent peer mobilizers can administer IPTp with sulphadoxine-pyrimethamine (SP) to pregnant women, reach those at greatest risk of malaria, and increase access and compliance with IPTp. STUDY DESIGN: An intervention study compared the delivery of IPTp in the community with routine delivery of IPTp at health units. The primary outcome measures were the proportion of adolescents and primigravidae accessed, and the proportion of women who received two doses of SP. The study also assessed the effect of the intervention on access to malaria treatment, antenatal care, other services and related costs. RESULTS: More women (67.5%) received two doses of SP through the community approach compared with health units (39.9%; P<0.0001). Women who accessed IPTp in the community were at an earlier stage of pregnancy (21.0 weeks of gestation) than women who accessed IPTp at health units (23.1 weeks of gestation; P<0.0001). However, health units were visited by a higher proportion of primigravidae (23.6% vs 20.0%; P<0.04) and adolescents (28.4% vs 25.0%; P<0.03). Generally, women who accessed IPTp at health units made more visits for malaria treatment (2.6 (1.0-4.7) vs 1.8 (1.4-2.2); P<0.03). At recruitment, more women who accessed IPTp at health units sought malaria treatment compared with those who accessed IPTp in the community (56.9% vs 49.2%). However, at delivery, a high proportion of women who accessed IPTp in the community had sought malaria treatment (70.3%), suggesting the possibility that the novel approach had a positive impact on care seeking for malaria. Similarly, utilization of antenatal care, insecticide-treated nets and delivery care by women in the community was high. The total costs per woman receiving two doses of SP for IPTp were 4093 Uganda shillings (US$ 2.3) for women who accessed IPTp at health units, and 4491 Uganda shillings (US$ 2.6) for women who accessed IPTp in the community. CONCLUSION: The community approach was effective for the delivery of IPTp, although women still accessed and benefited from malaria treatment and other services at health units. However, the costs for accessing malaria treatment and other services are high and could be a limiting factor in mitigating the burden of malaria in Uganda.     

Ethnographic study of factors influencing compliance to intermittent preventive treatment of malaria during pregnancy among Yao women in rural Malawi

In Africa today one of the main strategies to reduce malaria infection during pregnancy is the promotion of intermittent preventive treatment (IPT). To date only a few studies have investigated the factors affecting compliance to IPT. This medical anthropology study aims to describe these factors from the perspective of pregnant women in rural Malawi. We examine women's knowledge and perceptions about the use of medication in pregnancy and the timing and motivation concerning use of antenatal clinic (ANC) services. In addition, the circumstances and interaction at the ANC and the IPT implementation process are described. The data were collected by applying an ethnographic approach, including focus group discussions (n=8), in-depth interviews (n=34), drug identification exercises, participant observation and a 'knowledge, attitudes and practices' survey (n=248). This study discovered several factors affecting IPT. These were: unclear messages about IPT with sulfadoxine-pyrimethamine (SP) from nurses; timing of SP-1; periodic shortages of SP; women's limited understanding of IPT-SP; tendency for late enrolment; and nurses' underperformance. The results of this study show that understanding of the multiple contexts affecting malaria prevention is important, and that ethnographic research is useful for discovering and solving problems beyond the scope of many other research approaches.     

Uptake of intermittent preventive treatment in pregnancy for malaria: further analysis of the 2016 Ghana Malaria Indicator Survey

Journal of Public Health - Significant proportions of pregnant women living in malaria-endemic countries throughout the world are exposed to the risk of malaria. The World Health Organization (WHO)...     

Impact of mobile phone intervention on intermittent preventive treatment of malaria during pregnancy in Burkina Faso : A pragmatic randomized trial

PurposeIntermittent preventive treatment of malaria with sulphadoxine-pyrimethamine for pregnant women (IPTp-SP) coverage remains far below the desirable goal of at least three doses before delivery. This study evaluates an innovative intervention using mobile phones as a means of increasing coverage for the third dose of IPTp-SP.MethodsThis study in Burkina Faso was designed as an open-label, pragmatic, two-arm, randomised trial. Pregnant women who attended antenatal clinic (ANC) visits were included at their first ANC visit and followed until delivery. The intervention was built around the use of mobile phones as means ensuring direct tracking of pregnant women.ResultsTwo hundred and forty-eight (248) pregnant women were included in the study. The proportion of women who received at least three doses of IPTp-SP was 54.6 %. In the intervention group, 54.1 % of women received at least three doses of IPTp-SP versus 55.1 % in the control group, a non-significant difference (adjusted odds ratio “aOR”, 0.86 ; 95 % confidence interval “95 % CI”, 0.49–1.51). Women in the intervention group were more likely to carry out their ANC visits in a timely manner than those in the control group (aOR, 3.21 ; 95 % CI, 1.91–5.39).ConclusionWhile mobile phone intervention did not increase the proportion of women receiving three doses of IPTp-SP, it did help to increase the proportion of timely ANC visits.Trial registrationPACTR202106905150440     

Comparative impact of three malaria preventive regimens during pregnancy on maternal anemia due to malaria in Burkina Faso

OBJECTIVES: The main objective of this study was to compare the efficacy of three regimens of malaria prevention during pregnancy for the reduction of anemia between the first and third antenatal consultations. The first treatment arm was the classical weekly chemoprophylaxis with chloroquine; the other two were the intermittent preventive treatment using either three doses of chloroquine or sulfadoxine-pyrimethamine. DESIGN: We conducted an open, randomized, three-arm study in a rural district of Burkina Faso. A cohort was constituted by 648 pregnant women of any parity. RESULTS: The hemoglobin gain was more significant with the intermittent preventive treatment using sulfadoxine-pyrimethamine compared to the other treatment arms. The hemoglobin increased from 10.3g/dl (at the first antenatal consultation) to 11.4 g/dl (at the third antenatal consultation). In the three arms of treatment, the chemoprophylaxis reduced the prevalence of moderate anemia and severe anemia. The reduction of moderate anemia was more substantial in the sulfadoxine-pyrimethamine arm (65.6 to 36.7%) at second antenatal consultation (p=0.069) and third antenatal consultation (p=0.014). Conversely, in the two chloroquine arms, there was no significant reduction either at second antenatal consultation (p=0.72) or third antenatal consultation (p=0.55). The prevalence of peripheral parasitemia decreased in all treatment groups. However, it was significantly higher in the sulfadoxine-pyrimethamine group (44.3%). CONCLUSIONS: Intermittent preventive treatment with three doses of sulfadoxine-pyrimethamine is a more effective strategy to prevent maternal anemia during pregnancy in Burkina Faso.     

Efficacy of chloroquine and sulfadoxine/pyrimethamine for the treatment of uncomplicated falciparum malaria in Koumantou, Mali

We report the results of an in vivo antimalarial efficacy study with chloroquine (CQ) and sulfadoxine/pyrimethamine (SP) conducted between 2003 and 2004 in Koumantou, southern Mali. A total of 244 children were included in the study; 210 children were followed-up for 28 days according to WHO recommendations, with PCR genotyping to distinguish late recrudescence from re-infection. Global failure proportions at Day 14, without taking into account re-infections, were 44.2% (95% CI 34.9-53.5%) in the CQ group and 2.0% (95% CI 0.0-4.8%) in the SP group. PCR-adjusted failure proportions at Day 28 were even higher in the CQ group (90.5% (95/105), 95% CI 84.8-96.2%) and relatively low in the SP group (7.0% (7/100), 95% CI 1.9-12.1%). These results show that CQ is no longer efficacious in Koumantou. The use of SP in monotherapy is likely to compromise its efficacy. We recommend the use of artemisinin-based combination therapy as first-line treatment for uncomplicated Plasmodium falciparum malaria in Koumantou.     

Intermittent preventive treatment of malaria in pregnancy: evaluation of a new delivery approach and the policy implications for malaria control in Uganda

The impact of intermittent preventive treatment (IPT) on malaria in pregnancy is well known. In countries where this policy is implemented, poor access and low compliance to this intervention has been widely reported. A study was designed to assess a new approach to deliver IPT to pregnant women through traditional birth attendants (TBAs), drug-shop vendors (DSVs), community reproductive health workers (CRHWs) and adolescent peer mobilisers (APMs); and compared this approach with IPT at health units. We evaluated this approach to assess user perceptions, its acceptability and sustainability. Results show that the new approach increased access and compliance to IPT. Mean gestational age at first dose of IPT was 21.0 weeks with the community approaches versus 23.1 weeks at health units, P>0.0001. Health units accessed a high proportion of adolescents, 28.4%, versus 25.0% at the new approaches, P<0.03; most primigravidae, 23.6%, versus 20.0% at the new approaches, P<0.04. The proportion of women who received two doses of SP was 67.5.2% with the new approaches versus 39.9% at health units, P<0.0001. The new approach was associated with a three-fold increase in use of ITNs from 8.8% at baseline to 23.4%. The factors that most influenced acceptability and use of IPT were trusted and easy accessible resource persons, their ability to make home visits especially with CRHWs and APMs; the support of spouses. Another factor was the high awareness on dangers of malaria in pregnancy and the benefits of IPT created by the resource persons. The women perceived better health using the first dose of sulphadoxine-pyremethamine (SP) and this compelled them to go for the second dose. IPT with this approach was highly acceptable with 89.1% of women at the new approaches intending to use it for the next pregnancy, while 48.0% of them had recommended it to other women. We suggest a review of the current policy on malaria prevention in pregnancy to allow provision of IPT through community structures that are feasible, practical and acceptable.     

A community-based delivery system of intermittent preventive treatment of malaria in pregnancy and its effect on use of essential maternity care at health units in Uganda

Community delivery of intermittent preventive treatment of malaria in pregnancy (IPTp) is one potential option that could mitigate malaria in pregnancy. However, there is concern that this approach may lead to complacency among women with low access to essential care at health units. A non-randomised community trial assessed a new delivery system of IPTp through traditional birth attendants, drug shop vendors, community reproductive health workers and adolescent peer mobilisers (the intervention) compared with IPTp at health units (control). The study enrolled a total of 2081 pregnant women with the new approaches. Data on care-seeking practices before and after the intervention were collected. The majority of women with the new approaches accessed IPTp in the second trimester and adhered to two doses of sulfadoxine/pyrimethamine (SP) (1404/2081; 67.5%). Antenatal care (four recommended visits) increased from 3.4% (27/805) to 56.8% (558/983) (P<0.001). The proportion of women delivering at health units increased from 34.3% (276/805) to 41.5% (434/1045) (P=0.02), whilst the proportion of women seeking care for malaria at health units increased from 16.7% (128/767) to 36.0% (146/405) (P<0.001). Similarly, use of insecticide-treated nets increased from 7.7% (160/2081) to 22.4% (236/1055) (P<0.001). In conclusion, the community-based system was effective in delivering IPTp, whilst women still accessed and benefited from essential care at health units.     

Cost-effectiveness of malaria intermittent preventive treatment in infants (IPTi) in Mozambique and the United Republic of Tanzania

Objective

To estimate the cost-effectiveness of malaria intermittent preventive treatment in infants (IPTi) using sulfadoxine-pyrimethamine (SP).

Methods

In two previous IPTi trials in Ifakara (United Republic of Tanzania) and Manhiça (Mozambique), SP was administered three times to infants before 9 months of age through the Expanded Programme on Immunization. Based on the efficacy results of the intervention and on malaria incidence in the target population, an estimate was made of the number of clinical malaria episodes prevented. This number and an assumed case-fatality rate of 1.57% were used, in turn, to estimate the number of disability-adjusted life years (DALY) averted and the number of deaths averted. The cost of the intervention, including start-up and recurrent costs, was then assessed on the basis of these figures.

Findings

The cost per clinical episode of malaria averted was US$ 1.57 (range: US$ 0.8–4.0) in Ifakara and US$ 4.73 (range: US$ 1.7–30.3) in Manhiça; the cost per DALY averted was US$ 3.7 (range: US$ 1.6–12.2) in Ifakara and US$ 11.2 (range: US$ 3.6–92.0) in Manhiça; and the cost per death averted was US$ 100.2 (range: US$ 43.0–330.9) in Ifakara and US$ 301.1 (range: US$ 95.6–2498.4) in Manhiça.

Conclusion

From the health system and societal perspectives, IPTi with SP is expected to produce health improvements in a cost-effective way. From an economic perspective, it offers good value for money for public health programmes.     

Efficacy of malaria prevention during pregnancy in an area of low and unstable transmission: an individually-randomised placebo-controlled trial using intermittent preventive treatment and insecticide-treated nets in the Kabale Highlands, southwestern Uganda

Intermittent preventive treatment of malaria during pregnancy (IPTp) and insecticide-treated nets (ITN) are recommended malaria interventions during pregnancy; however, there is limited information on their efficacy in areas of low malaria transmission in sub-Saharan Africa. An individually-randomised placebo-controlled trial involving 5775 women of all parities examined the effect of IPTp, ITNs alone, or ITNs used in combination with IPTp on maternal anaemia and low birth weight (LBW) in a highland area of southwestern Uganda. The overall prevalence of malaria infection, maternal anaemia and LBW was 15.0%, 14.7% and 6.5%, respectively. Maternal and fetal outcomes were generally remarkably similar across all intervention groups (P > 0.05 for all outcomes examined). A marginal difference in maternal haemoglobin was observed in the dual intervention group (12.57 g/dl) compared with the IPTp and ITN alone groups (12.40 g/dl and 12.44 g/dl, respectively; P = 0.04), but this was too slight to be of clinical importance. In conclusion, none of the preventive strategies was found to be superior to the others, and no substantial additional benefit to providing both IPTp and ITNs during routine antenatal services was observed. With ITNs offering a number of advantages over IPTp, yet showing comparable efficacy, we discuss why ITNs could be an appropriate preventive strategy for malaria control during pregnancy in areas of low and unstable transmission. [ClinicalTrials.gov identifier: NCT00142207]     

Artemether in the treatment of falciparum malaria during pregnancy in eastern Sudan

This study was carried in New Halfa Hospital, eastern Sudan from October 1997 to February 2001. Twenty-eight pregnant Sudanese women infected with Plasmodium falciparum were treated with intramuscular artemether (six injections, 480 mg) after failure of chloroquine and quinine therapy. The patients were followed-up until delivery; the babies were followed-up until the age of 1 year. Artemether was given to one patient in the tenth week of gestation, to 12 during the second trimester, and to 15 during the third trimester. It was well tolerated, the parasitaemia was cleared and the patients were symptom-free within three days. One patient (3.5%) delivered at 32 weeks and the baby died six hours after delivery. The other 27 (96.5%) delivered full-term live babies. None of the pregnant women died and there was no abortion, stillbirth or congenital abnormalities in the newborn babies.     

Amodiaquine combined with sulfadoxine/pyrimethamine versus artemisinin-based combinations for the treatment of uncomplicated falciparum malaria in Africa: a meta-analysis

Drug resistance in Plasmodium falciparum is a major obstacle to malaria control. Artemisinin-based combination therapy (ACT) is being advocated to improve treatment efficacy and to delay development of resistance. Here we summarise the available data on the efficacy of amodiaquine plus sulfadoxine/pyrimethamine (AQ+SP) versus ACTs in the treatment of uncomplicated malaria in sub-Saharan Africa. We searched for randomised trials in which patients with uncomplicated malaria treated with AQ+SP were compared with those treated with either amodiaquine plus artesunate (AQ+AS), artesunate plus sulfadoxine/pyrimethamine (AS+SP) or artemether/lumefantrine (AL). Medline, EMBASE, Cochrane Central Register of Controlled Trials and reference lists up to July 2005 were searched. Two reviewers independently extracted the data. The primary outcome measure was treatment failure by Day 28. Outcome measures were combined using a random effects model. Seven randomised trials of 4472 children were included. Trial quality was generally high. Treatment failure of AQ+SP was significantly reduced compared with AS+SP (relative risk (RR)=0.56, 95% CI 0.42-0.75), but increased compared with AL (RR=2.80, 95% CI 2.32-3.39). The overall failure rate of AQ+SP was similar compared with AQ+AS (RR=1.12, 95% CI 0.81-1.54), but there was significant heterogeneity of results across the studies. All the treatment regimens were safe and well tolerated. AQ+SP should be considered in some settings before the full implementation of an ACT.     

Intermittent preventive treatment of malaria in pregnancy: the incremental cost-effectiveness of a new delivery system in Uganda

The main objective of this study was to assess whether traditional birth attendants, drug-shop vendors, community reproductive health workers and adolescent peer mobilisers could administer intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine (SP) to pregnant women. The study was implemented in 21 community clusters (intervention) and four clusters where health centres provided routine IPTp (control). The primary outcome measures were the proportion of women who completed two doses of SP; the effect on anaemia, parasitaemia and low birth weight; and the incremental cost-effectiveness of the intervention. The study enrolled 2785 pregnant women. The majority, 1404/2081 (67.5%) receiving community-based care, received SP early and adhered to the two recommended doses compared with 281/704 (39.9%) at health centres (P<0.001). In addition, women receiving community-based care had fewer episodes of anaemia or severe anaemia and fewer low birth weight babies. The cost per woman receiving the full course of IPTp was, however, higher when delivered via community care at US$2.60 compared with US$2.30 at health centres, due to the additional training costs. The incremental cost-effectiveness ratio of the community delivery system was Uganda shillings 1869 (US$1.10) per lost disability-adjusted life-year (DALY) averted. In conclusion, community-based delivery increased access and adherence to IPTp and was cost-effective.     

Race-linked differences in serum concentrations of dapsone,monoacetyldapsone and pyrimethamine during malaria prophylaxis

Serum concentrations of dapsone (DDS), monoacetyldapsone (MADDS), the principal acetylated metabolite of DDS, and pyrimethamine (PYR) were measured in 55 Caucasian adults (31 males, 24 females) and 159 Papua New Guinean adults (140 males, 19 females) following the oral administration of Folaprim^R (100mg DDS; 12·5mg PYR). Blood samples were collected at mean sampling times of eight hours after medication and 18 hours before the next weekly dose for malaria prophylaxis. Clearance of DDS and MADDS from serum were significantly faster (p<0·001) in Caucasians than in Papua New Guineans. Significantly lower (p<0·001) serum concentrations of PYR were found in Papua New Guineans than in Caucasians at both sampling times, an observation which may reflect differences in the bioavailability of PYR between the two racial groups. The theoretical implications of these results are that Caucasians may be more susceptible to PYR-resistant Plasmodium falciparum malaria than Papua New Guineans whilst Papua New Guineans may be more susceptible to P. vivax malaria than Caucasians.     

Intermittent preventive treatment of malaria in pregnancy: a new delivery system and its effect on maternal health and pregnancy outcomes in Uganda

Objective

To assess whether traditional birth attendants, drug-shop vendors, community reproductive-health workers, or adolescent peer mobilizers could administer intermittent preventive treatment (IPTp) for malaria with sulfadoxine-pyrimethamine to pregnant women.

Methods

A non-randomized community trial was implemented in 21 community clusters (intervention) and four clusters where health units provided routine IPTp (control). The primary outcome measures were access and adherence to IPTp, number of malaria episodes, prevalence of anaemia, and birth weight. Numbers of live births, abortions, still births, and maternal and child deaths were secondary endpoints.

Findings

1404 (67.5%) of 2081 with the new delivery system received two doses of sulfadoxine-pyrimethamine versus 281 (39.9%) of 704 with health units (P < 0.0001). The prevalence of malaria episodes decreased from 906 (49.5%) of 1830 to 160 (17.6%) of 909 (P < 0.001) with the new delivery system and from 161 (39.1%) of 412 to 13 (13.1%) of 99 (P < 0.001) with health units. Anaemia was significantly less prevalent in both arms. There was a lower proportion of low birth weight 6.0% with the new delivery system versus 8.3% with health units (P < 0.03). Few abortions and stillbirths were recorded in either arm. Fewer children and women who accessed IPTp with health units died than in the intervention group.

Conclusion

The new approaches were associated with early access and increased adherence to IPTp. Health units were, however, more effective in reducing parasitaemia and malaria episodes. We recommend further studies to assess programming modalities linking the new approaches and health units.