Impact on pregnancy outcomes of intermittent preventive treatment with sulfadoxine-pyrimethamine in urban and peri-urban Papua New Guinea: a retrospective cohort study.

BACKGROUND: Intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) reduces malaria-attributable adverse pregnancy outcomes and may also prevent low birth weight (< 2,500 g) through mechanisms independent of malaria. Malaria transmission in Papua New Guinea (PNG) is highly heterogeneous. The impact of IPTp-SP on adverse birth outcomes in settings with little or no malaria transmission, such as PNG's capital city Port Moresby, is unknown. METHODS: A retrospective cohort study was conducted amongst HIV-negative women with a singleton pregnancy who delivered at Port Moresby General Hospital between 18 July and 21 August 2022. The impact of IPTp-SP doses on adverse birth outcomes and anaemia was assessed using logistic and linear regression models, as appropriate. RESULTS: Of 1,140 eligible women amongst 1,228 consecutive births, 1,110 had a live birth with a documented birth weight. A total of 156 women (13.7%) did not receive any IPTp-SP, 347 women (30.4%) received one, 333 (29.2%) received two, and 304 (26.7%) received the recommended ≥ 3 doses of IPTp-SP. A total of 65 of 1,110 liveborn babies (5.9%) had low birth weight and there were 34 perinatal deaths (3.0%). Anaemia (haemoglobin < 100 g/L) was observed in 30.6% (243/793) of women, and 14 (1.2%) had clinical malaria in pregnancy. Compared to women receiving 0-1 dose of IPTp-SP, women receiving ≥ 2 doses had lower odds of LBW (adjusted odds ratio [aOR] 0.50; 95% confidence interval [CI] 0.26, 0.96), preterm birth (aOR 0.58; 95% CI 0.32, 1.04), perinatal death (aOR 0.49; 95% CI 0.18, 1.38), LBW/perinatal death (aOR 0.55; 95% CI 0.27, 1.12), and anaemia (OR 0.50; 95% CI 0.36, 0.69). Women who received 2 doses versus 0-1 had 45% lower odds of LBW (aOR 0.55, 95% CI 0.27, 1.10), and a 16% further (total 61%) reduction with ≥ 3 doses (aOR 0.39, 95% CI 0.14, 1.05). Birth weights for women who received 2 or ≥ 3 doses versus 0-1 were 81 g (95% CI -3, 166) higher, and 151 g (58, 246) higher, respectively. CONCLUSIONS: Provision of IPTp-SP in a low malaria-transmission setting in PNG appears to translate into substantial health benefits, in a dose-response manner, supporting the strengthening IPTp-SP uptake across all transmission settings in PNG.

The readiness of malaria services and uptake of intermittent preventive treatment in pregnancy in six sub-Saharan countries.

Background: Malaria infection during pregnancy is associated with an increased risk of maternal death, as well as adverse birth outcomes. Intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) is known to improve pregnancy outcomes. However, the coverage of IPTp-SP in antenatal care (ANC) in sub-Saharan Africa remains well below the target. This study aims to estimate to what extent malaria service readiness affects the uptake of IPTp-SP during ANC visits in sub-Saharan African countries. Methods: This study included 3267 pregnant women attending ANC for the first time and 2797 pregnant women who had attended ANC more than a month ago in six sub-Saharan African countries. The readiness of malaria services at each institution includes four indicators: the presence of IPTp-SP guidelines, SP availability, integration of IPTp-SP service into ANC, and provider training on IPTp-SP. The outcome variable indicates whether a pregnant woman received IPTp-SP at her current ANC visit. A modified Poisson regression model estimated the associations between malaria service readiness and IPTp-SP uptake for women eligible for the first and subsequent doses. Results: For women eligible for their first dose, visiting an institution with available SP was associated with an increased probability of receiving IPTp-SP (risk ratio (RR) = 1.43; 95% confidence interval (CI) = 1.22 to 1.67, P < 0.001). For women who were eligible for their next dose, the availability of SP (RR = 1.17; 95% CI = 1.04 to 1.32, P = 0.008) and integration of IPTp-SP service into ANC (RR = 1.82; 95% CI = 1.21 to 2.74, P = 0.004) in the institution were associated with increased likelihood of IPTp-SP uptake. Counterfactual predictions indicated that enhanced provider training could boost IPTp-SP uptake in high-uptake countries, while better SP availability and IPTp-SP integration into ANC would significantly impact low-uptake countries. Conclusions: For better IPTp-SP coverage, strategies should be customised. High uptake countries should focus on provider training, while low uptake ones should ensure IPTp-SP availability and service integration.

Impact of seasonal malaria chemoprevention based on the number of medicines doses received on malaria burden among children aged 3-59 months in Nigeria: A propensity score-matched analysis.

BACKGROUND: Seasonal malaria chemoprevention using sulfadoxine-pyrimethamine plus amodiaquine (sulfadoxine-pyrimethamine plus amodiaquine on Day 1 and amodiaquine on both Day 2 and Day 3) is delivered to children aged 3-59 months in areas of highly season malaria transmission. While the overall population-level impact of seasonal malaria chemoprevention on malaria control has been documented in various countries and time periods, there is no clear evidence regarding seasonal malaria chemoprevention impact based on the number of medicine doses children receive in one cycle in routine programmatic conditions. METHODS: Data were extracted from Nigeria's routinely collected seasonal malaria chemoprevention end-of-round coverage surveys (2021, 2022). We matched seasonal malaria chemoprevention-targeted children who received specific numbers of seasonal malaria chemoprevention medicines with those who did not receive any doses of seasonal malaria chemoprevention medicines (non-sulfadoxine-pyrimethamine plus amodiaquine) using multiple sets of propensity score matches. We performed multilevel logistic regression for each matched group to evaluate the association between the number of doses of seasonal malaria chemoprevention medicines and monthly confirmed malaria cases (caregiver-reported malaria infection diagnosed by rapid diagnostic test at a health facility following the penultimate cycle of seasonal malaria chemoprevention). RESULTS: Among 21,621 SMC-targeted children, 9.7% received non-sulfadoxine-pyrimethamine plus amodiaquine, 0.5% received only Day 1 sulfadoxine-pyrimethamine plus amodiaquine, 1.0% received Day 1 sulfadoxine-pyrimethamine plus amodiaquine and either Day 2 amodiaquine or Day 3 amodiaquine (sulfadoxine-pyrimethamine plus amodiaquine + amodiaquine), and 88.8% received Day 1 sulfadoxine-pyrimethamine plus amodiaquine and both Day 2 and Day 3 amodiaquine (sulfadoxine-pyrimethamine plus amodiaquine + amodiaquine + amodiaquine). Children receiving only Day 1 sulfadoxine-pyrimethamine plus amodiaquine did not have significant lower odds of rapid diagnostic tests-confirmed malaria than those receiving non-sulfadoxine-pyrimethamine plus amodiaquine (OR 0.77, 0.42-1.42). However, children receiving sulfadoxine-pyrimethamine plus amodiaquine + amodiaquine had significantly lower odds of rapid diagnostic tests-confirmed malaria than those receiving non-sulfadoxine-pyrimethamine plus amodiaquine (OR 0.42, 95% CI 0.28-0.63). Similarly, children receiving sulfadoxine-pyrimethamine plus amodiaquine + amodiaquine + amodiaquine also had significantly lower odds of rapid diagnostic test-confirmed malaria than those receiving non-sulfadoxine-pyrimethamine plus amodiaquine (OR 0.54, 95% CI 0.47-0.62). CONCLUSION: Adherence to at least one daily dose of amodiaquine administration following receipt of Day 1 sulfadoxine-pyrimethamine plus amodiaquine by eligible children is crucial to ensure the effectiveness of seasonal malaria chemoprevention. This demonstrates the importance of enhancing caregiver awareness regarding the importance of amodiaquine and identifying barriers toward amodiaquine administration at the community level.

Field testing of user-friendly perennial malaria chemoprevention packaging in Benin, Côte d'Ivoire and Mozambique.

BACKGROUND: Perennial malaria chemoprevention (PMC) aims to protect children at risk from severe malaria by the administration of anti-malarial drugs to children of defined ages throughout the year. Sulfadoxine-pyrimethamine (SP) has been widely used for chemoprevention in Africa and a child-friendly dispersible tablet formulation has recently become available. METHODS: This qualitative non-interventional observational study was conducted in Benin, Côte d'Ivoire, and Mozambique between February and June 2022. Prototype blister packs, dispensing boxes and job aids designed to support dispersible SP deployment for PMC were evaluated using focus group discussions (FGD) and semi-structured in-depth individual interviews (IDI) with health authorities, health personnel, community health workers (CHWs) and caregivers. The aim was to evaluate knowledge and perceptions of malaria and chemoprevention, test understanding of the tools and identify gaps in understanding, satisfaction, user-friendliness and acceptability, and assess the potential role of CHWs in PMC implementation. Interviews were transcribed and imported to ATLAS.ti for encoding and categorization. Thematic content analysis used deductive and inductive coding with cross-referencing of findings between countries and participants to enrich data interpretation. Continuous comparison across the IDI and FGD permitted iterative, collaborative development of materials. RESULTS: Overall, 106 participants completed IDIs and 70 contributed to FGDs. Malaria was widely recognised as the most common disease affecting children, and PMC was viewed as a positive intervention to support child health. The role of CHWs was perceived differently by the target groups, with caregivers appreciating their trusted status in the community, whereas health authorities preferred clinic-based deployment of PMC by health professionals. Empirical testing of the prototype blister packs, dispensing boxes and job aids highlighted the context-specific expectations of respondents, such as familiar situations and equipment, and identified areas of confusion or low acceptance. A key finding was the need for a clear product identity reflecting malaria. CONCLUSION: Simple modifications profoundly affected the perception of PMC and influenced acceptability. Iterative quantitative investigation resulted in PMC-specific materials suited to the local context and socio-cultural norms of the target population with the aim of increasing access to chemoprevention in children most at risk of severe malaria.

Impact of Sulfadoxine-Pyrimethamine and Dihydroartemisinin-Piperaquine as Intermittent Preventive Treatment in Pregnancy on Stool Antimicrobial Resistance Gene Abundance.

Increasing antimicrobial resistance (AMR) is a global public health emergency. Although chemoprevention has improved malaria-related pregnancy outcomes, the downstream effects on AMR have not been characterized. We compared the abundance of 10 AMR genes in stool samples from pregnant women receiving sulfadoxine-pyrimethamine (SP) as intermittent preventive treatment against malaria in pregnancy (IPTp) to that in samples from women receiving dihydroartemisinin-piperaquine (DP) for IPTp. All participants had at least one AMR gene at baseline. Mean quantities of the antifolate gene dfrA17 were increased after two or more doses of SP (mean difference = 1.6, 95% CI: 0.4-2.7, P = 0.008). Antimicrobial resistance gene abundance tended to increase from baseline in SP recipients compared with a downward trend in the DP group. Overall, IPTp-SP had minimal effects on the abundance of antifolate resistance genes (except for dfrA17), potentially owing to a high starting prevalence. However, the trend toward increasing AMR in SP recipients warrants further studies.

Artemether-lumefantrine with or without single-dose primaquine and sulfadoxine-pyrimethamine plus amodiaquine with or without single-dose tafenoquine to reduce Plasmodium falciparum transmission: a phase 2, single-blind, randomised clinical trial in Ouelessebougou, Mali.

BACKGROUND: Artemether-lumefantrine is widely used for uncomplicated Plasmodium falciparum malaria; sulfadoxine-pyrimethamine plus amodiaquine is used for seasonal malaria chemoprevention. We aimed to determine the efficacy of artemether-lumefantrine with and without primaquine and sulfadoxine-pyrimethamine plus amodiaquine with and without tafenoquine for reducing gametocyte carriage and transmission to mosquitoes. METHODS: In this phase 2, single-blind, randomised clinical trial conducted in Ouelessebougou, Mali, asymptomatic individuals aged 10-50 years with P falciparum gametocytaemia were recruited from the community and randomly assigned (1:1:1:1) to receive either artemether-lumefantrine, artemether-lumefantrine with a single dose of 0·25 mg/kg primaquine, sulfadoxine-pyrimethamine plus amodiaquine, or sulfadoxine-pyrimethamine plus amodiaquine with a single dose of 1·66 mg/kg tafenoquine. All trial staff other than the pharmacist were masked to group allocation. Participants were not masked to group allocation. Randomisation was done with a computer-generated randomisation list and concealed with sealed, opaque envelopes. The primary outcome was the median within-person percent change in mosquito infection rate in infectious individuals from baseline to day 2 (artemether-lumefantrine groups) or day 7 (sulfadoxine-pyrimethamine plus amodiaquine groups) after treatment, assessed by direct membrane feeding assay. All participants who received any trial drug were included in the safety analysis. This study is registered with ClinicalTrials.gov, NCT05081089. FINDINGS: Between Oct 13 and Dec 16, 2021, 1290 individuals were screened and 80 were enrolled and randomly assigned to one of the four treatment groups (20 per group). The median age of participants was 13 (IQR 11-20); 37 (46%) of 80 participants were female and 43 (54%) were male. In individuals who were infectious before treatment, the median percentage reduction in mosquito infection rate 2 days after treatment was 100·0% (IQR 100·0-100·0; n=19; p=0·0011) with artemether-lumefantrine and 100·0% (100·0-100·0; n=19; p=0·0001) with artemether-lumefantrine with primaquine. Only two individuals who were infectious at baseline infected mosquitoes on day 2 after artemether-lumefantrine and none at day 5. By contrast, the median percentage reduction in mosquito infection rate 7 days after treatment was 63·6% (IQR 0·0-100·0; n=20; p=0·013) with sulfadoxine-pyrimethamine plus amodiaquine and 100% (100·0-100·0; n=19; p<0·0001) with sulfadoxine-pyrimethamine plus amodiaquine with tafenoquine. No grade 3-4 or serious adverse events occurred. INTERPRETATION: These data support the effectiveness of artemether-lumefantrine alone for preventing nearly all mosquito infections. By contrast, there was considerable post-treatment transmission after sulfadoxine-pyrimethamine plus amodiaquine; therefore, the addition of a transmission-blocking drug might be beneficial in maximising its community impact. FUNDING: Bill & Melinda Gates Foundation.

Spatial distribution and determinants of intermittent preventive treatment for malaria during pregnancy: a secondary data analysis of the 2019 Ghana malaria indicators survey.

BACKGROUND: Malaria during pregnancy is associated with poor maternal, foetal, and neonatal outcomes. To prevent malaria infection during pregnancy, the World Health Organization recommended the use of intermittent preventive therapy with sulfadoxine-pyrimethamine (IPTp-SP) in addition to vector control strategies. Although Ghana's target is to ensure that all pregnant women receive at least three (optimal) doses of SP, the uptake of SP has remained low; between 2020 and 2022, only 60% of pregnant women received optimal SP during their most recent pregnancy. This study sought to map the geospatial distribution and identify factors associated with SP uptake during pregnancy in Ghana. METHODS: Secondary data analysis was conducted using the 2019 Ghana Malaria Indicator Survey dataset. The data analysed were restricted to women aged 15-49 years who reported having a live birth within the two years preceding the survey. A modified Poisson regression model was used to determine factors associated with SP uptake during pregnancy. Geospatial analysis was employed to map the spatial distribution of optimal SP uptake across the ten regions of Ghana using R software. RESULTS: The likelihood that pregnant women received optimal SP correlated with early initiation of first antenatal care (ANC), number of ANC contacts, woman's age, region of residence, and family size. Overall, the greater the number of ANC contacts, the more likely for pregnant women to receive optimal SP. Women with four or more ANC contacts were 2 times (aPR: 2.16; 95% CI: [1.34-3.25]) more likely to receive optimal SP than pregnant women with fewer than four ANC contacts. In addition, early initiation and a high number of ANC contacts were associated with a high number of times a pregnant woman received SP. Regarding spatial distribution, a high uptake of optimal SP was significantly observed in the Upper East and Upper West Regions, whereas the lowest was observed in the Eastern Region of Ghana. CONCLUSIONS: In Ghana, there were regional disparities in the uptake of SP during pregnancy, with the uptake mainly correlated with the provision of ANC services. To achieve the country's target for malaria control during pregnancy, there is a need to strengthen intermittent preventive treatment for malaria during pregnancy by prioritizing comprehensive ANC services.

Sustained clinical benefit of malaria chemoprevention with sulfadoxine-pyrimethamine (SP) in pregnant women in a region with high SP resistance markers.

OBJECTIVE: The effectiveness of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) is threatened by increasing SP-resistance in Africa. We assessed the level of SP-resistance markers, and the clinical and parasitological effectiveness of IPTp-SP in southern Mozambique. METHODS: P. falciparum infection, antimalarial antibodies and dhfr/dhps SP-resistance mutants were detected by quantitative polymerase chain reaction (qPCR), suspension array technology and targeted deep sequencing, respectively, among 4016 HIV-negative women in Maputo province (2016-2019). Univariate and multivariate regression models were used to assess the association between taking the recommended three or more IPTp-SP doses (IPTp3+) and parasitological and clinical outcomes. RESULTS: 84.3% (3385/4016) women received three or more IPTp-SP doses. The prevalence of quintuple mutants at first antenatal care (ANC) visit was 94.2%. IPTp3+ was associated with a higher clearance rate of qPCR-detected infections from first ANC visit to delivery (adjusted odds ratio [aOR]=5.9, 95% CI: 1.5-33.3; p = 0.012), lower seroprevalence at delivery of antibodies against the pregnancy-specific antigen VAR2CSADBL34 (aOR=0.72, 95% CI: 0.54-0.95; p = 0.022), and lower prevalence of low birth weight deliveries (aOR: 0.61, 95% CI: 0.41-0.90; p = 0.013). CONCLUSION: A sustained parasitological effect of IPTp-SP contributes to the clinical effectiveness of IPTp3+ in areas with high prevalence of SP-resistance markers.

Predicting the effect of sulfadoxine-pyrimethamine uptake by pregnant women on birth weight using a generalized ordered partial proportional odds model.

BACKGROUND: Low birth weight is a public health problem in Africa with the cause attributable to malaria in pregnancy. World Health Organization recommends the use of intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine to prevent malaria during pregnancy. The objective of this study was to evaluate the prevalence and trajectories of birth weight and the direct impact and relationship between sulfadoxine-pyrimethamine and birth weight in Ghana since 2003. METHOD: This study used secondary data obtained from the Demographic and Health Survey conducted in Ghana since 2003. Low birth weight was defined as weight < 2500 g irrespective of the gestational age of the foetus, while normal birth weight was between 2500 g to < 4000 g and macrosomia was = > 4000 g. In all the analysis, we adjusted for clustering, stratification and weighting to reduce bias and improve precision of the estimates. Analysis was performed on each survey year as well as the pooled dataset. The generalized ordered partial proportional odds model was used due to violations of the parallel regression model assumptions. Efforts were made to identify all confounding variables and these were adjusted for. Predictive analysis was also executed. RESULTS: The overall prevalence of low birth weight was 9% while that of macrosomia was 13%. The low birth weight for 2003 was 12% while in 2008 it was 21% and then 68% in 2014. The mean birth weight of the children in 2014 was 3.16 (3.14, 3.19), 2008 was 3.37 (3.28, 3.45) and 2003 was 3.59 (3.49, 3.69) while that of the pooled data was 3.28 (3.25, 3.30). The adjusted model (taking into consideration all confounding variables) showed that non-uptake of SP could result in 51% odds of giving birth to a low-birth-weight compared with normal birth weight child. An insignificant result was observed between macrosomia and low birth weight. CONCLUSION: There is higher probability that low birth weight could increase over the next couple of years if measures are not taking to reverse the current trajectories. The uptake of sulfadoxine-pyrimethamine should continue to be encouraged and recommended because it has a direct beneficial effect on the weight of the child.

The provider's checklist to improve pregnant women coverage by intermittent preventive malaria treatment in Mali: a pilot implementation study.

BACKGROUND: Intermittent preventive treatment of malaria in pregnancy (IPTp) is a comprehensive treatment protocol of anti-malarial drugs administered to pregnant women to prevent malaria, started at the fourth pregnancy month, with at least three doses of sulfadoxine-pyrimethamine (SP), taken as directly observed treatment (DOT) every 30 days at intervals until childbirth, in combination with other preventive measures. This paper introduces feasibility and adoption concepts as implementation research outcomes (IRO), allowing after a defined intervention, to assess the coverage improvement by IPTp for women attending a reference district hospital in Mali. Specifically, the purpose is to evaluate the feasibility of a reminder tool (provider checklist) to enhance pregnant women's adoption of information about IPTp-SP uptake as immediate and sustained women practices. METHODS: The implementation strategy used a reminder checklist about malaria knowledge and the recommended preventive tools. Then, the checklist feasibility was assessed during routine practices with the adoption-level about pregnant women' knowledge. Quantitative data were collected through a questionnaire distributed to a non-probability purposive sampling targeting 200 pregnant women divided into two groups before and after the checklist intervention. In contrast, the qualitative data were based on in-depth face-to-face gynaecologists' interviews. RESULTS: Both the IROs (feasibility and adoption) were satisfactory. The gynaecologists agreed to the use of this checklist during routine practice with a recommendation to generalize it to other health providers. After a gynaecologist visit, a significant increase of the adoption-level about prior knowledge and preventive tools was noticed. A total of 83% of participants were not knowledgeable about malaria disease before checklist use versus 15% after. Similarly, coverage of women's SP DOT rose from 0 to 59% after introducing the checklist and the IPTp-SP uptake after the visit was highly significant in the second group. The latter reached 95% of pregnant women with 4-8 months' gestational age, that mostly respected all SP future visits as theoretically scheduled. CONCLUSIONS: Generalizing such a checklist reminder will improve women's knowledge about malaria prevention.

Risk factors for Plasmodium falciparum infection in pregnant women in Burkina Faso: a community-based cross-sectional survey.

BACKGROUND: Malaria in pregnancy remains a public health problem in sub-Saharan Africa. Identifying risk factors for malaria in pregnancy could assist in developing interventions to reduce the risk of malaria in Burkina Faso and other countries in the region. METHODS: Two cross-sectional surveys were carried out to measure Plasmodium falciparum infection using microscopy in pregnant women in Saponé Health District, central Burkina Faso. Data were collected on individual, household and environmental variables and their association with P. falciparum infection assessed using multivariable analysis. RESULTS: A total of 356 pregnant women were enrolled in the surveys, 174 during the dry season and 182 during the wet season. The mean number of doses of sulfadoxine-pyrimethamine for Intermittent Preventive Treatment in pregnancy (IPTp-SP) was 0.4 doses during the first trimester, 1.1 doses at the second and 2.3 doses at the third. Overall prevalence of P. falciparum infection by microscopy was 15.7%; 17.8% in the dry season and 13.7% in the wet season. 88.2% of pregnant women reported sleeping under an insecticide-treated net (ITN) on the previous night. The odds of P. falciparum infection was 65% lower in women who reported using an ITN compared to those that did not use an ITN (Odds ratio, OR = 0.35, 95% CI 0.14-0.86, p = 0.02). IPTp-SP was also associated with reduced P. falciparum infection, with each additional dose of IPTp-SP reducing the odds of infection by 44% (OR = 0.56, 95% CI 0.39-0.79, p = 0.001). Literate women had a 2.54 times higher odds of P. falciparum infection compared to illiterate women (95% CI 1.31-4.91, p = 0.006). CONCLUSIONS: The prevalence of P. falciparum infection among pregnant women remains high in Burkina Faso, although use of IPTp-SP and ITNs were found to reduce the odds of infection. Despite this, compliance with IPTp-SP remains far from that recommended by the National Malaria Control Programme and World Health Organization. Behaviour change communication should be strengthened to encourage compliance with protective malaria control tools during pregnancy.

Knowledge of malaria control and attitudes towards community involvement among female community volunteers: effect of capacity building in a rural community, Southeast Nigeria.

INTRODUCTION: community volunteers have limited skills but are an important link between the community and health facilities. We determined the effect of a capacity building intervention on knowledge of malaria control and attitudes towards community involvement among female community volunteers as part of a larger community-based intervention study on pregnant women and children under five. METHODS: we conducted a before and after intervention study (no randomization or controls) among female community volunteers in Amagu community in Abakaliki Local Government Area. The intervention consisted of training sessions on knowledge of malaria and its control. The training took the form of lectures, role plays and practical demonstrations. Supportive supervision by trained community health extension workers was also provided during their field work. We compared pre-training test and post-training test scores after six months interval and analysed the data using paired t test at 5% level of significance with EPI INFO software version 7.2.3. RESULTS: the mean age of the participants was 28.5(± 6.0) years. All had a minimum level of secondary education. There was significant improvement in the mean scores of their knowledge of malaria signs and symptoms (p < 0.001), preventive measures (p < 0.001) and appropriate drug treatment (p < 0.001) in the post-training test when compared with the pre-training test. The overall mean knowledge scores pre and posttest were 147.8 and 169.8 respectively (p < 0.001) out of a maximum achievable score of 195. Also there was significant improvement in the perception of the participants on community involvement in promoting referral of pregnant women with fever (p = 0.001), the use of intermittent preventive therapy with sulphadoxine-pyrimethamine (p = 0.048) and funding initiatives to sustain activities (p = 0.037). CONCLUSION: capacity building of female community volunteers coupled with supportive supervision by trained community health workers improved the female community volunteers´ knowledge of malaria, its control and their perception of community involvement in control activities. It is recommended that the use of community volunteers as a low cost health resource can be explored further for incorporation into existing policies on malaria control in resource constrained environments.

Effect of seasonal malaria chemoprevention plus azithromycin on Plasmodium falciparum transmission: gametocyte infectivity and mosquito fitness.

BACKGROUND: Seasonal malaria chemoprevention (SMC) consists of administration of sulfadoxine-pyrimethamine (SP) + amodiaquine (AQ) at monthly intervals to children during the malaria transmission period. Whether the addition of azithromycin (AZ) to SMC could potentiate the benefit of the intervention was tested through a double-blind, randomized, placebo-controlled trial. The effect of SMC and the addition of AZ, on malaria transmission and on the life history traits of Anopheles gambiae mosquitoes have been investigated. METHODS: The study included 438 children randomly selected from among participants in the SMC + AZ trial and 198 children from the same area who did not receive chemoprevention. For each participant in the SMC + AZ trial, blood was collected 14 to 21 days post treatment, examined for the presence of malaria sexual and asexual stages and provided as a blood meal to An. gambiae females using a direct membrane-feeding assay. RESULTS: The SMC treatment, with or without AZ, significantly reduced the prevalence of asexual Plasmodium falciparum (LRT X22 = 69, P < 0.0001) and the gametocyte prevalence (LRT X22 = 54, P < 0.0001). In addition, the proportion of infectious feeds (LRT X22 = 61, P < 0.0001) and the prevalence of oocysts among exposed mosquitoes (LRT X22 = 22.8, P < 0.001) was reduced when mosquitoes were fed on blood from treated children compared to untreated controls. The addition of AZ to SPAQ was associated with an increased proportion of infectious feeds (LRT X21 = 5.2, P = 0.02), suggesting a significant effect of AZ on gametocyte infectivity. There was a slight negative effect of SPAQ and SPAQ + AZ on mosquito survival compared to mosquitoes fed with blood from control children (LRTX22 = 330, P < 0.0001). CONCLUSION: This study demonstrates that SMC may contribute to a reduction in human to mosquito transmission of P. falciparum, and the reduced mosquito longevity observed for females fed on treated blood may increase the benefit of this intervention in control of malaria. The addition of AZ to SPAQ in SMC appeared to enhance the infectivity of gametocytes providing further evidence that this combination is not an appropriate intervention.

Decomposition of socioeconomic inequalities in the uptake of intermittent preventive treatment of malaria in pregnancy in Nigeria: evidence from Demographic Health Survey.

BACKGROUND: Although malaria in pregnancy is preventable with the use of intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP), it still causes maternal morbidity and mortality, in sub-Saharan Africa and Nigeria in particular. Socioeconomic inequality leads to limited uptake of IPTp-SP by pregnant women and is, therefore, a public health challenge in Nigeria. This study aimed to measure and identify factors explaining socioeconomic inequality in the uptake of IPTp-SP in Nigeria. METHODS: The study re-analysed dataset of 12,294 women aged 15-49 years from 2018 Nigeria Demographic Health Survey (DHS). The normalized concentration index (Cn) and concentration curve were used to quantify and graphically present socioeconomic inequalities in the uptake of IPTp-SP among pregnant women in Nigeria. The Cn was decomposed to identify key factors contributing to the observed socioeconomic inequality in the uptake of adequate (≥ 3) IPTp-SP. RESULTS: The study showed a higher concentration of the adequate uptake of IPTp-SP among socioeconomically advantaged women (Cn = 0.062; 95% confidence interval [CI] 0.048 to 0.076) in Nigeria. There is a pro-rich inequality in the uptake of IPTp-SP in urban areas (Cn = 0.283; 95%CI 0.279 to 0.288). In contrast, a pro-poor inequality in the uptake of IPTp-SP was observed in rural areas (Cn = - 0.238; 95%CI - 0.242 to - 0.235). The result of the decomposition analysis indicated that geographic zone of residence and antenatal visits were the two main drivers for the concentration of the uptake of IPTp-SP among wealthier pregnant women in Nigeria. CONCLUSION: The pro-rich inequalities in the uptake of IPTp-SP among pregnant women in Nigeria, particularly in urban areas, warrant further attention. Strategies to improve the uptake of IPTp-SP among women residing in socioeconomically disadvantaged geographic zones (North-East and North-West) and improving antenatal visits among the poor women may reduce pro-rich inequality in the uptake of IPTp-SP among pregnant women in Nigeria.

Predictors for the uptake of optimal doses of sulfadoxine-pyrimethamine for intermittent preventive treatment of malaria during pregnancy in Tanzania: further analysis of the data of the 2015-2016 Tanzania demographic and health survey and malaria indicator survey.

BACKGROUND: In Tanzania, the uptake of optimal doses (≥ 3) of sulfadoxine-pyrimethamine for intermittent preventive treatment of malaria (IPTp-SP) during pregnancy has remained below the recommended target of 80%. Therefore, this study aimed to investigate the predictors for the uptake of optimal IPTp-SP among pregnant women in Tanzania. METHODS: This study used data from the 2015-16 Tanzania demographic and health survey and malaria indicator survey (TDHS-MIS). The study had a total of 4111 women aged 15 to 49 who had live births 2 years preceding the survey. The outcome variable was uptake of three or more doses of IPTp-SP, and the independent variables were age, marital status, education level, place of residence, wealth index, occupation, geographic zone, parity, the timing of first antenatal care (ANC), number of ANC visits and type of the health facility for ANC visits. Predictors for the optimal uptake of IPTp-SP were assessed using univariate and multivariable logistic regression. RESULTS: A total of 327 (8%) women had optimal uptake of IPTp-SP doses. Among the assessed predictors, the following were significantly associated with optimal uptake of IPTp-SP doses; education level [primary (AOR: 2.2, 95% CI 1.26-3.67); secondary or higher education (AOR: 2.1, 95% CI 1.08-4.22)], attended ANC at the first trimester (AOR: 2.4, 95% CI 1.20-4.96), attended ≥ 4 ANC visits (AOR: 1.9, 95% CI 1.34-2.83), attended government health facilities (AOR: 1.5, 95% CI 1.07-1.97) and geographic zone [Central (AOR: 5, 95% CI 2.08-11.95); Southern Highlands (AOR: 2.8, 95% CI 1.15-7.02); Southwest Highlands (AOR: 2.7, 95% CI 1.03-7.29); Lake (AOR: 3.5, 95% CI 1.51-8.14); Eastern (AOR: 1.5, 95% CI 1.88-11.07)]. CONCLUSIONS: The uptake of optimal IPTp-SP doses is still low in Tanzania. The optimal uptake of IPTp-SP was associated with attending ANC in the first trimester, attending more than four ANC visits, attending government health facility for ANC, having primary, secondary, or higher education level, and geographic zone. Therefore, there is a need for health education and behavior change interventions with an emphasis on the optimal use of IPTp-SP doses.

Suboptimal Intermittent Preventive Treatment in Pregnancy (IPTp) is Associated With an Increased Risk of Submicroscopic Plasmodium falciparum Infection in Pregnant Women: A Prospective Cohort Study in Benin.

BACKGROUND: Harmful maternal and neonatal health outcomes result from malaria in pregnancy, the prevention of which primarily relies on intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP). The World Health Organization recommends IPTp-SP in sub-Saharan Africa, but implementation is highly heterogeneous and often suboptimal in terms of the number of doses and their timing. In this study, we assessed the impact of this heterogeneity on malaria in pregnancy, mainly with respect to submicroscopic Plasmodium falciparum infections. METHODS: We used data from 273 Beninese women followed throughout pregnancy. Screening for P. falciparum infections, using both microscopy-based and polymerase chain reaction (PCR)-based methods, was performed monthly, and information on IPTp-SP doses was collected. Gestational age was estimated by repeated ultrasound scans. Using a negative binomial model, we investigated the effect of IPTp-SP doses and timing after 17 weeks of gestation on the number of P. falciparum infections, focusing on submicroscopic infections detectable only by PCR. RESULTS: At least 2 IPTp-SP doses were taken by 77.3% of the women. The median gestational age at the first IPTp-SP dose was 22 weeks. A late first IPTp-SP dose (>21.2 weeks) was marginally associated with an increased number of P. falciparum infections (adjusted incidence rate ratio [aIRR] = 1.3; P = .098). The number of IPTp-SP doses was not associated with the number of submicroscopic infections (aIRR = 1.2, P = .543). CONCLUSIONS: A late first IPTp-SP dose failed to provide optimal protection against P. falciparum, especially submicroscopic infections. This highlights the need for a new antimalarial drug for IPTp that could be taken early in pregnancy.

Infant sex modifies associations between placental malaria and risk of malaria in infancy.

BACKGROUND: Placental malaria (PM) has been associated with a higher risk of malaria during infancy. However, it is unclear whether this association is causal, and is modified by infant sex, and whether intermittent preventive treatment in pregnancy (IPTp) can reduce infant malaria by preventing PM. METHODS: Data from a birth cohort of 656 infants born to HIV-uninfected mothers randomised to IPTp with dihydroartemisinin-piperaquine (DP) or Sulfadoxine-pyrimethamine (SP) was analysed. PM was categorized as no PM, active PM (presence of parasites), mild-moderate past PM (> 0-20% high powered fields [HPFs] with pigment), or severe past PM (> 20% HPFs with pigment). The association between PM and incidence of malaria in infants stratified by infant sex was examined. Causal mediation analysis was used to test whether IPTp can impact infant malaria incidence via preventing PM. RESULTS: There were 1088 malaria episodes diagnosed among infants during 596.6 person years of follow-up. Compared to infants born to mothers with no PM, the incidence of malaria was higher among infants born to mothers with active PM (adjusted incidence rate ratio [aIRR] 1.30, 95% CI 1.00-1.71, p = 0.05) and those born to mothers with severe past PM (aIRR 1.28, 95% CI 0.89-1.83, p = 0.18), but the differences were not statistically significant. However, when stratifying by infant sex, compared to no PM, severe past PM was associated a higher malaria incidence in male (aIRR 2.17, 95% CI 1.45-3.25, p < 0.001), but not female infants (aIRR 0.74, 95% CI 0.46-1.20, p = 0.22). There were no significant associations between active PM or mild-moderate past PM and malaria incidence in male or female infants. Male infants born to mothers given IPTp with DP had significantly less malaria in infancy than males born to mothers given SP, and 89.7% of this effect was mediated through prevention of PM. CONCLUSION: PM may have more severe consequences for male infants, and interventions which reduce PM could mitigate these sex-specific adverse outcomes. More research is needed to better understand this sex-bias between PM and infant malaria risk. Trial registration ClinicalTrials.gov, NCT02793622. Registered 8 June 2016, https://clinicaltrials.gov/ct2/show/NCT02793622.

Effectiveness of seasonal malaria chemoprevention at scale in west and central Africa: an observational study.

BACKGROUND: Seasonal malaria chemoprevention (SMC) aims to prevent malaria in children during the high malaria transmission season. The Achieving Catalytic Expansion of SMC in the Sahel (ACCESS-SMC) project sought to remove barriers to the scale-up of SMC in seven countries in 2015 and 2016. We evaluated the project, including coverage, effectiveness of the intervention, safety, feasibility, drug resistance, and cost-effectiveness. METHODS: For this observational study, we collected data on the delivery, effectiveness, safety, influence on drug resistance, costs of delivery, impact on malaria incidence and mortality, and cost-effectiveness of SMC, during its administration for 4 months each year (2015 and 2016) to children younger than 5 years, in Burkina Faso, Chad, The Gambia, Guinea, Mali, Niger, and Nigeria. SMC was administered monthly by community health workers who visited door-to-door. Drug administration was monitored via tally sheets and via household cluster-sample coverage surveys. Pharmacovigilance was based on targeted spontaneous reporting and monitoring systems were strengthened. Molecular markers of resistance to sulfadoxine-pyrimethamine and amodiaquine in the general population before and 2 years after SMC introduction was assessed from community surveys. Effectiveness of monthly SMC treatments was measured in case-control studies that compared receipt of SMC between patients with confirmed malaria and neighbourhood-matched community controls eligible to receive SMC. Impact on incidence and mortality was assessed from confirmed outpatient cases, hospital admissions, and deaths associated with malaria, as reported in national health management information systems in Burkina Faso and The Gambia, and from data from selected outpatient facilities (all countries). Provider costs of SMC were estimated from financial costs, costs of health-care staff time, and volunteer opportunity costs, and cost-effectiveness ratios were calculated as the total cost of SMC in each country divided by the predicted number of cases averted. FINDINGS: 12 467 933 monthly SMC treatments were administered in 2015 to a target population of 3 650 455 children, and 25 117 480 were administered in 2016 to a target population of 7 551 491. In 2015, among eligible children, mean coverage per month was 76·4% (95% CI 74·0-78·8), and 54·5% children (95% CI 50·4-58·7) received all four treatments. Similar coverage was achieved in 2016 (74·8% [72·2-77·3] treated per month and 53·0% [48·5-57·4] treated four times). In 779 individual case safety reports over 2015-16, 36 serious adverse drug reactions were reported (one child with rash, two with fever, 31 with gastrointestinal disorders, one with extrapyramidal syndrome, and one with Quincke's oedema). No cases of severe skin reactions (Stevens-Johnson or Lyell syndrome) were reported. SMC treatment was associated with a protective effectiveness of 88·2% (95% CI 78·7-93·4) over 28 days in case-control studies (2185 cases of confirmed malaria and 4370 controls). In Burkina Faso and The Gambia, implementation of SMC was associated with reductions in the number of malaria deaths in hospital during the high transmission period, of 42·4% (95% CI 5·9 to 64·7) in Burkina Faso and 56·6% (28·9 to 73·5) in The Gambia. Over 2015-16, the estimated reduction in confirmed malaria cases at outpatient clinics during the high transmission period in the seven countries ranged from 25·5% (95% CI 6·1 to 40·9) in Nigeria to 55·2% (42·0 to 65·3) in The Gambia. Molecular markers of resistance occurred at low frequencies. In individuals aged 10-30 years without SMC, the combined mutations associated with resistance to amodiaquine (pfcrt CVIET haplotype and pfmdr1 mutations [86Tyr and 184Tyr]) had a prevalence of 0·7% (95% CI 0·4-1·2) in 2016 and 0·4% (0·1-0·8) in 2018 (prevalence ratio 0·5 [95% CI 0·2-1·2]), and the quintuple mutation associated with resistance to sulfadoxine-pyrimethamine (triple mutation in pfdhfr and pfdhps mutations [437Gly and 540Glu]) had a prevalence of 0·2% (0·1-0·5) in 2016 and 1·0% (0·6-1·6) in 2018 (prevalence ratio 4·8 [1·7-13·7]). The weighted average economic cost of administering four monthly SMC treatments was US$3·63 per child. INTERPRETATION: SMC at scale was effective in preventing morbidity and mortality from malaria. Serious adverse reactions were rarely reported. Coverage varied, with some areas consistently achieving high levels via door-to-door campaigns. Markers of resistance to sulfadoxine-pyrimethamine and amodiaquine remained uncommon, but with some selection for resistance to sulfadoxine-pyrimethamine, and the situation needs to be carefully monitored. These findings should support efforts to ensure high levels of SMC coverage in west and central Africa. FUNDING: Unitaid.

Reaching the unreached: effectiveness and satisfaction with community-directed distribution of sulfadoxine-pyrimethamine for preventing malaria in pregnancy in rural South-East, Nigeria.

BACKGROUND: Innovative community strategies to increase intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) coverage is advocated particularly in rural areas, where health infrastructure is weakest and malaria transmission highest. This study involved proof-of-concept implementation research to determine satisfaction with and effectiveness of community-directed distribution of IPTp-SP on uptake among pregnant women in Ebonyi State, Nigeria. METHODS: This before-and-after study was carried out in 2019 in a rural community in Ebonyi State Nigeria. The intervention involved advocacy visits, community-wide sensitizations on malaria prevention, house-to-house directly observed IPTp-SP administration, and follow-up visits by trained community-selected community-directed distributors (CDDs). Monthly IPTp-SP coverage was assessed over 5 months and data analysed using SPSS version 20. RESULTS: During the study, 229 women received the first dose of IPTp while 60 pregnant women received 5 or more doses of IPTp. The uptake of ≥ 3 IPTp doses increased from 31.4% before the community-directed distribution of IPTp to 71.6% (P < 0.001) by the fourth month post-initiation of the community-directed distribution of IPTp. Sleeping under insecticide-treated net (ITN) the night before the survey increased from 62.4 to 84.3% (P < 0.001) while reporting of fever during pregnancy decreased from 64.9 to 17.0% (P < 0.001). Although antenatal clinic utilization increased in the primary health centre serving the community, traditional birth attendants and patent medicine vendors in the community remained more patronized. Post-intervention, most mothers rated CDD services well (93.6%), were satisfied (97.6%), and preferred community IPTp administration to facility administration (92.3%). CONCLUSION: Community-directed distribution of IPTp-SP improved uptake of IPTp-SP and ITN use. Mothers were satisfied with the services. The authors recommend sustained large-scale implementation of community-directed distribution of IPTp with active community engagement.

A cluster randomized trial of delivery of intermittent preventive treatment of malaria in pregnancy at the community level in Burkina Faso.

BACKGROUND: Malaria in pregnancy is responsible for 8-14% of low birth weight and 20% of stillbirths in sub-Saharan Africa. To prevent these adverse consequences, the World Health Organization recommends intermittent preventive treatment of pregnant women (IPTp) with sulfadoxine-pyrimethamine be administered at each ANC visit starting as early as possible in the second trimester. Global IPTp coverage in targeted countries remains unacceptably low. Community delivery of IPTp was explored as a means to improve coverage. METHODS: A cluster randomized, controlled trial was conducted in 12 health facilities in a 1:1 ratio to either an intervention group (IPTp delivered by CHWs) or a control group (standard practice, with IPTp delivered at HFs) in three districts of Burkina Faso to assess the effect of IPTp administration by community health workers (CHWs) on the coverage of IPTp and antenatal care (ANC). The districts and facilities were purposively selected taking into account malaria epidemiology, IPTp coverage, and the presence of active CHWs. Pre- and post-intervention surveys were carried out in March 2017 and July-August 2018, respectively. A difference in differences (DiD) analysis was conducted to assess the change in coverage of IPTp and ANC over time, accounting for clustering at the health facility level. RESULTS: Altogether 374 and 360 women were included in the baseline and endline surveys, respectively. At baseline, women received a median of 2.1 doses; by endline, women received a median of 1.8 doses in the control group and 2.8 doses in the intervention group (p-value < 0.0001). There was a non-statistically significant increase in the proportion of women attending four ANC visits in the intervention compared to control group (DiD = 12.6%, p-value = 0.16). By the endline, administration of IPTp was higher in the intervention than control, with a DiD of 17.6% for IPTp3 (95% confidence interval (CI) - 16.3, 51.5; p-value 0.31) and 20.0% for IPTp4 (95% CI - 7.2, 47.3; p-value = 0.15). CONCLUSIONS: Community delivery of IPTp could potentially lead to a greater number of IPTp doses delivered, with no apparent decrease in ANC coverage.