Feasibility, safety, and impact of the RTS,S/AS01E malaria vaccine when implemented through national immunisation programmes: evaluation of cluster-randomised introduction of the vaccine in Ghana, Kenya, and Malawi.

BACKGROUND: The RTS,S/AS01E malaria vaccine (RTS,S) was introduced by national immunisation programmes in Ghana, Kenya, and Malawi in 2019 in large-scale pilot schemes. We aimed to address questions about feasibility and impact, and to assess safety signals that had been observed in the phase 3 trial that included an excess of meningitis and cerebral malaria cases in RTS,S recipients, and the possibility of an excess of deaths among girls who received RTS,S than in controls, to inform decisions about wider use. METHODS: In this prospective evaluation, 158 geographical clusters (66 districts in Ghana; 46 sub-counties in Kenya; and 46 groups of immunisation clinic catchment areas in Malawi) were randomly assigned to early or delayed introduction of RTS,S, with three doses to be administered between the ages of 5 months and 9 months and a fourth dose at the age of approximately 2 years. Primary outcomes of the evaluation, planned over 4 years, were mortality from all causes except injury (impact), hospital admission with severe malaria (impact), hospital admission with meningitis or cerebral malaria (safety), deaths in girls compared with boys (safety), and vaccination coverage (feasibility). Mortality was monitored in children aged 1-59 months throughout the pilot areas. Surveillance for meningitis and severe malaria was established in eight sentinel hospitals in Ghana, six in Kenya, and four in Malawi. Vaccine uptake was measured in surveys of children aged 12-23 months about 18 months after vaccine introduction. We estimated that sufficient data would have accrued after 24 months to evaluate each of the safety signals and the impact on severe malaria in a pooled analysis of the data from the three countries. We estimated incidence rate ratios (IRRs) by comparing the ratio of the number of events in children age-eligible to have received at least one dose of the vaccine (for safety outcomes), or age-eligible to have received three doses (for impact outcomes), to that in non-eligible age groups in implementation areas with the equivalent ratio in comparison areas. To establish whether there was evidence of a difference between girls and boys in the vaccine's impact on mortality, the female-to-male mortality ratio in age groups eligible to receive the vaccine (relative to the ratio in non-eligible children) was compared between implementation and comparison areas. Preliminary findings contributed to WHO's recommendation in 2021 for widespread use of RTS,S in areas of moderate-to-high malaria transmission. FINDINGS: By April 30, 2021, 652 673 children had received at least one dose of RTS,S and 494 745 children had received three doses. Coverage of the first dose was 76% in Ghana, 79% in Kenya, and 73% in Malawi, and coverage of the third dose was 66% in Ghana, 62% in Kenya, and 62% in Malawi. 26 285 children aged 1-59 months were admitted to sentinel hospitals and 13 198 deaths were reported through mortality surveillance. Among children eligible to have received at least one dose of RTS,S, there was no evidence of an excess of meningitis or cerebral malaria cases in implementation areas compared with comparison areas (hospital admission with meningitis: IRR 0·63 [95% CI 0·22-1·79]; hospital admission with cerebral malaria: IRR 1·03 [95% CI 0·61-1·74]). The impact of RTS,S introduction on mortality was similar for girls and boys (relative mortality ratio 1·03 [95% CI 0·88-1·21]). Among children eligible for three vaccine doses, RTS,S introduction was associated with a 32% reduction (95% CI 5-51%) in hospital admission with severe malaria, and a 9% reduction (95% CI 0-18%) in all-cause mortality (excluding injury). INTERPRETATION: In the first 2 years of implementation of RTS,S, the three primary doses were effectively deployed through national immunisation programmes. There was no evidence of the safety signals that had been observed in the phase 3 trial, and introduction of the vaccine was associated with substantial reductions in hospital admission with severe malaria. Evaluation continues to assess the impact of four doses of RTS,S. FUNDING: Gavi, the Vaccine Alliance; the Global Fund to Fight AIDS, Tuberculosis and Malaria; and Unitaid.

Ferric carboxymaltose versus standard-of-care oral iron to treat second-trimester anaemia in Malawian pregnant women: a randomised controlled trial.

BACKGROUND: Anaemia affects 46% of pregnancies in Africa; oral iron is recommended by WHO but uptake and adherence are suboptimal. We tested a single dose of a modern intravenous iron formulation, ferric carboxymaltose, for anaemia treatment in Malawian pregnant women. METHODS: In this open-label, individually randomised controlled trial, we enrolled women with a singleton pregnancy of 13-26 weeks' gestation in primary care and outpatient settings across two regions in southern Malawi. Women were eligible if they had capillary haemoglobin of less than 10·0 g/dL and negative malaria rapid diagnostic test. Participants were randomised by sealed envelope 1:1. Assessors for efficacy outcomes (laboratory parameters and birthweight) were masked to intervention; participants and study nurses were not masked. Participants were given ferric carboxymaltose up to 1000 mg (given once at enrolment in an outpatient primary care setting), or standard of care (60 mg elemental iron twice daily for 90 days), along with intermittent preventive malaria treatment. The primary maternal outcome was anaemia at 36 weeks' gestation. The primary neonatal outcome was birthweight. Analyses were performed in the intention-to-treat population for mothers and liveborn neonates, according to their randomisation group. Safety outcomes included incidence of adverse events during infusion and all adverse events from randomisation to 4 weeks' post partum. The trial is registered with ANZCTR, ACTRN12618001268235. The trial has completed follow-up. FINDINGS: Between Nov 12, 2018, and March 2, 2021, 21 258 women were screened, and 862 randomly assigned to ferric carboxymaltose (n=430) or standard of care (n=432). Ferric carboxymaltose did not reduce anaemia prevalence at 36 weeks' gestation compared with standard of care (179 [52%] of 341 in the ferric carboxymaltose group vs 189 [57%] of 333 in the standard of care group; prevalence ratio [PR] 0·92, 95% CI 0·81 to 1·06; p=0·27). Anaemia prevalence was numerically lower in mothers randomly assigned to ferric carboxymaltose compared with standard of care at all timepoints, although significance was only observed at 4 weeks' post-treatment (PR 0·91 [0·85 to 0·97]). Birthweight did not differ between groups (mean difference -3·1 g [-75·0 to 68·9, p=0·93). There were no infusion-related serious adverse events or differences in adverse events by any organ class (including malaria; ≥1 adverse event: ferric carboxymaltose 183 [43%] of 430 vs standard of care 170 [39%] of 432; risk ratio 1·08 [0·92 to 1·27]; p=0·34). INTERPRETATION: In this malaria-endemic sub-Saharan African setting, treatment of anaemic pregnant women with ferric carboxymaltose was safe but did not reduce anaemia prevalence at 36 weeks' gestation or increase birthweight. FUNDING: Bill & Melinda Gates Foundation (INV-010612).

An intervention to improve lumbar puncture rates for meningitis surveillance in children at four secondary health facilities in Malawi: A before/after analysis.

OBJECTIVES: A lumbar puncture (LP) procedure plays a key role in meningitis diagnosis. In Malawi and other sub-Saharan African countries, LP completion rates are sometimes poor, making meningitis surveillance challenging. Our objective was to measure LP rates following an intervention to improve these during a sentinel hospital meningitis surveillance exercise in Malawi. METHODS: We conducted a before/after intervention analysis among under-five children admitted to paediatric wards at four secondary health facilities in Malawi. We used local and World Health Organization (WHO) guidelines to determine indications for LP, as these are widely used in low- and middle-income countries (LMIC). The intervention comprised of refresher trainings for facility staff on LP indications and procedure, use of automated reminders to perform LP in real time in the wards, with an electronic data management system, and addition of surveillance-specific clinical officers to support existing health facility staff with performing LPs. Due to the low numbers in the before/after analysis, we also performed a during/after analysis to supplement the findings. RESULTS: A total of 13,375 under-five children were hospitalised over the 21 months window for this analysis. The LP rate was 10.4% (12/115) and 60.4% (32/53) in the before/after analysis, respectively, and 43.8% (441/1006) and 72.5% (424/599) in the supplemental during/after analysis, respectively. In our intervention-specific analysis among the three individual components, there were improvements in the LP rate by 48% (p < 0.001) following the introduction of surveillance-specific clinical officers, 10% (p < 0.001) following the introduction of automated reminders to perform an LP and 13% following refresher training. CONCLUSIONS: This analysis demonstrated a rise in LP rates following our intervention. This intervention package may be considered for planning future facility-based meningitis surveillances in similar low-resource settings.

Prompt treatment-seeking behaviour varies within communities among guardians of children with malaria-related fever in Malawi.

BACKGROUND: In Malawi, malaria is responsible for 40% of hospital deaths. Prompt diagnosis and effective treatment within 24 h of fever onset is critical to prevent progression from uncomplicated to severe disease and to reduce transmission. METHODS: As part of the large evaluation of the malaria vaccine implementation programme (MVIP), this study analysed survey data to investigate whether prompt treatment-seeking behaviour is clustered at community-level according to socio-economic demographics. RESULTS: From 4563 households included in the survey, 4856 children aged 5-48 months were enrolled. Out of 4732 children with documented gender, 52.2% were female and 47.8% male. Among the 4856 children, 33.8% reported fever in the two weeks prior to the survey. Fever prevalence was high in communities with low socio-economic status (SES) (38.3% [95% CI: 33.7-43.5%]) and low in areas with high SES (29.8% [95% CI: 25.6-34.2%]). Among children with fever, 648 (39.5%) sought treatment promptly i.e., within 24 h from onset of fever symptoms. Children were more likely to be taken for prompt treatment among guardians with secondary education compared to those without formal education (aOR:1.37, 95% CI: 1.11-3.03); in communities with high compared to low SES [aOR: 2.78, 95% CI: 1.27-6.07]. Children were less likely to be taken for prompt treatment if were in communities far beyond 5 km to health facility than within 5 km [aOR: 0.44, 95% CI: 0.21-0.92]. CONCLUSION: The high heterogeneity in prevalence of fever and levels of prompt treatment-seeking behaviour underscore the need to promote community-level malaria control interventions (such as use of long-lasting insecticide-treated nets (LLINs), indoor residual spraying (IRS), intermittent preventive therapy (IPT), presumptive treatment and education). Programmes aimed at improving treatment-seeking behaviour should consider targeting communities with low SES and those far from health facility.

Plasmodium falciparum infection and disease in infancy associated with increased risk of malaria and anaemia in childhood.

BACKGROUND: Infants under 6 months of age are often excluded from malaria surveillance and observational studies. The impact of malaria during early infancy on health later in childhood remains unknown. METHODS: Infants from two birth cohorts in Malawi were monitored at quarterly intervals and whenever they were ill from birth through 24 months for Plasmodium falciparum infections and clinical malaria. Poisson regression and linear mixed effects models measured the effect of exposure to malaria in infancy on subsequent malaria incidence, weight-for-age z-scores (WAZ), and haemoglobin concentrations after 6 months. RESULTS: Infants with at least one P. falciparum infection during their first 6 months had increased incidence ratio (IRR) of P. falciparum infection (IRR = 1.27, 95% CI, 1.06-1.52) and clinical malaria (IRR = 2.37, 95% CI, 2.02-2.80) compared to infants without infection. Infants with clinical malaria had increased risk of P. falciparum infection incidence between 6 and 24 months (IRR = 1.64, 95% CI, 1.38-1.94) and clinical malaria (IRR = 1.85, 95% CI, 1.48-2.32). Exposure to malaria was associated with lower WAZ over time (p = 0.02) and lower haemoglobin levels than unexposed infants at every time interval (p = 0.02). CONCLUSIONS: Infants experiencing malaria infection or clinical malaria are at increased risk of subsequent infection and disease, have poorer growth, and lower haemoglobin concentrations.

A qualitative study on the feasibility and acceptability of institutionalizing health technology assessment in Malawi.

OBJECTIVE: The objective of this study was to assess the feasibility and acceptability of institutionalizing Health Technology Assessment (HTA) in Malawi. METHODS: This study employed a document review and qualitative research methods, to understand the status of HTA in Malawi. This was complemented by a review of the status and nature of HTA institutionalization in selected countries.Qualitative research employed a Focus Group Discussion (FGD ) with 7 participants, and Key Informant Interviews (KIIs) with12 informants selected based on their knowledge and expertise in policy processes related to HTA in Malawi.Data extracted from the literature was organized in Microsoft Excel, categorized according to thematic areas and analyzed using a literature review framework. Qualitative data from KIIs and the FGD was analyzed using a thematic content analysis approach. RESULTS: Some HTA processes exist and are executed through three structures namely: Ministry of Health Senior Management Team, Technical Working Groups, and Pharmacy and Medicines Regulatory Authority (PMRA) with varyingdegrees of effectiveness.The main limitations of current HTA mechanisms include limited evidence use, lack of a standardized framework for technology adoption, donor pressure, lack of resources for the HTA process and technology acquisition, laws and practices that undermine cost-effectiveness considerations. KII and FGD results showed overwhelming demand for strengthening HTA in Malawi, with a stronger preference for strengthening coordination and capacity of existing entities and structures. CONCLUSION: The study has shown that HTA institutionalization is acceptable and feasible in Malawi. However, the current committee based processes are suboptimal to improve efficiency due to lack of a structured framework. A structured HTA framework has the potential to improve processes in pharmaceuticals and medical technologies decision-making.In the short to medium term, HTA capacity building should focus on generating demand and increasing capacity in cost-effectiveness assessments. Country-specific assessments should precede HTA institutionalization as well as recommendations for new technology adoptions.

The Effect of Intermittent Preventive Treatment of Malaria During Pregnancy and Placental Malaria on Infant Risk of Malaria.

BACKGROUND: Intermittent preventive treatment of malaria during pregnancy (IPTp) with dihydroartemisinin-piperaquine (DP) provides greater protection from placental malaria than sulfadoxine-pyrimethamine (SP). Some studies suggest placental malaria alters risk of malaria infection in infants, but few have quantified the effect of IPTp on infant susceptibility to malaria. METHODS: Infants born to women enrolled in a randomized clinical trial comparing IPTp-SP and IPTp-DP in Malawi were followed from birth to 24 months to assess effect of IPTp and placental malaria on time to first malaria episode and Plasmodium falciparum incidence. RESULTS: In total, 192 infants born to mothers randomized to IPTp-SP and 195 randomized to IPTp-DP were enrolled. Infants in IPTp exposure groups did not differ significantly regarding incidence of clinical malaria (incidence rate ratio [IRR], 1.03; 95% confidence interval [CI], .58-1.86) or incidence of infection (IRR, 1.18; 95% CI, .92-1.55). Placental malaria exposure was not associated with incidence of clinical malaria (IRR, 1.03; 95% CI, .66-1.59) or infection (IRR, 1.15; 95% CI, .88-1.50). Infant sex, season of birth, and maternal gravidity did not confound results. CONCLUSIONS: We did not find evidence that IPTp regimen or placental malaria exposure influenced risk of malaria during infancy in this population. Clinical Trials Registration. NCT03009526.

Impact of school-based malaria intervention on primary school teachers' time in Malawi: evidence from a time and motion study.

BACKGROUND: School-based health (SBH) programmes that are contingent on primary school teachers are options to increase access to malaria treatment among learners. However, perceptions that provision of healthcare by teachers may be detrimental to teaching activities can undermine efforts to scale up school-based malaria control. The objective of this study was to assess the impact of school-based malaria diagnosis and treatment using the Learner Treatment Kit (LTK) on teachers' time. METHODS: A time and motion study was conducted in 10 primary schools in rural Malawi. Teachers who had been trained to diagnose and treat uncomplicated malaria were continuously observed in real time during school sessions and the time they spent on all activities were recorded by independent observers before and after LTK implementation. A structured form, programmed digitally, was used for data collection. Paired sample t-tests were used to assess pre-post differences in average hours teachers spent on the following key activities: direct teaching; indirect teaching; administration; LTK and non-teaching tasks. Multivariable repeated measures mixed regression models were used to ascertain impact of LTK on average durations teachers spent on the key activities. RESULTS: Seventy-four teachers, trained to use LTK, were observed. Their mean age and years of teaching experience were 34.7 and 8.7, respectively. Overall, 739.8 h of teacher observations took place. The average time teachers spent in school before relative to after LTK was 5.8 vs. 4.8 h, p = 0.01. The cumulative percentage of time teachers spent on core teaching activities (teaching and administration) was approximately 76% and did not change substantially before and after LTK. Some 24.3% of teachers' time is spent on non-teaching activities. On average, teachers spent 2.9% of their time providing LTK services daily. Per day, each teacher spent less time on administrative (0.74 vs. 1.07 h, p = 0.02) and non-teaching activities (0.96 vs. 1.41 h, p = 0.01) during LTK compared with the period before LTK. CONCLUSION: School-based health (SBH) programmes are not detrimental to teaching activities. Teachers manage their time to ensure additional time required for SBH services is not at the expense of teaching duties. Programming and policy implications of tasking teachers with SBH does not have substantial opportunity costs. Teachers should continue delivering SBH programmes to promote learners' health.

The choice of reference chart affects the strength of the association between malaria in pregnancy and small for gestational age: an individual participant data meta-analysis comparing the Intergrowth-21 with a Tanzanian birthweight chart.

BACKGROUND: The prevalence of small for gestational age (SGA) may vary depending on the chosen weight-for-gestational-age reference chart. An individual participant data meta-analysis was conducted to assess the implications of using a local reference (STOPPAM) instead of a universal reference (Intergrowth-21) on the association between malaria in pregnancy and SGA. METHODS: Individual participant data of 6,236 newborns were pooled from seven conveniently identified studies conducted in Tanzania and Malawi from 2003-2018 with data on malaria in pregnancy, birthweight, and ultrasound estimated gestational age. Mixed-effects regression models were used to compare the association between malaria in pregnancy and SGA when using the STOPPAM and the Intergrowth-21 references, respectively. RESULTS: The 10th percentile for birthweights-for-gestational age was lower for STOPPAM than for Intergrowth-21, leading to a prevalence of SGASTOPPAM of 14.2% and SGAIG21 of 18.0%, p < 0.001. The association between malaria in pregnancy and SGA was stronger for STOPPAM (adjusted odds ratio (aOR) 1.30 [1.09-1.56], p < 0.01) than for Intergrowth-21 (aOR 1.19 [1.00-1.40], p = 0.04), particularly among paucigravidae (SGASTOPPAM aOR 1.36 [1.09-1.71], p < 0.01 vs SGAIG21 aOR 1.21 [0.97-1.50], p = 0.08). CONCLUSIONS: The prevalence of SGA may be overestimated and the impact of malaria in pregnancy underestimated when using Intergrowth-21. Comparing local reference charts to global references when assessing and interpreting the impact of malaria in pregnancy may be appropriate.

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

BACKGROUND: Malaria in pregnancy doubles the risk of low birthweight; up to 11% of all neonatal deaths in sub-Saharan Africa are associated with malaria in pregnancy. To prevent these and other adverse health consequences, the World Health Organization recommends administering intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine for all pregnant women at each antenatal care (ANC) visit, starting as early as possible in the second trimester. The target is for countries to administer a minimum of three doses (IPTp3+) to at least 85% of pregnant women. METHODS: A cluster randomized, controlled trial was conducted to assess the effect of delivery of IPTp by community health workers on the coverage of IPTp3 + and ANC visits in Malawi. Community delivery of IPTp was implemented within two districts in Malawi over a 21-month period, from November 2018 to July 2020. In control sites, IPTp was delivered at health facilities. Representative samples of women who delivered in the prior 12 months were surveyed at baseline (n = 370, December 2017) and endline (n = 687, August 2020). A difference in differences analysis was conducted to assess the change in coverage of IPTp and ANC over time, accounting for clustering at the health facility level. RESULTS: Overall IPTp coverage increased over the study period. At baseline, women received a mean of 2.3 IPTp doses (range 0-5 doses) across both arms, and at endline, women received a mean of 2.8 doses (range 0-9 doses). Despite overall increases, the change in IPTp3 + coverage was not significantly different between intervention and control groups (6.9%, 95% CI: -5.9%, 19.6%). ANC4 + coverage increased significantly in the intervention group compared with the control group, with a difference-in-differences of 25.3% points (95% CI: 1.3%, 49.3%). CONCLUSIONS: In order to reduce the burden of malaria in pregnancy, new strategies are needed to improve uptake of effective interventions such as IPTp. While community health workers' delivery of IPTp did not increase uptake in this study, they may be effective in other settings or circumstances. Further research can help identify the health systems characteristics that are conducive to community delivery of IPTp and the operational requirements for effective implementation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03376217. Registered December 6, 2017, https://clinicaltrials.gov/ct2/show/NCT03376217 .

Assessing community health workers' time allocation for a cervical cancer screening and treatment intervention in Malawi: a time and motion study.

BACKGROUND: Community health workers (CHWs) are essential field-based personnel and increasingly used to deliver priority interventions to achieve universal health coverage. Existing literature allude to the potential for detrimental effects of multi-tasking CHWs. This study objective was to assess the impact of integrating cervical cancer screening and prevention therapy (CCSPT) with family planning (FP) on time utilization among CHWs. METHODS: A time and motion study was conducted in 7 health facilities in Malawi. Data was collected at baseline between October-July 2019, and 12 months after CCSPT implementation between July and August 2021. CHWs trained to deliver CCSPT were continuously observed in real time while their activities were timed by independent observers. We used paired sample t-test to assess pre-post differences in average hours CHWs spent on the following key activities, before and after CCSPT implementation: clinical and preventive care; administration; FP; and non-work-related tasks. Regression models were used to ascertain impact of CCSPT on average durations CHWs spent on key activities. RESULTS: Thirty-seven (n = 37) CHWs were observed. Their mean age and years of experience were 42 and 17, respectively. Overall, CHWs were observed for 323 hours (inter quartile range: 2.8-5.5). Compared with the period before CCSPT, the proportion of hours CHWs spent on clinical and preventive care, administration and non-work-related activities were reduced by 13.7, 8.7 and 34.6%, respectively. CHWs spent 75% more time on FP services after CCSPT integration relative to the period before CCSPT. The provision of CCSPT resulted in less time that CHWs devoted towards clinical and preventive care but this reduction was not significant. Following CCPST, CHWs spent significantly few hours on non-work-related activities. CONCLUSION: Introduction of CCSPT was not very detrimental to pre-existing community services. CHWs managed their time ensuring additional efforts required for CCSPT were not at the expense of essential activities. The programming and policy implications are that multi-tasking CHWs with CCSPT will not have substantial opportunity costs.

Implementation of a performance-based financing scheme in Malawi and resulting externalities on the quality of care of non-incentivized services.

BACKGROUND: Countries in Africa progressively implement performance-based financing schemes to improve the quality of care provided by maternal, newborn and child health services. Beyond its direct effects on service provision, evidence suggests that performance-based financing can also generate positive externalities on service utilization, such as increased use of those services that reached higher quality standards after effective scheme implementation. Little, however, is known about externalities generated within non-incentivized health services, such as positive or negative effects on the quality of services within the continuum of maternal care. METHODS: We explored whether a performance-based financing scheme in Malawi designed to improve the quality of childbirth service provision resulted positive or negative externalities on the quality of non-targeted antenatal care provision. This non-randomized controlled pre-post-test study followed the phased enrolment of facilities into a performance-based financing scheme across four districts over a two-year period. Effects of the scheme were assessed by various composite scores measuring facilities' readiness to provide quality antenatal care, as well as the quality of screening, prevention, and education processes offered during observed antenatal care consultations. RESULTS: Our study did not identify any statistically significant effects on the quality of ANC provision attributable to the implemented performance-based financing scheme. Our findings therefore suggest not only the absence of positive externalities, but also the absence of any negative externalities generated within antenatal care service provision as a result of the scheme implementation in Malawi. CONCLUSIONS: Prior research has shown that the Malawian performance-based financing scheme was sufficiently effective to improve the quality of incentivized childbirth service provision. Our findings further indicate that scheme implementation did not affect the quality of non-incentivized but clinically related antenatal care services. While no positive externalities could be identified, we also did not observe any negative externalities attributable to the scheme's implementation. While performance-based incentives might be successful in improving targeted health care processes, they have limited potential in producing externalities - neither positive nor negative - on the provision quality of related non-incentivized services.

Malaria knowledge and experiences with community health workers among recently pregnant women in Malawi.

BACKGROUND: The World Health Organization recommends three or more doses of intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) to mitigate the negative effects of malaria in pregnancy (MIP). Many pregnant women in Malawi are not receiving the recommended number of doses. Community delivery of IPTp (cIPTp) is being piloted as a new approach to increase coverage. This survey assessed recently pregnant women's knowledge of MIP and their experiences with community health workers (CHWs) prior to implementing cIPTp. METHODS: Data were collected via a household survey in Ntcheu and Nkhata Bay Districts, Malawi, from women aged 16-49 years who had a pregnancy resulting in a live birth in the previous 12 months. Survey questions were primarily open response and utilized review of the woman's health passport whenever possible. Analyses accounted for selection weighting and clustering at the health facility level and explored heterogeneity between districts. RESULTS: A total of 370 women were interviewed. Women in both districts found their community health workers (CHWs) to be helpful (77.9%), but only 35.7% spoke with a CHW about antenatal care and 25.8% received assistance for malaria during their most recent pregnancy. A greater proportion of women in Nkhata Bay than Ntcheu reported receiving assistance with malaria from a CHW (42.7% vs 21.9%, p = 0.01); women in Nkhata Bay were more likely to cite IPTp-SP as a way to prevent MIP (41.0% vs 24.8%, p = 0.02) and were more likely to cite mosquito bites as the only way to spread malaria (70.6% vs 62.0% p = 0.03). Women in Nkhata Bay were more likely to receive 3 + doses of IPTp-SP (IPTp3) (59.2% vs 41.8%, p = 0.0002). Adequate knowledge was associated with increased odds of receiving IPTp3, although not statistically significantly so (adjusted odds ratio = 1.50, 95% confidence interval 0.97-2.32, p-value 0.066). CONCLUSIONS: Women reported positive experiences with CHWs, but there was not a focus on MIP. Women in Nkhata Bay were more likely to be assisted by a CHW, had better knowledge, and were more likely to receive IPTp3+ . Increasing CHW focus on the dangers of MIP and implementing cIPTp has the potential to increase IPTp coverage.

Quality of maternal obstetric and neonatal care in low-income countries: development of a composite index.

BACKGROUND: In low-income countries, studies demonstrate greater access and utilization of maternal and neonatal health services, yet mortality rates remain high with poor quality increasingly scrutinized as a potential point of failure in achieving expected goals. Comprehensive measures reflecting the multi-dimensional nature of quality of care could prove useful to quality improvement. However, existing tools often lack a systematic approach reflecting all aspects of quality considered relevant to maternal and newborn care. We aim to address this gap by illustrating the development of a composite index using a step-wise approach to evaluate the quality of maternal obstetric and neonatal healthcare in low-income countries. METHODS: The following steps were employed in creating a composite index: 1) developing a theoretical framework; 2) metric selection; 3) imputation of missing data; 4) initial data analysis 5) normalization 6) weighting and aggregating; 7) uncertainty and sensitivity analysis of resulting composite score; 8) and deconstruction of the index into its components. Based on this approach, we developed a base composite index and tested alternatives by altering the decisions taken at different stages of the construction process to account for missing values, normalization, and aggregation. The resulting single composite scores representing overall maternal obstetric and neonatal healthcare quality were used to create facility rankings and further disaggregated into sub-composites of quality of care. RESULTS: The resulting composite scores varied considerably in absolute values and ranges based on method choice. However, the respective coefficients produced by the Spearman rank correlations comparing facility rankings by method choice showed a high degree of correlation. Differences in method of aggregation had the greatest amount of variation in facility rankings compared to the base case. Z-score standardization most closely aligned with the base case, but limited comparability at disaggregated levels. CONCLUSIONS: This paper illustrates development of a composite index reflecting the multi-dimensional nature of maternal obstetric and neonatal healthcare. We employ a step-wise process applicable to a wide range of obstetric quality of care assessment programs in low-income countries which is adaptable to setting and context. In exploring alternative approaches, certain decisions influencing the interpretation of a given index are highlighted.

Impact of results-based financing on effective obstetric care coverage: evidence from a quasi-experimental study in Malawi.

BACKGROUND: Results-based financing (RBF) describes health system approaches addressing both service quality and use. Effective coverage is a metric measuring progress towards universal health coverage (UHC). Although considered a means towards achieving UHC in settings with weak health financing modalities, the impact of RBF on effective coverage has not been explicitly studied. METHODS: Malawi introduced the Results-Based Financing For Maternal and Neonatal Health (RBF4MNH) Initiative in 2013 to improve quality of maternal and newborn health services at emergency obstetric care facilities. Using a quasi-experimental design, we examined the impact of the RBF4MNH on both crude and effective coverage of pregnant women across four districts during the two years following implementation. RESULTS: There was no effect on crude coverage. With a larger proportion of women in intervention areas receiving more effective care over time, the overall net increase in effective coverage was 7.1%-points (p = 0.07). The strongest impact on effective coverage (31.0%-point increase, p = 0.02) occurred only at lower cut-off level (60% of maximum score) of obstetric care effectiveness. Design-specific and wider health system factors likely limited the program's potential to produce stronger effects. CONCLUSION: The RBF4MNH improved effective coverage of pregnant women and seems to be a promising reform approach towards reaching UHC. Given the short study period, the full potential of the current RBF scheme has likely not yet been reached.

Implementation research to improve quality of maternal and newborn health care, Malawi.

OBJECTIVE: To evaluate the impact of a performance-based financing scheme on maternal and neonatal health service quality in Malawi. METHODS: We conducted a non-randomized controlled before and after study to evaluate the effects of district- and facility-level performance incentives for health workers and management teams. We assessed changes in the facilities' essential drug stocks, equipment maintenance and clinical obstetric care processes. Difference-in-difference regression models were used to analyse effects of the scheme on adherence to obstetric care treatment protocols and provision of essential drugs, supplies and equipment. FINDINGS: We observed 33 health facilities, 23 intervention facilities and 10 control facilities and 401 pregnant women across four districts. The scheme improved the availability of both functional equipment and essential drug stocks in the intervention facilities. We observed positive effects in respect to drug procurement and clinical care activities at non-intervention facilities, likely in response to improved district management performance. Birth assistants' adherence to clinical protocols improved across all studied facilities as district health managers supervised and coached clinical staff more actively. CONCLUSION: Despite nation-wide stock-outs and extreme health worker shortages, facilities in the study districts managed to improve maternal and neonatal health service quality by overcoming bottlenecks related to supply procurement, equipment maintenance and clinical performance. To strengthen and reform health management structures, performance-based financing may be a promising approach to sustainable improvements in quality of health care.

Household costs among patients hospitalized with malaria: evidence from a national survey in Malawi, 2012.

BACKGROUND: With 71% of Malawians living on < $1.90 a day, high household costs associated with severe malaria are likely a major economic burden for low income families and may constitute an important barrier to care seeking. Nevertheless, few efforts have been made to examine these costs. This paper describes household costs associated with seeking and receiving inpatient care for malaria in health facilities in Malawi. METHODS: A cross-sectional survey was conducted in a representative nationwide sample of 36 health facilities providing inpatient treatment for malaria from June-August, 2012. Patients admitted at least 12 h before study team visits who had been prescribed an antimalarial after admission were eligible to provide cost information for their malaria episode, including care seeking at previous health facilities. An ingredients-based approach was used to estimate direct costs. Indirect costs were estimated using a human capital approach. Key drivers of total household costs for illness episodes resulting in malaria admission were assessed by fitting a generalized linear model, accounting for clustering at the health facility level. RESULTS: Out of 100 patients who met the eligibility criteria, 80 (80%) provided cost information for their entire illness episode to date and were included: 39% of patients were under 5 years old and 75% had sought care for the malaria episode at other facilities prior to coming to the current facility. Total household costs averaged $17.48 per patient; direct and indirect household costs averaged $7.59 and $9.90, respectively. Facility management type, household distance from the health facility, patient age, high household wealth, and duration of hospital stay were all significant drivers of overall costs. CONCLUSIONS: Although malaria treatment is supposed to be free in public health facilities, households in Malawi still incur high direct and indirect costs for malaria illness episodes that result in hospital admission. Finding ways to minimize the economic burden of inpatient malaria care is crucial to protect households from potentially catastrophic health expenditures.

Adherence to national guidelines for the diagnosis and management of severe malaria: a nationwide, cross-sectional survey in Malawi, 2012.

BACKGROUND: Severe malaria has a case fatality rate of 10-20 %; however, few studies have addressed the quality of severe malaria case management. This study evaluated the diagnostic and treatment practices of malaria patients admitted to inpatient health facilities (HF) in Malawi. METHODS: In July-August 2012, a nationwide, cross-sectional survey of severe malaria management was conducted in 36 HFs selected with equal probability from all eligible public sector HFs in Malawi. Patient records from all admissions during October 2011 and April 2012 (low and high season, respectively) were screened for an admission diagnosis of malaria or prescription of any anti-malarial. Eligible records were stratified by age (< 5 or ≥ 5 years). A maximum of eight records was randomly selected within each age and month stratum. Severe malaria was defined by admission diagnosis or documentation of at least one sign or symptom of severe malaria. Treatment with intravenous (IV) quinine or artesunate was considered correct. Patients without documentation of severe malaria were analysed as uncomplicated malaria patients; treatment with an artemisinin-based combination therapy (ACT) or oral quinine based on malaria test results was considered correct. All analyses accounted for HF level clustering and sampling weights. RESULTS: The analysis included 906 records from 35 HFs. Among these, 42 % (95 % confidence interval [CI] 35-49) had a severe malaria admission diagnosis and 50 % (95 % CI 44-57) had at least one severe malaria sign or symptom documented. Severe malaria patients defined by admission diagnosis (93, 95 % CI 86-99) were more likely to be treated correctly compared to patients defined by a severe sign (82, 95 % CI 75-89) (p < 0.0001). Among uncomplicated malaria patients, 26 % (95 % CI 18-35) were correctly treated and 53 % (95 % CI 42-64) were adequately treated with IV quinine alone or in combination with an ACT or oral quinine. CONCLUSIONS: A majority of patients diagnosed with severe malaria received the recommended IV therapy in accordance with national treatment guidelines. However, the inconsistencies between diagnosis of severe malaria and documentation of severe signs and symptoms highlight the need to improve healthcare worker recognition and documentation of severe signs and symptoms.

Factors associated with delivery outside a health facility: cross-sectional study in rural Malawi.

OBJECTIVE: To identify factors associated with delivery outside a health facility in rural Malawi. METHOD: A cross-sectional survey was conducted in Balaka, Dedza, Mchinji and Ntcheu districts in Malawi in 2013 among women who had completed a pregnancy 12 months prior to the day of the survey. Multilevel logistic regression was used to assess factors associated with delivery outside a facility. RESULTS: Of the 1812 study respondents, 9% (n = 159) reported to have delivered outside a facility. Unmarried women were significantly more likely [OR = 1.88; 95% CI (1.086-3.173)] to deliver outside a facility, while women from households with higher socio-economic status [third-quartile OR = 0.51; 95% CI (0.28-0.95) and fourth-quartile OR = 0.48; 95% CI (0.29-0.79)] and in urban areas [OR = 0.39; 95%-CI (0.23-0.67)] were significantly less likely to deliver outside a facility. Women without formal education [OR 1.43; 95% CI (0.96-2.14)] and multigravidae [OR = 1.14; 95% CI (0.98-1.73)] were more likely to deliver outside a health facility at 10% level of significance. CONCLUSION: About 9% of women deliver outside a facility. Policies to encourage facility delivery should not only focus on health systems but also be multisectoral to address women's vulnerability and inequality. Facility-based delivery can contribute to curbing the high maternal illness burden if authorities provide incentives to those not delivering at the facility without losing existing users.

Patient-, health worker-, and health facility-level determinants of correct malaria case management at publicly funded health facilities in Malawi: results from a nationally representative health facility survey.

BACKGROUND: Prompt and effective case management is needed to reduce malaria morbidity and mortality. However, malaria diagnosis and treatment is a multistep process that remains problematic in many settings, resulting in missed opportunities for effective treatment as well as overtreatment of patients without malaria. METHODS: Prior to the widespread roll-out of malaria rapid diagnostic tests (RDTs) in late 2011, a national, cross-sectional, complex-sample, health facility survey was conducted in Malawi to assess patient-, health worker-, and health facility-level factors associated with malaria case management quality using multivariate Poisson regression models. RESULTS: Among the 2,019 patients surveyed, 34% had confirmed malaria defined as presence of fever and parasitaemia on a reference blood smear. Sixty-seven per cent of patients with confirmed malaria were correctly prescribed the first-line anti-malarial, with most cases of incorrect treatment due to missed diagnosis; 31% of patients without confirmed malaria were overtreated with an anti-malarial. More than one-quarter of patients were not assessed for fever or history of fever by health workers. The most important determinants of correct malaria case management were patient-level clinical symptoms, such as spontaneous complaint of fever to health workers, which increased both correct treatment and overtreatment by 72 and 210%, respectively (p<0.0001). Complaint of cough was associated with a 27% decreased likelihood of correct malaria treatment (p=0.001). Lower-level cadres of health workers were more likely to prescribe anti-malarials for patients, increasing the likelihood of both correct treatment and overtreatment, but no other health worker or health facility-level factors were significantly associated with case management quality. CONCLUSIONS: Introduction of RDTs holds potential to improve malaria case management in Malawi, but health workers must systematically assess all patients for fever, and then test and treat accordingly, otherwise, malaria control programmes might miss an opportunity to dramatically improve malaria case management, despite better diagnostic tools.