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BACKGROUND: TB preventive treatment (TPT) reduces morbidity and mortality among people living with HIV (PLHIV). Despite the successful scale-up of TPT in Malawi, monitoring and evaluation have been suboptimal. We utilized the Malawi Population-Based HIV Impact Assessment (MPHIA) 2020–2021 survey data to estimate TPT uptake and completion among self-reported HIV-positive persons. METHODS: We estimated the proportion of HIV-positive respondents who had ever undergone TPT, and determined the percentage of those currently on TPT who had completed more than 6 months of treatment. Bivariate and multivariable logistic regression were performed to calculate the odds ratios for factors associated with ever-taking TPT. All variables were self-reported, and the analysis was weighted and accounted for in the survey design. RESULTS: Of the HIV+ respondents, 38.8% (95% CI 36.4–41.3) had ever taken TPT. The adjusted odds of ever taking TPT were 8.0 and 5.2 times as high in the Central and Southern regions, respectively, compared to the Northern region; 1.9 times higher among those in the highest wealth quintile, and 2.1 times higher for those on antiretroviral therapy >10 years. Of those currently taking TPT, 56.2% completed >6 months of TPT. CONCLUSIONS: These results suggest low TPT uptake and >6 months’ completion rates among self-reported HIV+ persons. Initiatives to create demand and strengthen adherence would improve TPT uptake.

Objective This scoping review will identify existing literature regarding contextual factors relevant to vector-control interventions to prevent malaria. We will use the findings of the scoping review to produce an interactive evidence and gap map. The map will assist in the priority setting, development, and conduct of targeted systematic reviews. These systematic reviews seek to assist the Vector Control and Insecticide Resistance Unit of the World Health Organization’s Global Malaria Programme by informing recommendation development by their Guidelines Development Group. Introduction Malaria contributes substantially to the global burden of disease, with an estimated 247 million cases and 619,000 deaths in 2021. Vector-control is key in reducing malaria transmission. Vector-control interventions directly target the mosquito, reducing the potential for parasite infections. These interventions commonly include insecticides used in indoor residual spraying or insecticide-treated nets and larval source management. Several new vector-control interventions are under evaluation to complement these. In addition to estimating the effects of interventions on health outcomes, it is critical to understand how populations at risk of malaria consider them in terms of their feasibility, acceptability, and values. Inclusion Criteria Eligible studies will have assessed the contextual factors of feasibility or acceptability of the interventions of interest, or the valuation of the outcomes of interests. These assessments will be from the perspective of people who receive (residents) or deliver (workers or technicians) the vector-control intervention for the purpose of preventing malaria. Methods We will conduct this scoping review in accordance with the JBI methodology for scoping reviews and report in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews (PRISMA-ScR). We will construct the evidence and gap map following guidance from the Campbell Collaboration.

Abstract Background The World Health Organization recommends Pre-Exposure Prophylaxis (PrEP) for all populations at substantial risk of HIV infection. Understanding PrEP awareness and interest is crucial for designing PrEP programs; however, data are lacking in sub-Saharan Africa. In Malawi, oral PrEP was introduced in 2018. We analyzed data from the 2020 Malawi Population-based HIV Impact Assessment (MPHIA) to assess PrEP awareness and factors associated with PrEP interest in Malawi. Methods MPHIA 2020 was a national cross-sectional household-based survey targeting adults aged 15 + years. Oral PrEP was first described to the survey participants as taking a daily pill to reduce the chance of getting HIV. To assess awareness, participants were asked if they had ever heard of PrEP and to assess interest, were asked if they would take PrEP to prevent HIV, regardless of previous PrEP knowledge. Only sexually active HIV-negative participants are included in this analysis. We used multivariable logistic regression to assess sociodemographic factors and behaviors associated with PrEP interest. All results were weighted. Results We included 13,995 HIV-negative sexually active participants; median age was 29 years old. Overall, 15.0%, 95% confidence interval (CI): 14.2–15.9% of participants were aware of PrEP. More males (adjusted odds ratio (aOR): 1.3, 95% CI: 1.2–1.5), those with secondary (aOR: 1.5, 95% CI: 1.2-2.0) or post-secondary (aOR: 3.4, 95% CI: 2.4–4.9) education and the wealthiest (aOR: 1.6, 95% CI: 1.2-2.0) were aware of PrEP than female, those without education and least wealthy participants, respectively. Overall, 73.0% (95% CI: 71.8–74.1%) of participants were willing to use PrEP. Being male (aOR: 1.2; 95% CI: 1.1–1.3) and having more than one sexual partner (aOR: 1.7 95% CI: 1.4–1.9), were associated higher willingness to use PrEP. Conclusions In this survey, prior PrEP knowledge and use were low while PrEP interest was high. High risk sexual behavior was associated with willingness to use PrEP. Strategies to increase PrEP awareness and universal access, may reduce HIV transmission.

Introduction The 68th World Health Assembly, in 2015, called for surgical and anaesthesia services strengthening. Acknowledging the healthcare staff shortages, they referred to task sharing, among others, as a more effective use of the healthcare workforce. While task sharing has been increasingly proposed as an important strategy to increase the reach and safety of anaesthesia as well as a means of supporting the workforce in low-resource settings, most data on task sharing relate to non-anaesthetic healthcare contexts. The aim of this study was to understand anaesthetic task sharing as currently experienced and/or envisaged by non-physician anaesthesia providers in Zambia and Somaliland.Methods An exploratory qualitative research methodology was used. Participants were recruited initially via contacts of the research team, then through snowballing using a purposive sampling strategy. There were 13 participants: 7 from Somaliland and 6 from Zambia. Semistructured interviews took place synchronously, then were recorded, anonymised, transcribed and analysed thematically. Triangulation and respondents’ validation were used to maximise data validity.Results Four major themes were identified in relation to task sharing practices: (1) participants recognised variable components of task sharing in their practice; (2) access to task sharing depends both on sources and resources; (3) implicit barriers may inhibit task sharing practices; (4) there is an appetite among participants for amelioration of current task sharing practices.Conclusions Empowering task sharing practices can be achieved only by understanding how these practices work, by identifying gaps and areas of improvement, and by addressing them. The findings from this exploratory study could help the global community understand how anaesthetic task sharing in low-resource settings works and inspire further research on the field. This could inform future modelling of workforce planning strategies in low-resource settings to maximise the effectiveness and professional well-being of the workforce.

Objective This scoping review will identify existing literature regarding contextual factors relevant to vector-control interventions to prevent malaria. We will use the findings of the scoping review to produce an interactive evidence and gap map. The map will assist in the priority setting, development, and conduct of targeted systematic reviews. These systematic reviews seek to assist the Vector Control and Insecticide Resistance Unit of the World Health Organization’s Global Malaria Programme by informing recommendation development by their Guidelines Development Group. Introduction Malaria contributes substantially to the global burden of disease, with an estimated 247 million cases and 619,000 deaths in 2021. Vector-control is key in reducing malaria transmission. Vector-control interventions directly target the mosquito, reducing the potential for parasite infections. These interventions commonly include insecticides used in indoor residual spraying or insecticide-treated nets and larval source management. Several new vector-control interventions are under evaluation to complement these. In addition to estimating the effects of interventions on health outcomes, it is critical to understand how populations at risk of malaria consider them in terms of their feasibility, acceptability, and values. Inclusion Criteria Eligible studies will have assessed the contextual factors of feasibility or acceptability of the interventions of interest, or the valuation of the outcomes of interests. These assessments will be from the perspective of people who receive (residents) or deliver (workers or technicians) the vector-control intervention for the purpose of preventing malaria. Methods We will conduct this scoping review in accordance with the JBI methodology for scoping reviews and report in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews (PRISMA-ScR). We will construct the evidence and gap map following guidance from the Campbell Collaboration.

Abstract Introduction Malaria presents a significant global public health burden, although substantial progress has been made, with vector control initiatives such as indoor residual surface spraying with insecticides and insecticide-treated nets. There now exists many different approaches to apply residual insecticide to indoor and outdoor surfaces in malaria-endemic settings, although no comprehensive systematic reviews exist evaluating these interventions. This manuscript outlines the protocol for a systematic review which aims to synthesise the best available evidence regarding full or partial indoor or outdoor residual insecticide surface treatment for preventing malaria. Methods and analysis This review will comprehensively search the literature (both published and unpublished) for any studies investigating the effectiveness of residual insecticide surface treatment for malaria. Studies will be screened to meet the inclusion criteria by a minimum of two authors, followed by assessment of risk of bias (using appropriate risk-of-bias tools for randomised and non-randomised studies) and extraction of relevant information using structured forms by two independent authors. Meta-analysis will be carried out where possible for epidemiological outcomes such as malaria, anaemia, malaria-related mortality, all-cause mortality and adverse effects. Certainty in the evidence will be established with GRADE assessments. Ethics and dissemination A full review report will be submitted to the Vector Control & Insecticide Resistance Unit, Global Malaria Program, WHO. A version of this report will be submitted for publication in an open access peer-reviewed journal. The report will inform the development of WHO recommendations regarding residual insecticide treatment for malaria. This systematic review does not require ethics approval as it is a review of primary studies. Systematic review registration PROSPERO 293194.

To determine early COVID-19 burden in Malawi, we conducted a multistage cluster survey in 5 districts. During October–December 2020, we recruited 5,010 community members (median age 32 years, interquartile range 21–43 years) and 1,021 health facility staff (HFS) (median age 35 years, interquartile range 28–43 years). Real-time PCR–confirmed SARS-CoV-2 infection prevalence was 0.3% (95% CI 0.2%–0.5%) among community and 0.5% (95% CI 0.1%–1.2%) among HFS participants; seroprevalence was 7.8% (95% CI 6.3%–9.6%) among community and 9.7% (95% CI 6.4%–14.5%) among HFS participants. Most seropositive community (84.7%) and HFS (76.0%) participants were asymptomatic. Seroprevalence was higher among urban community (12.6% vs. 3.1%) and HFS (14.5% vs. 7.4%) than among rural community participants. Cumulative infection findings 113-fold higher from this survey than national statistics (486,771 vs. 4,319) and predominantly asymptomatic infections highlight a need to identify alternative surveillance approaches and predictors of severe disease to inform national response.

We used publicly available data to describe epidemiology, genomic surveillance, and public health and social measures from the first 3 COVID-19 pandemic waves in southern Africa during April 6, 2020–September 19, 2021. South Africa detected regional waves on average 7.2 weeks before other countries. Average testing volume 244 tests/million/day) increased across waves and was highest in upper-middle-income countries. Across the 3 waves, average reported regional incidence increased (17.4, 51.9, 123.3 cases/1 million population/day), as did positivity of diagnostic tests (8.8%, 12.2%, 14.5%); mortality (0.3, 1.5, 2.7 deaths/1 million populaiton/day); and case-fatality ratios (1.9%, 2.1%, 2.5%). Beta variant (B.1.351) drove the second wave and Delta (B.1.617.2) the third. Stringent implementation of safety measures declined across waves. As of September 19, 2021, completed vaccination coverage remained low (8.1% of total population). Our findings highlight opportunities for strengthening surveillance, health systems, and access to realistically available therapeutics, and scaling up risk-based vaccination.

Abstract Background Malaria, acute respiratory infections (ARIs) and diarrhoea are the leading causes of morbidity and mortality among children under 5 years old. Estimates of the malaria incidence are available from a previous study conducted in southern Malawi in the absence of community-led malaria control strategies; however, the incidence of the other diseases is lacking, owing to understudying and competing disease priorities. Extensive malaria control measures through a community participation strategy were implemented in Chikwawa, southern Malawi from May 2016 to reduce parasite prevalence and incidence. This study assessed the incidence of clinical malaria, ARIs and acute diarrhoea among under-five children in a rural community involved in malaria control through community participation. Methods A prospective cohort study was conducted from September 2017 to May 2019 in Chikwawa district, southern Malawi. Children aged 6–48 months were recruited from a series of repeated cross-sectional household surveys. Recruited children were followed up two-monthly for 1 year to record details of any clinic visits to designated health facilities. Incidence of clinical malaria, ARIs and diarrhoea per child-years at risk was estimated, compared between age groups, area of residence and time. Results A total of 274 out of 281 children recruited children had complete results and contributed 235.7 child-years. Malaria incidence was 0.5 (95% CI (0.4, 0.5)) cases per child-years at risk, (0.04 in 6.0–11.9 month-olds, 0.5 in 12.0–23.9 month-olds, 0.6 in 24.0–59.9 month-olds). Incidences of ARIs and diarrhoea were 0.3 (95% CI (0.2, 0.3)), (0.1 in 6.0–11.9 month-olds, 0.4 in 12.0–23.9 month-olds, 0.3 in 24.0–59.9 month-olds), and 0.2 (95% CI (0.2, 0.3)), (0.1 in 6.0–11.9 month-olds, 0.3 in 12.0–23.9 month-olds, 0.2 in 24.0–59.9 month-olds) cases per child-years at risk, respectively. There were temporal variations of malaria and ARI incidence and an overall decrease over time. Conclusion In comparison to previous studies, there was a lower incidence of clinical malaria in Chikwawa. The incidence of ARIs and diarrhoea were also low and decreased over time. The results are promising because they highlight the importance of community participation and the integration of malaria prevention strategies in contributing to disease burden reduction.

Malaria vectors have demonstrated resistance to pyrethroid-based insecticides used in insecticide-treated nets, diminishing their effectiveness. This systematic review and meta-analysis investigated two forms of dual active-ingredient (DAI) insecticide-treated nets (ITN(s)) for malaria prevention. A comprehensive search was conducted on July 6th 2022. The databases searched included PubMed, Embase, CINAHL, amongst others. Trials were eligible if they were conducted in a region with ongoing malaria transmission. The first DAI ITN investigated were those that combined a pyrethroid with a non-pyrethroid insecticides. The second DAI ITN investigated were that combined a pyrethroid with an insect growth regulator. These interventions were compared against either a pyrethroid-only ITN, or ITNs treated with pyrethroid and piperonyl-butoxide. Assessment of risk of bias was conducted in duplicate using the Cochrane risk of bias 2 tool for cluster-randomised trials. Summary data was extracted using a custom data-extraction instrument. This was conducted by authors THB, JCS and SH. Malaria case incidence was the primary outcome and has been meta-analysed, adverse events were narratively synthesised. The review protocol is registered on PROSPERO (CRD42022333044). From 9494 records, 48 reports were screened and 13 reports for three studies were included. These studies contained data from 186 clusters and all reported a low risk of bias. Compared to pyrethroid-only ITNs, clusters that received pyrethroid-non-pyrethroid DAI ITNs were associated with 305 fewer cases per 1000-person years (from 380 fewer cases to 216 fewer cases) (IRR = 0.55, 95%CI: 0.44–0.68). However, this trend was not observed in clusters that received pyrethroid-insect growth regulator ITNs compared to pyrethroid-only ITNs (from 280 fewer cases to 135 more) (IRR = 0.90, 95%CI: 0.73–1.13). Pyrethroid-non-pyrethroid DAI ITNs demonstrated consistent reductions in malaria case incidence and other outcomes across multiple comparisons. Pyrethroid-non-pyrethroid DAI ITNs may present a novel intervention for the control of malaria.

Background: Malaria is caused by the Plasmodium parasite and is a highly transmissible disease representing a significant global public health burden. The provision of insecticide-treated mosquito nets (ITNs) has contributed to the reduction of malaria across endemic countries. However, the detection of insecticide resistance in many mosquito vector species potentially threatens the long-term effectiveness of ITNs. A novel method to reduce the impact of insecticide resistance is to treat mosquito nets with multiple active ingredients. Methods and analysis: This review will comprehensively search the literature (both published and unpublished) for any studies investigating the effectiveness of mosquito nets treated with multiple active ingredients, known henceforth as dual-active-ingredient (DAI) ITNs. The DAI ITNs of interest include those treated with a pyrethroid and non-pyrethroid insecticide (review question 1) or with a pyrethroid and an insect growth regulator (review question 2). Studies will be screened to meet the inclusion criteria by a minimum of two authors, followed by assessment of risk of bias (using appropriate risk of bias tools for randomised and non-randomised studies) and extraction of relevant information using structured forms by two independent authors. Meta-analyses will be carried out where possible for epidemiological outcomes and subgrouping will be considered. Certainty in the evidence will be established with GRADE assessments. Ethics and dissemination: A full review report will be submitted to the Vector Control and Insecticide Resistance Unit, Global Malaria Program, WHO. A version of this report will be submitted for publication in an open access peer-reviewed journal. The report will inform the development of WHO recommendations regarding the use of DAI ITNs for the prevention of malaria. This systematic review does not require ethics approval as it is a review of primary studies. Registration: PROSPERO ID: CRD42022333044

Abstract Background House improvement (HI) to prevent mosquito house entry, and larval source management (LSM) targeting aquatic mosquito stages to prevent development into adult forms, are promising complementary interventions to current malaria vector control strategies. Lack of evidence on costs and cost-effectiveness of community-led implementation of HI and LSM has hindered wide-scale adoption. This study presents an incremental cost analysis of community-led implementation of HI and LSM, in a cluster-randomized, factorial design trial, in addition to standard national malaria control interventions in a rural area (25,000 people), in southern Malawi. Methods In the trial, LSM comprised draining, filling, and Bacillus thuringiensis israelensis-based larviciding, while house improvement (henceforth HI) involved closing of eaves and gaps on walls, screening windows/ventilation spaces with wire mesh, and doorway modifications. Communities implemented all interventions. Costs were estimated retrospectively using the ‘ingredients approach’, combining ‘bottom-up’ and ‘top-down approaches’, from the societal perspective. To estimate the cost of independently implementing each intervention arm, resources shared between trial arms (e.g. overheads) were allocated to each consuming arm using proxies developed based on share of resource input quantities consumed. Incremental implementation costs (in 2017 US$) are presented for HI-only, LSM-only and HI + LSM arms. In sensitivity analyses, the effect of varying costs of important inputs on estimated costs was explored. Results The total economic programme costs of community-led HI and LSM implementation was $626,152. Incremental economic implementation costs of HI, LSM and HI + LSM were estimated as $27.04, $25.06 and $33.44, per person per year, respectively. Project staff, transport and labour costs, but not larvicide or screening material, were the major cost drivers across all interventions. Costs were sensitive to changes in staff costs and population covered. Conclusions In the trial, the incremental economic costs of community-led HI and LSM implementation were high compared to previous house improvement and LSM studies. Several factors, including intervention design, year-round LSM implementation and low human population density could explain the high costs. The factorial trial design necessitated use of proxies to allocate costs shared between trial arms, which limits generalizability where different designs are used. Nevertheless, costs may inform planners of similar intervention packages where cost-effectiveness is known. Trial registration Not applicable. The original trial was registered with The Pan African Clinical Trials Registry on 3 March 2016, trial number PACTR201604001501493

Abstract Background Current standard interventions are not universally sufficient for malaria elimination. The effects of community-based house improvement (HI) and larval source management (LSM) as supplementary interventions to the Malawi National Malaria Control Programme (NMCP) interventions were assessed in the context of an intensive community engagement programme. Methods The study was a two-by-two factorial, cluster-randomized controlled trial in Malawi. Village clusters were randomly assigned to four arms: a control arm; HI; LSM; and HI + LSM. Malawi NMCP interventions and community engagement were used in all arms. Household-level, cross-sectional surveys were conducted on a rolling, 2-monthly basis to measure parasitological and entomological outcomes over 3 years, beginning with one baseline year. The primary outcome was the entomological inoculation rate (EIR). Secondary outcomes included mosquito density, Plasmodium falciparum prevalence, and haemoglobin levels. All outcomes were assessed based on intention to treat, and comparisons between trial arms were conducted at both cluster and household level. Results Eighteen clusters derived from 53 villages with 4558 households and 20,013 people were randomly assigned to the four trial arms. The mean nightly EIR fell from 0.010 infectious bites per person (95% CI 0.006–0.015) in the baseline year to 0.001 (0.000, 0.003) in the last year of the trial. Over the full trial period, the EIR did not differ between the four trial arms (p = 0.33). Similar results were observed for the other outcomes: mosquito density and P. falciparum prevalence decreased over 3 years of sampling, while haemoglobin levels increased; and there were minimal differences between the trial arms during the trial period. Conclusions In the context of high insecticide-treated bed net use, neither community-based HI, LSM, nor HI + LSM contributed to further reductions in malaria transmission or prevalence beyond the reductions observed over two years across all four trial arms. This was the first trial, as far as the authors are aware, to test the potential complementary impact of LSM and/or HI beyond levels achieved by standard interventions. The unexpectedly low EIR values following intervention implementation indicated a promising reduction in malaria transmission for the area, but also limited the usefulness of this outcome for measuring differences in malaria transmission among the trial arms. Trial registration PACTR, PACTR201604001501493, Registered 3 March 2016, https://pactr.samrc.ac.za/ .

Abstract Background To further reduce malaria burden, identification of areas with highest burden for targeted interventions needs to occur. Routine health information has the potential to indicate where and when clinical malaria occurs the most. Developing countries mostly use paper-based data systems however they are error-prone as they require manual aggregation, tallying and transferring of data. Piloting was done using electronic data capture (EDC) with a cheap and user friendly software in rural Malawian primary healthcare setting to improve the quality of health records. Methods Audit and feedback tools from the Joanna Briggs Institute (Practical Application of Clinical Evidence System and Getting Research into Practice) were used in four primary healthcare facilities. Using this approach, the best available evidence for a malaria information system (MIS) was identified. Baseline audit of the existing MIS was conducted in the facilities based on available best practice for MIS; this included ensuring data consistency and completeness in MIS by sampling 25 random records of malaria positive cases. Implementation of an adapted evidence-based EDC system using tablets on an OpenDataKit platform was done. An end line audit following implementation was then conducted. Users had interviews on experiences and challenges concerning EDC at the beginning and end of the survey. Results The existing MIS was paper-based, occupied huge storage space, had some data losses due to torn out papers and were illegible in some facilities. The existing MIS did not have documentation of necessary parameters, such as malaria deaths and treatment within 14 days. Training manuals and modules were absent. One health centre solely had data completeness and consistency at 100% of the malaria-positive sampled records. Data completeness and consistency rose to 100% with readily available records containing information on recent malaria treatment. Interview findings at the end of the survey showed that EDC was acceptable among users and they agreed that the tablets and the OpenDataKit were easy to use, improved productivity and quality of care. Conclusions Improvement of data quality and use in the Malawian rural facilities was achieved through the introduction of EDC using OpenDataKit. Health workers in the facilities showed satisfaction with the use of EDC.

Malaria hotspots have been the focus of public health managers for several years due to the potential elimination gains that can be obtained from targeting them. The identification of hotspots must be accompanied by the description of the overall network of stable and unstable hotspots of malaria, especially in medium and low transmission settings where malaria elimination is targeted. Targeting hotspots with malaria control interventions has, so far, not produced expected benefits. In this work we have employed a mechanistic-stochastic algorithm to identify clusters of super-spreader houses and their related stable hotspots by accounting for mosquito flight capabilities and the spatial configuration of malaria infections at the house level. Our results show that the number of super-spreading houses and hotspots is dependent on the spatial configuration of the villages. In addition, super-spreaders are also associated to house characteristics such as livestock and family composition. We found that most of the transmission is associated with winds between 6pm and 10pm although later hours are also important. Mixed mosquito flight (downwind and upwind both with random components) were the most likely movements causing the spread of malaria in two out of the three study areas. Finally, our algorithm (named MALSWOTS) provided an estimate of the speed of malaria infection progression from house to house which was around 200-400 meters per day, a figure coherent with mark-release-recapture studies of Anopheles dispersion. Cross validation using an out-of-sample procedure showed accurate identification of hotspots. Our findings provide a significant contribution towards the identification and development of optimal tools for efficient and effective spatio-temporal targeted malaria interventions over potential hotspot areas.

Abstract Background Drug safety assessments in clinical trials present unique analytical challenges. Some of these include adjusting for individual follow-up time, repeated measurements of multiple outcomes and missing data among others. Furthermore, pre-specifying appropriate analysis becomes difficult as some safety endpoints are unexpected. Although existing guidelines such as CONSORT encourage thorough reporting of adverse events (AEs) in clinical trials, they provide limited details for safety data analysis. The limited guidelines may influence suboptimal analysis by failing to account for some analysis challenges above. A typical example where such challenges exist are trials of anti-malarial drugs for malaria prevention during pregnancy. Lack of proper standardized evaluation of the safety of antimalarial drugs has limited the ability to draw conclusions about safety. Therefore, a systematic review was conducted to establish the current practice in statistical analysis for preventive antimalarial drug safety in pregnancy. Methods The search included five databases (PubMed, Embase, Scopus, Malaria in Pregnancy Library and Cochrane Central Register of Controlled Trials) to identify original English articles reporting Phase III randomized controlled trials (RCTs) on anti-malarial drugs for malaria prevention in pregnancy published from January 2010 to July 2019. Results Eighteen trials were included in this review that collected multiple longitudinal safety outcomes including AEs. Statistical analysis and reporting of the safety outcomes in all the trials used descriptive statistics; proportions/counts (n = 18, 100%) and mean/median (n = 2, 11.1%). Results presentation included tabular (n = 16, 88.9%) and text description (n = 2, 11.1%). Univariate inferential methods were reported in most trials (n = 16, 88.9%); including Chi square/Fisher’s exact test (n = 12, 66.7%), t test (n = 2, 11.1%) and Mann–Whitney/Wilcoxon test (n = 1, 5.6%). Multivariable methods, including Poisson and negative binomial were reported in few trials (n = 3, 16.7%). Assessment of a potential link between missing efficacy data and safety outcomes was not reported in any of the trials that reported efficacy missing data (n = 7, 38.9%). Conclusion The review demonstrated that statistical analysis of safety data in anti-malarial drugs for malarial chemoprevention in pregnancy RCTs is inadequate. The analyses insufficiently account for multiple safety outcomes potential dependence, follow-up time and informative missing data which can compromise anti-malarial drug safety evidence development, based on the available data.

House improvement (HI) refers to the full screening or closing of openings such as windows, doors, and eaves, as well as the installation of ceilings, to reduce mosquito-human contact indoors. HI is a viable supplementary intervention that reduces malaria transmission further than the existing strategies alone. In Malawi, HI has not been widely implemented and evaluated for malaria control. Concerns about lack of local evidence, durability in different epidemiological and cultural settings, and the cost of large-scale implementation are among the reasons the strategy is not utilised in many low-income countries. This study assessed community perceptions, experiences, and acceptability of community-led HI in Chikwawa district, southern Malawi. This was a qualitative study where separate focus group discussions were conducted with members from the general community (n = 3); health animators (n = 3); and HI committee members (n = 3). In-depth interviews were conducted with community members (n = 20), and key-informant interviews were conducted with health surveillance assistants and chiefs (n = 23). All interviews were transcribed and coded before performing a thematic content analysis to identify the main themes. Coded data were analysed using Nvivo 12 Plus software. Study participants had a thorough understanding of HI. Participants expressed satisfaction with HI, and they reported enabling factors to HI acceptability, such as the reduction in malaria cases in their villages and the safety and effectiveness of HI use. Participants also reported barriers to effective HI implementation, such as the unavailability and inaccessibility of some HI materials, as well as excessive heat and darkness in HI houses compared to non-HI houses. Participants indicated that they were willing to sustain the intervention but expressed the need for strategies to address barriers to ensure the effectiveness of HI. Our results showed the high knowledge and acceptability of HI by participants in the study area. Intensive and continued health education and community engagement on the significance of HI could help overcome the barriers and improve the acceptability and sustainability of the intervention.

Background: Monitoring malaria transmission is a critical component of efforts to achieve targets for elimination and eradication. Two commonly monitored metrics of transmission intensity are parasite prevalence (PR) and the entomological inoculation rate (EIR). Comparing the spatial and temporal variations in the PR and EIR of a given geographical region and modelling the relationship between the two metrics may provide a fuller picture of the malaria epidemiology of the region to inform control activities. Methods: Using geostatistical methods, we compare the spatial and temporal patterns of Plasmodium falciparum EIR and PR using data collected over 38 months in a rural area of Malawi. We then quantify the relationship between EIR and PR by using empirical and mechanistic statistical models. Results: Hotspots identified through the EIR and PR partly overlapped during high transmission seasons but not during low transmission seasons. The estimated relationship showed a 1-month delayed effect of EIR on PR such that at lower levels of EIR, increases in EIR are associated with rapid rise in PR, whereas at higher levels of EIR, changes in EIR do not translate into notable changes in PR. Conclusions: Our study emphasises the need for integrated malaria control strategies that combine vector and human host managements monitored by both entomological and parasitaemia indices. Funding: This work was supported by Stichting Dioraphte grant number 13050800.

Abstract Background Reducing the burden of malaria highly depends on access to prompt and effective malaria diagnosis and treatment. The aim of this study was to identify challenges affecting prompt access to effective uncomplicated malaria case management in children below 10 years old in rural primary health care facilities in Malawi. Methods A cross sectional health facility survey was conducted in six primary health facilities in Chikhwawa district, Malawi. Officers-in-charge of health facilities were interviewed on availability of staff, supplies and drugs. All consecutive children presenting at the facility with fever or suspected malaria, aged 6 months to 10 years old, were eligible to participate in exit interviews. Exit interviews with participants’ guardians assessed duration of illness, demographic information and distance travelled. Adherence to recommended malaria case management guidelines included performing malaria rapid diagnostic tests (mRDTs) in children with fever or suspected malaria and prescribing recommended weight-based dose of artemether-lumefantrine (AL) when mRDT was positive. Multivariate logistic regression was used to determine factors associated with prompt care seeking within 24 h of onset of illness. Results Health facilities were staffed by at least two health workers. Of 265 children screened, nine were excluded due to severe illness. Twenty-one percent of children presenting at a health facility with fever were not tested for malaria. Adherence to positive and negative mRDT results for those tested was 99.4, 95% CI [98.1–100] and 97, 95% CI [88.9–100], respectively. AL was prescribed as recommended by weight in 152 children (92.2%). Temporary stock outs of AL occurred in five of six facilities. In total, 146 (57, 95% CI [52.7–64.1]) guardians of patients sought care within 24 h after fever onset. Children aged 5 to 10 years were less likely to present within 24 h of fever onset than children below 5 years of age (unadjusted odds ratio 0.40, 95% CI [0.2–0.7]). Conclusion Adherence to malaria diagnosis and treatment guidelines was high. However, delayed care seeking and stock outs may affect prompt and effective malaria case management. Further qualitative work is required to determine, and address factors associated with delay in care seeking for fever.

Abstract Background Malaria continues to place a high burden on communities due to challenges reaching intervention target levels in Chikwawa District, Malawi. The Hunger Project Malawi is using a health animator approach (HA) to address gaps in malaria control coverage. We explored the influence of community-based volunteers known as health animators (HAs) in malaria control. We assessed the impact of HAs on knowledge, attitudes, and practices towards malaria interventions. Methods This paper draws on the qualitative data collected to explore the roles of communities, HAs and formal health workers attending and not attending malaria workshops for malaria control. Purposive sampling was used to select 78 respondents. We conducted 10 separate focus group discussions (FGDs)-(n = 6) with community members and (n = 4) key informants. Nine in-depth interviews (IDIs) were held with HAs and Health Surveillance Assistants (HSAs) in three focal areas near Majete Wildlife Reserve. Nvivo 11 was used for coding and analysis. We employed the framework analysis and social capital theory to determine how the intervention influenced health and social outcomes. Results Using education, feedback sessions and advocacy in malaria workshop had mixed outcomes. There was a high awareness of community participation and comprehensive knowledge of the HA approach as key to malaria control. HAs were identified as playing a complementary role in malaria intervention. Community members’ attitudes towards advocacy for better health services were poor. Attendance in malaria workshops was sporadic towards the final year of the intervention. Respondents mentioned positive attitudes and practices on net usage for prevention and prompt health-seeking behaviours. Conclusion The HA approach is a useful strategy for complementing malaria prevention strategies in rural communities and improving practices for health-seeking behaviour. Various factors influence HAs’ motivation, retention, community engagement, and programme sustainability. However, little is known about how these factors interact to influence volunteers’ motivation, community participation and sustainability over time. More research is needed to explore the acceptability of an HA approach and the impact on malaria control in other rural communities in Malawi.

Abstract Background Increased engagement of communities has been emphasized in global plans for malaria control and elimination. Three interventions to reinforce and complement national malaria control recommendations were developed and applied within the context of a broad-based development initiative, targeting a rural population surrounding a wildlife reserve. The interventions, which were part of a 2-year research trial, and assigned to the village level, were implemented through trained local volunteers, or ‘health animators’, who educated the community and facilitated collective action. Results Community workshops on malaria were designed to increase uptake of national recommendations; a manual was developed, and training of health animators conducted, with educational content and analytical tools for a series of fortnightly community workshops in annual cycles at village level. The roll-back malaria principle of diagnosis, treatment and use of long-lasting insecticidal nets was a central component of the workshops. Structural house improvement to reduce entry of malaria vectors consisted of targeted activities in selected villages to mobilize the community into voluntarily closing the eaves and screening the windows of their houses; the project provided wire mesh for screening. Corrective measures were introduced to respond to field challenges. Committees were established at village level to coordinate the house improvement activities. Larval source management (LSM) in selected villages consisted of two parts: one on removal of standing water bodies by the community at large; and one on larviciding with bacterial insecticide Bacillus thuringiensis israelensis by trained village committees. Community workshops on malaria were implemented as ‘core intervention’ in all villages. House improvement and LSM were implemented in addition to community workshops on malaria in selected villages. Conclusions Three novel interventions for community mobilization on malaria prevention and control were described. The interventions comprised local organizational structure, education and collective action, and incorporated elements of problem identification, planning and evaluation. These methods could be applicable to other countries and settings.

Abstract Background Despite the availability of cost effective malaria control interventions, such as insecticide-treated bed nets (ITN), diagnosis and effective treatment of malaria, and intermittent preventive treatment during pregnancy (IPTp), the lack of equitable access and coverage affect utilization of these interventions in rural communities. Aggregated rates of access and utilization of malaria interventions in national surveys mask substantial variations in intervention coverage. Utilization of interventions and factors affecting utilization need investigation in rural communities. Methods One year of quantitative data collected from a rolling Malaria Indicator Survey (April 2015–April 2016) in Chikhwawa District, Malawi, before the ITN distribution campaign, were analysed. Univariate analyses were used to quantify rates of ITN usage, care-seeking for fever in children aged 6–59 months and women aged 15–49 years and IPTp uptake (for women aged 15–49 years with a recent delivery). Results were compared to national survey estimates; factors associated with these outcomes were determined using multivariate regression models. Results A total of 2046 participants were included from 1328 households; 56.6% were women aged 15–49 years and 43.4% were children aged 6–59 months. Reported ownership of at least one ITN per household and under-five children ITN use the previous night were 35.3 and 33.5% compared to 70.2 and 67.1%, respectively, in the national survey; ITN use was higher in high wealth quintile households than low quintile ones. For participants with recent fever, 37.6 and 19.5% sought care and sought care within 24 h, respectively. Care-seeking was lower for febrile women than febrile children [aOR, 95% CI 0.53 (0.35–0.81)]. Uptake of two and three or more doses of IPTp were 40.6 and 15.0%, respectively, among women with a pregnancy in the last 2 years. Conclusion To achieve effective malaria control, fine-scale or district-based surveillance should be used to identify and target communities requiring scaling up of interventions. Qualitative research and a participatory community approach should be used to address behavioural factors affecting how people make use of interventions.

Abstract Background Spatio-temporal variations in malaria burden are currently complex and costly to measure, but are important for decision-making. We measured the spatio-temporal variation of clinical malaria incidence at a fine scale in a cohort of children under five in an endemic area in rural Chikhwawa, Malawi, determined associated factors, and monitored adult mosquito abundance. Methods We followed-up 285 children aged 6–48 months with recorded geolocations, who were sampled in a rolling malaria indicator survey, for one year (2015–2016). Guardians were requested to take the children to a nearby health facility whenever ill, where health facility personnel were trained to record malaria test results and temperature on the child’s sick-visit card; artemisinin-based combination therapy was provided if indicated. The cards were collected and replaced 2-monthly. Adult mosquitoes were collected from 2-monthly household surveys using a Suna trap. The head/thorax of adult Anopheles females were tested for presence of Plasmodium DNA. Binomial logistic regression and geospatial modelling were performed to determine predictors of and to spatially predict clinical malaria incidence, respectively. Results Two hundred eighty two children, with complete results, and 267.8 child-years follow-up time were included in the analysis. The incidence rate of clinical malaria was 1.2 cases per child-year at risk; 57.1% of the children had at least one clinical malaria case during follow-up. Geographical groups of households where children experienced repeated malaria infections overlapped with high mosquito densities and high entomological inoculation rate locations. Conclusions Repeated malaria infections within household groups account for the majority of cases and signify uneven distribution of malaria risk within a small geographical area.

Abstract Background Adolescents living with HIV face challenges, such as disclosure of HIV status, adherence to antiretroviral therapy, mental health, and sexual and reproductive health (SRH). These challenges affect their future quality of life. However, little evidence is available on their sexual behaviors and SRH needs in Zambia. This study aimed at assessing their sexual behaviors and SRH needs and identifying factors associated with marriage concerns and a desire to have children. Methods This cross-sectional study was conducted at the University Teaching Hospital from April to July 2014. We recruited 200 adolescents aged 15–19 years who were aware of their HIV-positive status. We collected data on their first and recent sexual behavior, concerns about marriage, and desire to have children. We used the Generalized Linear Model to identify factors associated with having concerns about marriage and desire to have children. We performed thematic analysis with open-ended data to determine their perceptions about marriage and having children in the future. Results Out of 175 studied adolescents, 20.6% had experienced sexual intercourse, and only 44.4% used condoms during the first intercourse. Forty-eight percent had concerns about marriage, and 87.4% desired to have children. Marriage-related concerns were high among those who desired to have children (adjusted relative risk [ARR] = 2.51, 95% CI = 1.02 to 6.14). Adolescents who had completed secondary school were more likely to desire to have children (ARR = 1.35, 95% CI = 1.07 to 1.71). Adolescents who had lost both parents were less likely to want children (ARR = 0.80, 95% CI = 0.68 to 0.95). Thematic analysis identified that major concerns about future marriage were fear of disclosing HIV status to partners and risk of infecting partners and/or children. The reasons for their willingness to have children were the desire to be a parent, having children as family assets, a human right, and a source of love and happiness. Conclusions Zambian adolescents living with HIV are at risk of engaging in risky sexual relationships and have difficulties in meeting needs of SRH. HIV care service must respond to a wide range of needs.

Background: Seizures are relatively common among children with HIV in low- and middle-income countries and are associated with significant morbidity and mortality. Early treatment with antiretro-viral therapy (ART) may reduce this risk by decreasing rates of central nervous system infections and HiV encephalopathy. Methods: We conducted a prospective, unmatched case-control study. We enrolled children with new-onset seizure from University Teaching Hospital in Lusaka, Zambia and 2 regional hospitals in rural Zambia. Controls were children with HIV and no history of seizures. Recruitment took place from 2016 to 2019. Early treatment was defined as initiation of ART before 12 months of age, at a CD4 percentage >15% in children aged 12-60 months or a CD4 count >350 cells/mm³ for children aged 60 months or older. Logistic regression models were used to evaluate the association between potential risk factors and seizures. Results: We identified 73 children with new-onset seizure and compared them with 254 control children with HIV but no seizures. Early treatment with ART was associated with a significant reduction in the odds of seizures [odds ratio (OR) 0.04, 95% confidence interval: 0.02 to 0.09; P < 0.001]. Having an undetectable viral load at the time of enrollment was strongly protective against seizures (OR 0.03, P < 0.001), whereas history of World Health Organization Stage 4 disease (OR 2.2, P = 0.05) or CD4 count <200 cells/ mm³ (OR 3.6, P < 0.001) increased risk of seizures. Conclusions: Early initiation of ART and successful viral suppression would likely reduce much of the excess seizure burden in children with HIV. [ABSTRACT FROM AUTHOR]

Abstract Background Interventions to reduce malaria burden are effective if communities use them appropriately and consistently. Several tools have been suggested to promote uptake and use of malaria control interventions. Community workshops on malaria, using the ‘Health Animator’ approach, are a potential behaviour change strategy for malaria control. The strategy aims to influence a change in mind-set of vulnerable populations to encourage self-reliance, using community volunteers known as Health Animators. The aim of the paper is to describe the process of implementing community workshops on malaria by Health Animators to improve uptake and use of malaria control interventions in rural Malawi. Methods This is a descriptive study reporting feasibility, acceptability, appropriateness and fidelity of using Health Animator-led community workshops for malaria control. Quantitative data were collected from self-reporting and researcher evaluation forms. Qualitative assessments were done with Health Animators, using three focus groups (October–December 2015) and seven in-depth interviews (October 2016–February 2017). Results Seventy seven health Animators were trained from 62 villages. A total of 2704 workshops were conducted, with consistent attendance from January 2015 to June 2017, representing 10–17% of the population. Attendance was affected by social responsibilities and activities, relationship of the village leaders and their community and involvement of Community Health Workers. Active discussion and participation were reported as main strengths of the workshops. Health Animators personally benefited from the mind-set change and were proactive peer influencers in the community. Although the information was comprehended and accepted, availability of adequate health services was a challenge for maintenance of behaviour change. Conclusion Community workshops on malaria are a potential tool for influencing a positive change in behaviour towards malaria, and applicable for other health problems in rural African communities. Social structures of influence and power dynamics affect community response. There is need for systematic monitoring of community workshops to ensure implementation fidelity and strengthening health systems to ensure sustainability of health behaviour change.

Abstract Background Prompt and effective malaria treatment are key in reducing transmission, disease severity and mortality. With the current scale-up of artemisinin-based combination therapy (ACT) coverage, there is need to focus on challenges affecting implementation of the intervention. Routine indicators focus on utilization and coverage, neglecting implementation quality. A health system in rural Malawi was assessed for uncomplicated malaria treatment implementation in children. Methods A cross-sectional health facility survey was conducted in six health centres around the Majete Wildlife Reserve in Chikwawa district using a health system effectiveness approach to assess uncomplicated malaria treatment implementation. Interviews with health facility personnel and exit interviews with guardians of 120 children under 5 years were conducted. Results Health workers appropriately prescribed an ACT and did not prescribe an ACT to 73% (95% CI 63–84%) of malaria rapid diagnostic test (RDT) positive and 98% (95% CI 96–100%) RDT negative children, respectively. However, 24% (95% CI 13–37%) of children receiving artemisinin–lumefantrine had an inappropriate dose by weight. Health facility findings included inadequate number of personnel (average: 2.1 health workers per 10,000 population), anti-malarial drug stock-outs or not supplied, and inconsistent health information records. Guardians of 59% (95% CI 51–69%) of children presented within 24 h of onset of child’s symptoms. Conclusion The survey presents an approach for assessing treatment effectiveness, highlighting bottlenecks which coverage indicators are incapable of detecting, and which may reduce quality and effectiveness of malaria treatment. Health service provider practices in prescribing and dosing anti-malarial drugs, due to drug stock-outs or high patient load, risk development of drug resistance, treatment failure and exposure to adverse effects.

Abstract Background Due to outdoor and residual transmission and insecticide resistance, long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) will be insufficient as stand-alone malaria vector control interventions in many settings as programmes shift toward malaria elimination. Combining additional vector control interventions as part of an integrated strategy would potentially overcome these challenges. Larval source management (LSM) and structural house improvements (HI) are appealing as additional components of an integrated vector management plan because of their long histories of use, evidence on effectiveness in appropriate settings, and unique modes of action compared to LLINs and IRS. Implementation of LSM and HI through a community-based approach could provide a path for rolling-out these interventions sustainably and on a large scale. Methods/design We will implement community-based LSM and HI, as additional interventions to the current national malaria control strategies, using a randomised block, 2 × 2 factorial, cluster-randomised design in rural, southern Malawi. These interventions will be continued for two years. The trial catchment area covers about 25,000 people living in 65 villages. Community participation is encouraged by training community volunteers as health animators, and supporting the organisation of village-level committees in collaboration with The Hunger Project, a non-governmental organisation. Household-level cross-sectional surveys, including parasitological and entomological sampling, will be conducted on a rolling, 2-monthly schedule to measure outcomes over two years (2016 to 2018). Coverage of LSM and HI will also be assessed throughout the trial area. Discussion Combining LSM and/or HI together with the interventions currently implemented by the Malawi National Malaria Control Programme is anticipated to reduce malaria transmission below the level reached by current interventions alone. Implementation of LSM and HI through a community-based approach provides an opportunity for optimum adaptation to the local ecological and social setting, and enhances the potential for sustainability. Trial Registration Registered with The Pan African Clinical Trials Registry on 3 March 2016, trial number PACTR201604001501493.