Master statistical analysis plan: attractive targeted sugar bait phase III trials in Kenya, Mali, and Zambia.

This manuscript is a master statistical analysis plan for each of three-cluster randomized controlled trials to evaluate the efficacy of attractive targeted sugar baits (ATSB) described in an already published protocol. The master SAP contains an overarching plan for all three trials, which can be adapted to trial-specific circumstances. The primary objective of the trials is to evaluate the efficacy of ATSB in the presence of universal vector control coverage with insecticide-treated nets (ITN) or indoor residual spraying (IRS) after two transmission seasons on clinical malaria incidence as compared with universal vector control coverage with ITN or IRS alone. The primary outcome measure is the incidence rate of clinical malaria, assessed in cohorts aged 12 months to less than 15 years (≥ 5 years to 15 years in Mali) during monthly follow-up visits. The primary unadjusted analysis will be conducted on the intention-to-treat analysis population without adjustment for any anticipated confounding variables. The primary outcome will be analyzed using a multi-level model constructed on a generalized linear model framework with a Poisson likelihood and a log link function. Random intercepts will be included for each study cluster and a fixed effect for study-arm. The analyst will be blinded to study arm assignment. Several secondary outcomes will be analyzed, as well as a pooled analysis (individual patient data meta-analysis) across the three trial sites. Additionally, a standard meta-analysis is expected to be conducted using combined data from all sites.

Systematic review of sporozoite infection rate of Anopheles mosquitoes in Ethiopia, 2001-2021.

BACKGROUND: Adult mosquitoes of the genus Anopheles are important vectors of Plasmodium parasites, causative agents of malaria. The aim of this review was to synthesize the overall and species-specific proportion of Anopheles species infected with sporozoites and their geographical distribution in the last 2 decades (2001-2021). METHODS: A comprehensive search was conducted using databases (PubMed, Google Scholar, Science Direct, Scopus, African Journals OnLine) and manual Google search between January 1 and February 15, 2022. Original articles describing work conducted in Ethiopia, published in English and reporting infection status, were included in the review. All the required data were extracted using a standardized data extraction form, imported to SPSS-24, and analyzed accordingly. The quality of each original study was assessed using a quality assessment tool adapted from the Joanna Briggs Institute critical appraisal checklist. This study was registered on PROSPERO (International Prospective Register of Systematic Reviews; registration no. CRD42022299078). RESULTS: A search for published articles produced a total of 3086 articles, of which 34 met the inclusion criteria. Data on mosquito surveillance revealed that a total of 129,410 anophelines comprising 25 species were captured, of which 48,365 comprising 21 species were tested for sporozoites. Anopheles arabiensis was the dominant species followed by An. pharoensis and An. coustani complex. The overall proportion infected with sporozoites over 21 years was 0.87%. Individual proportions included Anopheles arabiensis (1.09), An. pharoensis (0.79), An. coustani complex (0.13), An. funestus (2.71), An. demeilloni (0.31), An. stephensi (0.70), and An. cinereus (0.73). Plasmodium falciparum sporozoites accounted 79.2% of Plasmodium species. Mixed infection of Plasmodium vivax and P. falciparum was only reported from one An. arabiensis sample. CONCLUSIONS: Anopheles arebiensis was the dominant malaria vector over the years, with the highest sporozoite infection proportion of 2.85% and an average of 0.90% over the years. Other species contributing to malaria transmission in the area were An. pharoensis, An. coustani complex, An. funestus, An. stephensi, and An. coustani. The emergence of new vector species, in particular An. stephensi, is particularly concerning and should be investigated further.

Regional and Age-Related Variations in Blood Calcium Levels among Patients with Plasmodium falciparum and P. vivax malaria: A Systematic Review and Meta-Analysis.

Despite several studies examining the relationship between calcium levels and malaria, inconsistencies and varied results remain in the literature. This study aimed to synthesize the evidence on the association between blood calcium levels and malaria severity. A systematic literature search was conducted in the Embase, Scopus, PubMed, Ovid, and Google Scholar databases. The studies that investigated calcium levels in participants with malaria were reviewed and included for synthesis. The quality of included studies was assessed based on a standardized checklist by the Joanna Briggs Institute (JBI) critical appraisal checklists. The thematic synthesis had been used for qualitative synthesis. For the quantitative synthesis, the meta-analysis was performed to estimate the pooled effect sizes for differences in calcium levels between groups of participants using a random effect model using Hedge's g as a measure of effect size. Out of the 4574 identified records, 14 studies were reviewed. The thematic synthesis across these studies noted a consistent theme: reduced calcium levels in malaria patients compared to uninfected controls. However, the meta-analysis encompassing three specific analyses-comparing calcium levels between malaria patients and controls, severe and non-severe malaria cases, and fatal cases versus survivors-showed no significant difference in calcium levels. The statistics were as follows: (1) p = 0.15, Hedge's g: -1.00, 95% CI: -2.37-0.38, I2: 98.97, 9 studies; (2) p = 0.35, Hedge's g: -0.33, 95% CI: -1.02-0.36, I2: 81.61, 3 studies; and (3) p = 0.71, Hedge's g: -0.14, 95% CI: -0.91-0.62, I2: 87.05, 3 studies. Subgroup analyses indicated that regional disparities, especially between Africa and Asia, and participant age groups may influence these outcomes. While a trend of decreased calcium levels in malaria patients was observed, the meta-analytical results suggest regional and age-related variations. Further investigations should emphasize these differences to better guide clinical management, prognostic applications, and the crafting of policies concerning malaria's metabolic effects.

Malaria vaccine-related adverse events among children under 5 in sub-Saharan Africa: systematic review and meta-analysis protocol.

INTRODUCTION: The RTS,S vaccine has been approved for use in children under 5 living in moderate to high malaria transmission areas. However, clinically important adverse events have been reported in countries in sub-Saharan Africa. This systematic review aims to assess the frequency, severity and clinical importance of vaccine-related adverse events. METHODS AND ANALYSIS: This systematic review protocol has been prepared following robust methods and reported in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses for protocols guidelines. We will search PubMed, CINAHL, LILACS, Google Scholar, SCOPUS, WEB OF SCIENCE, Cochrane library, HINARI, African Journals Online, Trip Pro and TOXNET from 2000 to 30 September 2023, without language restrictions. We will also search conference proceedings, dissertations, World Bank Open Knowledge Repository, and WHO, PATH, UNICEF, Food and Drugs Authorities and European Medicines Agency databases, preprint repositories and reference lists of relevant studies for additional studies. Experts in the field will be contacted for unpublished or published studies missed by our searches. At least two reviewers will independently select studies and extract data using pretested tools and assess risk of bias in the included studies using the Cochrane risk of bias tool. Any disagreements will be resolved through discussion between the reviewers. Heterogeneity will be explored graphically, and statistically using the I2 statistic. We will conduct random-effects meta-analysis when heterogeneity is appreciable, and express dichotomous outcomes (serious adverse events, cerebral malaria and febrile convulsion) as risk ratio (RR) with their 95% CI. We will perform subgroup analysis to assess the impact of heterogeneity and sensitivity analyses to test the robustness of the effect estimates. The overall level of evidence will be assessed using Grading of Recommendations Assessment, Development and Evaluation. ETHICS AND DISSEMINATION: Ethical approval is not required for a systematic review. The findings of this study will be disseminated through stakeholder forums, conferences and peer-review publications. PROSPERO REGISTRATION NUMBER: CRD42021275155.

Increasing prevalence of malaria and acute dengue virus coinfection in Africa: a meta-analysis and meta-regression of cross-sectional studies.

BACKGROUND: Malaria and dengue fever are the leading causes of acute, undifferentiated febrile illness. In Africa, misdiagnosis of dengue fever as malaria is a common scenario. Through a systematic review of the published literature, this study seeks to estimate the prevalence of dengue and malaria coinfection among acute undifferentiated febrile diseases in Africa. METHODS: Relevant publications were systematically searched in the PubMed, Cochrane Library, and Google Scholar until May 19, 2023. A random-effects meta-analysis and meta-regression were used to summarize and examine the prevalence estimates. RESULTS: Twenty-two studies with 22,803 acute undifferentiated febrile patients from 10 countries in Africa were included. The meta-analysis findings revealed a pooled prevalence of malaria and dengue coinfection of 4.2%, with Central Africa having the highest rate (4.7%), followed by East Africa (2.7%) and West Africa (1.6%). Continent-wide, Plasmodium falciparum and acute dengue virus coinfection prevalence increased significantly from 0.9% during 2008-2013 to 3.8% during 2014-2017 and to 5.5% during 2018-2021 (p = 0.0414). CONCLUSION: There was a high and increasing prevalence of malaria and acute dengue virus coinfection in Africa. Healthcare workers should bear in mind the possibility of dengue infection as a differential diagnosis for acute febrile illness, as well as the possibility of coexisting malaria and dengue in endemic areas. In addition, high-quality multicentre studies are required to verify the above conclusions. Protocol registration number: CRD42022311301.

Effects of COVID-19 on malaria elimination initiatives in sub-Saharan Africa: a scoping review protocol.

INTRODUCTION: The occurrence of the COVID-19 pandemic significantly impacted health systems, resulting in varied outcomes of different variables in terms of health. Due to the nature of the causative organism that is spread mainly in the air, the disease rapidly spread to numerous countries, leading to a series of mitigation measures being proposed and implemented, including but not limited to travel restrictions, decongesting and in some instances closure of workplaces and schools and banning of social gatherings. This could have negatively impacted implementing strategies meant to ensure the effective management of malaria, hoping to eliminate it in different countries in sub-Saharan Africa (SSA). This review seeks to explore the effect of the COVID-19 pandemic on malaria elimination initiatives in SSA. METHODS AND ANALYSIS: An exploratory scoping review will be conducted on literature (searched using keywords and a search strategy) sources published in English on Web of Science, Cochrane Library, PUBMED, Dimensions, ProQuest, Scopus and African Journals Online. These would then be imported to Rayyan Software for screening for possible inclusion. The JBI Guidelines on Reviews, Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist would guide the data collection, extraction and analysis from the accessed literature. Furthermore, charting, trends and developing themes would ensure the findings are presented comprehensively and yet understandable. The data collection and analysis process leading to the final submission of a review paper to a journal will be conducted from September 2023 to February 2024. ETHICS AND DISSEMINATION: An application for ethical approval was lodged with the Health Sciences Research Ethics Committee at the University of the Free State in Bloemfontein, South Africa. This ethics committee granted ethics clearance (ethics number: UFS-HSD2022/1754). Results will be communicated through peer-reviewed publications, presentations, conferences, workshops and other means and forums to reach the critical stakeholders.

Differences in catalase levels between malaria-infected individuals and uninfected controls: a systematic review and meta-analysis.

Inconsistent catalase (CAT) research necessitates a comprehensive review of CAT levels among patients with malaria to achieve better therapeutic strategies. This study aimed to systematically review and meta-analyze available literature on CAT levels in nonpregnant and pregnant individuals with malaria compared with those in uninfected controls, with the goal of providing a robust evidence base for future research and potential interventions. Following PRISMA guidelines, a systematic literature search across six databases was conducted to examine CAT levels in patients with malaria. Data was extracted independently by two reviewers, and study quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklist. The standardized mean difference of CAT levels was calculated with heterogeneity assessment. Subgroup and sensitivity analyses were conducted to explore heterogeneity and assess the robustness of the findings. Publication bias was visually and statistically assessed and corrected, if necessary. Statistical analyses were performed using Stata software, with a significance level set at P < 0.05. Nineteen studies were included in the review. These studies, published from before 2000 to 2023, primarily from Africa and Asia, focused on different Plasmodium species and age groups. Results of qualitative synthesis among nonpregnant individuals consistently showed lower CAT levels in malaria-infected individuals, although some studies reported higher levels. No significant differences in CAT levels were found between malaria-infected and uninfected individuals, as demonstrated by a meta-analysis overall (P = 0.05, Hedges' g: - 0.78, 95% confidence interval (CI): (- 1.56)-0.01, I2: 98.47, 15 studies), but subgroup analyses showed significant differences in CAT levels in studies conducted in Africa (P = 0.02, Hedges' g: - 0.57, 95% CI: - 1.02-(0.11), I2: 91.81, 7 studies), and in studies that specifically focused on children (P = 0.03, Hedges' g: - 0.57, 95% CI: - 1.07-(- 0.07), I2: 87.52, 4 studies). Pregnant women showed variations in CAT levels across trimesters. This study provides valuable insights into the association between malaria infection and CAT enzyme levels, particularly in nonpregnant individuals. Furthermore, well-designed studies are essential to decoding the intricacies of this relationship, which could have significant implications for understanding disease processes and improving patient care.

Association of severe malaria with cognitive and behavioural outcomes in low- and middle-income countries: a meta-analysis and systematic review.

BACKGROUND: Malaria affects 24 million children globally, resulting in nearly 500,000 child deaths annually in low- and middle-income countries (LMICs). Recent studies have provided evidence that severe malaria infection results in sustained impairment in cognition and behaviour among young children; however, a formal meta-analysis has not been published. The objective was to assess the association between severe malaria infection with cognitive and behavioural outcomes among children living in LMICs. METHODS: Six online bibliographic databases were searched and reviewed in November 2022. Studies included involved children < 18 years of age living in LMICs with active or past severe malaria infection and measured cognitive and/or behaviour outcomes. The quality of studies was assessed. Definitions of severe malaria included cerebral malaria, severe malarial anaemia, and author-defined severe malaria. Results from all studies were qualitatively summarized. For studies with relevant data on attention, learning, memory, language, internalizing behaviour and externalizing behaviour, results were pooled and a meta-analysis was performed. A random-effects model was used across included cohorts, yielding a standardized mean difference between the severe malaria group and control group. RESULTS: Out of 3,803 initial records meeting the search criteria, 24 studies were included in the review, with data from 14 studies eligible for meta-analysis inclusion. Studies across sub-Saharan Africa assessed 11 cohorts of children from pre-school to school age. Of all the studies, composite measures of cognition were the most affected areas of development. Overall, attention, memory, and behavioural problems were domains most commonly found to have lower scores in children with severe malaria. Meta-analysis revealed that children with severe malaria had worse scores compared to children without malaria in attention (standardized mean difference (SMD) -0.68, 95% CI -1.26 to -0.10), memory (SMD -0.52, 95% CI -0.99 to -0.06), and externalizing behavioural problems (SMD 0.45, 95% CI 0.13-0.78). CONCLUSION: Severe malaria is associated with worse neuropsychological outcomes for children living in LMICs, specifically in attention, memory, and externalizing behaviours. More research is needed to identify the long-term implications of these findings. Further interventions are needed to prevent cognitive and behavioural problems after severe malaria infection. TRIAL REGISTRATION: This systematic review was registered under PROSPERO: CRD42020154777.

Effectiveness of health education interventions to improve malaria knowledge and insecticide-treated nets usage among populations of sub-Saharan Africa: systematic review and meta-analysis.

Introduction: Malaria health education intervention is a community-directed approach that has long been considered important in preventing malaria in sub-Saharan Africa. However, its effectiveness is being questioned due to a lack of strong evidence. We aim to synthesize the evidence of the impact of health education on malaria knowledge and insecticide-treated nets (ITN) usage. Specifically, we analyzed the odds of correctly answering malaria-related questions and the odds of using ITN between the intervention and control groups. Methods: Experimental and observational studies conducted in sub-Saharan Africa between 2000 and 2021 which had quantitatively evaluated the impact of health education interventions on malaria knowledge and ITN usage were included in the review. Results: A total of 11 studies (20,523 participants) were included. Four studies used educational interventions to teach appropriate ITN strategies and promote ITN usage. Two others focused on improving knowledge of malaria transmission, prevention, treatment, and its signs and symptoms. The remaining five studies assessed both ITN use and malaria knowledge. Of these, 10 were eligible for meta-analysis. On average, the odds of a person in the intervention group reporting better malaria knowledge (odds ratio 1.30, 95% CI: 1.00 to 1.70, p = 0.05) and higher ITN usage (odds ratio 1.53, 95% CI: 1.02 to 2.29, p = 0.004) increased significantly after receiving health education interventions compared to those in the control group. The odds of ITN usage also substantially increased when the interventions were based on a theory or model (odds ratio 5.27, 95% CI: 3.24 to 8.58, p = 0.05). Discussion: Our review highlights sub-Saharan Africa's various health education strategies to curb malaria over the past two decades. Meta-analysis findings show that health education interventions are moderately effective in improving malaria knowledge and ITN usage and have contributed to the effort of global malaria strategy.

Insecticide-treated bed net utilization and associated factors among pregnant women in Ethiopia: a systematic review and meta-analysis.

BACKGROUND: Malaria infection during pregnancy endangers the pregnant woman, fetus, and newborn child. Thus, the use of an insecticide-treated net (ITN) is one of the most frequently advised methods for preventing malaria during pregnancy. Contrary findings have been reported in various studies on ITN utilization among pregnant women in Ethiopia. Therefore, this study was aimed to estimate the pooled prevalence of ITN utilization and its associated factors among pregnant women in Ethiopia. METHODS: Published articles from PubMed, Google Scholar, Science Direct, AJOL and Cochrane library were systematically searched. All cross-sectional studies on ITN utilization among pregnant women were included in this meta-analysis. To estimate the pooled prevalence and odds ratio, a random-effect model was used; and a subgroup analysis was performed to identify the possible source of heterogeneity. Begg's and Egger's tests were used to identify possible publication bias. RESULTS: Ten cross-sectional studies with 7,161 participants were included. The pooled prevalence of ITN utilization among all pregnant women who had access to ITN in Ethiopia was 59.42% (95% CI 51.14, 67.69). Statistically significant heterogeneity was observed (I2 = 97.7%; p < 0.0001). Higher educational status (OR = 3.47, 95% CI 2.32, 5.2), pregnant women who had antenatal care visits (OR = 2.37, 95% CI 1.97, 2.65) and having good knowledge of malaria prevention practices (OR = 10.63, 95% CI 5.31, 21.29) were associated with ITN utilization among pregnant women. CONCLUSION: The utilization of ITNs among pregnant women was much lower than the national target. Higher education status, attending ANC and a good level of knowledge were found to be independent predictors of ITN utilization. Improving women's understanding of ITNs will enhance their use, and the government and health sectors should encourage pregnant mothers to enroll in antenatal care.

PARIST study protocol: a phase I/II randomised, controlled clinical trial to assess the feasibility, safety and effectiveness of paracetamol in resolving acute kidney injury in children with severe malaria.

BACKGROUND: Acute kidney injury (AKI) has in the past been considered a rare complication of malaria in children living in high-transmission settings. More recently, however, a growing number of paediatric case series of AKI in severe malaria studies in African children have been published (Artesunate vs Quinine in the Treatment of Severe P. falciparum Malaria in African children and Fluids Expansion as Supportive Therapy trials). The Paracetamol for Acute Renal Injury in Severe Malaria Trial (PARIST) therefore, aims to assess feasibility, safety and determine the effective dose of paracetamol, which attenuates nephrotoxicity of haemoproteins, red-cell free haemoglobin and myoglobin in children with haemoglobinuric severe malaria. METHODS: PARIST is a phase I/II unblinded randomised controlled trial of 40 children aged >6 months and <12 years admitted with confirmed haemoglobinuric severe malaria (blackwater fever), a positive blood smear for P. falciparum malaria and either serum creatinine (Cr) increase by ≥0.3 mg/dL within 48 hours or to ≥1.5 times baseline and elevated blood urea nitrogen (BUN) >20 mg/dL. Children will be randomly allocated on a 1:1 basis to paracetamol intervention dose arm (20 mg/kg orally 6-hourly for 48 hours) or to a control arm to receive standard of care for temperature control (ie, tepid sponging for 30 min if fever persists give rescue treatment). Primary outcome is renal recovery at 48 hours as indicated by stoppage of progression and decrease of Cr level below baseline, BUN (<20 mg/dL). Data analysis will be on the intention-to-treat principle and a per-protocol basis.Results from this phase I/II clinical trial will provide preliminary effectiveness data of this highly potential treatment for AKI in paediatric malaria (in particular for haemoglobinuric severe malaria) for a larger phase III trial. ETHICS AND DISSEMINATION: Ethical and regulatory approvals have been granted by the Mbale Hospital Institutional Ethics Review Committee (MRRH-REC OUT 002/2019), Uganda National Council of Science and Technology (UNCST-HS965ES) and the National drug Authority (NDA-CTC 0166/2021). We will be disseminating results through journals, conferences and policy briefs to policy makers and primary care providers. TRIAL REGISTRATION NUMBER: ISRCTN84974248.

Seasonal malaria chemoprevention in Africa and China's upgraded role as a contributor: a scoping review.

BACKGROUND: Children under five are the vulnerable population most at risk of being infected with Plasmodium parasites, especially in the Sahel region. Seasonal malaria chemoprevention (SMC) recommended by World Health Organization (WHO), has proven to be a highly effective intervention to prevent malaria. Given more deaths reported during the COVID-19 pandemic than in previous years due to the disruptions to essential medical services, it is, therefore, necessary to seek a more coordinated and integrated approach to increasing the pace, coverage and resilience of SMC. Towards this end, fully leverage the resources of major players in the global fight against malaria, such as China could accelerate the SMC process in Africa. METHODS: We searched PubMed, MEDLINE, Web of Science, and Embase for research articles and the Institutional Repository for Information Sharing of WHO for reports on SMC. We used gap analysis to investigate the challenges and gaps of SMC since COVID-19. Through the above methods to explore China's prospective contribution to SMC. RESULTS: A total of 68 research articles and reports were found. Through gap analysis, we found that despite the delays in the SMC campaign, 11.8 million children received SMC in 2020. However, there remained some challenges: (1) a shortage of fully covered monthly courses; (2) lack of adherence to the second and third doses of amodiaquine; (3) four courses of SMC are not sufficient to cover the entire malaria transmission season in areas where the peak transmission lasts longer; (4) additional interventions are needed to consolidate SMC efforts. China was certified malaria-free by WHO in 2021, and its experience and expertise in malaria elimination can be shared with high-burden countries. With the potential to join the multilateral cooperation in SMC, including the supply of quality-assured health commodities, know-how transfer and experience sharing, China is expected to contribute to the ongoing scale-up of SMC. CONCLUSIONS: A combination of necessary preventive and curative activities may prove beneficial both for targeted populations and for health system strengthening in the long run. More actions are entailed to promote the partnership and China can be one of the main contributors with various roles.

Combating malaria in Kenya through collaborative population health education: a systematic review and pilot case study.

BACKGROUND: Malaria continues to be a public health problem in Kenya, with an estimated 37.2 million people at high risk of the disease. The disease burden is compounded by inequalities in health service availability, housing, socioeconomic conditions, and access to education. OBJECTIVES: We aimed to determine the status of community-based, health education interventions. Based on the findings, to develop an educational module for medical students to combat malaria in Kenya. METHODS: A systematic review was conducted to identify different educational interventions, their successes and limitations, and legal challenges leading to low uptake and adherence to malaria prevention interventions from 2000-2023. Consequently, a 6-week online educational pilot was conducted with healthcare students from Kenya, Japan, the UK, and Cyprus. RESULTS: Despite developing a national malaria strategy and monitoring and evaluation strategies, Kenya has not been able to meet the incidence reduction targets set by the World Health Organisation, underscoring the need for more work in identifying the barriers to implementing strategies and optimising the distribution of public health interventions. Student teams proposed innovative solutions, including two-tier malaria control strategies, maternal malaria clinical education, community awareness through schools and NGOs, and a 10-year health system strengthening and immunisation plan. CONCLUSIONS: Public education regarding prevention strategies and increasing their adoption remains a key challenge in combating malaria in Kenya. In this regard, digital tools can facilitate international collaborative health education and exchange of best practices, allowing students and faculty to engage across boundaries and prepare them to be future-ready physicians connected to the global community.

What are the pathways between poverty and malaria in sub-Saharan Africa? A systematic review of mediation studies.

BACKGROUND: Malaria remains a major burden in sub-Saharan Africa (SSA). While an association between poverty and malaria has been demonstrated, a clearer understanding of explicit mechanisms through which socioeconomic position (SEP) influences malaria risk is needed to guide the design of more comprehensive interventions for malaria risk mitigation. This systematic review provides an overview of the current evidence on the mediators of socioeconomic disparities in malaria in SSA. METHODS: We searched PubMed and Web of Science for randomised controlled trials, cohort, case-control and cross-sectional studies published in English between January 1, 2000 to May 31, 2022. Further studies were identified following reviews of reference lists of the studies included. We included studies that either (1) conducted a formal mediation analysis of risk factors on the causal pathway between SEP and malaria infections or (2) adjusted for these potential mediators as confounders on the association between SEP and malaria using standard regression models. At least two independent reviewers appraised the studies, conducted data extraction, and assessed risk of bias. A systematic overview is presented for the included studies. RESULTS: We identified 41 articles from 20 countries in SSA for inclusion in the final review. Of these, 30 studies used cross-sectional design, and 26 found socioeconomic inequalities in malaria risk. Three formal mediation analyses showed limited evidence of mediation of food security, housing quality, and previous antimalarial use. Housing, education, insecticide-treated nets, and nutrition were highlighted in the remaining studies as being protective against malaria independent of SEP, suggesting potential for mediation. However, methodological limitations included the use of cross-sectional data, insufficient confounder adjustment, heterogeneity in measuring both SEP and malaria, and generally low or moderate-quality studies. No studies considered exposure mediator interactions or considered identifiability assumptions. CONCLUSIONS: Few studies have conducted formal mediation analyses to elucidate pathways between SEP and malaria. Findings indicate that food security and housing could be more feasible (structural) intervention targets. Further research using well-designed longitudinal studies and improved analysis would illuminate the current sparse evidence into the pathways between SEP and malaria and adduce evidence for more potential targets for effective intervention.

Co-trimoxazole prophylaxis for children who are HIV-exposed and uninfected: a systematic review.

INTRODUCTION: Co-trimoxazole prophylaxis is recommended for children born to women with HIV to protect those who acquire HIV from opportunistic infections, severe bacterial infections and malaria. With scale-up of maternal antiretroviral therapy, most children remain HIV-exposed uninfected (HEU) and the benefits of universal co-trimoxazole are uncertain. We assessed the effect of co-trimoxazole on mortality and morbidity of children who are HEU. METHODS: We performed a systematic review (PROSPERO number: CRD42021215059). We systematically searched MEDLINE, Embase, Cochrane CENTRAL, Global Health, CINAHL Plus, Africa-Wide Information, SciELO and WHO Global Index Medicus for peer-reviewed articles from inception to 4th January 2022 without limits. Ongoing randomized controlled trials (RCTs) were identified through registries. We included RCTs reporting mortality or morbidity in children who are HEU receiving co-trimoxazole versus no prophylaxis/placebo. The risk of bias was assessed using the Cochrane 2.0 tool. Data were summarized using narrative synthesis and findings were stratified by malaria endemicity. RESULTS: We screened 1257 records and included seven reports from four RCTs. Two trials from Botswana and South Africa of 4067 children who are HEU found no difference in mortality or infectious morbidity in children randomized to co-trimoxazole prophylaxis started at 2-6 weeks of age compared to those randomized to placebo or no treatment, although event rates were low. Sub-studies found that antimicrobial resistance was higher in infants receiving co-trimoxazole. Two trials in Uganda investigating prolonged co-trimoxazole after breastfeeding cessation showed protection against malaria but no other morbidity or mortality differences. All trials had some concerns or a high risk of bias, which limited the certainty of evidence. DISCUSSION: Studies show no clinical benefit of co-trimoxazole prophylaxis in children who are HEU, except to prevent malaria. Potential harms were identified for co-trimoxazole prophylaxis leading to antimicrobial resistance. The trials in non-malarial regions were conducted in populations with low mortality potentially reducing generalizability to other settings. CONCLUSIONS: In low-mortality settings with few HIV transmissions and well-performing early infant diagnosis and treatment programmes, universal co-trimoxazole may not be required.

A systematic review of mixed studies on malaria in Colombia 1980-2022: what the "bifocal vision" discovers.

Mixed methods are essential in public health research and malaria control, because they allow grasping part of the complexity and diversity of the factors that determine health-disease. This study analyzes the mixed studies on malaria in Colombia, 1980-2022, through a systematic review in 15 databases and institutional repositories. The methodological quality was assessed with Mixed Methods Appraisal Tool (MMAT), STrengthening the Reporting of OBservational studies in Epidemiology (STROBE), and Standards for Reporting Qualitative Research (SRQR). The qualitative and quantitative findings were grouped into a four-level hierarchical matrix. The epidemiological profile of malaria morbidity, from traditional epidemiology, has been sustained by environmental problems, armed conflict, individual risk behaviors, and low adherence to recommendations from health institutions. However, the qualitative component reveals deeper causes that are less studied, of greater theoretical complexity, and that reflect challenges to design and implement health interventions, such as socioeconomic and political crises, poverty, and the neoliberal orientation in the malaria control policy; the latter reflected in the change in the role of the State, the fragmentation of control actions, the predominance of insurance over social assistance, the privatization of the provision of health services, the individualistic and economistic predominance of health, and low connection with popular tradition and community initiatives. The above confirms the importance of expanding mixed studies as a source of evidence to improve malaria research and control models in Colombia, and to identify the underlying causes of the epidemiological profile.

Coinfections of malaria and sexually transmitted and reproductive tract infections in pregnancy in sub-Saharan Africa: a systematic review and individual participant data meta-analysis protocol.

INTRODUCTION: Malaria infection and curable sexually transmitted infections and reproductive tract infections (STIs/RTIs) adversely impact pregnancy outcomes. In sub-Saharan Africa, the prevalence of malaria and curable STIs/RTIs is high and, where coinfection is common, combination interventions may be needed to improve pregnancy outcomes. The aim of this systematic review is to estimate the prevalence of malaria and curable STI/RTI coinfection during pregnancy, risk factors for coinfection and prevalence of associated adverse pregnancy outcomes. METHODS AND ANALYSIS: We will use three electronic databases, PubMed, EMBASE and Malaria in Pregnancy Library to identify studies involving pregnant women attending routine antenatal care facilities in sub-Saharan Africa and reporting malaria and curable STI/RTI test results, published in any language since 2000. We will search databases in the second quarter of 2023 and repeat the search before completion of our analyses. The first two authors will screen titles and abstracts, selecting studies that meet inclusion criteria and qualify for full-text screening. If agreement on inclusion/exclusion cannot be reached, the last author will serve as arbiter. We will extract data from eligible publications for a study-level meta-analysis. We will contact research groups of included studies and request individual participant data for meta-analysis. The first two authors will conduct a quality appraisal of included studies using the GRADE system. The last author will adjudicate if the first two authors do not agree on any appraisals. We will conduct sensitivity analyses to test the robustness of effect estimates over time (by decade and half-decade periods), geography (East/Southern Africa vs West/Central Africa), gravidity (primigravidae, secundigravidae, multigravidae), treatment type and dosing frequency, and malaria transmission intensity. ETHICS AND DISSEMINATION: We obtained ethics approval from the London School of Hygiene & Tropical Medicine (LSHTM Ethics Ref: 26167). Results of this study will be disseminated via peer-reviewed publication and presentation at scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42021224294.

Malaria prevalence in Mauritania: a systematic review and meta-analysis.

BACKGROUND: Understanding malaria epidemiology is a critical step toward efficient malaria control and elimination. The objective of this meta-analysis was to derive robust estimates of malaria prevalence and Plasmodium species from studies conducted in Mauritania and published since 2000. METHODS: The present review followed the PRISMA guidelines. Searches were conducted in various electronic databases such as PubMed, Web of Science, and Scopus. To obtain pooled prevalence of malaria, meta-analysis was performed using the DerSimonian-Laird random-effects model. Methodological quality of eligible prevalence studies was assessed using Joanna Briggs Institute tool. Inconsistency and heterogeneity between studies were quantified by the I2 index and Cochran's Q test. Publication bias was assessed with funnel plots and Egger's regression tests. RESULTS: A total of 16 studies with a good individual methodological quality were included and analysed in this study. The overall random effects pooled prevalence of malaria infection (symptomatic and asymptomatic) across all included studies was 14.9% (95% confidence interval [95% CI]: 6.64, 25.80, I2 = 99.8%, P < 0.0001) by microscopy, 25.6% (95% CI: 8.74, 47.62, I2 = 99.6%, P < 0.0001) by PCR and 24.3% (95% CI: 12.05 to 39.14, I2 = 99.7%, P < 0.0001) by rapid diagnostic test. Using microscopy, the prevalence of asymptomatic malaria was 1.0% (95% CI: 0.00, 3.48) against 21.46% (95% CI: 11.03, 34.21) in symptomatic malaria. The overall prevalence of Plasmodium falciparum and Plasmodium vivax was 51.14% and 37.55%, respectively. Subgroup analysis showed significant variation (P = 0.039) in the prevalence of malaria between asymptomatic and symptomatic cases. CONCLUSION: Plasmodium falciparum and P. vivax are widespread in Mauritania. Results of this meta-analysis implies that distinct intervention measures including accurate parasite-based diagnosis and appropriate treatment of confirmed malaria cases are critical for a successful malaria control and elimination programme in Mauritania.

Post introduction evaluation of the malaria vaccine implementation programme in Ghana, 2021.

BACKGROUND: Malaria remains a public health challenge in Sub-Saharan Africa with the region contributing to more than 90% of global cases in 2020. In Ghana, the malaria vaccine was piloted to assess the feasibility, safety, and its impact in the context of routine use alongside the existing recommended malaria control measures. To obtain context-specific evidence that could inform future strategies of introducing new vaccines, a standardized post-introduction evaluation (PIE) of the successes and challenges of the malaria vaccine implementation programme (MVIP) was conducted. METHODS: From September to December 2021, the WHO Post-Introduction Evaluation (PIE) tool was used to conduct a mixed methods evaluation of the MVIP in Ghana. To ensure representativeness, study sites and participants from the national level, 18 vaccinating districts, and 54 facilities from six of the seven pilot regions were purposively selected. Quantitative and qualitative data were collected using data collection tools that were adapted based on the WHO PIE protocol. We performed summary descriptive statistics on quantitative data, thematic analysis on qualitative data, and triangulation of the results from both sets of analyses. RESULTS: About 90.7% (49/54) of health workers stated that the vaccine introduction process was smooth and contributed to an overall improvement of routine immunisation services. About 87.5% (47/54) of healthcare workers, and 95.8% (90/94) of caregivers accepted RTS,S malaria vaccine. Less than half [46.3%; (25/54)] of the healthcare workers participated in the pre-vaccine introduction training but almost all [94.4%; (51/54)] were able to constitute and administer the vaccine appropriately. About 92.5% (87/94) of caregivers were aware of the RTS,S introduction but only 44.0% (44/94) knew the number of doses needed for maximum protection. Health workers believed that the MVIP has had a positive impact on under five malaria morbidity. CONCLUSIONS: The malaria vaccine has been piloted successfully in Ghana. Intensive advocacy; community engagement, and social mobilization; and regular onsite supportive supervision are critical enablers for successful introduction of new vaccines. Stakeholders are convinced of the feasibility of a nationwide scale up using a phased subnational approach taking into consideration malaria epidemiology and global availability of vaccines.

Malaria amongst children under five in sub-Saharan Africa: a scoping review of prevalence, risk factors and preventive interventions.

INTRODUCTION: Africa has a higher burden of malaria-related cases and deaths globally. Children under five accounted for over two-thirds of all malaria deaths in sub-Saharan Africa (SSA). This scoping review aims to map evidence of the prevalence, contextual factors and health education interventions of malaria amongst children under 5 years (UN5) in SSA. METHOD: Four main databases (PubMed, Central, Dimensions and JSTOR) produced 27,841 records of literature. Additional searches in Google, Google Scholar and institutional repositories produced 37 records. Finally, 255 full-text records were further screened, and 100 records were used for this review. RESULTS: Low or no formal education, poverty or low income and rural areas are risk factors for malaria amongst UN5. Evidence on age and malnutrition as risk factors for malaria in UN5 is inconsistent and inconclusive. Furthermore, the poor housing system in SSA and the unavailability of electricity in rural areas and unclean water make UN5 more susceptible to malaria. Health education and promotion interventions have significantly reduced the malaria burden on UN5 in SSA. CONCLUSION: Well-planned and resourced health education and promotion interventions that focus on prevention, testing and treatment of malaria could reduce malaria burden amongst UN5 in SSA.