Simon Kariuki

Background: Malaria prevalence data are not collected with the resolution or frequency required to tailor malaria control interventions to the local level. Routine malaria test-positivity data from screening pregnant women attending antenatal clinics (ANC) has been shown to correlate with sub-national malaria prevalence estimates obtained via household surveys. This approach may become increasingly important given uncertainty around funding for traditional survey platforms such as Demographic Health Surveys (DHS). We assessed whether rapid diagnostic test (RDT) results from ANC screening correlated with monthly malaria prevalence data from all-age household surveys in health facility catchment areas in western Kenya.Methods: Monthly likelihood of malaria RDT test-positivity among women attending their first ANC visit was compared to RDT results from community-based, all-age, year-round continuous malaria indicator household surveys (cMIS) in the same catchment area. Statistical models were used to associate monthly facility-catchment odds of RDT positivity from the ANC data, accounting for gravidity, with odds of positivity from cMIS data.Findings: From January 2016 to December 2021, 6,994 pregnant women attending ANC and 11,525 participants aged ≥1 month from cMIS contributed to the analysis. A model assuming a constant odds ratio between ANC test-positivity and cMIS prevalence identified malaria dynamics across the study area, including declines after long-lasting insecticidal net distributions and increases in prevalence during COVID-19-related disruptions.Interpretation: In addition to indicating malaria infection in pregnancy, monthly ANC-based screening data were associated with malaria RDT prevalence in surrounding communities. This suggests the potential to use test-positivity data from pregnant women attending ANC for tracking community-level malaria dynamics at finer spatial scales than previously achieved. The continuity of ANC screening during the pandemic highlights its potential as a resilient surveillance tool to monitor changes in transmission in near-real-time at higher resolution than currently feasible through prevalence surveys, especially amid reductions to global funding for such platforms.

Background/Objectives: A contributory factor to childhood undernutrition is poor gut health occurring within the first 6–12 weeks of life despite exclusive breastfeeding. Pro/synbiotic administration may protect gut health. A qualitative study was conducted amongst mothers/carers and healthcare workers (HCWs) to explore their perceptions and the acceptability of pro/synbiotics administration in early life. Methods: This study was nested within a randomised, open, clinical trial of pro/synbiotics with 32 doses administered under supervision to infants between ages 0 and 5 months in western Kenya. Semi-structured interviews were conducted with 14 mothers/carers, 12 Peer Mothers and 7 healthcare workers (HCWs) selected by purposive critical and key informant sampling. Interviews were transcribed and analysed using a thematic coding framework. Results: The satisfaction with the pro/synbiotic administration was very high amongst all three groups. Commonly perceived benefits included protection from diseases, healthy growth of the infant and improved appetite. The main barriers were working mothers and other commitments making it difficult to stick to scheduled administration visits, adverse judgement and opinions in the community, and a lack of engagement from fathers. Insights were gained into different means of administering pro/synbiotics to young infants. Triangulation of the findings of the mothers/carers with HCWs showed that most identified motivations and challenges were similar. Conclusions: Pro/synbiotic administration was well accepted by the mothers/carers and HCWs and generally perceived to have health benefits. The administration of pro/synbiotics by the mothers/carers themselves to their infants may be feasible and overcome logistical challenges. Greater efforts to sensitise and engage fathers and communities would likely be critical for a community-based program.

Background A contributory factor to childhood undernutrition is poor gut health occurring within the first 6-12 weeks of life despite exclusive breast feeding. Pro/synbiotic administration may protect gut health. A qualitative study was conducted amongst mothers/carers and healthcare workers (HCWs) to explore their perceptions and the acceptability of pro/synbiotics administration in early life. Methods This study was nested within a randomised, open, clinical trial of pro/synbiotics with 32 doses administered under supervision to infants between age 0-5 months in western Kenya. Semi-structured interviews were conducted with mothers/carers, Peer Mothers and health care workers (HCWs) selected by purposive critical and key informant sampling. Interviews were transcribed and analysed using a thematic coding framework. Findings Satisfaction with pro/synbiotic administration was very high amongst all three groups. Commonly perceived benefits included protection from diseases, healthy growth of the infant and improved appetite. The main barriers were working mothers and other commitments making it difficult to stick to scheduled administration visits, adverse judgment and opinions in the community and lack of engagement of fathers. Insights were gained into different means of administering pro/synbiotics to young infants. Triangulation of findings of the mothers/carers with HCWs showed that most identified motivations and challenges were similar. Conclusions Pro/synbiotic administration was well-accepted by mothers/carers and HCWs and generally perceived to have health benefits. Administration of pro/synbiotics by mothers/carers themselves to their infants may be feasible and overcome logistical challenges. Greater efforts to sensitise and engage fathers and communities would likely be critical for a community-based program.

The substantial decline observed in the global trends of malaria incidence since the year 2000, largely attributable to the scale-up of malaria control interventions, has been stagnating since 2020, with the burden remaining disproportionately high in sub-Saharan Africa [1]. Changes in climatic factors threaten to expand the transmission areas and further reverse the gains made […]

Objective To perform critical methodological assessments on designs, outcomes, quality and implementation limitations of studies evaluating the impact of malaria rapid diagnostic tests (mRDTs) on patient-important outcomes in sub-Saharan Africa. Design A systematic review of study methods. Data sources MEDLINE, EMBASE, Cochrane Library, African Index Medicus and clinical trial registries were searched up to May 2022. Eligibility criteria Primary quantitative studies that compared mRDTs to alternative diagnostic tests for malaria on patient-important outcomes within sub-Sahara Africa. Data extraction and synthesis Studies were sought by an information specialist and two independent reviewers screened for eligible records and extracted data using a predesigned form using Covidence. Methodological quality was assessed using the National Institutes of Health tools. Descriptive statistics and thematic analysis guided by the Supporting the Use of Research Evidence framework were used for analysis. Findings were presented narratively, graphically and by quality ratings. Results Our search yielded 4717 studies, of which we included 24 quantitative studies; (15, 62.5%) experimental, (5, 20.8%) quasi-experimental and (4, 16.7%) observational studies. Most studies (17, 70.8%) were conducted within government-owned facilities. Of the 24 included studies, (21, 87.5%) measured the therapeutic impact of mRDTs. Prescription patterns were the most reported outcome (20, 83.3%). Only (13, 54.2%) of all studies reported statistically significant findings, in which (11, 45.8%) demonstrated mRDTs’ potential to reduce over-prescription of antimalarials. Most studies (17, 70.8%) were of good methodological quality; however, reporting sample size justification needs improvement. Implementation limitations reported were mostly about health system constraints, the unacceptability of the test by the patients and low trust among health providers. Conclusion Impact evaluations of mRDTs in sub-Saharan Africa are mostly randomised trials measuring mRDTs’ effect on therapeutic outcomes in real-life settings. Though their methodological quality remains good, process evaluations can be incorporated to assess how contextual concerns influence their interpretation and implementation. PROSPERO registration number CRD42018083816.

Background Malaria mortality is influenced by several factors including climatic and environmental factors, interventions, socioeconomic status (SES) and access to health systems. Here, we investigated the joint effects of climatic and non-climatic factors on under-five malaria mortality at different spatial scales using data from a Health and Demographic Surveillance System (HDSS) in western Kenya. Methods We fitted Bayesian spatiotemporal (zero-inflated) negative binomial models to monthly mortality data aggregated at the village scale and over the catchment areas of the health facilities within the HDSS, between 2008 and 2019. First order autoregressive temporal and conditional autoregressive spatial processes were included as random effects to account for temporal and spatial variation. Remotely sensed climatic and environmental variables, bed net use, SES, travel time to health facilities, proximity from water bodies/streams and altitude were included in the models to assess their association with malaria mortality. Results Increase in rainfall (mortality rate ratio (MRR)=1.12, 95% Bayesian credible interval (BCI): 1.04–1.20), Normalized Difference Vegetation Index (MRR=1.16, 95% BCI: 1.06–1.28), crop cover (MRR=1.17, 95% BCI: 1.11–1.24) and travel time to the hospital (MRR=1.09, 95% BCI: 1.04–1.13) were associated with increased mortality, whereas increase in bed net use (MRR=0.84, 95% BCI: 0.70–1.00), distance to the nearest streams (MRR=0.89, 95% BCI: 0.83–0.96), SES (MRR=0.95, 95% BCI: 0.91–1.00) and altitude (MRR=0.86, 95% BCI: 0.81–0.90) were associated with lower mortality. The effects of travel time and SES were no longer significant when data was aggregated at the health facility catchment level. Conclusion Despite the relatively small size of the HDSS, there was spatial variation in malaria mortality that peaked every May–June. The rapid decline in malaria mortality was associated with bed nets, and finer spatial scale analysis identified additional important variables. Time and spatially targeted control interventions may be helpful, and fine spatial scales should be considered when data are available.

Article summary: This study suggests that: 1) patients given AL infected with parasites carrying N86 were statistically more likely to experience a recurrent infection; 2) patients given ASAQ infected with parasites carrying 86Y were statistically more likely to experience a recurrent infection. Background: Plasmodium falciparum multidrug resistance transporter 1 ( Pfmdr1 ) gene mutations are associated with altered response to artemisinin-based combination therapies (ACTs), particularly those containing the partner drugs lumefantrine and amodiaquine (i.e., artemether-lumefantrine [AL] and artesunate-amodiaquine [ASAQ]). Past studies of Pfmdr1 single nucleotide polymorphisms (SNPs) at codons 86, 184, and 1246 have shown different responses to AL and ASAQ. Methods: To determine whether infection with parasites carrying specific Pfmdr1 SNPs leads to increased risk of recurrent parasitemia (recrudescent or new infection), data from 4,129 samples from 16 therapeutic efficacy studies from 13 African countries between 2013–2019 were analyzed. Results: Patients treated with AL and infected with parasites carrying Pfmdr1 N86 were at greater risk of treatment failure than those whose parasites carried 86Y. After treatment with ASAQ, individuals infected with parasites that carried Pfmdr1 86Y were more likely to experience a recurrent infection. Conclusions: Our results support prior studies that suggested: 1) patients given AL and infected with parasites carrying N86 were more likely to experience a recurrent infection; 2) patients given ASAQ and infected with parasites carrying 86Y were more likely to experience recurrent infection. These findings suggest that ACT and Pfmdr1 genotype may influence outcome after P. falciparum infection.

A systems analysis was conducted to determine the potential molecular mechanisms underlying differential immunogenicity and protective efficacy results of a clinical trial of the radiation-attenuated whole-sporozoite PfSPZ vaccine in African infants. Innate immune activation and myeloid signatures at prevaccination baseline correlated with protection from P. falciparum parasitemia in placebo controls. These same signatures were associated with susceptibility to parasitemia among infants who received the highest and most protective PfSPZ vaccine dose. Machine learning identified spliceosome, proteosome, and resting DC signatures as prevaccination features predictive of protection after highest-dose PfSPZ vaccination, whereas baseline circumsporozoite protein–specific (CSP-specific) IgG predicted nonprotection. Prevaccination innate inflammatory and myeloid signatures were associated with higher sporozoite-specific IgG Ab response but undetectable PfSPZ-specific CD8 ⁺ T cell responses after vaccination. Consistent with these human data, innate stimulation in vivo conferred protection against infection by sporozoite injection in malaria-naive mice while diminishing the CD8 ⁺ T cell response to radiation-attenuated sporozoites. These data suggest a dichotomous role of innate stimulation for malaria protection and induction of protective immunity by whole-sporozoite malaria vaccines. The uncoupling of vaccine-induced protective immunity achieved by Abs from more protective CD8 ⁺ T cell responses suggests that PfSPZ vaccine efficacy in malaria-endemic settings may be constrained by opposing antigen presentation pathways.

Background The RTS,S/AS01 malaria vaccine was introduced in Ghana, Kenya, and Malawi in 2019. Evaluation includes case-control studies designed to monitor individual-level safety and effectiveness to complement population-level estimates derived from the MVPE. Here, we discuss design and practical considerations for conducting case-control studies to measure vaccine effectiveness against severe malaria, the need for a 4th dose, and for assessment of safety outcomes. Methods For the severe malaria study we aimed to estimate the effectiveness of the primary 3 doses, and of the 4th dose. We also aimed to estimate rebound, if any, in children who received only the primary 3 doses. Cases were patients with severe malaria admitted to a study hospital, residing in an RTS,S/AS01 implementation area, and eligible to have received the 3rd or 4th dose of the vaccine. The case patient’s home is visited to collect data on vaccination status and other details. Four controls are then recruited from the same community, matched closely on date of birth. Vaccination status is determined from home-based records, and from clinic registers. Similar approaches were used for studies of safety outcomes. Results We share preliminary results and discuss the challenges encountered and lessons learned about implementing a multi-centre case control study for a malaria vaccine, and approaches to data collection which have proved effective, including establishing surveillance, the use of specific case definitions standardized across centres, recruiting closely age-matched community controls, and obtaining reliable information from both cases and controls on potential confounding factors which may be associated with both risk of the outcome and with access to vaccination. Conclusion Case control studies are an efficient means of monitoring vaccine effectiveness and safety, but require care in design and implementation. The lessons learned from the malaria vaccine pilots will be useful for countries planning introduction of a malaria vaccine.

: Limited evidence suggests that children in sub-Saharan Africa hospitalized with all-cause severe anemia or severe acute malnutrition (SAM) are at high risk of dying in the first few months after discharge. We aimed to compare the risks of post-discharge mortality by health condition among hospitalized children in an area with high malaria transmission in western Kenya. We conducted a retrospective cohort study among recently discharged children aged < 5 years using mortality data from a health and demographic surveillance system that included household and pediatric in-hospital surveillance. Cox regression was used to compare post-discharge mortality. Between 2008 and 2013, overall in-hospital mortality was 2.8% (101/3,639). The mortality by 6 months after discharge (primary outcome) was 6.2% (159/2,556) and was highest in children with SAM (21.6%), followed by severe anemia (15.5%), severe pneumonia (5.6%), “other conditions” (5.6%), and severe malaria (0.7%). Overall, the 6-month post-discharge mortality in children hospitalized with SAM (hazard ratio [HR] = 3.95, 2.60–6.00, P < 0.001) or severe anemia (HR = 2.55, 1.74–3.71, P < 0.001) was significantly higher than that in children without these conditions. Severe malaria was associated with lower 6-month post-discharge mortality than children without severe malaria (HR = 0.33, 0.21–0.53, P < 0.001). The odds of dying by 6 months after discharge tended to be higher than during the in-hospital period for all children, except for those admitted with severe malaria. The first 6 months after discharge is a high-risk period for mortality among children admitted with severe anemia and SAM in western Kenya. Strategies to address this risk period are urgently needed.