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Background: Informing and evaluating malaria control efforts relies on knowledge of local transmission dynamics. Serological and molecular tools have demonstrated great sensitivity to quantify transmission intensity in low endemic settings where the sensitivity of traditional methods is limited. Filter paper blood spots are commonly used a source of both DNA and antibodies. To enhance the operational practicability of malaria surveys, a method is presented for combined DNA extraction and antibody elution., Methods: Filter paper blood spots were collected as part of a large cross-sectional survey in the Kenyan highlands. DNA was extracted using a saponin/chelex method. The eluate of the first wash during the DNA extraction process was used for antibody detection and compared with previously validated antibody elution procedures. Antibody elution efficiency was assessed by total IgG ELISA for malaria antigens apical membrane antigen-1 (AMA-1) and merozoite-surface protein-1 (MSP-142). The sensitivity of nested 18S rRNA and cytochrome b PCR assays and the impact of doubling filter paper material for PCR sensitivity were determined. The distribution of cell material and antibodies throughout filter paper blood spots were examined using luminescent and fluorescent reporter assays., Results: Antibody levels measured after the combined antibody/DNA extraction technique were strongly correlated to those measured after standard antibody elution (p < 0.0001). Antibody levels for both AMA-1 and MSP-142 were generally slightly lower (11.3-21.4%) but age-seroprevalence patterns were indistinguishable. The proportion of parasite positive samples ranged from 12.9% to 19.2% in the different PCR assays. Despite strong agreement between outcomes of different PCR assays, none of the assays detected all parasite-positive individuals. For all assays doubling filter paper material for DNA extraction increased sensitivity. The concentration of cell and antibody material was not homogenously distributed throughout blood spots., Conclusion: Combined DNA extraction and antibody elution is an operationally attractive approach for high throughput assessment of cumulative malaria exposure and current infection prevalence in endemic settings. Estimates of antibody prevalence are unaffected by the combined extraction and elution procedure. The choice of target gene and the amount and source of filter paper material for DNA extraction can have a marked impact on PCR sensitivity.

Background: Malaria remains a public health problem in Kenya despite several concerted control efforts. Empirical evidence regarding malaria effects in Kenya suggests that the disease imposes substantial economic costs, jeopardizing the achievement of sustainable development goals. The Kenya Malaria Strategy (2019–2023), which is currently being implemented, is one of several sequential malaria control and elimination strategies. The strategy targets reducing malaria incidences and deaths by 75% of the 2016 levels by 2023 through spending around Kenyan Shillings 61.9 billion over 5 years. This paper assesses the economy-wide implications of implementing this strategy. Methods: An economy-wide simulation model is calibrated to a comprehensive 2019 database for Kenya, considering different epidemiological zones. Two scenarios are simulated with the model. The first scenario (GOVT) simulates the annual costs of implementing the Kenya Malaria Strategy by increasing government expenditure on malaria control and elimination programmes. The second scenario (LABOR) reduces malaria incidences by 75% in all epidemiological malaria zones without accounting for the changes in government expenditure, which translates into rising the household labour endowment (benefits of the strategy). Results: Implementing the Kenya Malaria Strategy (2019–2023) enhances gross domestic product at the end of the strategy implementation period due to more available labour. In the short term, government health expenditure (direct malaria costs) increases significantly, which is critical in controlling and eliminating malaria. Expanding the health sector raises the demand for production factors, such as labour and capital. The prices for these factors rise, boosting producer and consumer prices of non-health-related products. Consequently, household welfare decreases during the strategy implementation period. In the long run, household labour endowment increases due to reduced malaria incidences and deaths (indirect malaria costs). However, the size of the effects varies across malaria epidemiological and agroecological zones depending on malaria prevalence and factor ownership. Conclusions: This paper provides policymakers with an ex-ante assessment of the implications of malaria control and elimination on household welfare across various malaria epidemiological zones. These insights assist in developing and implementing related policy measures that reduce the undesirable effects in the short run. Besides, the paper supports an economically beneficial long-term malaria control and elimination effect. [ABSTRACT FROM AUTHOR]

Background: Ivermectin (IVM) mass drug administration is a candidate complementary malaria vector control tool. Ingestion of blood from IVM treated hosts results in reduced survival in mosquitoes. Estimating bio-efficacy of IVM on wild-caught mosquitoes requires they ingest the drug in a blood meal either through a membrane or direct feeding on a treated host. The latter, has ethical implications, and the former results in low feeding rates. Therefore, there is a need to develop a safe and effective method for IVM bio-efficacy monitoring in wild mosquitoes. Methods: Insectary-reared Anopheles gambiae s.s. were exposed to four IVM doses: 85, 64, 43, 21 ng/ml, and control group (0 ng/ml) in three different solutions: (i) blood, (ii) 10% glucose, (iii) four ratios (1:1, 1:2, 1:4, 1:8) of blood in 10% glucose, and fed through filter paper. Wild-caught An. gambiae s.l. were exposed to 85, 43 and 21 ng/ml IVM in blood and 1:4 ratio of blood-10% glucose mixture. Survival was monitored for 28 days and a pool of mosquitoes from each cohort sacrificed immediately after feeding and weighed to determine mean weight of each meal type. Results: When administered in glucose solution, mosquitocidal effect of IVM was not comparable to the observed effects when similar concentrations were administered in blood. Equal concentrations of IVM administered in blood resulted in pronounced reductions in mosquito survival compared to glucose solution only. However, by adding small amounts of blood to glucose solution, mosquito mortality rates increased resulting in similar effects to what was observed during blood feeding. Conclusion: Bio-efficacy of ivermectin is strongly dependent on mode of drug delivery to the mosquito and likely influenced by digestive processes. The assay developed in this study is a good candidate for field-based bio-efficacy monitoring: wild mosquitoes readily feed on the solution, the assay can be standardized using pre-selected concentrations and by not involving treated blood hosts (human or animal) variation in individual pharmacokinetic profiles as well as ethical issues are bypassed. Meal volumes did not explain the difference in the lethality of IVM across the different meal types necessitating further research on the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: In malaria serology analysis, the standard approach to obtain seroprevalence, i.e the proportion of seropositive individuals in a population, is based on a threshold which is used to classify individuals as seropositive or seronegative. The choice of this threshold is often arbitrary and is based on methods that ignore the age-dependency of the antibody distribution., Methods: Using cross-sectional antibody data from the Western Kenyan Highlands, this paper introduces a novel approach that has three main advantages over the current threshold-based approach: it avoids the use of thresholds; it accounts for the age dependency of malaria antibodies; and it allows us to propagate the uncertainty from the classification of individuals into seropositive and seronegative when estimating seroprevalence. The reversible catalytic model is used as an example for illustrating how to propagate this uncertainty into the parameter estimates of the model., Results: This paper finds that accounting for age-dependency leads to a better fit to the data than the standard approach which uses a single threshold across all ages. Additionally, the paper also finds that the proposed threshold-free approach is more robust against the selection of different age-groups when estimating seroprevalence., Conclusion: The novel threshold-free approach presented in this paper provides a statistically principled and more objective approach to estimating malaria seroprevalence. The introduced statistical framework also provides a means to compare results across studies which may use different age ranges for the estimation of seroprevalence., (© 2021. The Author(s).)

Background: Health workers' knowledge deficiencies about artesunate-based severe malaria treatment recommendations have been reported. However, predictors of the treatment knowledge have not been examined. In this paper, predictors of artesunate-based treatment knowledge among inpatient health workers in two hospital sectors in Kenya are reported., Methods: Secondary analysis of 367 and 330 inpatient health workers randomly selected and interviewed at 47 government hospitals in 2016 and 43 faith-based hospitals in 2017 respectively, was undertaken. Multilevel ordinal and binary logistic regressions examining the effects of 11 factors on five knowledge outcomes in government and faith-based hospital sectors were performed., Results: Among respective government and faith-based health workers, about a third of health workers had high knowledge of artesunate treatment policies (30.8% vs 32.9%), a third knew all dosing intervals (33.5% vs 33.3%), about half knew preparation solutions (49.9% vs 55.8%), half to two-thirds knew artesunate dose for both weight categories (50.8% vs 66.7%) and over three-quarters knew the preferred route of administration (78.7% vs 82.4%). Eight predictors were significantly associated with at least one of the examined knowledge outcomes. In the government sector, display of artesunate administration posters, paediatric ward allocation and repeated surveys were significantly associated with more than one of the knowledge outcomes. In the faith-based hospitals, availability of artesunate at hospitals and health worker pre-service training were associated with multiple outcomes. Exposure to in-service malaria case-management training and access to malaria guidelines were only associated with higher knowledge about artesunate treatment policy., Conclusion: Programmatic interventions ensuring display of artesunate administration posters in the wards, targeting of health workers managing adult patients in the medical wards, and repeated knowledge assessments are likely to be beneficial for improving the knowledge of government health workers about artesunate-based severe malaria treatment recommendations. The availability of artesunate and focus on improvements of nurses' knowledge should be prioritized at the faith-based hospitals.

Background: Malaria transmission is high in western Kenya and the asymptomatic infected population plays a significant role in driving the transmission. Mathematical modelling and simulation programs suggest that interventions targeting asymptomatic infections through mass testing and treatment (MTaT) or mass drug administration (MDA) have the potential to reduce malaria transmission when combined with existing interventions., Objective: This paper describes the study site, capacity development efforts required, and lessons learned for implementing a multi-year community-based cluster-randomized controlled trial to evaluate the impact of MTaT for malaria transmission reduction in an area of high transmission in western Kenya., Methods: The study partnered with Kenya's Ministry of Health (MOH) and other organizations on community sensitization and engagement to mobilize, train and deploy community health volunteers (CHVs) to deliver MTaT in the community. Within the health facilities, the study availed staff, medical and laboratory supplies and strengthened health information management system to monitor progress and evaluate impact of intervention., Results: More than 80 Kenya MOH CHVs, 13 clinical officers, field workers, data and logistical staff were trained to carry out MTaT three times a year for 2 years in a population of approximately 90,000 individuals. A supply chain management was adapted to meet daily demands for large volumes of commodities despite the limitation of few MOH facilities having ideal storage conditions. Modern technology was adapted more to meet the needs of the high daily volume of collected data., Conclusions: In resource-constrained settings, large interventions require capacity building and logistical planning. This study found that investing in relationships with the communities, local governments, and other partners, and identifying and equipping the appropriate staff with the skills and technology to perform tasks are important factors for success in delivering an intervention like MTaT.

Background: In Kenya, infant mortality rate increased from 59 deaths per 1000 live births in 1988 to 78 deaths per 1000 live births by 2003. This was an increase of about 32 percent in 15 years. The reasons behind this upturn are poorly understood. This paper investigates the probable factors behind the upsurge in infant mortality in Kenya during the 1988-2003 period. Understanding the causes behind the upsurge is critical in designing high impact public health strategies for the acceleration of national and international public health goals such as the Millennium Development Goals (MDGs). The reversals in early child mortality is also regarded as one of the most important topics in contemporary demography. Methods: A merged dataset drawn from the Kenya Demographic and Health Surveys of 1993, 1998 and 2003 was used. The merged KDHS included a total of 5265 singletons. Permission to use the KDHS data was obtained from ICF international on the following website: http://www.measuredhs.com. Stata version 11.0 was used for data analysis. The paper used regression decomposition techniques as the main method for analysing the contribution of the selected covariates on the upsurge in infant mortality. Results: The duration of breastfeeding; maternal education, regional HIV prevalence and malaria endemicity were the factors that appeared to have contributed much to the observed rise in infant mortality in Kenya over the period. If all the live births that occurred in the 1996/03 period had the same mean values of all explanatory variables as those of live births that occurred in the 1988/95 period, then infant mortality would have increased by a massive 14 deaths per 1000 live births. However, if the live births that occurred in the 1988/95 period had the same mean values of all explanatory variables as those that occurred in the 1996/03 period, the upsurge in infant mortality would have been negligible. While the role of HIV in the upturn in infant mortality in Kenya and other sub Saharan African countries is indisputable, this study demonstrates that it is the duration of breastfeeding and Malaria endemicity that played a more significant role in Kenya's upsurge in infant mortality during the 1988-2003 period. Conclusions: Efforts aimed at controlling and preventing malaria and HIV should be stepped up to avert an upsurge in infant mortality. There is need to step up alternative baby feeding practices among mothers who are HIV positive especially after the first six months of breastfeeding. Owing to the widely known inverse relationship between maternal education and infant mortality, there is need for concerted efforts to promote girl child education. Owing to the important role played by the short preceding birth interval to the upsurge in infant mortality, there is need to promote family planning methods in Kenya. [ABSTRACT FROM AUTHOR]

Background: Vector surveillance is among the World Health Organization global vector control response (2017–2030) pillars. Human landing catches are a gold standard but difficult to implement and potentially expose collectors to malaria infection. Other methods like light traps, pyrethrum spray catches and aspiration are less expensive and less risky to collectors. Methods: Three mosquito sampling methods (UV light traps, CDC light traps and Prokopack aspiration) were evaluated against human landing catches (HLC) in two villages of Rarieda sub-county, Siaya County, Kenya. UV-LTs, CDC-LTs and HLCs were conducted hourly between 17:00 and 07:00. Aspiration was done indoors and outdoors between 07:00 and 11:00 a.m. Analyses of mosquito densities, species abundance and sporozoite infectivity were performed across all sampling methods. Species identification PCR and ELISAs were done for Anopheles gambiae and Anopheles funestus complexes and data analysis was done in R. Results: Anopheles mosquitoes sampled from 608 trapping efforts were 5,370 constituting 70.3% Anopheles funestus sensu lato (s.l.), 19.7% Anopheles coustani and 7.2% An. gambiae s.l. 93.8% of An. funestus s.l. were An. funestus sensu stricto (s.s.) and 97.8% of An. gambiae s.l. were Anopheles arabiensis. Only An. funestus were sporozoite positive with 3.1% infection prevalence. Indoors, aspiration captured higher An. funestus (mean = 6.74; RR = 8.83, P < 0.001) then UV-LT (mean = 3.70; RR = 3.97, P < 0.001) and CDC-LT (mean = 1.74; RR = 1.89, P = 0.03) compared to HLC. UV-LT and CDC-LT indoors captured averagely 0.18 An. arabiensis RR = 5.75, P = 0.028 and RR = 5.87, P = 0.028 respectively. Outdoors, UV-LT collected significantly higher Anopheles mosquitoes compared to HLC (An. funestus: RR = 5.18, P < 0.001; An. arabiensis: RR = 15.64, P = 0.009; An. coustani: RR = 11.65, P < 0.001). Anopheles funestus hourly biting indoors in UV-LT and CDC-LT indicated different peaks compared to HLC. Conclusions: Anopheles funestus remains the predominant mosquito species. More mosquitoes were collected using aspiration, CDC-LTs and UV-LTs indoors and UV-LTs and CD-LTs outdoors compared to HLCs. UV-LTs collected more mosquitoes than CDC-LTs. The varied trends observed at different times of the night suggest that these methods collect mosquitoes with diverse activities and care must be taken when interpreting the results. [ABSTRACT FROM AUTHOR]

Background: Understanding of malaria ecology is a prerequisite for designing locally adapted control strategies in resource-limited settings. The aim of this study was to utilize the spatial heterogeneity in malaria transmission for the designing of adaptive interventions. Methods: Field collections of clinical malaria incidence, asymptomatic Plasmodium infection, and malaria vector data were conducted from 108 randomly selected clusters which covered different landscape settings including irrigated farming, seasonal flooding area, lowland dryland farming, and highlands in western Kenya. Spatial heterogeneity of malaria was analyzed and classified into different eco-epidemiological zones. Results: There was strong heterogeneity and detected hot/cold spots in clinical malaria incidence, Plasmodium prevalence, and vector abundance. The study area was classified into four zones based on clinical malaria incidence, parasite prevalence, vector density, and altitude. The two irrigated zones have either the highest malaria incidence, parasite prevalence, or the highest malaria vector density; the highlands have the lowest vector density and parasite prevalence; and the dryland and flooding area have the average clinical malaria incidence, parasite prevalence and vector density. Different zones have different vector species, species compositions and predominant species. Both indoor and outdoor transmission may have contributed to the malaria transmission in the area. Anopheles gambiae sensu stricto (s.s.), Anopheles arabiensis, Anopheles funestus s.s., and Anopheles leesoni had similar human blood index and malaria parasite sporozoite rate. Conclusion: The multi-transmission-indicator-based eco-epidemiological zone classifications will be helpful for making decisions on locally adapted malaria interventions. [ABSTRACT FROM AUTHOR]

Background: In the Lake Victoria basin of western Kenya, malaria remains highly endemic despite high coverage of interventions such as mass distribution of long-lasting insecticidal nets (LLIN), indoor residual spraying (IRS) programs, and improvement of availability and accessibility of rapid diagnostic tests (RDT) and artemisinin-based combination therapy (ACT) at community healthcare facilities. We hypothesize that one major cause of the residual transmission is the lack of motivation among residents for malaria prevention and early treatment. Methods: This study will aim to develop a demand-side policy tool to encourage local residents' active malaria prevention and early treatment-seeking behaviors. We examine the causal impact of a financial incentive intervention complemented with malaria education to residents in malaria-prone areas. A cluster-randomized controlled trial is designed to assess the effect of the financial incentive intervention on reducing malaria prevalence in residents of Suba South in Homa Bay County, Kenya. The intervention includes two components. The first component is the introduction of a financial incentive scheme tied to negative RDT results for malaria infection among the target population. This study is an attempt to promote behavioral changes in the residents by providing them with monetary incentives. The project has two different forms of incentive schemes. One is a conditional cash transfer (CCT) that offers a small reward (200 Ksh) for non-infected subjects during the follow-up survey, and the other is a lottery incentive scheme (LIS) that gives a lottery with a 10% chance of winning a large reward (2000 Ksh) instead of the small reward. The second component is a knowledge enhancement with animated tablet-based malaria educational material (EDU) developed by the research team. It complements the incentive scheme by providing the appropriate knowledge to the residents for malaria elimination. We evaluate the intervention's impact on the residents' malaria prevalence using a cluster-randomized control trial. Discussion: A policy tool to encourage active malaria prevention and early treatment to residents in Suba South, examined in this trial, may benefit other malaria-endemic counties and be incorporated as part of Kenya's national malaria elimination strategy. Trial registration: UMIN000047728. Registered on 29th July 2022. [ABSTRACT FROM AUTHOR]

Background: Insecticide-treated nets (ITNs) contributed significantly to the decline in malaria since 2000. Their protective efficacy depends not only on access, use, and net integrity, but also location of people within the home environment and mosquito biting profiles. Anopheline mosquito biting and human location data were integrated to identify potential gaps in protection and better understand malaria transmission dynamics in Busia County, western Kenya. Methods: Direct observation of human activities and human landing catches (HLC) were performed hourly between 1700 to 0700 h. Household members were recorded as home or away; and, if at home, as indoors/outdoors, awake/asleep, and under a net or not. Aggregated data was analysed by weighting hourly anopheline biting activity with human location. Standard indicators of human-vector interaction were calculated using a Microsoft Excel template. Results: There was no significant difference between indoor and outdoor biting for Anopheles gambiae sensu lato (s.l.) (RR = 0.82; 95% CI 0.65–1.03); significantly fewer Anopheles funestus were captured outdoors than indoors (RR = 0.41; 95% CI 0.25–0.66). Biting peaked before dawn and extended into early morning hours when people began to awake and perform routine activities, between 0400–0700 h for An. gambiae and 0300–0700 h for An. funestus. The study population away from home peaked at 1700–1800 h (58%), gradually decreased and remained constant at 10% throughout the night, before rising again to 40% by 0600–0700 h. When accounting for resident location, nearly all bites within the peri-domestic space (defined as inside household structures and surrounding outdoor spaces) occurred indoors for unprotected people (98%). Using an ITN while sleeping was estimated to prevent 79% and 82% of bites for An. gambiae and An. funestus, respectively. For an ITN user, most remaining exposure to bites occurred indoors in the hours before bed and early morning. Conclusion: While use of an ITN was estimated to prevent most vector bites in this context, results suggest gaps in protection, particularly in the early hours of the morning when biting peaks and many people are awake and active. Assessment of additional human exposure points, including outside of the peri-domestic setting, are needed to guide supplementary interventions for transmission reduction. [ABSTRACT FROM AUTHOR]

Background: Malaria imposes significant costs on households and the poor are disproportionately affected. However, cost data are often from quantitative surveys with a fixed recall period. They do not capture costs that unfold slowly over time, or seasonal variations. Few studies investigate the different pathways through which malaria contributes towards poverty. In this paper, a framework indicating the complex links between malaria, poverty and vulnerability at the household level is developed and applied using data from rural Kenya. Methods: Cross-sectional surveys in a wet and dry season provide data on treatment-seeking, cost-burdens and coping strategies (n = 294 and n = 285 households respectively). 15 case study households purposively selected from the survey and followed for one year provide in-depth qualitative information on the links between malaria, vulnerability and poverty. Results: Mean direct cost burdens were 7.1% and 5.9% of total household expenditure in the wet and dry seasons respectively. Case study data revealed no clear relationship between cost burdens and vulnerability status at the end of the year. Most important was household vulnerability status at the outset. Households reporting major malaria episodes and other shocks prior to the study descended further into poverty over the year. Wealthier households were better able to cope. Conclusion: The impacts of malaria on household economic status unfold slowly over time. Coping strategies adopted can have negative implications, influencing household ability to withstand malaria and other contingencies in future. To protect the poor and vulnerable, malaria control policies need to be integrated into development and poverty reduction programmes. [ABSTRACT FROM AUTHOR]

Background: Health in low and middle income countries is on one hand characterized by a high burden associated with preventable communicable diseases and on the other hand considered to be under-documented due to improper basic health and demographic record-keeping. health and demographic surveillance systems (HDSSs) have provided researchers, policy makers and governments with data about local population dynamics and health related information. In order for an HDSS to deliver high quality data, effective organization of data collection and management are vital. HDSSs impose a challenging logistical process typically characterized by door to door visits, poor navigational guidance, conducting interviews recorded on paper, error prone data entry, an extensive staff and marginal data quality management possibilities., Methods: A large trial investigating the effect of odour-baited mosquito traps on malaria vector populations and malaria transmission on Rusinga Island, western Kenya, has deployed an HDSS. By means of computer tablets in combination with Open Data Kit and OpenHDS data collection and management software experiences with time efficiency, cost effectiveness and high data quality are illustrate. Step by step, a complete organization of the data management infrastructure is described, ranging from routine work in the field to the organization of the centralized data server., Results and Discussion: Adopting innovative technological advancements has enabled the collection of demographic and malaria data quickly and effectively, with minimal margin for errors. Real-time data quality controls integrated within the system can lead to financial savings and a time efficient work flow., Conclusion: This novel method of HDSS implementation demonstrates the feasibility of integrating electronic tools in large-scale health interventions.

Background: Patients' low adherence to artemisinin-based combination therapy has been reported in areas of Kenya bordering the Lake Victoria region, where the burden of malaria remains high. A randomized controlled trial is underway to determine the efficacy of short message service (SMS) text reminders on adherence to artemether-lumefantrine and post-treatment review of children under the age of five. This paper reports on the iterative process of intervention and delivery system development., Methods: An intervention development workshop involving the research team and other stakeholders was held to determine the content of the text messages. Three focus group discussions were conducted to test caregivers' understanding of the messages developed during the workshop. The tested messages were refined and incorporated into an automated SMS distribution system and piloted with 20 caregivers drawn from facilities neighbouring the study sites. The automated SMS distribution system was repeatedly refined following the pilot and implemented at the start of the trial., Results: The content of SMS messages underwent major revisions following the focus group discussions. Technical terms and abbreviations were replaced with simplified general terms. Message sign-off was modified to reflect the name of health facility, removing references to health workers. Day 3 post-treatment review visit reminder was modified to state the purpose of the visit while wording 'day 28' was added to the last post-treatment review visit reminder to help the caregiver recall the appointment date. The unscheduled visit prompt was modified to reflect flexibility and practicality of taking the child back to the facility if unwell. Reception of SMS reminders during the pilot was low with only 169/240 (70%) of scheduled messages delivered to the caregivers. The automated distribution system underwent major refinement and repeated testing following the pilot until effective delivery of all scheduled messages was achieved and sustained over a period of 3 months., Conclusions: Text message interventions should be carefully developed, tested and refined before implementation to ensure they are written in the most appropriate way for their target population. SMS distribution systems should be rigorously tested to ensure efficient delivery of the messages before they are deployed.

Background: Timely molecular surveillance of Plasmodium falciparum kelch 13 (k13) gene mutations is essential for monitoring the emergence and stemming the spread of artemisinin resistance. Widespread artemisinin resistance, as observed in Southeast Asia, would reverse significant gains that have been made against the malaria burden in Africa. The purpose of this study was to assess the prevalence of k13 polymorphisms in western Kenya and Ethiopia at sites representing varying transmission intensities between 2018 and 2022. Methods: Dried blood spot samples collected through ongoing passive surveillance and malaria epidemiological studies, respectively, were investigated. The k13 gene was genotyped in P. falciparum isolates with high parasitaemia: 775 isolates from four sites in western Kenya (Homa Bay, Kakamega, Kisii, and Kombewa) and 319 isolates from five sites across Ethiopia (Arjo, Awash, Gambella, Dire Dawa, and Semera). DNA sequence variation and neutrality were analysed within each study site where mutant alleles were detected. Results: Sixteen Kelch13 haplotypes were detected in this study. Prevalence of nonsynonymous k13 mutations was low in both western Kenya (25/783, 3.19%) and Ethiopia (5/319, 1.57%) across the study period. Two WHO-validated mutations were detected: A675V in three isolates from Kenya and R622I in four isolates from Ethiopia. Seventeen samples from Kenya carried synonymous mutations (2.17%). No synonymous mutations were detected in Ethiopia. Genetic variation analyses and tests of neutrality further suggest an excess of low frequency polymorphisms in each study site. Fu and Li's F test statistic in Semera was 0.48 (P > 0.05), suggesting potential population selection of R622I, which appeared at a relatively high frequency (3/22, 13.04%). Conclusions: This study presents an updated report on the low frequency of k13 mutations in western Kenya and Ethiopia. The WHO-validated R622I mutation, which has previously only been reported along the north-west border of Ethiopia, appeared in four isolates collected from eastern Ethiopia. The rapid expansion of R622I across Ethiopia signals the need for enhanced monitoring of the spread of drug-resistant P. falciparum parasites in East Africa. Although ACT remains currently efficacious in the study areas, continued surveillance is necessary to detect early indicators of artemisinin partial resistance. [ABSTRACT FROM AUTHOR]

Background: Children in Kenya spend a substantial amount of time at school, including at dawn and dusk when mosquitoes are active. With changing vector behaviour towards early morning biting, it is important to determine whether there is an additional risk of transmission in schools. This study sought to understand whether late morning biting by Anopheles funestus, previously documented in households in western Kenya, was replicated in schools. Methods: From the 4th to the 6th of August 2023, human landing collections were conducted hourly in four schools in Alego Usonga sub-County, Siaya County. The collections were conducted in and outside five classrooms in each school and ran for 17 h, starting at 18:00 until 11:00 h the next morning. Results: Anopheles funestus was the predominant species collected, forming 93.2% (N = 727) of the entire collection, with peak landing between 06:00 and 07:00 h and continuing until 11:00 h. More than half of the collected An. funestus were either fed or gravid, potentially indicative of multiple bloodmeals within each gonotrophic cycle, and had a sporozoite rate of 2.05%. Conclusion: School children spend up to 10 h of their daytime in schools, reporting between 06:00 and 07:00 h and staying in school until as late as 17:00 h, meaning that they receive potentially infectious mosquito bites during the morning hours in these settings. There is a need to consider vector control approaches targeting schools and other peridomestic spaces in the morning hours when An. funestus is active. [ABSTRACT FROM AUTHOR]

Background: A major unresolved safety concern for malaria case management is the use of artemisinin combination therapies (ACTs) in the first trimester of pregnancy. There is a need for human data to inform policy makers and treatment guidelines on the safety of artemisinin combination therapies (ACT) when used during early pregnancy. Methods: The overall goal of this paper is to describe the methods and implementation of a study aimed at developing surveillance systems for identifying exposures to antimalarials during early pregnancy and for monitoring pregnancy outcomes using health and demographic surveillance platforms. This was a multi-center prospective observational cohort study involving women at health and demographic surveillance sites in three countries in Africa: Burkina Faso, Kenya and Mozambique [(ClinicalTrials.gov Identifier: NCT01232530)]. The study was designed to identify pregnant women with artemisinin exposure in the first trimester and compare them to: 1) pregnant women without malaria, 2) pregnant women treated for malaria, but exposed to other antimalarials, and 3) pregnant women with malaria and treated with artemisinins in the 2nd or 3rd trimesters from the same settings. Pregnant women were recruited through community-based surveys and attendance at health facilities, including antenatal care clinics and followed until delivery. Data from the three sites will be pooled for analysis at the end of the study. Results are forthcoming. Discussion: Despite few limitations, the methods described here are relevant to the development of sustainable pharmacovigilance systems for drugs used by pregnant women in the tropics using health and demographic surveillance sites to prospectively ascertain drug safety in early pregnancy. Trial registration: NCT01232530 [ABSTRACT FROM AUTHOR]

Background: Monitoring and evaluation of malaria programmes may require a combination of approaches to detect any effects of control. This is particularly true at lower transmission levels where detecting both infection and exposure to infection will provide additional evidence of any change. This paper describes use of three transmission metrics to explore the malaria epidemiology in the highlands of western Kenya. Methods: A malariometric survey was conducted in June 2009 in two highland districts, Kisii and Rachuonyo South, Nyanza Province, Kenya using a cluster design. Enumeration areas were used to sample 46 clusters from which 12 compounds were randomly sampled. Individuals provided a finger-blood sample to assess malaria infection (rapid diagnostic test, PCR) and exposure (anti-Plasmodium falciparum MSP-1 antibodies) and a questionnaire was administered to record household factors and assess use of vector control interventions. Results: Malaria prevalence infection rates were 3.0 % (95 % CI 2.2–4.2 %) by rapid diagnostic test (RDT) and 8.5 % (95 % CI 7.0–10.4 %) by PCR and these ranged from 0–13.1 to 0–14.8 % between clusters for RDT and PCR, respectively. Seroprevalence was 36.8 % (95 % CI 33.9–39.8) ranging from 18.6 to 65.8 %. Both RDT and PCR prevalences were highest in children aged 5–10 years but the proportion of infections that were sub-patent was highest in those between 15 and 20 years of age (78.1 %, 95 % CI 63.0–93.3 %) and those greater than 20 years (73.3 %, 95 % CI 64.5– 81.9 %). Those reporting both indoor residual spraying (IRS) in their home and use of bed nets had lower exposure to malaria compared to those who reported using IRS or bed nets alone. Conclusions: In this highland site in western Kenya malaria transmission was low, but highly heterogeneous. To accurately characterize the true extent of malaria transmission, more sensitive and complementary metrics such as PCR or serology are required in addition to the standard microscopy and/or RDTs that are routinely used. This is likely to be the case in other low endemicity settings. [ABSTRACT FROM AUTHOR]

Background: Malaria prevalence in Kenya is 6%, with a three-fold higher prevalence in western Kenya. Adherence to malaria treatment guidelines improves care for suspected malaria cases and can reduce unnecessary anti-malarial use. Data on adherence to guidelines in retail drug outlets (DOs) is limited, yet approximately 50% of people with fever access treatment first in these outlets. This study assessed adherence to the national malaria treatment guidelines among DOs in a high transmission area of Western Kenya. Methods: In a cross-sectional survey of DOs in Kisumu Central and Seme sub-counties in 2021, DO staff were interviewed using structured questionnaires to assess outlet characteristics (location, testing services), staff demographics (age, sex, training), and health system context (supervision, inspection). Mystery shoppers (research assistants disguised as clients) observed malaria management practices and recorded observations on a standardized tool. Adherence was defined as dispensing artemether-lumefantrine (AL) to patients with a confirmed positive test, accompanied by appropriate medication counseling. Logistic regression was used to test for association between adherence to guidelines and DO-related factors. Results: None of the 70 DOs assessed had a copy of the guidelines, and 60 (85.7%) were in an urban setting. Staff adhered to the guidelines in 14 (20%) outlets. The odds of adherence were higher among staff who had a bachelor's degree {odds ratio (OR) 6.0, 95% confidence interval (95% CI) 1.66–21.74}, those trained on malaria rapid diagnostic test (RDT) {OR 4.4, 95% CI 1.29–15.04}, and those who asked about patient's symptoms {OR 3.6, 95% CI 1.08–12.25}. DOs that had higher odds of adherence included those with functional thermometers {OR 5.3, 95% CI 1.46–19.14}, those recently inspected (within three months) by Pharmacy and Poisons Board (PPB) {OR 9.4, 95% CI 2.55–34.67}, and those with all basic infrastructure {OR 3.9, 95% CI 1.01–15.00}. On logistic regression analysis, recent PPB inspection {adjusted OR (AOR) 4.6, 95% CI 1.03–20.77} and malaria RDT-trained staff (aOR 4.5, 95% CI 1.02–19.84) were independently associated with adherence. Conclusion: Most outlets didn't adhere to malaria guidelines. Regular interaction with regulatory bodies could improve adherence. Ministry of Health should enhance private sector engagement and train DOs on RDT use. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization approved the RTS,S/AS01 malaria vaccine for wider rollout, and Kenya participated in a phased pilot implementation from 2019 to understand its impact under routine conditions. Vaccine delivery requires coverage measures at national and sub-national levels to evaluate progress over time. This study aimed to estimate the coverage of the RTS,S/AS01 vaccine during the first 36 months of the Kenyan pilot implementation. Methods: Monthly dose-specific immunization data for 23 sub-counties were obtained from routine health information systems at the facility level for 2019–2022. Coverage of each RTS,S/AS01 dose was determined using reported doses as a numerator and service-based (Penta 1 and Measles) or population (projected infant populations from WorldPop) as denominators. Descriptive statistics of vaccine delivery, dropout rates and coverage estimates were computed across the 36-month implementation period. Results: Over 36 months, 818,648 RTSS/AS01 doses were administered. Facilities managed by the Ministry of Health and faith-based organizations accounted for over 88% of all vaccines delivered. Overall, service-based malaria vaccine coverage was 96%, 87%, 78%, and 39% for doses 1–4 respectively. Using a population-derived denominator for age-eligible children, vaccine coverage was 78%, 68%, 57%, and 24% for doses 1–4, respectively. Of the children that received measles dose 1 vaccines delivered at 9 months (coverage: 95%), 82% received RTSS/AS01 dose 3, only 66% of children who received measles dose 2 at 18 months (coverage: 59%) also received dose 4. Conclusion: The implementation programme successfully maintained high levels of coverage for the first three doses of RTSS/AS01 among children defined as EPI service users up to 9 months of age but had much lower coverage within the community with up to 1 in 5 children not receiving the vaccine. Consistent with vaccines delivered over the age of 1 year, coverage of the fourth malaria dose was low. Vaccine uptake, service access and dropout rates for malaria vaccines require constant monitoring and intervention to ensure maximum protection is conferred. [ABSTRACT FROM AUTHOR]

Background: The demonstration that the recently discovered Anopheles symbiont Microsporidia MB blocks malaria transmission in Anophelesarabiensis and undergoes vertical and horizontal transmission suggests that it is a promising candidate for the development of a symbiont-based malaria transmission-blocking strategy. The infection prevalence and characteristics of Microsporidia MB in Anopheles gambiae sensu stricto (s.s.), another primary vector species of malaria in Kenya, were investigated. Methods: Field-collected females were confirmed to be Microsporidia MB-positive after oviposition. Egg counts of Microsporidia MB-infected and non-infected individuals were used to infer the effects of Microsporidia MB on fecundity. The time to pupation, adult sex ratio and survival were used to determine if Microsporidia MB infection has similar characteristics in the host mosquitoes An. gambiae and An. arabiensis. The intensity of Microsporidia MB infection in tissues of the midgut and gonads, and in carcasses, was determined by quantitative polymerase chain reaction. To investigate horizontal transmission, virgin males and females that were either Microsporidia MB-infected or non-infected were placed in standard cages for 48 h and allowed to mate; transmission was confirmed by quantitative polymerase chain reaction targeting Microsporidia MB genes. Results: Microsporidia MB was found to naturally occur at a low prevalence in An. gambiae s.s. collected in western Kenya. Microsporidia MB shortened the development time from larva to pupa, but other fitness parameters such as fecundity, sex ratio, and adult survival did not differ between Microsporidia MB-infected and non-infected hosts. Microsporidia MB intensities were high in the male gonadal tissues. Transmission experiments indicated that Microsporidia MB undergoes both maternal and horizontal transmission in An. gambiae s.s. Conclusions: The findings that Microsporidia MB naturally infects, undergoes maternal and horizontal transmission, and is avirulent in An. gambiae s.s. indicate that many of the characteristics of its infection in An. arabiensis hold true for the former. The results of the present study indicate that Microsporidia MB could be developed as a tool for the transmission-blocking of malaria across different Anopheles species. [ABSTRACT FROM AUTHOR]

Background: Centers for Disease Control and Prevention (CDC) light traps are widely used for sampling mosquitoes. However, this trap, manufactured in the USA, poses challenges for use in sub-Saharan Africa due to procurement costs and shipping time. Traps that are equally efficient than the CDC light trap, but which are amenable for use in remote African settings and made in Africa, are desirable to improve local vector surveillance. This study evaluated a novel solar-powered light trap made in South Africa (Silver Bullet trap; SB), for its efficiency in malaria vector sampling in western Kenya. Methods: Large cage (173.7 m3) experiments and field evaluations were conducted to compare the CDC-incandescent light trap (CDC-iLT), CDC-UV fluorescent tube light trap (CDC-UV), SB with white diodes (SB-White) and SB with UV diodes (SB-UV) for sampling Anopheles mosquitoes. Field assessments were done indoors and outdoors following a Latin square design. The wavelengths and absolute spectral irradiance of traps were compared using spectrometry. Results: The odds of catching a released Anopheles in the large cage experiments with the SB-UV under ambient conditions in the presence of a CDC-iLT in the same system was three times higher than what would have been expected when the two traps were equally attractive (odds ratio (OR) 3.2, 95% confidence interval CI 2.8–3.7, P < 0.01)). However, when the white light diode was used in the SB trap, it could not compete with the CDC-iLT (OR 0.56, 95% CI 0.48–0.66, p < 0.01) when the two traps were provided as choices in a closed system. In the field, the CDC and Silver Bullet traps were equally effective in mosquito sampling. Irrespective of manufacturer, traps emitting UV light performed better than white or incandescent light for indoor sampling, collecting two times more Anopheles funestus sensu lato (s.l.) (RR 2.5; 95% CI 1.7–3.8) and Anopheles gambiae s.l. (RR 2.5; 95% 1.7–3.6). Outdoor collections were lower than indoor collections and similar for all light sources and traps. Conclusions: The solar-powered SB trap compared well with the CDC trap in the field and presents a promising new surveillance device especially when charging on mains electricity is challenging in remote settings. [ABSTRACT FROM AUTHOR]

Background: Emergence of Plasmodium falciparum resistance to artemether-lumefantrine in Africa prompted the pilot introduction of multiple first-line therapies (MFT) against malaria in Kenya, potentially exposing women-of-childbearing-age (WOCBAs) to anti-malarials with unknown safety profiles in the first trimester. This qualitative study explored knowledge and perceptions among healthcare providers providing malaria treatment to WOCBAs and pregnant women. Methods: In-depth interviews were conducted with purposively selected public and private health facility (HF) and drug outlet (DO) providers within and outside the pilot-MFT area. County health managers were interviewed about their knowledge of the national treatment guidelines. Transcripts were coded by content analysis using the World Health Organization health system building blocks (leadership/governance, financing, health workforce, health information systems, access to medicines, and service delivery). Results: Thirty providers (HF:21, DO:9) and three health managers were interviewed. Eighteen providers were from HFs in the pilot-MFT area; the remaining three and all nine DOs were outside the pilot-MFT area. The analysis revealed that providers had not been trained in malaria case management in the previous twelve months. DO providers were unfamiliar with national treatment guidelines in pregnancy and reported having no pregnancy tests. Health managers were unable to supervise DOs due to resource limitations. Providers from HFs and DOs noted poor sensitivity of malaria rapid diagnostic tests (RDTs) and hesitancy among patients who associated malaria-RDTs with HIV testing. Almost all providers reported anti-malarial stock-outs, with quinine most affected. Patient preference was a major factor in prescribing anti-malarials. Providers in HFs and DOs reported preferentially using artemether-lumefantrine in the first trimester due to the side effects and unavailability of quinine. Conclusion: Knowledge of malaria case management in drug outlets and health facilities remains poor. Improved regulation of DO providers is warranted. Optimizing treatment of malaria in pregnancy requires training, availability of malaria commodities, and pregnancy tests. [ABSTRACT FROM AUTHOR]

Background: Concerns about emerging resistance to artemether-lumefantrine (AL) in Africa prompted the pilot introduction of multiple first-line therapies (MFT) in Western Kenya, potentially exposing women-of-childbearing-age (WOCBA) to anti-malarials with unknown safety profiles in the first trimester. The study assessed healthcare provider knowledge and adherence to national guidelines for managing malaria in pregnancy in the context of the MFT pilot. Methods: From March to April 2022, a cross-sectional study was conducted in 50 health facilities (HF) and 40 drug outlets (DO) using structured questionnaires to assess pregnancy detection, malaria diagnosis, and treatment choices by trimester. Differences between HF and DO providers and between MFT and non-MFT HFs were assessed using Chi-square tests. Results: Of 174 providers (77% HF, 23% DO), 56% were from MFT pilot facilities. Most providers had tertiary education; 5% HF and 20% DO had only primary or secondary education. More HF than DO providers had knowledge of malaria treatment guidelines (62% vs. 40%, p = 0.023), received training in malaria in pregnancy (49% vs. 20%, p = 0.002), and reported assessing for pregnancy in WOCBA (98% vs. 78%, p < 0.001). Most providers insisted on parasitological diagnosis, with 59% HF using microscopy and 85% DO using rapid diagnostic tests. More HF than DO providers could correctly name the drugs for treating uncomplicated malaria in the first trimester (oral quinine, or AL if quinine is unavailable) (90% vs. 58%, p < 0.001), second and third trimesters (artemisinin-based combination therapy) (84% vs. 70%, p = 0.07), and for severe malaria (parenteral artesunate/artemether) (94% vs. 60%, p < 0.001). Among HF providers, those in the MFT pilot had more knowledge of malaria treatment guidelines (67% vs. 49%, p = 0.08) and had received training on treatment of malaria in pregnancy (56% vs. 32%, p = 0.03). Few providers (10% HF and 12% DO) had adequate knowledge of malaria treatment in pregnancy, defined as the correct drug and dose for uncomplicated and severe malaria in all trimesters. Conclusions: Knowledge of national malaria in pregnancy treatment guidelines among providers in Western Kenya is suboptimal. Robust training on appropriate anti-malarial and dosage is needed, particularly given the recent change in recommendation for artemether-lumefantrine use in the first trimester. Supervision of DO and HF practices is essential for correct treatment of malaria in pregnancy in the context of MFT programmes. [ABSTRACT FROM AUTHOR]

Background: Malaria in pregnancy remains a major public health problem in endemic areas of the sub-Saharan African (SSA) region. However, there is limited understanding of the association between women's empowerment and the uptake of sulfadoxine–pyrimethamine for intermittent preventive treatment of malaria during pregnancy (IPTp-SP) in Kenya. This study examines the association between women's empowerment indicators (decision-making power, control of assets, education, and employment status) and the uptake of three or more doses of IPTp-SP in the Lake endemic region of Kenya. Methods: The analysis utilized a dataset from a cross-sectional baseline survey of 3129 women aged 15–49 years in Kisumu and Migori Counties who had a live birth within the last 2 years preceding the study. Data were collected between June to August 2021. A descriptive analysis was conducted to show the distribution of respondents by key background characteristics, and bivariate and multivariate logistic regression to examine statistically significant associations between women's empowerment measures and the uptake of 3+ doses of IPTp-SP. Results: Among the 3129 women surveyed, 1978 (65.7%) received 3+ doses of IPTp-SP during their most recent pregnancy. Controlling for individual characteristics and the number of ANC visits, the odds of taking 3+ doses of IPTp-SP increased among women who had high decision-making autonomy (AOR = 2.33; CI = 1.81–3.01; P < 0.001); and tertiary level of educational attainment (AOR = 1.51; CI = 1.10–2.06). However, the association between control of assets and uptake of IPTp-SP was positive but not statistically significant. Conclusion: Women's decision-making autonomy and educational attainment were positively associated with the uptake of IPTp-SP. As a result, maternal health interventions should focus on less empowered women, specifically those with less decision-making autonomy and no/low formal education, as they are less likely to achieve optimal uptake of IPTp-SP during pregnancy. [ABSTRACT FROM AUTHOR]

Background: The control of malaria in schools is receiving increasing attention, but there remains currently no consensus as to the optimal intervention strategy. This paper analyses the costs of intermittent screening and treatment (IST) of malaria in schools, implemented as part of a cluster-randomized controlled trial on the Kenyan coast., Methods: Financial and economic costs were estimated using an ingredients approach whereby all resources required in the delivery of IST are quantified and valued. Sensitivity analysis was conducted to investigate how programme variation affects costs and to identify potential cost savings in the future implementation of IST., Results: The estimated financial cost of IST per child screened is US$ 6.61 (economic cost US$ 6.24). Key contributors to cost were salary costs (36%) and malaria rapid diagnostic tests (RDT) (22%). Almost half (47%) of the intervention cost comprises redeployment of existing resources including health worker time and use of hospital vehicles. Sensitivity analysis identified changes to intervention delivery that can reduce programme costs by 40%, including use of alternative RDTs and removal of supervised treatment. Cost-effectiveness is also likely to be highly sensitive to the proportion of children found to be RDT-positive., Conclusion: In the current context, school-based IST is a relatively expensive malaria intervention, but reducing the complexity of delivery can result in considerable savings in the cost of intervention. (Costs are reported in US$ 2010).

Background: Widespread urbanization over the next 20 years has the potential to drastically change the risk of malaria within Africa. The burden of the disease, its management, risk factors and appropriateness of targeted intervention across varied urban environments in Africa remain largely undefined. This paper presents a combined historical and contemporary review of the clinical burden of malaria within one of Africa's largest urban settlements, Nairobi, Kenya., Methods: A review of historical reported malaria case burdens since 1911 within Nairobi was undertaken using archived government and city council reports. Contemporary information on out-patient case burdens due to malaria were assembled from the National Health Management and Information System (HMIS). Finally, an audit of 22 randomly selected health facilities within Nairobi was undertaken covering 12 months 2009-2010. The audit included interviews with health workers, and a checklist of commodities and guidelines necessary to diagnose, treat and record malaria., Results: From the 1930's through to the mid-1960's malaria incidence declined coincidental with rapid population growth. During this period malaria notification and prevention were a priority for the city council. From 2001-2008 reporting systems for malaria were inadequate to define the extent or distribution of malaria risk within Nairobi. A more detailed facility review suggests, however that malaria remains a common diagnosis (11% of all paediatric diagnoses made) and where laboratories (n = 15) exist slide positivity rates are on average 15%. Information on the quality of diagnosis, slide reading and whether those reported as positive were imported infections was not established. The facilities and health workers included in this study were not universally prepared to treat malaria according to national guidelines or identify foci of risks due to shortages of national first-line drugs, inadequate record keeping and a view among some health workers (17%) that slide negative patients could still have malaria., Conclusion: Combined with historical evidence there is a strong suggestion that very low risks of locally acquired malaria exist today within Nairobi's city limits and this requires further investigation. To be prepared for effective prevention and case-management of malaria among a diverse, mobile population in Nairobi requires a major paradigm shift and investment in improved quality of malaria diagnosis and case management, health system strengthening and case reporting.

Background: Prompt access to effective malaria treatment is central to the success of malaria control worldwide, but few fevers are treated with effective anti-malarials within 24 hours of symptoms onset. The last two decades saw an upsurge of initiatives to improve access to effective malaria treatment in many parts of sub-Saharan Africa. Evidence suggests that the poorest populations remain least likely to seek prompt and effective treatment, but the factors that prevent them from accessing interventions are not well understood. With plans under way to subsidize ACT heavily in Kenya and other parts of Africa, there is urgent need to identify policy actions to promote access among the poor. This paper explores access barriers to effective malaria treatment among the poorest population in four malaria endemic districts in Kenya., Methods: The study was conducted in the poorest areas of four malaria endemic districts in Kenya. Multiple data collection methods were applied including: a cross-sectional survey (n=708 households); 24 focus group discussions; semi-structured interviews with health workers (n=34); and patient exit interviews (n=359)., Results: Multiple factors related to affordability, acceptability and availability interact to influence access to prompt and effective treatment. Regarding affordability, about 40 percent of individuals who self-treated using shop-bought drugs and 42 percent who visited a formal health facility reported not having enough money to pay for treatment, and having to adopt coping strategies including borrowing money and getting treatment on credit in order to access care. Other factors influencing affordability were seasonality of illness and income sources, transport costs, and unofficial payments. Regarding acceptability, the major interrelated factors identified were provider patient relationship, patient expectations, beliefs on illness causation, perceived effectiveness of treatment, distrust in the quality of care and poor adherence to treatment regimes. Availability barriers identified were related to facility opening hours, organization of health care services, drug and staff shortages., Conclusions: Ensuring that all individuals suffering from malaria have prompt access to effective treatment remains a challenge for resource constrained health systems. Policy actions to address the multiple barriers of access should be designed around access dimensions, and should include broad interventions to revitalize the public health care system. Unless additional efforts are directed towards addressing access barriers among the poor and vulnerable, malaria will remain a major cause of morbidity and mortality in sub-Saharan Africa.

Background: In sub-Saharan Africa, knowledge of malaria transmission across rapidly proliferating urban centres and recommendations for its prevention or management remain poorly defined. This paper presents the results of an investigation into infection prevalence and treatment of recent febrile events among a slum population in Nairobi, Kenya., Methods: In July 2008, a community-based malaria parasite prevalence survey was conducted in Korogocho slum, which forms part of the Nairobi Urban Health and Demographic Surveillance system. Interviewers visited 1,069 participants at home and collected data on reported fevers experienced over the preceding 14 days and details on the treatment of these episodes. Each participant was tested for malaria parasite presence with Rapid Diagnostic Test (RDT) and microscopy. Descriptive analyses were performed to assess the period prevalence of reported fever episodes and treatment behaviour., Results: Of the 1,069 participants visited, 983 (92%) consented to be tested. Three were positive for Plasmodium falciparum using RDT; however, all were confirmed negative on microscopy. Microscopic examination of all 953 readable slides showed zero prevalence. Overall, from the 1,004 participants who have data on fever, 170 fever episodes were reported giving a relatively high period prevalence (16.9%, 95% CI:13.9%-20.5%) and higher among children below five years (20.1%, 95%CI:13.8%-27.8%). Of the fever episodes with treatment information 54.3% (95%CI:46.3%-62.2%) were treated as malaria using mainly sulphadoxine-pyrimethamine or amodiaquine, including those managed at a formal health facility. Only four episodes were managed using the nationally recommended first-line treatment, artemether-lumefantrine., Conclusion: The study could not demonstrate any evidence of malaria in Korogocho, a slum in the centre of Nairobi. Fever was a common complaint and often treated as malaria with anti-malarial drugs. Strategies, including testing for malaria parasites to reduce the inappropriate exposure of poor communities to expensive anti-malarial drugs provided by clinical services and drug vendors, should be a priority for district planners.

Background: Awareness of the potential impact of malaria among school-age children has stimulated investigation into malaria interventions that can be delivered through schools. However, little evidence is available on the costs and cost-effectiveness of intervention options. This paper evaluates the costs and cost-effectiveness of intermittent preventive treatment (IPT) as delivered by teachers in schools in western Kenya., Methods: Information on actual drug and non-drug associated costs were collected from expenditure and salary records, government budgets and interviews with key district and national officials. Effectiveness data were derived from a cluster-randomised-controlled trial of IPT where a single dose of sulphadoxine-pyrimethamine and three daily doses of amodiaquine were provided three times in year (once termly). Both financial and economic costs were estimated from a provider perspective, and effectiveness was estimated in terms of anaemia cases averted. A sensitivity analysis was conducted to assess the impact of key assumptions on estimated cost-effectiveness., Results: The delivery of IPT by teachers was estimated to cost US$ 1.88 per child treated per year, with drug and teacher training costs constituting the largest cost components. Set-up costs accounted for 13.2% of overall costs (equivalent to US$ 0.25 per child) whilst recurrent costs accounted for 86.8% (US$ 1.63 per child per year). The estimated cost per anaemia case averted was US$ 29.84 and the cost per case of Plasmodium falciparum parasitaemia averted was US$ 5.36, respectively. The cost per case of anaemia averted ranged between US$ 24.60 and 40.32 when the prices of antimalarial drugs and delivery costs were varied. Cost-effectiveness was most influenced by effectiveness of IPT and the background prevalence of anaemia. In settings where 30% and 50% of schoolchildren were anaemic, cost-effectiveness ratios were US$ 12.53 and 7.52, respectively., Conclusion: This study provides the first evidence that IPT administered by teachers is a cost-effective school-based malaria intervention and merits investigation in other settings.

Plants in Kenya are becoming increasingly important as sources of traditional medicines. The World Health Organization (WHO) has estimated that malaria kills about 2.7 million people every year, 90% of who are from Africa. Malaria continues to be a national concern in Kenya as it plays a major role in the high mortality rates being experienced currently. The use and mis-use of chloroquine to prevent and treat falciparium malaria has led to widespread appearance of chloroquine resistant parasites in Kenya and other tropical countries. These factors and the rising costs of non-chloroquine drugs have made the local people to turn to traditional remedies for management of this menace. This paper examines the current utilization of traditional plant medicines in managing malaria menace in Central Kenya. The results show both indigenous and introduced species are in use indicating traditional medicinal practices in this region are dynamic. In total 58 species in 54 genera and 33 families were identified. The family Rubiaceae was found to have the highest number of reported species. Use of the various taxa is compared between five districts within Central Province of Kenya. The commonest species in this pharmacopoeia are: Caesalpinia volkensii Harms, Strychnos henningsii Gilg, Ajuga remota Benth., Warbugia ugandensis Sprague and Olea europaea L. The first three species are used in all the five districts while the others are restricted in some of the districts. In 74% of the anti-malarial plant species reported in this study, the remedies are obtained in destructive manner and may need conservation measures to ensure sustainable utilization. The results of this study become a basis for selecting plants for further pharmacological and phytochemical studies in developing new and locally relevant anti-malarial agents.

Background: There are a number of practical and ethical issues raised in school-based health research, particularly those related to obtaining consent from parents and assent from children. One approach to developing, strengthening, and supporting appropriate consent and assent processes is through community engagement. To date, much of the literature on community engagement in biomedical research has concentrated on community or hospital-based research, with little documentation, if any, of community engagement in school-based health research. In this paper we discuss our experiences of consent, assent and community engagement in implementing a large school-based cluster randomized trial in rural Kenya. Methods: Data collected as part of a qualitative study investigating the acceptability of the main trial, focus group discussions with field staff, observations of practice and authors' experiences are used to: 1) highlight the challenges faced in obtaining assent/consent; and 2) strategies taken to try to both protect participant rights (including to refuse and to withdraw) and ensure the success of the trial. Results: Early meetings with national, district and local level stakeholders were important in establishing their cooperation and support for the project. Despite this support, both practical and ethical challenges were encountered during consenting and assenting procedures. Our strategy for addressing these challenges focused on improving communication and understanding of the trial, and maintaining dialogue with all the relevant stakeholders throughout the study period. Conclusions: A range of stakeholders within and beyond schools play a key role in school based health trials. Community entry and information dissemination strategies need careful planning from the outset, and with ongoing consultation and feedback mechanisms established in order to identify and address concerns as they arise. We believe our experiences, and the ethical and practical issues and dilemmas encountered, will be of interest for others planning to conduct school-based research in Africa. [ABSTRACT FROM AUTHOR]

Background: A detailed knowledge of the distribution of the main Anopheles malaria vectors in Kenya should guide national vector control strategies. However, contemporary spatial distributions of the locally dominant Anopheles vectors including Anopheles gambiae, Anopheles arabiensis, Anopheles merus, Anopheles funestus, Anopheles pharoensis and Anopheles nili are lacking. The methods and approaches used to assemble contemporary available data on the present distribution of the dominant malaria vectors in Kenya are presented here. Method: Primary empirical data from published and unpublished sources were identified for the period 1990 to 2009. Details recorded for each source included the first author, year of publication, report type, survey location name, month and year of survey, the main Anopheles species reported as present and the sampling and identification methods used. Survey locations were geo-positioned using national digital place name archives and on-line geo-referencing resources. The geo-located species-presence data were displayed and described administratively, using first-level administrative units (province), and biologically, based on the predicted spatial margins of Plasmodium falciparum transmission intensity in Kenya for the year 2009. Each geo-located survey site was assigned an urban or rural classification and attributed an altitude value. Results: A total of 498 spatially unique descriptions of Anopheles vector species across Kenya sampled between 1990 and 2009 were identified, 53% were obtained from published sources and further communications with authors. More than half (54%) of the sites surveyed were investigated since 2005. A total of 174 sites reported the presence of An. gambiae complex without identification of sibling species. Anopheles arabiensis and An. funestus were the most widely reported at 244 and 265 spatially unique sites respectively with the former showing the most ubiquitous distribution nationally. Anopheles gambiae, An. arabiensis, An. funestus and An. pharoensis were reported at sites located in all the transmission intensity classes with more reports of An. gambiae in the highest transmission intensity areas than the very low transmission areas. Conclusion: A contemporary, spatially defined database of the main malaria vectors in Kenya provides a baseline for future compilations of data and helps identify areas where information is currently lacking. The data collated here are published alongside this paper where it may help guide future sampling location decisions, help with the planning of vector control suites nationally and encourage broader research inquiry into vector species niche modeling. [ABSTRACT FROM AUTHOR]

Background: We performed an economic analysis of a new technology used in antenatal care (ANC) clinics, the ANC panel. Introduced in 2019–2020 in five Rwandan districts, the ANC panel screens for four infections [hepatitis B virus (HBV), human immunodeficiency virus (HIV), malaria, and syphilis] using blood from a single fingerstick. It increases the scope and sensitivity of screening over conventional testing. Methods: We developed and applied an Excel-based economic and epidemiologic model to perform cost-effectiveness and cost-benefit analyses of this technology in Kenya, Rwanda, and Uganda. Costs include the ANC panel itself, its administration, and follow-up treatment. Effectiveness models predicted impacts on maternal and infant mortality and other outcomes. Key parameters are the baseline prevalence of each infection and the effectiveness of early treatment using observations from the Rwanda pilot, national and international literature, and expert opinion. For each parameter, we found the best estimate (with 95% confidence bound). Results: The ANC panel averted 92 (69–115) disability-adjusted life years (DALYs) per 1,000 pregnant women in ANC in Kenya, 54 (52–57) in Rwanda, and 258 (156–360) in Uganda. Net healthcare costs per woman ranged from $0.53 ($0.02-$4.21) in Kenya, $1.77 ($1.23-$5.60) in Rwanda, and negative $5.01 (-$6.45 to $0.48) in Uganda. Incremental cost-effectiveness ratios (ICERs) in dollars per DALY averted were $5.76 (-$3.50-$11.13) in Kenya, $32.62 ($17.54-$46.70) in Rwanda, and negative $19.40 (-$24.18 to -$15.42) in Uganda. Benefit-cost ratios were $17.48 ($15.90-$23.71) in Kenya, $6.20 ($5.91-$6.45) in Rwanda, and $25.36 ($16.88-$33.14) in Uganda. All results appear very favorable and cost-saving in Uganda. Conclusion: Though subject to uncertainty, even our lowest estimates were still favorable. By combining field data and literature, the ANC model could be applied to other countries. [ABSTRACT FROM AUTHOR]

Background: Entomological surveillance is traditionally conducted by supervised teams of trained technicians. However, it is expensive and limiting in the number of sites visited. Surveillance through community-based collectors (CBC) may be more cost-effective and sustainable for longitudinal entomological monitoring. This study evaluated the efficiency of CBCs in monitoring mosquito densities compared to quality-assured sampling conducted by experienced entomology technicians. Methods: Entomological surveillance employing CBCs was conducted in eighteen clusters of villages in western Kenya using indoor and outdoor CDC light traps and indoor Prokopack aspiration. Sixty houses in each cluster were enrolled and sampled once every month. Collected mosquitoes were initially identified to the genus level by CBCs, preserved in 70% ethanol and transferred to the laboratory every 2 weeks. Parallel, collections by experienced entomology field technicians were conducted monthly by indoor and outdoor CDC light traps and indoor Prokopack aspiration and served as a quality assurance of the CBCs. Results: Per collection, the CBCs collected 80% fewer Anopheles gambiae sensu lato (s.l.) [RR = 0.2; (95% CI 0.14–0.27)] and Anopheles coustani [RR = 0.2; (95% CI 0.06–0.53)] and 90% fewer Anopheles funestus [RR = 0.1; (95% CI 0.08–0.19)] by CDC light traps compared to the quality assured (QA) entomology teams. Significant positive correlations were however observed between the monthly collections by CBCs and QA teams for both An. gambiae and An. funestus. In paired identifications of pooled mosquitoes, the CBCs identified 4.3 times more Anopheles compared to experienced technicians. The cost per person-night was lower in the community-based sampling at $9.1 compared to $89.3 by QA per collection effort. Conclusion: Unsupervised community-based mosquito surveillance collected substantially fewer mosquitoes per trap-night compared to quality-assured collection by experienced field teams, while consistently overestimating the number of Anopheles mosquitoes during identification. However, the numbers collected were significantly correlated between the CBCs and the QA teams suggesting that trends observed by CBCs and QA teams were similar. Further studies are needed to evaluate whether adopting low-cost, devolved supervision with spot checks, coupled with remedial training of the CBCs, can improve community-based collections to be considered a cost-effective alternative to surveillance conducted by experienced entomological technicians. [ABSTRACT FROM AUTHOR]

Background: Malaria deaths among children have been declining worldwide during the last two decades. Despite preventive, epidemiologic and therapy-development work, mortality rate decline has stagnated in western Kenya resulting in persistently high child malaria morbidity and mortality. The aim of this study was to identify public health determinants influencing the high burden of malaria deaths among children in this region. Methods: A total of 221,929 children, 111,488 females and 110,441 males, under the age of 5 years were enrolled in the Kenya Medical Research Institute/Center for Disease Control Health and Demographic Surveillance System (KEMRI/CDC HDSS) study area in Siaya County during the period 2003–2013. Cause of death was determined by use of verbal autopsy. Age-specific mortality rates were computed, and cox proportional hazard regression was used to model time to malaria death controlling for the socio-demographic factors. A variety of demographic, social and epidemiologic factors were examined. Results: In total 8,696 (3.9%) children died during the study period. Malaria was the most prevalent cause of death and constituted 33.2% of all causes of death, followed by acute respiratory infections (26.7%) and HIV/AIDS related deaths (18.6%). There was a marked decrease in overall mortality rate from 2003 to 2013, except for a spike in the rates in 2008. The hazard of death differed between age groups with the youngest having the highest hazard of death HR 6.07 (95% CI 5.10–7.22). Overall, the risk attenuated with age and mortality risks were limited beyond 4 years of age. Longer distance to healthcare HR of 1.44 (95% CI 1.29–1.60), l ow maternal education HR 3.91 (95% CI 1.86–8.22), and low socioeconomic status HR 1.44 (95% CI 1.26–1.64) were all significantly associated with increased hazard of malaria death among children. Conclusions: While child mortality due to malaria in the study area in Western Kenya, has been decreasing, a final step toward significant risk reduction is yet to be accomplished. This study highlights residual proximal determinants of risk which can further inform preventive actions. [ABSTRACT FROM AUTHOR]

Background: Residual malaria transmission is the result of adaptive mosquito behavior that allows malaria vectors to thrive and sustain transmission in the presence of good access to bed nets or insecticide residual spraying. These behaviors include crepuscular and outdoor feeding as well as intermittent feeding upon livestock. Ivermectin is a broadly used antiparasitic drug that kills mosquitoes feeding on a treated subject for a dose-dependent period. Mass drug administration with ivermectin has been proposed as a complementary strategy to reduce malaria transmission. Methods: A cluster randomized, parallel arm, superiority trial conducted in two settings with distinct eco-epidemiological conditions in East and Southern Africa. There will be three groups: human intervention, consisting of a dose of ivermectin (400 mcg/kg) administered monthly for 3 months to all the eligible population in the cluster (>15 kg, non-pregnant and no medical contraindication); human and livestock intervention, consisting human treatment as above plus treatment of livestock in the area with a single dose of injectable ivermectin (200 mcg/kg) monthly for 3 months; and controls, consisting of a dose of albendazole (400 mg) monthly for 3 months. The main outcome measure will be malaria incidence in a cohort of children under five living in the core of each cluster followed prospectively with monthly RDTs Discussion: The second site for the implementation of this protocol has changed from Tanzania to Kenya. This summary presents the Mozambique-specific protocol while the updated master protocol and the adapted Kenya-specific protocol undergo national approval in Kenya. BOHEMIA will be the first large-scale trial evaluating the impact of ivermectin-only mass drug administration to humans or humans and cattle on local malaria transmission Trial registration: ClinicalTrials.govNCT04966702. Registered on July 19, 2021. Pan African Clinical Trials Registry PACTR202106695877303. [ABSTRACT FROM AUTHOR]

Background: The contribution of artefenomel to the clinical and parasiticidal activity of ferroquine and artefenomel in combination in uncomplicated Plasmodium falciparum malaria was investigated. Methods: This Phase 2a, randomized, open-label, parallel-group study was conducted from 11th September 2018 to 6th November 2019 across seven centres in Benin, Burkina Faso, Gabon, Kenya, and Uganda. Patients aged ≥ 14–69 years with microscopically confirmed infection (≥ 3000 to ≤ 50,000 parasites/µL blood) were randomized 1:1:1:1 to 400 mg ferroquine, or 400 mg ferroquine plus artefenomel 300, 600, or 1000 mg, administered as a single oral dose. The primary efficacy analysis was a logistic regression evaluating the contribution of artefenomel exposure to Day 28 PCR-adjusted adequate clinical and parasitological response (ACPR). Safety was also evaluated. Results: The randomized population included 140 patients. For the primary analysis in the pharmacokinetic/pharmacodynamic efficacy population (N = 121), the contribution of artefenomel AUC0–∞ to Day 28 PCR-adjusted ACPR was not demonstrated when accounting for ferroquine AUC0–d28, baseline parasitaemia, and other model covariates: odds ratio 1.1 (95% CI 0.98, 1.2; P = 0.245). In the per-protocol population, Day 28 PCR-adjusted ACPR was 80.8% (21/26; 95% CI 60.6, 93.4) with ferroquine alone and 90.3% (28/31; 95% CI 74.2, 98.0), 90.9% (30/33; 95% CI 75.7, 98.1) and 87.1% (27/31; 95% CI 70.2, 96.4) with 300, 600, and 1000 mg artefenomel, respectively. Median time to parasite clearance (Kaplan–Meier) was 56.1 h with ferroquine, more rapid with artefenomel, but similar for all doses (30.0 h). There were no deaths. Adverse events (AEs) of any cause occurred in 51.4% (18/35) of patients with ferroquine 400 mg alone, and 58.3% (21/36), 66.7% (24/36), and 72.7% (24/33) with 300, 600, and 1000 mg artefenomel, respectively. All AEs were of mild-to-moderate severity, and consistent with the known profiles of the compounds. Vomiting was the most reported AE. There were no cases of QTcF prolongation ≥ 500 ms or > 60 ms from baseline. Conclusion: The contribution of artefenomel exposure to the clinical and parasitological activity of ferroquine/artefenomel could not be demonstrated in this study. Parasite clearance was faster with ferroquine/artefenomel versus ferroquine alone. All treatments were well tolerated. Trial registration: ClinicalTrials.gov, NCT03660839 (7 September, 2018). [ABSTRACT FROM AUTHOR]

Background: Detection of malaria parasitaemia in samples that are negative by rapid diagnostic tests (RDTs) requires resource-intensive molecular tools. While pooled testing using a two-step strategy provides a cost-saving alternative to the gold standard of individual sample testing, statistical adjustments are needed to improve accuracy of prevalence estimates for a single step pooled testing strategy. Methods: A random sample of 4670 malaria RDT negative dried blood spot samples were selected from a mass testing and treatment trial in Asembo, Gem, and Karemo, western Kenya. Samples were tested for malaria individually and in pools of five, 934 pools, by one-step quantitative polymerase chain reaction (qPCR). Maximum likelihood approaches were used to estimate subpatent parasitaemia (RDT-negative, qPCR-positive) prevalence by pooling, assuming poolwise sensitivity and specificity was either 100% (strategy A) or imperfect (strategy B). To improve and illustrate the practicality of this estimation approach, a validation study was constructed from pools allocated at random into main (734 pools) and validation (200 pools) subsets. Prevalence was estimated using strategies A and B and an inverse-variance weighted estimator and estimates were weighted to account for differential sampling rates by area. Results: The prevalence of subpatent parasitaemia was 14.5% (95% CI 13.6–15.3%) by individual qPCR, 9.5% (95% CI (8.5–10.5%) by strategy A, and 13.9% (95% CI 12.6–15.2%) by strategy B. In the validation study, the prevalence by individual qPCR was 13.5% (95% CI 12.4–14.7%) in the main subset, 8.9% (95% CI 7.9–9.9%) by strategy A, 11.4% (95% CI 9.9–12.9%) by strategy B, and 12.8% (95% CI 11.2–14.3%) using inverse-variance weighted estimator from poolwise validation. Pooling, including a 20% validation subset, reduced costs by 52% compared to individual testing. Conclusions: Compared to individual testing, a one-step pooled testing strategy with an internal validation subset can provide accurate prevalence estimates of PCR-positivity among RDT-negatives at a lower cost. [ABSTRACT FROM AUTHOR]

Background: Estimation of the composition and densities of mosquito species populations is crucial for monitoring the epidemiology of mosquito-borne diseases and provide information on local vectors to public health officials and policy-makers. The aim of this study was to evaluate malaria vector bionomics in ecologically distinct sites in Taita-Taveta County, Kenya. Methods: Adult mosquitoes were collected using backpack aspirators and paired indoor/outdoor CDC light traps in 10 randomly selected households in six villages with distinct ecologies over a study period of 3 years. All Anopheles mosquitoes were morphotyped, and sibling species of Anopheles gambiae sensu lato (An. gambiae s.l.) were identified and separated by PCR analysis of extracted ribosomal DNA. All female anophelines were tested for sporozoite infectivity, with engorged females screened for blood-meal sources using the enzyme-linked immunosorbent assay technique. A subsample of those testing positive and those testing negative for Plasmodium in the ELISA were subjected to PCR assay. Results: A total of eight different Anopheles species were collected both indoors and outdoors. Anopheles gambiae s.l. (82.6%, n = 5252) was the predominant species sensu lato, followed by Anopheles coustani sensu lato (An. coustani s.l.; (10.5%, n = 666) and Anopheles funestus sensu lato (An. funestus s.l.; 5.6%, n = 357). A subset of 683 mosquito samples representing An. gambiae s.l. (n = 580, approx. 11.0%) and An. funestus s.l. (n = 103, approx. 28.9%) were identified by molecular diagnostic assays into sibling species. The An. gambiae s.l. complex was composed of Anopheles arabiensis (62.5%, n = 363/580), An. gambiae sensu stricto (An. gambiae s.s.; 0.7%, n = 4/580), Anopheles merus (0.7%, n = 4/580) and Anopheles quadriannulatus (0.2%, n = 1/580), with the remaining samples (35.5%, n = 206/580) unamplified. Anopheles funestus s.l. was composed of An. rivulorum (14.6%, n = 15/103) and An. leesoni (11.6%, n = 12/103); the remaining samples were unamplified (73.8%, n = 76/103). A total of 981 samples were subjected to PCR analysis for malaria parasite detection; of these 16 (1.6%) were confirmed to be positive for Plasmodium falciparum. The overall human blood index was 0.13 (32/238). Conclusions: Anopheles gambiae, An. funestus and An. coustani are key malaria vectors in the Taveta region of Kenya, showing concurrent indoor and outdoor transmission. All of the vectors tested showed a higher propensity for bovine and goat blood than for human blood. [ABSTRACT FROM AUTHOR]

Background: Identification and characterization of larval habitats, documentation of Anopheles spp. composition and abundance, and Plasmodium spp. infection burden are critical components of integrated vector management. The present study aimed to investigate the effect of landscape heterogeneity on entomological and parasitological indices of malaria in western Kenya. Methods: A cross-sectional entomological and parasitological survey was conducted along an altitudinal transect in three eco-epidemiological zones: lakeshore along the lakeside, hillside, and highland plateau during the wet and dry seasons in 2020 in Kisumu County, Kenya. Larval habitats for Anopheles mosquitoes were identified and characterized. Adult mosquitoes were sampled using pyrethrum spray catches (PSC). Finger prick blood samples were taken from residents and examined for malaria parasites by real-time PCR (RT-PCR). Results: Increased risk of Plasmodium falciparum infection was associated with residency in the lakeshore zone, school-age children, rainy season, and no ITNs (χ2 = 41.201, df = 9, P < 0.0001). Similarly, lakeshore zone and the rainy season significantly increased Anopheles spp. abundance. However, house structures such as wall type and whether the eave spaces were closed or open, as well as the use of ITNs, did not affect Anopheles spp. densities in the homes (χ2 = 38.695, df = 7, P < 0.0001). Anopheles funestus (41.8%) and An. arabiensis (29.1%) were the most abundant vectors in all zones. Sporozoite prevalence was 5.6% and 3.2% in the two species respectively. The lakeshore zone had the highest sporozoite prevalence (4.4%, 7/160) and inoculation rates (135.2 infective bites/person/year). High larval densities were significantly associated with lakeshore zone and hillside zones, animal hoof prints and tire truck larval habitats, wetland and pasture land, and the wet season. The larval habitat types differed significantly across the landscape zones and seasonality (χ2 = 1453.044, df = 298, P < 0.0001). Conclusion: The empirical evidence on the impact of landscape heterogeneity and seasonality on vector densities, parasite transmission, and Plasmodium infections in humans emphasizes the importance of tailoring specific adaptive environmental management interventions to specific landscape attributes to have a significant impact on transmission reduction. [ABSTRACT FROM AUTHOR]

Background: Simple and accurate diagnosis is a key component of malaria control programmes. Microscopy is the current gold standard, however it requires extensive training and the results largely rely on the skill of the microscopists. Malaria rapid diagnostic tests (RDT) can be performed with minimal training and offer timely diagnosis, but results are not quantitative. Moreover, some Plasmodium falciparum parasites have evolved and can no longer be detected by existing RDT. Developed by the Sysmex Corporation, the XN-31 prototype (XN-31p) is an automated haematology analyser capable of detecting Plasmodium-infected erythrocytes and providing species differentiation and stage specific parasite counts in venous blood samples without any preparation in approximately one minute. However, factors such as stable electricity supply in a temperature-controlled room, cost of the instrument and its initial set-up, and need for proprietary reagents limit the utility of the XN-31p across rural settings. To overcome some of these limitations, a hub and spoke diagnosis model was designed, in which peripheral health facilities were linked to a central hospital where detection of Plasmodium infections by the XN-31p would take place. To explore the feasibility of this concept, the applicability of capillary blood samples with the XN-31p was evaluated with respect to the effect of sample storage time and temperature on the stability of results. Methods: Paired capillary and venous blood samples were collected from 169 malaria-suspected outpatients in Homa Bay County Referral Hospital, Kenya. Malaria infections were diagnosed with the XN-31p, microscopy, RDT, and PCR. Capillary blood samples were remeasured on the XN-31p after 24 h of storage at either room (15–25 °C) or chilled temperatures (2–8 °C). Results: Identical results in malaria diagnosis were observed between venous and capillary blood samples processed immediately after collection with the XN-31p. Relative to PCR, the sensitivity and specificity of the XN-31p with capillary blood samples were 0.857 and 1.000, respectively. Short-term storage of capillary blood samples at chilled temperatures had no adverse impact on parasitaemia and complete blood counts (CBC) measured by the XN-31p. Conclusion: These results demonstrate the potential of the XN-31p to improve routine malaria diagnosis across remote settings using a hub and spoke model. [ABSTRACT FROM AUTHOR]

Background: Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) target night-time indoor biting mosquitoes and effectively reduce malaria transmission in rural settings across Africa, but additional vector control tools are needed to interrupt transmission. Attractive targeted sugar baits (ATSBs) attract and kill mosquitoes, including those biting outdoors. Deployment of ATSBs incorporating the insecticide dinotefuran was associated with major reductions in mosquito density and longevity in Mali. The impact of this promising intervention on malaria transmission and morbidity now needs to be determined in a range of transmission settings.Methods/design: We will conduct three similar stand-alone, open-label, two-arm, cluster-randomized, controlled trials (cRCTs) in Mali, Kenya, and Zambia to determine the impact of ATSB + universal vector control versus universal vector control alone on clinical malaria. The trials will use a "fried-egg" design, with primary outcomes measured in the core area of each cluster to reduce spill-over effects. All household structures in the ATSB clusters will receive two ATSBs, but the impact will be measured in the core of clusters. Restricted randomization will be used. The primary outcome is clinical malaria incidence among children aged 5-14 years in Mali and 1-14 years in Kenya and Zambia. A key secondary outcome is malaria parasite prevalence across all ages. The trials will include 76 clusters (38 per arm) in Mali and 70 (35 per arm) in each of Kenya and Zambia. The trials are powered to detect a 30% reduction in clinical malaria, requiring a total of 3850 person-years of follow-up in Mali, 1260 person-years in Kenya, and 1610 person-years in Zambia. These sample sizes will be ascertained using two seasonal 8-month cohorts in Mali and two 6-month seasonal cohorts in Zambia. In Kenya, which has year-round transmission, four 6-month cohorts will be used (total 24 months of follow-up). The design allows for one interim analysis in Mali and Zambia and two in Kenya.Discussion: Strengths of the design include the use of multiple study sites with different transmission patterns and a range of vectors to improve external validity, a large number of clusters within each trial site, restricted randomization, between-cluster separation to minimize contamination between study arms, and an adaptive trial design. Noted threats to internal validity include open-label design, risk of contamination between study arms, risk of imbalance of covariates across study arms, variation in durability of ATSB stations, and potential disruption resulting from the COVID-19 pandemic.Trial Registration: Zambia: ClinicalTrials.gov NCT04800055 . Registered on March 15, 2021 Mali: ClinicalTrials.gov NCT04149119 . Registered on November 4, 2019 Kenya: ClinicalTrials.gov NCT05219565 . Registered on February 2, 2022. [ABSTRACT FROM AUTHOR]

Background: Following a 30-year development process, RTS,S/AS01E (GSK, Belgium) is the first malaria vaccine to reach Phase IV assessments. The World Health Organization-commissioned Malaria Vaccine Implementation Programme (MVIP) is coordinating the delivery of RTS,S/AS01E through routine national immunization programmes in areas of 3 countries in sub-Saharan Africa. The first doses were given in the participating MVIP areas in Malawi on 23 April, Ghana on 30 April, and Kenya on 13 September 2019. The countries participating in the MVIP have little or no baseline incidence data on rare diseases, some of which may be associated with immunization, a deficit that could compromise the interpretation of possible adverse events reported following the introduction of a new vaccine in the paediatric population. Further, effects of vaccination on malaria transmission, existing malaria control strategies, and possible vaccine-mediated selective pressure on Plasmodium falciparum variants, could also impact long-term malaria control. To address this data gap and as part of its post-approval commitments, GSK has developed a post-approval plan comprising of 4 complementary Phase IV studies that will evaluate safety, effectiveness and impact of RTS,S/AS01E through active participant follow-up in the context of its real-life implementation. Methods: EPI-MAL-002 (NCT02374450) is a pre-implementation safety surveillance study that is establishing the background incidence rates of protocol-defined adverse events of special interest. EPI-MAL-003 (NCT03855995) is an identically designed post-implementation safety and vaccine impact study. EPI-MAL-005 (NCT02251704) is a cross-sectional pre- and post-implementation study to measure malaria transmission intensity and monitor the use of other malaria control interventions in the study areas, and EPI-MAL-010 (EUPAS42948) will evaluate the P. falciparum genetic diversity in the periods before and after vaccine implementation. Conclusion: GSK's post-approval plan has been designed to address important knowledge gaps in RTS,S/AS01E vaccine safety, effectiveness and impact. The studies are currently being conducted in the MVIP areas. Their implementation has provided opportunities and posed challenges linked to conducting large studies in regions where healthcare infrastructure is limited. The results from these studies will support ongoing evaluation of RTS,S/AS01E's benefit-risk and inform decision-making for its potential wider implementation across sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Background: The prevalence of malaria parasites in adults in Africa is less well researched than in children. Therefore, a demographic surveillance site was used to conduct a household survey of adults in the malaria endemic area of Maseno division in Kisumu County near Lake Victoria. Methods: A random survey of 1,190 adults living in a demographic health surveillance site in a malaria endemic area of 70,805 population size was conducted, measuring presence of malaria parasites by slide microscopy. Data were analysed using STATA to calculate the prevalence of malaria and associated risk factors. Results: The adult prevalence of presence of malaria parasites in Maseno was 28% (95% CI: 25.4-31.0%). Gender was a significant sociodemographic risk factor in both univariate (OR 1.5, p = 0.005) and multivariate (OR 1.4, p = 0.019) analyses. Females were 50% more likely to have malaria than men. Conclusions: Presence of malaria parasites is common in the adult population of this endemic area, and the rate is greatly increased in women. The presence of such an adult pool of malaria parasites represents a key reservoir factor in transmission of parasites to children, and is relevant for plans to eradicate malaria. [ABSTRACT FROM AUTHOR]

Background: In 2010, the World Health Organization shifted its malaria guidelines from recommending the empiric treatment of all febrile children to treating only those with laboratory-confirmed malaria. This study evaluated the frequency and predictors of malaria over-treatment among febrile malaria-negative children in Kenya. Methods: Between 2012 and 2013, 1,362 children presenting consecutively with temperature ≥37.5°C to Kisii and Homa Bay hospitals were enrolled in a cross-sectional study evaluating causes of fever. Children were screened for malaria using smear microscopy and rapid diagnostic tests and managed according to standard of care at the hospitals. The frequency of anti-malarial prescriptions among children with laboratory-confirmed malaria negative children (malaria over-treatment) was determined; and clinical and demographic correlates of overtreatment evaluated using logistic regression. Because of differences in malaria endemicity, analyses were stratified and compared by site. Results: Among 1,362 children enrolled, 46 (7%) of 685 children in Kisii, and 310 (45.8%) of 677 in Homa Bay had laboratory-confirmed malaria; p < 0.001. Among malaria-negative children; 210 (57.2%) in Homa Bay and 45 (7.0%) in Kisii received anti-malarials; p < 0.001. Predictors of over-treatment in Homa Bay included ≥ one integrated management of childhood illness (IMCI) danger sign (aOR = 8.47; 95% CI: 4.81-14.89), fever lasting ≥ seven days (aOR = 4.94; 95% CI: 1.90-12.86), and fever ≥39°C (aOR = 3.07; 95% CI: 1.58-5.96). In Kisii, only fever ≥39°C predicted over-treatment (aOR = 2.13; 95% CI: 1.02-4.45). Conclusions: Malaria over-treatment was common, particularly in Homa Bay, where the prevalence of malaria was extremely high. Severe illness and high or prolonged fever were associated with overtreatment. Overtreatment may result in failure to treat other serious causes of fever, drug resistance, and unnecessarily treatment costs. [ABSTRACT FROM AUTHOR]

Background: Accurate malaria diagnosis and appropriate treatment at local health facilities are critical to reducing morbidity and human reservoir of infectious gametocytes. The current study assessed the accuracy of malaria diagnosis and treatment practices in three health care facilities in rural western Kenya. Methods: The accuracy of malaria detection and treatment recommended compliance was monitored in two public and one private hospital from November 2019 through March 2020. Blood smears from febrile patients were examined by hospital laboratory technicians and re-examined by an expert microscopists thereafter subjected to real-time polymerase chain reaction (RT-PCR) for quality assurance. In addition, blood smears from patients diagnosed with malaria rapid diagnostic tests (RDT) and presumptively treated with anti-malarial were re-examined by an expert microscopist. Results: A total of 1131 febrile outpatients were assessed for slide positivity (936), RDT (126) and presumptive diagnosis (69). The overall positivity rate for Plasmodium falciparum was 28% (257/936). The odds of slide positivity was higher in public hospitals, 30% (186/624, OR:1.44, 95% CI = 1.05–1.98, p < 0.05) than the private hospital 23% (71/312, OR:0.69, 95% CI = 0.51–0.95, p < 0.05). Anti-malarial treatment was dispensed more at public hospitals (95.2%, 177/186) than the private hospital (78.9%, 56/71, p < 0.0001). Inappropriate anti-malarial treatment, i.e. artemether-lumefantrine given to blood smear negative patients was higher at public hospitals (14.6%, 64/438) than the private hospital (7.1%, 17/241) (p = 0.004). RDT was the most sensitive (73.8%, 95% CI = 39.5–57.4) and specific (89.2%, 95% CI = 78.5–95.2) followed by hospital microscopy (sensitivity 47.6%, 95% CI = 38.2–57.1) and specificity (86.7%, 95% CI = 80.8–91.0). Presumptive diagnosis had the lowest sensitivity (25.7%, 95% CI = 13.1–43.6) and specificity (75.0%, 95% CI = 50.6–90.4). RDT had the highest non-treatment of negatives [98.3% (57/58)] while hospital microscopy had the lowest [77.3% (116/150)]. Health facilities misdiagnosis was at 27.9% (77/276). PCR confirmed 5.2% (4/23) of the 77 misdiagnosed cases as false positive and 68.5% (37/54) as false negative. Conclusions: The disparity in malaria diagnosis at health facilities with many slide positives reported as negatives and high presumptive treatment of slide negative cases, necessitates augmenting microscopic with RDTs and calls for Ministry of Health strengthening supportive infrastructure to be in compliance with treatment guidelines of Test, Treat, and Track to improve malaria case management. [ABSTRACT FROM AUTHOR]

Background: Low dose aspirin (LDA) is an effective strategy to reduce preterm birth. However, LDA might have differential effects globally, based on the etiology of preterm birth. In some regions, malaria in pregnancy could be an important modifier of LDA on birth outcomes and anemia.Methods: This is a sub-study of the ASPIRIN trial, a multi-national, randomized, placebo controlled trial evaluating LDA effect on preterm birth. We enrolled a convenience sample of women in the ASPIRIN trial from the Democratic Republic of Congo (DRC), Kenya and Zambia. We used quantitative polymerase chain reaction to detect malaria. We calculated crude prevalence proportion ratios (PRs) for LDA by malaria for outcomes, and regression modelling to evaluate effect measure modification. We evaluated hemoglobin in late pregnancy based on malaria infection in early pregnancy.Results: One thousand four hundred forty-six women were analyzed, with a malaria prevalence of 63% in the DRC site, 38% in the Kenya site, and 6% in the Zambia site. Preterm birth occurred in 83 (LDA) and 90 (placebo) women, (PR 0.92, 95% CI 0.70, 1.22), without interaction between LDA and malaria (p = 0.75). Perinatal mortality occurred in 41 (LDA) and 43 (placebo) pregnancies, (PR 0.95, 95% CI 0.63, 1.44), with an interaction between malaria and LDA (p = 0.014). Hemoglobin was similar by malaria and LDA status.Conclusions: Malaria in early pregnancy did not modify the effects of LDA on preterm birth, but modified the effect of LDA on perinatal mortality. This effect measure modification deserves continued study as LDA is used in malaria endemic regions. [ABSTRACT FROM AUTHOR]

Background: Spatial repellents are widely used for prevention of mosquito bites and evidence is building on their public health value, but their efficacy against malaria incidence has never been evaluated in Africa. To address this knowledge gap, a trial to evaluate the efficacy of Mosquito Shield™, a spatial repellent incorporating transfluthrin, was developed for implementation in Busia County, western Kenya where long-lasting insecticidal net coverage is high and baseline malaria transmission is moderate to high year-round.Methods: This trial is designed as a cluster-randomized, placebo-controlled, double-blinded clinical trial. Sixty clusters will be randomly assigned in a 1:1 ratio to receive spatial repellent or placebo. A total of 6120 children aged ≥6 months to 10 years of age will be randomly selected from the study clusters, enrolled into an active cohort (baseline, cohort 1, and cohort 2), and sampled monthly to determine time to first infection by smear microscopy. Each cohort following the implementation of the intervention will be split into two groups, one to estimate direct effect of the spatial repellent and the other to estimate degree of diversion of mosquitoes and malaria transmission to unprotected persons. Malaria incidence in each cohort will be estimated and compared (primary indicator) to determine benefit of using a spatial repellent in a high, year-round malaria transmission setting. Mosquitoes will be collected monthly using CDC light traps to determine if there are entomological correlates of spatial repellent efficacy that may be useful for the evaluation of new spatial repellents. Quarterly human landing catches will assess behavioral effects of the intervention.Discussion: Findings will serve as the first cluster-randomized controlled trial powered to detect spatial repellent efficacy to reduce malaria in sub-Saharan Africa where transmission rates are high, insecticide-treated nets are widely deployed, and mosquitoes are resistant to insecticides. Results will be submitted to the World Health Organization Vector Control Advisory Group for assessment of public health value towards an endorsement to recommend inclusion of spatial repellents in malaria control programs.Trial Registration: ClinicalTrials.gov NCT04766879 . Registered February 23, 2021. [ABSTRACT FROM AUTHOR]

Background: Community case management of malaria (CCMm) is an equity-focused strategy that complements and extends the reach of health services by providing timely and effective management of malaria to populations with limited access to facility-based healthcare. In Kenya, CCMm involves the use of malaria rapid diagnostic tests (RDT) and treatment of confirmed uncomplicated malaria cases with artemether lumefantrine (AL) by community health volunteers (CHVs). The test positivity rate (TPR) from CCMm reports collected by the Ministry of Health in 2018 was two-fold compared to facility-based reports for the same period. This necessitated the need to evaluate the performance of CHVs in conducting malaria RDTs. Methods: The study was conducted in four counties within the malaria-endemic lake zone in Kenya with a malaria prevalence in 2018 of 27%; the national prevalence of malaria was 8%. Multi-stage cluster sampling and random selection were used. Results from 200 malaria RDTs performed by CHVs were compared with test results obtained by experienced medical laboratory technicians (MLT) performing the same test under the same conditions. Blood slides prepared by the MLTs were examined microscopically as a back-up check of the results. A Kappa score was calculated to assess level of agreement. Sensitivity, specificity, and positive and negative predictive values were calculated to determine diagnostic accuracy. Results: The median age of CHVs was 46 (IQR: 38, 52) with a range (26–73) years. Females were 72% of the CHVs. Test positivity rates were 42% and 41% for MLTs and CHVs respectively. The kappa score was 0.89, indicating an almost perfect agreement in RDT results between CHVs and MLTs. The overall sensitivity and specificity between the CHVs and MLTs were 95.0% (95% CI 87.7, 98.6) and 94.0% (95% CI 88.0, 97.5), respectively. Conclusion: Engaging CHVs to diagnose malaria cases under the CCMm strategy yielded results which compared well with the results of qualified experienced laboratory personnel. CHVs can reliably continue to offer malaria diagnosis using RDTs in the community setting. [ABSTRACT FROM AUTHOR]