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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: Currently, chemotherapy stands out as the major malaria intervention strategy, however, anti-malarial resistance may hamper global elimination programs. Artemisinin-based combination therapy (ACT) stands as the drug of choice for the treatment of Plasmodium falciparum malaria. Plasmodium falciparum kelch13 gene mutations are associated with artemisinin resistance. Thus, this study was aimed at evaluating the circulation of P. falciparum k13 gene polymorphisms from Kisii County, Kenya during an era of ACT deployment. Methods: Participants suspected to have malaria were recruited. Plasmodium falciparum was confirmed using the microscopy method. Malaria-positive patients were treated with artemether-lumefantrine (AL). Blood from participants who tested positive for parasites after day 3 was kept on filter papers. DNA was extracted using chelex-suspension method. A nested polymerase chain reaction (PCR) was conducted and the second-round products were sequenced using the Sanger method. Sequenced products were analysed using DNAsp 5.10.01 software and then blasted on the NCBI for k13 propeller gene sequence identity using the Basic Local Alignment Search Tool (BLAST). To assess the selection pressure in P. falciparum parasite population, Tajima' D statistic and Fu & Li's D test in DnaSP software 5.10.01 was used. Results: Out of 275 enrolled participants, 231 completed the follow-up schedule. 13 (5.6%) had parasites on day 28 hence characterized for recrudescence. Out of the 13 samples suspected of recrudescence, 5 (38%) samples were positively amplified as P. falciparum, with polymorphisms in the k13-propeller gene detected. Polymorphisms detected in this study includes R539T, N458T, R561H, N431S and A671V, respectively. The sequences have been deposited in NCBI with bio-project number PRJNA885380 and accession numbers SAMN31087434, SAMN31087433, SAMN31087432, SAMN31087431 and SAMN31087430 respectively. Conclusions: WHO validated polymorphisms in the k13-propeller gene previously reported to be associated with ACT resistance were not detected in the P. falciparum isolates from Kisii County, Kenya. However, some previously reported un-validated k13 resistant single nucleotide polymorphisms were reported in this study but with limited occurrences. The study has also reported new SNPs. More studies need to be carried out in the entire country to understand the association of reported mutations if any, with ACT resistance. [ABSTRACT FROM AUTHOR]

Background: Simultaneous infection with multiple malaria parasite strains is common in high transmission areas. Quantifying the number of strains per host, or the multiplicity of infection (MOI), provides additional parasite indices for assessing transmission levels but it is challenging to measure accurately with current tools. This paper presents new laboratory and analytical methods for estimating the MOI of Plasmodium falciparum. Methods: Based on 24 single nucleotide polymorphisms (SNPs) previously identified as stable, unlinked targets across 12 of the 14 chromosomes within P. falciparum genome, three multiplex PCRs of short target regions and subsequent next generation sequencing (NGS) of the amplicons were developed. A bioinformatics pipeline including B4Screening pathway removed spurious amplicons to ensure consistent frequency calls at each SNP location, compiled amplicons by SNP site diversity, and performed algorithmic haplotype and strain reconstruction. The pipeline was validated by 108 samples generated from cultured-laboratory strain mixtures in different proportions and concentrations, with and without pre-amplification, and using whole blood and dried blood spots (DBS). The pipeline was applied to 273 smear-positive samples from surveys conducted in western Kenya, then providing results into StrainRecon Thresholding for Infection Multiplicity (STIM), a novel MOI estimator. Results: The 24 barcode SNPs were successfully identified uniformly across the 12 chromosomes of P. falciparum in a sample using the pipeline. Pre-amplification and parasite concentration, while non-linearly associated with SNP read depth, did not influence the SNP frequency calls. Based on consistent SNP frequency calls at targeted locations, the algorithmic strain reconstruction for each laboratory-mixed sample had 98.5% accuracy in dominant strains. STIM detected up to 5 strains in field samples from western Kenya and showed declining MOI over time (q < 0.02), from 4.32 strains per infected person in 1996 to 4.01, 3.56 and 3.35 in 2001, 2007 and 2012, and a reduction in the proportion of samples with 5 strains from 57% in 1996 to 18% in 2012. Conclusion: The combined approach of new multiplex PCRs and NGS, the unique bioinformatics pipeline and STIM could identify 24 barcode SNPs of P. falciparum correctly and consistently. The methodology could be applied to field samples to reliably measure temporal changes in MOI. [ABSTRACT FROM AUTHOR]

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. [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: 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: 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: 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: 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. [ABSTRACT FROM AUTHOR]

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: 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. [ABSTRACT FROM AUTHOR]

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. [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: 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. [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: 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: 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: 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: 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. [ABSTRACT FROM AUTHOR]

Background: Long-lasting insecticidal nets (LLINs) have been the primary vector control strategy until indoor residual spraying (IRS) was added in Homa Bay and Migori Counties in western Kenya. The objective of this study was to evaluate the impact of LLINs integrated with IRS on the prevalence of asymptomatic and submicroscopic Plasmodium infections in Homa Bay County. Methods: A two-stage cluster sampling procedure was employed to enroll study participants aged ≥ 6 months old. Four consecutive community cross-sectional surveys for Plasmodium infection were conducted in residents of Homa Bay county, Kenya. Prior to the start of the study, all study households received LLINs, which were distributed between June 2017 and March 2018. The first (February 2018) and second (June 2018) surveys were conducted before and after the first round of IRS (Feb–Mar 2018), while the third (February 2019) and fourth (June 2019) surveys were conducted before and after the second application of IRS (February–March 2019). Finger-prick blood samples were obtained to prepare thick and thin smears for microscopic determination and qPCR diagnosis of Plasmodium genus. Results: Plasmodium spp. infection prevalence by microscopy was 18.5% (113/610) before IRS, 14.2% (105/737) and 3.3% (24/720) after the first round of IRS and 1.3% (11/849) after the second round of IRS (p < 0.0001). Submicroscopic (blood smear negative, qPCR positive) parasitaemia reduced from 18.9% (115/610) before IRS to 5.4% (46/849) after IRS (p < 0.0001). However, the proportion of PCR positive infections that were submicroscopic increased from 50.4% (115/228) to 80.7% (46/57) over the study period (p < 0.0001). Similarly, while the absolute number and proportions of microscopy positives which were asymptomatic decreased from 12% (73/610) to 1.2% (9/849) (p < 0.0001), the relative proportion increased. Geometric mean density of P. falciparum parasitaemia decreased over the 2-year study period (p < 0.0001). Conclusions: These data suggest that two annual rounds of IRS integrated with LLINs significantly reduced the prevalence of Plasmodium parasitaemia, while the proportion of asymptomatic and submicroscopic infections increased. To reduce cryptic P. falciparum transmission and improve malaria control, strategies aimed at reducing the number of asymptomatic and submicroscopic infections should be considered. [ABSTRACT FROM AUTHOR]

Background: Over the last two decades, the scale-up of vector control and changes in the first-line anti-malarial, from chloroquine (CQ) to sulfadoxine-pyrimethamine (SP) and then to artemether-lumefantrine (AL), have resulted in significant decreases in malaria burden in western Kenya. This study evaluated the long-term effects of control interventions on molecular markers of Plasmodium falciparum drug resistance using parasites obtained from humans and mosquitoes at discrete time points. Methods: Dried blood spot samples collected in 2012 and 2017 community surveys in Asembo, Kenya were genotyped by Sanger sequencing for markers associated with resistance to SP (Pfdhfr, Pfdhps), CQ, AQ, lumefantrine (Pfcrt, Pfmdr1) and artemisinin (Pfk13). Temporal trends in the prevalence of these markers, including data from 2012 to 2017 as well as published data from 1996, 2001, 2007 from same area, were analysed. The same markers from mosquito oocysts collected in 2012 were compared with results from human blood samples. Results: The prevalence of SP dhfr/dhps quintuple mutant haplotype C50I51R59N108I164/S436G437E540A581A613 increased from 19.7% in 1996 to 86.0% in 2012, while an increase in the sextuple mutant haplotype C50I51R59N108I164/H436G437E540A581A613 containing Pfdhps-436H was found from 10.5% in 2012 to 34.6% in 2017. Resistant Pfcrt-76 T declined from 94.6% in 2007 to 18.3% in 2012 and 0.9% in 2017. Mutant Pfmdr1-86Y decreased across years from 74.8% in 1996 to zero in 2017, mutant Pfmdr1-184F and wild Pfmdr1-D1246 increased from 17.9% to 58.9% in 2007 to 55.9% and 90.1% in 2017, respectively. Pfmdr1 haplotype N86F184S1034N1042D1246 increased from 11.0% in 2007 to 49.6% in 2017. No resistant mutations in Pfk13 were found. Prevalence of Pfdhps-436H was lower while prevalence of Pfcrt-76 T was higher in mosquitoes than in human blood samples. Conclusion: This study showed an increased prevalence of dhfr/dhps resistant markers over 20 years with the emergence of Pfdhps-436H mutant a decade ago in Asembo. The reversal of Pfcrt from CQ-resistant to CQ-sensitive genotype occurred following 19 years of CQ withdrawal. No Pfk13 markers associated with artemisinin resistance were detected, but the increased haplotype of Pfmdr1 N86F184S1034N1042D1246 was observed. The differences in prevalence of Pfdhps-436H and Pfcrt-76 T SNPs between two hosts and the role of mosquitoes in the transmission of drug resistant parasites require further investigation. [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: 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: 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: 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: 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]

Background: Health workers' compliance with outpatient malaria 'test and treat' guidelines has improved since 2010 but plateaued from 2014 at suboptimal levels in Kenya. This study examined the factors associated with high but suboptimal compliance levels at facilities with available malaria tests and drugs. Methods: Data from four national, cross-sectional health facility surveys undertaken between 2014 and 2016 in Kenya were analysed. Association between 31 factors and compliance with malaria testing (survey range (SR): 65–69%) and no anti-malarial treatment for test negative patients (SR: 90–92%) were examined using multilevel logistic regression models. Results: A total of 2,752 febrile patients seen by 594 health workers at 486 health facilities were analysed. Higher odds of malaria testing were associated with lake endemic (aOR = 12.12; 95% CI: 5.3–27.6), highland epidemic (aOR = 5.06; 95% CI: 2.7–9.5) and semi-arid seasonal (aOR = 2.07; 95% CI: 1.2–3.6) compared to low risk areas; faith-based (FBO)/ non-governmental organization (NGO)-owned compared to government-owned facilities (aOR = 5.80; 95% CI: 3.2–10.6); health workers' perception of malaria endemicity as high-risk (aOR = 3.05; 95% CI: 1.8–5.2); supervision with feedback (aOR = 1.84; 95% CI: 1.2–2.9); access to guidelines (aOR = 1.96; 95% CI: 1.1–3.4); older patients compared to infants, higher temperature measurements and main complaints of fever, diarrhoea, headache, vomiting and chills. Lower odds of testing were associated with febrile patients having main complaints of a cough (aOR = 0.65; 95% CI: 0.5–0.9), a rash (aOR = 0.32; 95% CI: 0.2–0.7) or a running nose (aOR = 0.59; 95% CI: 0.4–0.9). Other factors associated with compliance with test negative results included the type of diagnostic test available at the facility, in-service training, health workers' age, and correct knowledge of the targeted treatment policy. Conclusions: To optimize outpatient malaria case-management, reduce testing compliance gaps and eliminate overtreatment of test negative patients, there is a need to focus on compliance within low malaria risk areas in addition to ensuring the universal and continuous availability of 'test and treat' commodities. Targeting of older and government health workers; dissemination of updated guidelines; and continuing with in-service training and supportive supervision with feedback is essential. Lastly, there is a need to improve health workers' knowledge about malaria testing criteria considering their perceptions of endemicity. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization recommends quinine plus clindamycin as first-line treatment of malaria in the first trimester of pregnancy and as a second-line treatment for uncomplicated falciparum malaria when artemisinin-based drug combinations are not available. The efficacy of quinine plus clindamycin was compared with that of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in children below 5 years of age. Methods: An open-label, phase 3, randomized trial was conducted in western Kenya. Children aged 6–59 months with uncomplicated falciparum malaria were randomly assigned (1:1) via a computer-generated randomization list to receive 3 days of twice a day treatment with either oral quinine (20 mg/kg/day) plus clindamycin (20 mg/kg/day) or artemether-lumefantrine (artemether 20 mg, lumefantrine 120 mg) as one (for those weighing 5–14 kg) or two (for those weighing 15–24 kg) tablets per dose. The primary outcome was a PCR-corrected rate of adequate clinical and parasitological response (ACPR) on day 28 in the per-protocol population. Results: Of the 384 children enrolled, 182/192 (94.8%) receiving quinine plus clindamycin and 171/192 (89.1%) receiving artemether-lumefantrine completed the study. The PCR-corrected ACPR rate was 44.0% (80 children) in the quinine plus clindamycin group and 97.1% (166 children) in the artemether-lumefantrine group (treatment difference − 53.1%, 95% CI − 43.5% to − 62.7%). At 72 h after starting treatment, 50.3% (94 children) in the quinine plus clindamycin group were still parasitaemic compared with 0.5% (1 child) in the artemether-lumefantrine group. Three cases of severe malaria were recorded as serious adverse events in the quinine plus clindamycin group. Conclusions: The study found no evidence to support the use of a 3-day low dose course of quinine plus clindamycin in the treatment of uncomplicated falciparum malaria in children under 5 years of age in Kenya, where artemether-lumefantrine is still effective. Trial Registration: This trial is registered with the Pan-African Clinical Trials Registry, PACTR20129000419241. [ABSTRACT FROM AUTHOR]

Background: Control of the Anopheline mosquito vectors of malaria by use of insecticides has been shown to impact on both morbidity and mortality due to this disease. Evidence of insecticide resistance in different settings necessitates surveillance studies to allow prompt detection of resistance should it arise and thus enable its management. Possible resistance by Anopheles arabiensis mosquitoes from Mwea rice irrigation scheme in Central Kenya to insecticides in the four classes of insecticides approved by WHO for indoor residual spraying was investigated. Methods: Susceptibility to DDT (an organochlorine), fenitrothion (an organophosphate), bendiocarb (a carbamate), lambdacyhalothrin and permethrin (both pyrethroids) was tested using standard WHO diagnostic bioassay kits. Bioassays were performed on non-blood fed mosquitoes one- to three-day old. Knockdown was recorded every 10 min and mortality 24 h post-exposure was noted. Results: Mortality 24 h post-exposure was 100% for all insecticides except for lambdacyhalothrin, which averaged 99.46%. Knockdown rates at 10 min intervals were not significantly different between the Mwea population and the susceptible KISUMU strain of Anopheles gambiae sensu stricto control. The KDT50 and KDT95 values for the Mwea population were either lower than those for the control or higher by factors of no more than 2 for most comparisons and compared well with those of An. gambiae sensu lato categorized as susceptible in other studies. Conclusion: These results suggest that the Mwea population of An. arabiensis is susceptible to all the insecticides tested. This implies that vector control measures employing any of these insecticides would not be hampered by resistance. [ABSTRACT FROM AUTHOR]

Background: The gold standard for diagnosing Plasmodium falciparum infection is microscopic examination of Giemsa-stained peripheral blood smears. The effectiveness of this procedure for infection surveillance and malaria control may be limited by a relatively high parasitaemia detection threshold. Persons with microscopically undetectable infections may go untreated, contributing to ongoing transmission to mosquito vectors. The purpose of this study was to determine the magnitude and determinants of undiagnosed submicroscopic P. falciparum infections in a rural area of western Kenya. Methods: A health facility-based survey was conducted, and 367 patients seeking treatment for symptoms consistent with uncomplicated malaria in Homa Bay County were enrolled. The frequency of submicroscopic P. falciparum infection was measured by comparing the prevalence of infection based on light microscopic inspection of thick blood smears versus real-time polymerase chain reaction (RT-PCR) targeting P. falciparum 18S rRNA gene. Long-lasting insecticidal net (LLIN) use, participation in nocturnal outdoor activities, and gender were considered as potential determinants of submicroscopic infections. Results: Microscopic inspection of blood smears was positive for asexual P. falciparum parasites in 14.7% (54/367) of cases. All of these samples were confirmed by RT-PCR. 35.8% (112/313) of blood smear negative cases were positive by RT-PCR, i.e., submicroscopic infection, resulting in an overall prevalence by RT-PCR alone of 45.2% compared to 14.7% for blood smear alone. Females had a higher prevalence of submicroscopic infections (35.6% or 72 out of 202 individuals, 95% CI 28.9–42.3) compared to males (24.2%, 40 of 165 individuals, 95% CI 17.6–30.8). The risk of submicroscopic infections in LLIN users was about half that of non-LLIN users (OR = 0.59). There was no difference in the prevalence of submicroscopic infections of study participants who were active in nocturnal outdoor activities versus those who were not active (OR = 0.91). Patients who participated in nocturnal outdoor activities and use LLINs while indoors had a slightly higher risk of submicroscopic infection than those who did not use LLINs (OR = 1.48). Conclusion: Microscopic inspection of blood smears from persons with malaria symptoms for asexual stage P. falciparum should be supplemented by more sensitive diagnostic tests in order to reduce ongoing transmission of P. falciparum parasites to local mosquito vectors. [ABSTRACT FROM AUTHOR]

Background: Efforts to improve the impact of long-lasting insecticidal nets (LLINs) should be informed by understanding of the causes of decay in effect. Holes in LLINs have been estimated to account for 7–11% of loss in effect on vectorial capacity for Plasmodium falciparum malaria in an analysis of repeated cross-sectional surveys of LLINs in Kenya. This does not account for the effect of holes as a cause of net attrition or non-use, which cannot be measured using only cross-sectional data. There is a need for estimates of how much these indirect effects of physical damage on use and attrition contribute to decay in effectiveness of LLINs. Methods: Use, physical integrity, and survival were assessed in a cohort of 4514 LLINs followed for up to 4 years in Kenya. Flow diagrams were used to illustrate how the status of nets, in terms of categories of use, physical integrity, and attrition, changed between surveys carried out at 6-month intervals. A compartment model defined in terms of ordinary differential equations (ODEs) was used to estimate the transition rates between the categories. Effects of physical damage to LLINs on use and attrition were quantified by simulating counterfactuals in which there was no damage. Results: Allowing for the direct effect of holes, the effect on use, and the effect on attrition, 18% of the impact on vectorial capacity was estimated to be lost because of damage. The estimated median lifetime of the LLINs was 2.9 years, but this was extended to 5.7 years in the counterfactual without physical damage. Nets that were in use were more likely to be in a damaged state than unused nets but use made little direct difference to LLIN lifetimes. Damage was reported as the reason for attrition for almost half of attrited nets, but the model estimated that almost all attrited nets had suffered some damage before attrition. Conclusions: Full quantification of the effects of damage will require measurement of the supply of new nets and of household stocks of unused nets, and also of their impacts on both net use and retention. The timing of mass distribution campaigns is less important than ensuring sufficient supply. In the Kenyan setting, nets acquired damage rapidly once use began and the damage led to rapid attrition. Increasing the robustness of nets could substantially increase their lifetime and impact but the impact of LLIN programmes on malaria transmission is ultimately limited by levels of use. Longitudinal analyses of net integrity data from different settings are needed to determine the importance of physical damage to nets as a driver of attrition and non-use, and the importance of frequent use as a cause of physical damage in different contexts. [ABSTRACT FROM AUTHOR]

Background: Further reductions in malaria incidence as more countries approach malaria elimination require the identification and treatment of asymptomatic individuals who carry mosquito-infective Plasmodium gametocytes that are responsible for furthering malaria transmission. Assessing the relationship between total parasitaemia and gametocytaemia in field surveys can provide insight as to whether detection of low-density, asymptomatic Plasmodium falciparum infections with sensitive molecular methods can adequately detect the majority of infected individuals who are potentially capable of onward transmission. Methods: In a cross-sectional survey of 1354 healthy children and adults in three communities in western Kenya across a gradient of malaria transmission (Ajigo, Webuye, and Kapsisywa–Kipsamoite), asymptomatic P. falciparum infections were screened by rapid diagnostic tests, blood smear, and quantitative PCR of dried blood spots targeting the varATS gene in genomic DNA. A multiplex quantitative reverse-transcriptase PCR assay targeting female and male gametocyte genes (pfs25, pfs230p), a gene with a transcriptional pattern restricted to asexual blood stages (piesp2), and human GAPDH was also developed to determine total parasite and gametocyte densities among parasitaemic individuals. Results: The prevalence of varATS-detectable asymptomatic infections was greatest in Ajigo (42%), followed by Webuye (10%). Only two infections were detected in Kapsisywa. No infections were detected in Kipsamoite. Across all communities, children aged 11–15 years account for the greatest proportion total and sub-microscopic asymptomatic infections. In younger age groups, the majority of infections were detectable by microscopy, while 68% of asymptomatically infected adults (> 21 years old) had sub-microscopic parasitaemia. Piesp2-derived parasite densities correlated poorly with microscopy-determined parasite densities in patent infections relative to varATS-based detection. In general, both male and female gametocytaemia increased with increasing varATS-derived total parasitaemia. A substantial proportion (41.7%) of individuals with potential for onward transmission had qPCR-estimated parasite densities below the limit of microscopic detection, but above the detectable limit of varATS qPCR. Conclusions: This assessment of parasitaemia and gametocytaemia in three communities with different transmission intensities revealed evidence of a substantial sub-patent infectious reservoir among asymptomatic carriers of P. falciparum. Experimental studies are needed to definitively determine whether the low-density infections in communities such as Ajigo and Webuye contribute significantly to malaria transmission. [ABSTRACT FROM AUTHOR]

Background: In malaria endemic regions in Kenya, pregnant women are offered long-lasting insecticidal nets and intermittent preventive treatment (IPTp) with sulfadoxine–pyrimethamine (SP) at antenatal care (ANC) to prevent the adverse effects of malaria. Fears of growing SP resistance have heightened the search for alternative strategies. The implementation feasibility of intermittent screening and treatment (ISTp) with dihydroartemisinin–piperaquine (DP) in routine ANC settings was evaluated using qualitative and quantitative methods, including the exploration of healthcare provider and pregnant women's perceptions. Methods: Qualitative methods included data from 13 focus group discussions (FGDs) with pregnant women and 43 in-depth interviews with healthcare providers delivering ANC services. FGDs were conducted with women who had received either ISTp-DP or current policy (IPTp-SP). Thematic analysis was used to explore experiences among women and providers and findings were used to provide insights into results of the parallel quantitative study. Results: Women were accepting of testing with rapid diagnostic tests (RDTs) and receiving treatment if malaria positive. Providers perceived DP to be an effective drug and well tolerated by women. Some providers indicated a preference for test and treat strategies to reduce unnecessary exposure to medication in pregnancy, others preferred a hybrid strategy combining screening at every ANC visit followed by IPTp-SP for women who tested negative, due to the perception that RDTs missed some infections and concerns about the growing resistance to SP. Testing with RDTs during ANC was appreciated as it was perceived to reduce wait times. The positive attitude of healthcare providers towards ISTp supports findings from the quantitative study that showed a high proportion (90%) of women were tested at ANC. There were concerns about affordability of DP and the availability of sufficient RDT stocks. Conclusion: In ANC settings, healthcare providers and pregnant women found ISTp-DP to be an acceptable strategy for preventing malaria in pregnancy when compared with IPTp-SP. DP was considered an effective anti-malarial and a suitable alternative to IPTp-SP in the context of SP resistance. Despite providers' lack of confidence in RDT results at current levels of sensitivity and specificity, the quantitative findings show their willingness to test women routinely at ANC. [ABSTRACT FROM AUTHOR]

Background: The lack of background disease incidence rates in sub-Saharan countries where the RTS,S/AS01E malaria vaccine is being implemented may hamper the assessment of vaccine safety and effectiveness. This study aimed to document baseline incidence rates of meningitis, malaria, mortality, and other health outcomes prior to vaccine introduction through the Malaria Vaccine Implementation Programme. Methods: An ongoing disease surveillance study is combining prospective cohort event monitoring and hospital-based disease surveillance in three study sites in Ghana and Kenya. An interim analysis was performed on the prospective cohort in which children were enrolled in two age-groups (the 5 to 17 months or 6 to 12 weeks age-group), capturing data in the framework of routine medical practice before the introduction of the malaria vaccine. Incidence and mortality rates were computed with 95% confidential intervals (CI) using an exact method for a Poisson variable. Results: This analysis includes 14,329 children; 7248 (50.6%) in the 6 to 12 weeks age-group and 7081 (49.4%) in the 5 to 17 months age-group. In the 5 to 17 months age-group (where the malaria vaccine was planned to be subsequently rolled out) the meningitis, malaria, severe malaria and cerebral malaria incidences were 92 (95% CI 25–236), 47,824 (95% CI 45,411–50,333), 1919 (95% CI 1461–2476) and 33 (95% CI 1–181) per 100,000 person-years, respectively. The all-cause mortality was 969 (95% CI 699–1310) per 100,000 person-years. Conclusion: Incidence estimates of multiple health outcomes are being generated to allow before-after vaccine introduction comparisons that will further characterize the benefit-risk profile of the RTS,S/AS01E vaccine. Trial registration: clinicaltrials.gov NCT02374450. [ABSTRACT FROM AUTHOR]

Background: Approximately 70% of Kenya's population is at risk for malaria. The core vector control methods in Kenya are insecticide-treated mosquito nets (ITNs) and indoor residual spraying, with supplementary larval source management. In 2015, 21% of ITNs were accessed through the private retail sector. Despite the private sector role in supplying mosquito control products (MCPs), there is little evidence on the availability, sales trends, and consumer preferences for MCPs other than ITNs. This study, a component of a larger research programme focused on evaluating a spatial repellent intervention class for mosquito-borne disease control, addressed this evidence gap on the role of the private sector in supplying MCPs. Methods: A cross-sectional survey was deployed in a range of retail outlets in Busia County to characterize MCP availability, sales trends, and distribution channels. The questionnaire included 32 closed-ended and four open-ended questions with short answer responses. Descriptive analysis of frequency counts and percentages was carried out to glean insights about commercially available MCPs and the weighted average rank was used to determine consumer preferences for MCPs. Open-ended data was analysed thematically. Results: Retail outlets that stocked MCPs commonly stocked mosquito coils (73.0%), topical repellents (38.1%), aerosol insecticide sprays (23.8%) and ITNs (14.3%). Overall, retailers reported the profits from selling MCPs were adequate and they overwhelmingly planned to continue stocking the products. Of respondents who stocked MCPs, 96.8% responded that sales increased during long rains and 36.5% that sales also surged during short rains. ITNs and baby-size nets were often delivered by the wholesaler. Retailers of aerosol sprays, mosquito coils, and topical repellents either collected stock from the wholesaler or products were delivered to them. Other commercially available MCPs included insecticide incense sticks, electric mosquito strikers, insecticide soaps, electrically heated insecticide mats, and electric insecticide emanators, indicating a well-established market. Conclusions: The wide range of MCPs in local retail outlets within the study area suggests the need and demand for mosquito control tools, in addition to ITNs, that are affordable, easy to use and effective. The presence of a wide range of MCPs, is a promising sign for the introduction of a spatial repellent intervention class of products that meets consumer needs and preferences. [ABSTRACT FROM AUTHOR]

Background: Integrated vector management (IVM) is defined as a rational decision-making process for the optimal use of resources for vector control. The IVM approach is based on the premise that effective control of vectors and the diseases they transmit is not the sole preserve of the health sector. It requires the collaboration and participation of communities and other stakeholders in public and private sectors. Community participation is key to the success of IVM implementation at the local level. Case description: The study was conducted in Nyabondo, a rural area of Kenya where malaria is endemic. The objective of the project was to promote adoption and sustainability of IVM and scale up IVM-related activities as well as increase community participation and partnership in malaria control through outreach, capacity-building and collaboration with other stakeholders in the area. Collaboration was pursued through forging partnership with various government departments and ministries, particularly the fisheries department, ministry of education, ministry of health, forestry department and the social services. In total, 33 community-based organizations working within the area were identified and their role documented. Through distribution of information, education and communication (IEC) materials alone, the project was able to reach 10,670 people using various social mobilization methods, such as convening of sensitization meetings—dubbed 'mosquito days'—mainly spearheaded by primary school pupils. A total of 23 local primary schools participated in creating awareness on malaria prevention and control during the project phase. The collaboration with other departments like fisheries led to stocking of more than 20 fishponds with a total of 18,000 fingerlings in the years 2017 and 2018. Fish ponds provided an opportunity for income generation to the community. In partnership with the county government health department, the project was able to re-train 40 CHVs on IVM and malaria case management in the area. Additionally, 40 fish farmers were re-trained on fish farming as part of income generating activity (IGA) while 10 CBOs made up of 509 members received both eucalyptus and Ocimum kilimandscharicum seedlings that were distributed to four CBOs composed of 152 members. Four primary schools made up of 113 health club members also received eucalyptus seedlings as part of IGA in addition to fish farming. In total, around 20,000 eucalyptus seedlings were distributed to the community as part of IGA initiatives. By the end of 2018, the project was able to reach 25,322 people in the community during its two-year advocacy and social mobilization initiatives. Conclusion: Through advocacy and social mobilization, the IVM strategy improved inter-sectoral collaboration, enhanced capacity building and community participation. However, more IVM related activities are needed to effectively mobilize available resources and increase community participation in malaria control. [ABSTRACT FROM AUTHOR]

Background: Insecticide resistance poses a growing challenge to malaria vector control in Kenya and around the world. Following evidence of associations between the mosquito microbiota and insecticide resistance, the microbiota of Anopheles gambiae sensu stricto (s.s.) from Tulukuyi village, Bungoma, Kenya, with differing permethrin resistance profiles were comparatively characterized. Methods: Using the CDC bottle bioassay, 133 2–3 day-old, virgin, non-blood fed female F1 progeny of field-caught An. gambiae s.s. were exposed to five times (107.5 µg/ml) the discriminating dose of permethrin. Post bioassay, 50 resistant and 50 susceptible mosquitoes were subsequently screened for kdr East and West mutations, and individually processed for microbial analysis using high throughput sequencing targeting the universal bacterial and archaeal 16S rRNA gene. Results: 47 % of the samples tested (n = 133) were resistant, and of the 100 selected for further processing, 99 % were positive for kdr East and 1 % for kdr West. Overall, 84 bacterial taxa were detected across all mosquito samples, with 36 of these shared between resistant and susceptible mosquitoes. A total of 20 bacterial taxa were unique to the resistant mosquitoes and 28 were unique to the susceptible mosquitoes. There were significant differences in bacterial composition between resistant and susceptible individuals (PERMANOVA, pseudo-F = 2.33, P = 0.001), with presence of Sphingobacterium, Lysinibacillus and Streptococcus (all known pyrethroid-degrading taxa), and the radiotolerant Rubrobacter, being significantly associated with resistant mosquitoes. On the other hand, the presence of Myxococcus, was significantly associated with susceptible mosquitoes. Conclusions: This is the first report of distinct microbiota in An. gambiae s.s. associated with intense pyrethroid resistance. The findings highlight differentially abundant bacterial taxa between resistant and susceptible mosquitoes, and further suggest a microbe-mediated mechanism of insecticide resistance in mosquitoes. These results also indicate fixation of the kdr East mutation in this mosquito population, precluding further analysis of its associations with the mosquito microbiota, but presenting the hypothesis that any microbe-mediated mechanism of insecticide resistance would be likely of a metabolic nature. Overall, this study lays initial groundwork for understanding microbe-mediated mechanisms of insecticide resistance in African mosquito vectors of malaria, and potentially identifying novel microbial markers of insecticide resistance that could supplement existing vector surveillance tools. [ABSTRACT FROM AUTHOR]

Background: Several types of insecticides, treating technologies and materials are available for long-lasting insecticide-treated nets (LLINs). The variations may result in different efficacies against mosquitoes and correspondingly infection risks for the Plasmodium falciparum malaria parasite. This cross-sectional study investigated whether infection risk varied among children who slept under different LLIN brands in rural villages of western Kenya. Methods: Children sleeping under various types of LLINs were tested for P. falciparum infection using a diagnostic polymerase chain reaction (PCR) assay. Data were collected for other potential factors associated with infection risk: sleeping location (with bed/without bed), number of persons sharing the same net, dwelling wall material, gap of eaves (open/close), proportional hole index, socio-economic status, and density of indoor resting anophelines. Bed-net efficacy against the Anopheles gambiae susceptible strain was estimated using the WHO cone test and the tunnel test. The residual insecticide content on nets was measured. Results: Seven LLIN brands were identified, and deltamethrin-based DawaPlus® 2.0 was the most popular (48%) followed by permethrin-based Olyset® Net (28%). The former LLIN was distributed in the area about six months before the present study was conducted, and the latter net was distributed at least three years before. Of 254 children analysed, P. falciparum PCR-positive prevalence was 58% for DawaPlus® 2.0 users and 38% for Olyset® users. The multiple regression analysis revealed that the difference was statistically significant (adjusted OR: 0.67, 95% credible interval: 0.45–0.97), whereas the confounders were not statistically important. Among randomly selected net samples, all DawaPlus® 2.0 (n = 20) and 95% of Olyset® (n = 19) passed either the cone test or the tunnel test. Conclusions: Olyset® was more effective in reducing infection risk compared with DawaPlus® 2.0. Although the data from the present study were too limited to explain the mechanism clearly, the results suggest that the characteristics of the former brand are more suitable for the conditions, such as vector species composition, of the study area. [ABSTRACT FROM AUTHOR]

Background: Declining malaria prevalence and pressure on external funding have increased the need for efficiency in malaria control in sub-Saharan Africa (SSA). Modelled Plasmodium falciparum parasite rate (PfPR) maps are increasingly becoming available and provide information on the epidemiological situation of countries. However, how these maps are understood or used for national malaria planning is rarely explored. In this study, the practices and perceptions of national decision-makers on the utility of malaria risk maps, showing prevalence of parasitaemia or incidence of illness, was investigated. Methods: A document review of recent National Malaria Strategic Plans was combined with 64 in-depth interviews with stakeholders in Kenya, Malawi and the Democratic Republic of Congo (DRC). The document review focused on the type of epidemiological maps included and their use in prioritising and targeting interventions. Interviews (14 Kenya, 17 Malawi, 27 DRC, 6 global level) explored drivers of stakeholder perceptions of the utility, value and limitations of malaria risk maps. Results: Three different types of maps were used to show malaria epidemiological strata: malaria prevalence using a PfPR modelled map (Kenya); malaria incidence using routine health system data (Malawi); and malaria prevalence using data from the most recent Demographic and Health Survey (DRC). In Kenya the map was used to target preventative interventions, including long-lasting insecticide-treated nets (LLINs) and intermittent preventive treatment in pregnancy (IPTp), whilst in Malawi and DRC the maps were used to target in-door residual spraying (IRS) and LLINs distributions in schools. Maps were also used for operational planning, supply quantification, financial justification and advocacy. Findings from the interviews suggested that decision-makers lacked trust in the modelled PfPR maps when based on only a few empirical data points (Malawi and DRC). Conclusions: Maps were generally used to identify areas with high prevalence in order to implement specific interventions. Despite the availability of national level modelled PfPR maps in all three countries, they were only used in one country. Perceived utility of malaria risk maps was associated with the epidemiological structure of the country and use was driven by perceived need, understanding (quality and relevance), ownership and trust in the data used to develop the maps. [ABSTRACT FROM AUTHOR]