Search

Background Consumption of very-hot beverages/food is a probable carcinogen. In East Africa, we investigated esophageal squamous cell carcinoma (ESCC) risk in relation to four thermal exposure metrics separately and in a combined score. Methods From the ESCCAPE case–control studies in Blantyre, Malawi (2017-20) and Kilimanjaro, Tanzania (2015-19), we used logistic regression models adjusted for country, age, sex, alcohol and tobacco, to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for self-reported thermal exposures whilst consuming tea, coffee and/or porridge. Results The study included 849 cases and 906 controls. All metrics were positively associated with ESCC: temperature of drink/food (OR 1.92 (95% CI: 1.50, 2.46) for ‘very hot’ vs ‘hot’), waiting time before drinking/eating (1.76 (1.37, 2.26) for Conclusions Thermal exposure metrics were strongly associated with ESCC risk. Avoidance of very-hot food/beverage consumption may contribute to the prevention of ESCC in East Africa.

Epigenetic mechanisms such as aberrant DNA methylation (DNAme) are known to drive esophageal squamous cell carcinoma (ESCC), yet they remain poorly understood. Here, we studied tumor-specific DNAme in ESCC cases from nine high-incidence countries of Africa, Asia, and South America. Infinium MethylationEPIC array was performed on 108 tumors and 51 normal tissues adjacent to the tumors (NAT) in the discovery phase, and targeted pyrosequencing was performed on 132 tumors and 36 NAT in the replication phase. Top genes for replication were prioritized by weighting methylation results using RNA-sequencing data from The Cancer Genome Atlas and GTEx and validated by qPCR. Methylome analysis comparing tumor and NAT identified 6,796 differentially methylated positions (DMP) and 866 differential methylated regions (DMR), with a 30% methylation (Δβ) difference. The majority of identified DMPs and DMRs were hypermethylated in tumors, particularly in promoters and gene-body regions of genes involved in transcription activation. The top three prioritized genes for replication, PAX9, SIM2, and THSD4, had similar methylation differences in the discovery and replication sets. These genes were exclusively expressed in normal esophageal tissues in GTEx and downregulated in tumors. The specificity and sensitivity of these DNAme events in discriminating tumors from NAT were assessed. Our study identified novel, robust, and crucial tumor-specific DNAme events in ESCC tumors across several high-incidence populations of the world. Methylome changes identified in this study may serve as potential targets for biomarker discovery and warrant further functional characterization.Significance:This largest genome-wide DNA methylation study on ESCC from high-incidence populations of the world identifies functionally relevant and robust DNAme events that could serve as potential tumor-specific markers.

7 supplementary figures

16 supplementary tables

Most malaria morbidity in Kenya is due toPlasmodium falciparumwith no cases attributed toP.vivax. Little is known about the epidemiology in northern Kenya along the border with Ethiopia and Sudan. We found that 2% of household members ofP.falciparumcases were infected withP.vivax, affecting all ages in urban and rural sites.

Summary Background The contribution of alcohol to the large burden of oesophageal squamous cell carcinoma (ESCC) in east Africa remains uncertain and difficult to assess owing to complex consumption patterns of traditional and commercial drinks. We aimed to assess whether alcohol drinking, overall and at specific intake levels, contributes to ESCC risk in east Africa. Methods We did a hospital-based case-control study in Kenya, Tanzania, and Malawi, which included comprehensive assessment of a variety of locally consumed alcohol that we used to classify drinkers as exclusively low alcohol-by-volume (ABV

Studies of human malaria infections with multiple, genetically distinct parasites have illuminated mechanisms of malaria transmission. However, few studies have used the genetic diversity in mosquito infections to understand how transmission is sustained. We identified likely human sources of mosquito infections from a longitudinal cohort in Western Kenya based on genetic similarity between parasites and the timing of infections. We found that several human infections were required to reconstitute each mosquito infection and that multiple parasite clones were likely transmitted from infected humans to mosquitoes in each bite, suggesting that superinfection and co-transmission occur simultaneously and are important mechanisms of transmission. We further investigated this using an individual human and mosquito simulation model and found that co-transmission alone was unlikely to reproduce the high complexity of mosquito infections. We concluded that the superinfection of mosquitoes likely plays an important, but under studied, role in sustaining moderate to high malaria transmission.

Esophageal squamous cell carcinoma (ESCC) shows remarkable variation in incidence that is not fully explained by known lifestyle and environmental risk factors. It has been speculated that an unknown exogenous exposure(s) could be responsible. Here we combine the fields of mutational signature analysis with cancer epidemiology to study 552 ESCC genomes from eight countries with varying incidence rates. Mutational profiles were similar across all countries studied. Associations between specific mutational signatures and ESCC risk factors were identified for tobacco, alcohol, opium and germline variants, with modest impacts on mutation burden. We find no evidence of a mutational signature indicative of an exogenous exposure capable of explaining differences in ESCC incidence. Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC)-associated mutational signatures single-base substitution (SBS)2 and SBS13 were present in 88% and 91% of cases, respectively, and accounted for 25% of the mutation burden on average, indicating that APOBEC activation is a crucial step in ESCC tumor development.

Background Incorporating social determinants of health into care delivery for chronic diseases is a priority. Objectives The goal of this study was to evaluate the impact of group medical visits and/or microfinance on blood pressure reduction. Methods The authors conducted a cluster randomized trial with 4 arms and 24 clusters: 1) usual care (UC); 2) usual care plus microfinance (MF); 3) group medical visits (GMVs); and 4) GMV integrated into MF (GMV-MF). The primary outcome was 1-year change in systolic blood pressure (SBP). Mixed-effects intention-to-treat models were used to evaluate the outcomes. Results A total of 2,890 individuals (69.9% women) were enrolled (708 UC, 709 MF, 740 GMV, and 733 GMV-MF). Average baseline SBP was 157.5 mm Hg. Mean SBP declined −11.4, −14.8, −14.7, and −16.4 mm Hg in UC, MF, GMV, and GMV-MF, respectively. Adjusted estimates and multiplicity-adjusted 98.3% confidence intervals showed that, relative to UC, SBP reduction was 3.9 mm Hg (−8.5 to 0.7), 3.3 mm Hg (−7.8 to 1.2), and 2.3 mm Hg (−7.0 to 2.4) greater in GMV-MF, GMV, and MF, respectively. GMV and GMV-MF tended to benefit women, and MF and GMV-MF tended to benefit poorer individuals. Active participation in GMV-MF was associated with greater benefit. Conclusions A strategy combining GMV and MF for individuals with diabetes or hypertension in Kenya led to clinically meaningful SBP reductions associated with cardiovascular benefit. Although the significance threshold was not met in pairwise comparison hypothesis testing, confidence intervals for GMV-MF were consistent with impacts ranging from substantive benefit to neutral effect relative to UC. Incorporating social determinants of health into care delivery for chronic diseases has potential to improve outcomes. (Bridging Income Generation With Group Integrated Care [BIGPIC]; NCT02501746 )

This study assessed the performance of modeling approaches to estimate personal exposure in Kenyan homes where cooking fuel combustion contributes substantially to household air pollution (HAP). We measured emissions (PM2.5 , black carbon, CO); household air pollution (PM2.5 , CO); personal exposure (PM2.5 , CO); stove use; and behavioral, socioeconomic, and household environmental characteristics (eg, ventilation and kitchen volume). We then applied various modeling approaches: a single-zone model; indirect exposure models, which combine person-location and area-level measurements; and predictive statistical models, including standard linear regression and ensemble machine learning approaches based on a set of predictors such as fuel type, room volume, and others. The single-zone model was reasonably well-correlated with measured kitchen concentrations of PM2.5 (R2 = 0.45) and CO (R2 = 0.45), but lacked precision. The best performing regression model used a combination of survey-based data and physical measurements (R2 = 0.76) and a root mean-squared error of 85 µg/m3 , and the survey-only-based regression model was able to predict PM2.5 exposures with an R2 of 0.51. Of the machine learning algorithms evaluated, extreme gradient boosting performed best, with an R2 of 0.57 and RMSE of 98 µg/m3 .

The incidence of esophageal squamous cell carcinoma (ESCC) is disproportionately high in the eastern corridor of Africa and parts of Asia. Emerging research has identified a potential association between poor oral health and ESCC. One possible link between poor oral health and ESCC involves the alteration of the microbiome. We performed an integrated analysis of four independent sequencing efforts of ESCC tumors from patients from high- and low-incidence regions of the world. Using whole genome sequencing (WGS) and RNA sequencing (RNAseq) of ESCC tumors from 61 patients in Tanzania, we identified a community of bacteria, including members of the genera Fusobacterium, Selenomonas, Prevotella, Streptococcus, Porphyromonas, Veillonella and Campylobacter, present at high abundance in ESCC tumors. We then characterized the microbiome of 238 ESCC tumor specimens collected in two additional independent sequencing efforts consisting of patients from other high-ESCC incidence regions (Tanzania, Malawi, Kenya, Iran, China). This analysis revealed similar ESCC-associated bacterial communities in these cancers. Because these genera are traditionally considered members of the oral microbiota, we next explored whether there was a relationship between the synchronous saliva and tumor microbiomes of ESCC patients in Tanzania. Comparative analyses revealed that paired saliva and tumor microbiomes were significantly similar with a specific enrichment of Fusobacterium and Prevotella in the tumor microbiome. Together, these data indicate that cancer-associated oral bacteria are associated with ESCC tumors at the time of diagnosis and support a model in which oral bacteria are present in high abundance in both saliva and tumors of some ESCC patients.

Human movement impacts the spread and transmission of infectious diseases. Recently, a large reservoir of Plasmodium falciparum malaria was identified in a semi-arid region of northwestern Kenya historically considered unsuitable for malaria transmission. Understanding the sources and patterns of transmission attributable to human movement would aid in designing and targeting interventions to decrease the unexpectedly high malaria burden in the region. Toward this goal, polymorphic parasite genes (ama1, csp) in residents and passengers traveling to Central Turkana were genotyped by amplicon deep sequencing. Genotyping and epidemiological data were combined to assess parasite importation. The contribution of travel to malaria transmission was estimated by modelling case reproductive numbers inclusive and exclusive of travelers. P. falciparum was detected in 6.7% (127/1891) of inbound passengers, including new haplotypes which were later detected in locally-transmitted infections. Case reproductive numbers approximated 1 and did not change when travelers were removed from transmission networks, suggesting that transmission is not fueled by travel to the region but locally endemic. Thus, malaria is not only prevalent in Central Turkana but also sustained by local transmission. As such, interrupting importation is unlikely to be an effective malaria control strategy on its own, but targeting interventions locally has the potential to drive down transmission.

Consumption of very-hot beverages/food is a probable carcinogen. In East Africa, we investigated esophageal squamous cell carcinoma (ESCC) risk in relation to four thermal exposure metrics separately and in a combined score.From the ESCCAPE case-control studies in Blantyre, Malawi (2017-20) and Kilimanjaro, Tanzania (2015-19), we used logistic regression models adjusted for country, age, sex, alcohol and tobacco, to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for self-reported thermal exposures whilst consuming tea, coffee and/or porridge.The study included 849 cases and 906 controls. All metrics were positively associated with ESCC: temperature of drink/food (OR 1.92 (95% CI: 1.50, 2.46) for 'very hot' vs 'hot'), waiting time before drinking/eating (1.76 (1.37, 2.26) for2 vs 2-5 minutes), consumption speed (2.23 (1.78, 2.79) for 'normal' vs 'slow') and mouth burning (1.90 (1.19, 3.01) for ≥6 burns per month vs none). Amongst consumers, the composite score ranged from 1 to 12, and ESCC risk increased with higher scores, reaching an OR of 4.6 (2.1, 10.0) for scores of ≥9 vs 3.Thermal exposure metrics were strongly associated with ESCC risk. Avoidance of very-hot food/beverage consumption may contribute to the prevention of ESCC in East Africa.

Household transitions to cleaner cooking fuels (for example, liquefied petroleum gas (LPG)) have historically been studied from a demand perspective, with clean energy usage expected to increase with improvements in household socio-economic status. Although recent studies demonstrate the importance of supply-side determinants in increasing clean cooking, few large-scale studies have assessed their importance quantitatively, relative to demand-related factors. Here, as part of the CLEAN-Air(Africa) study, we examine a population-based survey (n = 5,638) of cooking practices in peri-urban communities within Cameroon, Kenya and Ghana. Multilevel logistic and log-linear regression assessed the demand and supply-side determinants of LPG usage (primary versus secondary fuel) and consumption (kilograms per capita per year), respectively. Supply-side factors (for example, cylinder refill and transportation costs) and the use of single versus multiburner stoves were better predictors than household socio-economic status for both the probability of primarily cooking with LPG and the annual LPG consumption. These results highlight the need for policies that promote LPG supply and stove equipment to meet household needs. Billions of people still rely on polluting fuels like wood or charcoal for cooking, which impacts health and livelihoods, despite efforts to transition to cleaner fuels. This Analysis integrates a comparison of supply- and demand-side factors that determine cooking fuel use among peri-urban households in Cameroon, Kenya and Ghana.

The incidence of esophageal squamous cell carcinoma (ESCC) is disproportionately high in the eastern corridor of Africa and parts of Asia. Emerging research has identified a potential association between poor oral health and ESCC. One proposed biological pathway linking poor oral health and ESCC involves the alteration of the microbiome. Thus, we performed an integrated analysis of four independent sequencing efforts of ESCC tumors from patients from high- and low-incidence regions of the world. Using whole genome sequencing (WGS) and RNA sequencing (RNAseq) of ESCC tumors and WGS of synchronous collections of saliva specimens from 61 patients in Tanzania, we identified a community of bacteria, including members of the genera Fusobacterium, Selenomonas, Prevotella, Streptococcus, Porphyromonas, Veillonella, and Campylobacter, present at high abundance in ESCC tumors. We then characterized the microbiome of 238 ESCC tumor specimens collected in two additional independent sequencing efforts consisting of patients from other high-ESCC incidence regions (Tanzania, Malawi, Kenya, Iran, China). This analysis revealed a similar tumor enrichment of the ESCC-associated bacterial community in these cancers. Because these genera are traditionally considered members of the oral microbiota, we explored if there is a relationship between the synchronous saliva and tumor microbiomes of ESCC patients in Tanzania. Comparative analyses revealed that paired saliva and tumor microbiomes are significantly similar with a specific enrichment of Fusobacterium and Prevotella in the tumor microbiome. Together, these data indicate that cancer-associated oral bacteria are associated with ESCC tumors at the time of diagnosis and support a model in which oral bacteria are present in high abundance in both saliva and tumors of ESCC patients. Longitudinal studies of the pre-diagnostic oral microbiome are needed to investigate whether these cross-sectional similarities reflect temporal associations.

Geophagia, the intentional practice of consuming soil, occurs across the African esophageal cancer corridor, particularly during pregnancy. We investigated whether this practice is linked to endemic esophageal squamous cell carcinoma (ESCC) in this region. We conducted ESCC case-control studies in Tanzania, Malawi and Kenya. Cases were patients with incident histologically/clinically confirmed ESCC and controls were hospital patients/visitors without digestive diseases. Participants were asked if they had ever eaten soil (never/regularly/pregnancy-only). Odds ratios (OR) are adjusted for sex, age, tobacco, alcohol, country, religion and marital status. Overall, 934 cases (Malawi 535, Tanzania 304 and Kenya females 95) and 995 controls provided geophagia information. Among controls, ever-geophagia was common in women (Malawi 49%, Kenya 43% and Tanzania 29%) but not in men (10% Malawi

Background: Maximizing the impact of community-based programs requires understanding how the supply of and demand for the intervention interact at the point of delivery. We present results from a large-scale community health worker study designed to increase the availability of and demand for malaria diagnostic testing in a rural, malaria-endemic region in western Kenya between 2015 and 2017. Methods: Community Health Workers (CHWs) provided free malaria Rapid Diagnostic Test(mRDT) in the community. Those with a positive malaria test were provided with a discounted first-line antimalarial over-the-counter. We conducted a community-based survey to collect individual study outcomes at 12- and 18-months post-implementation. In addition, we collected monthly testing data from the 244 participating CHWs and also conducted in-depth interviews with a random sample of 70 CHWs. Results: From the survey, 55% (n=948/1738) reported having a malaria test for their recent illness with 38% having been tested by a CHW. Being aware of a local CHW (95% CI:1.10-2.04) and belonging to a wealthy household (95% CI:1.14-2.06) were associated with higher malaria testing uptake from any source. Poorer households were more likely to receive a test from a CHW. School-aged children between 5-17 years were more than twice as likely to be tested by a CHW (95% CI:1.47-4.14). Both confidence in AL treatment (95% CI:1.54-4.92) and perceived accuracy of an RDT performed by a CHW (95% CI:1.12-5.27) were strongly and positively associated with testing by a CHW. In adjusted analyses, specific CHWs attributes were significantly associated with higher testing rates including formal employment (95% CI:0.05-2.70), those serving more than 50 households (95% CI:0.70-2.74) and those serving areas with a higher proportion of positive tests (95% CI:1.05, 3.22). On both the supply side and the demand side, confidence in a test performed by a CHW was strongly correlated with the success of the intervention.Conclusion: Scale-up of community-based malaria testing intervention through CHWs is feasible and effective at reaching the poorest households. In order to maximize the impact of such interventions, it is important to recognize factors that may restrict both delivery and demand for such services.

Spot urinary elemental concentrations are presented for 357 adults from Western Kenya collected between 2016 and 2019 as part of a wider environmental geochemical survey. The aim of this study was to establish population level urinary elemental concentrations in Western Kenya for micronutrients and potentially harmful elements for inference of health status against established thresholds. For elements where thresholds inferring health status were not established in the literature using urine as a non-invasive matrix, this study generated reference values with a 95% confidence interval (RV95s) to contextualise urinary elemental data for this population group. Data are presented with outliers removed based upon creatinine measurements leaving 322 individuals, for sub-categories (e.g. age, gender) and by county public health administrative area. For Western Kenya, reference values with a 95% confidence interval (RV95s) were calculated as follows (μg/L): 717 (I), 89 (Se), 1753 (Zn), 336 (Mo), 24 (Cu), 15.6 (Ni), 22.1 (As), 0.34 (Cd), 0.47 (Sn), 0.46 (Sb), 7.0 (Cs), 13.4 (Ba and 1.9 (Pb). Urinary concentrations at the 25th/75th percentiles were as follows (μg/L): 149/368 (I), 15/42 (Se), 281/845 (Zn), 30/128 (Mo), 6/13 (Cu), 1.7/6.1 (Ni), 2.0/8.2 (As). 0.1/0.3 (Cd), 0.05/0.22 (Sn), 0.04/0.18 (Sb), 1.2/3.6 (Cs), 0.8/4.0 (Ba) and 0.2/0.9 (Pb). Urinary concentrations at a population level inferred excess intake of micronutrients I, Se, Zn and Mo in 38, 6, 57 and 14% of individuals, respectively, versus a bioequivalent (BE) upper threshold limit, whilst rates of deficiency were relatively low at 15, 15, 9 and 18%, respectively. Each of the administrative counties showed a broadly similar range of urinary elemental concentrations, with some exceptions for counties bordering Lake Victoria where food consumption habits may differ significantly to other counties e.g. I, Se, Zn. Corrections for urinary dilution using creatinine, specific gravity and osmolality provided a general reduction in RV95s for I, Mo, Se, As and Sn compared to uncorrected data, with consistency between the three correction methods.

In northwestern Kenya, Turkana County has been historically considered unsuitable for stable malaria transmission because of its unfavorable climate and predominantly semi-nomadic population; consequently, it is overlooked during malaria control planning. However, the area is changing, with substantial development, an upsurge in travel associated with resource extraction, and more populated settlements forming. Recently, numerous malaria outbreaks have highlighted the need to characterize malaria transmission and its associated risk factors in the region to inform control strategies. Reactive case detection of confirmed malaria cases at six health facilities across central Turkana was conducted from 2018 to 2019. Infections in household members of index cases were detected by malaria rapid diagnostic tests (RDTs) and PCR tests, and they were grouped according household and individual characteristics. The relationships between putative risk factors and infection were quantified by multilevel logistic regression models. Of the 3,189 household members analyzed, 33.6% had positive RDT results and/or PCR test results. RDT-detected infections were more prevalent in children; however, PCR-detected infections were similarly prevalent across age groups. Recent travel was rarely reported and not significantly associated with infection. Bed net coverage was low and net crowding was associated with increased risks of household infections. Infections were present year-round, and fluctuations in prevalence were not associated with rainfall. These findings indicate year-round, endemic transmission with moderate population immunity. This is in stark contrast to recent estimates in this area. Therefore, further investigations to design effective intervention approaches to address malaria in this rapidly changing region and other similar settings across the Horn of Africa are warranted.

Esophageal squamous cell carcinoma (ESCC) shows a remarkable variation in incidence which is not fully explained by known lifestyle and environmental risk factors. It has been speculated that an unknown exogenous exposure(s) could be responsible. Here we combine the fields of mutational signature analysis with cancer epidemiology to study 552 ESCC genomes from eight countries with varying incidence rates. The mutational profiles of ESCC were similar across all countries studied. Associations between specific mutational signatures and ESCC risk factors were identified for tobacco, alcohol, opium and germline variants, with modest impacts on mutation burden. We find no evidence of a mutational signature indicative of an exogenous exposure capable of explaining the differences in ESCC incidence. APOBEC associated mutational signatures SBS2 and SBS13 were present in 88% and 91% of cases respectively and accounted for a quarter of the mutation burden on average, indicating that activation of APOBEC is a crucial step in ESCC tumor development.

Universal access to cleaner cooking fuels (including liquefied petroleum gas (LPG)) is a key target of Sustainable Development Goal 7. Currently, approximately 40 million Kenyans rely on polluting cooking fuels (e.g. charcoal, wood). While the Kenyan government aims to rapidly scale up use of LPG for cooking by 2030, COVID-19 restrictions and a 16% value added tax (VAT) re-introduced on LPG in 2021 have likely hampered progress in LPG uptake. We aimed to quantify the effect of these economic shocks on food and energy security in Langas informal urban settlement in western Kenya. We further evaluated whether households most adversely affected by COVID-19 restrictions were more likely to be socioeconomically impacted by the VAT re-imposition. A cross-sectional survey (n = 1542) assessed changes in cooking fuel patterns, food security and livelihoods of primary cooks due to these two economic shocks. While under COVID-19 restrictions, 75% (n = 1147) of participants reported income declines and 18% (n = 164) of participants using LPG (n = 922) switched their primary cooking fuel to charcoal, wood or kerosene. Households reporting lower income while under COVID-19 restrictions had 5.3 times (95% CI:[3.8,7.4]) the odds of experiencing food insecurity as those with no change in income. Unemployment and food insecurity under COVID-19 restrictions were substantially higher among informal sector workers (70% and 60%, respectively) compared with business/government employees (45% and 37%, respectively). Following the VAT re-introduction, 44% (n = 356) of households using LPG consumed less, and 34% (n = 276) cooked more frequently with polluting fuels. Individuals switching away from LPG under COVID-19 restrictions had 3.0 times (95% CI:[2.1,4.3]) the odds of reducing their LPG consumption due to the VAT re-introduction as those maintaining use of LPG. COVID-19 restrictions and the VAT re-introduction disproportionately negatively affected informal sector workers’ livelihoods. A zero-rating of VAT on LPG can help alleviate deepened inequities in LPG access in Kenya.

Background Case-control studies remain an important study design for aetiologic research on cancer, particularly when cohorts are not available. In addition to the potential biases inherent in this design, conducting fieldwork in settings with weak health care and information systems for cancer, such as in sub Saharan Africa, confer additional challenges which we present here with the aim to share experience to guide future studies. Methods We undertook a hospital-based case-control study of squamous cell esophageal cancer at the Moi Teaching and Referral Hospital in Eldoret, West Kenya. Cases were recruited at endoscopy and controls from hospital wards, age and gender frequency-matched to cases. Urine, toenails, blood and tumour biopsy were collected and a questionnaire administered. Results During this pilot phase, 143 cases and 155 controls were successfully recruited. Complete questionnaire data was obtained through e-data collection. Biospecimen collection was possible with support of an already existing equipped laboratory. We introduce changes made in the main study phase, including on expansion of the control groups to allow to consideration of selection bias. Conclusions Extra attention and funding to train and monitor data quality and biospecimen collection and collaboration of a large group held together by strong leadership are essential. We recommend studies based on regional treatment centres with their more defined catchment areas rather than in the capital cities as referral routes in multi-level health care systems are severely attrition prone.

A large proportion of artemisinin-combination therapy (ACT) anti-malarial medicines is consumed by individuals that do not have malaria. The over-consumption of ACTs is largely driven by retail sales in high malaria-endemic countries to clients who have not received a confirmatory diagnosis. This study aims to target ACT sales to clients receiving a confirmatory diagnosis using malaria rapid diagnostic tests (mRDTs) at retail outlets in Kenya and Nigeria. This study comprises two linked four-arm 2 × 2 factorial cluster randomized controlled trials focused on malaria diagnostic testing and conditional ACT subsidies with the goal to evaluate provider-directed and client-directed interventions. The linked trials will be conducted at two contrasting study sites: a rural region around Webuye in western Kenya and the urban center of Lagos, Nigeria. Clusters are 41 and 48 participating retail outlets in Kenya and Nigeria, respectively. Clients seeking care at participating outlets across all arms will be given the option of paying for a mRDT—at a study-recommended price—to be conducted at the outlet. In the provider-directed intervention arm, the outlet owner receives a small monetary incentive to perform the mRDT. In the client-directed intervention arm, the client receives a free ACT if they purchase an mRDT and receive a positive test result. Finally, the fourth study arm combines both the provider- and client-directed interventions. The diagnosis and treatment choices made during each transaction will be captured using a mobile phone app. Study outcomes will be collected through exit interviews with clients, who sought care for febrile illness, at each of the enrolled retail outlets. The primary outcome measure is the proportion of all ACTs that are sold to malaria test-positive clients in each study arm. For all secondary outcomes, we will evaluate the degree to which the interventions affect purchasing behavior among people seeking care for a febrile illness at the retail outlet. If our study demonstrates that malaria case management can be improved in the retail sector, it could reduce overconsumption of ACTs and enhance targeting of publicly funded treatment reimbursements, lowering the economic barrier to appropriate diagnosis and treatment for patients with malaria. ClinicalTrials.gov NCT04428307 , registered June 9, 2020, and NCT04428385 , registered June 9, 2020.

Household transition to cleaner cooking fuels (e.g. liquefied petroleum gas (LPG)) has historically been understood as an “energy ladder” with clean energy access resulting from improvements in household socioeconomic status (SES). Recent studies have demonstrated the importance of supply-side determinants in increasing clean cooking, yet few large-scale studies have assessed their significance quantitatively. As part of the CLEAN-Air(Africa) study, a population-based survey was conducted (N = 5,638) assessing cooking practices in peri-urban communities within Cameroon, Kenya and Ghana. Multilevel logistic and log-linear regression were used to assess socioeconomic and supply-side determinants of LPG usage (primary versus secondary fuel) and consumption (kilograms/capita/year), respectively. Supply-side factors (e.g. cylinder refill and transportation costs) and using single versus multi-burner stoves were better predictors of both the probability of primarily cooking with LPG and annual LPG consumption than household SES. These results suggest the need for policies promoting LPG access and stove equipment that meet household needs.

Background A large proportion of artemisinin-combination therapy (ACT) anti-malarial medicines is consumed by individuals that do not have malaria. The over-consumption of ACTs is largely driven by retail sales in high malaria-endemic countries to clients who have not received a confirmatory diagnosis. This study aims to target ACT sales to clients receiving a confirmatory diagnosis using malaria rapid diagnostic tests (mRDTs) at retail outlets in Kenya and Nigeria. Methods This study comprises two linked four-arm 2x2 factorial cluster randomized controlled trials focused on malaria diagnostic testing and conditional ACT subsidies with the goal to evaluate provider directed- and client-directed interventions. The study will be conducted at two contrasting study sites: a rural region around Webuye in western Kenya and the urban center of Lagos, Nigeria. Clusters are 41 and 48 participating retail outlets in Kenya and Nigeria, respectively. Clients seeking care at participating outlets across all arms will be given the option of paying for a mRDT – at a study-recommended price – to be conducted at the outlet. In the provider-directed intervention arm, the outlet owner receives a small monetary incentive to perform the mRDT. In the client-directed intervention arm, the client receives a free ACT if they purchase an mRDT and receive a positive test result. Finally, the fourth study arm combines both the provider- and client- directed interventions. The diagnosis and treatment choices made during each transaction will be captured using a mobile phone app. Study outcomes will be collected through exit interviews with clients, who sought care for febrile illness, at each of the enrolled retail outlets. Results The primary outcome measure is the proportion of all ACTs that are sold to malaria test-positive clients in each study arm. For all secondary outcomes we will evaluate the degree to which the interventions affect purchasing behavior among people seeking care for a febrile illness at the retail outlet. Conclusions If our study demonstrates that malaria case management can be improved in the retail sector, it could reduce overconsumption of ACTs and enhance targeting of publicly funded treatment reimbursements, lowering the economic barrier to appropriate diagnosis and treatment for patients with malaria.

Approximately 2.8 billion people rely on polluting cooking fuels (e.g. wood, kerosene), exposing them to health-damaging household air pollution. A key access barrier to clean cooking fuels (e.g. liquefied petroleum gas (LPG)) is affordability. By enabling households to pay in small increments, pay-as-you-go (PAYG) LPG could help promote clean cooking, and support continued LPG use through periods of economic downturn. We investigate the ability of PAYG LPG to sustain access to clean cooking from January 2018-June 2020, including during COVID-19 lockdown (March-June 2020) in an informal settlement in Nairobi, Kenya. We utilize novel PAYG LPG smart meter data to document cooking/spending patterns from 426 PAYG LPG customers and semi-structured interviews among a subset of seven households. Objective cooking pattern comparisons are made to those cooking with full 6kg cylinder LPG and polluting fuel users from 23 households in peri-urban Eldoret in western Kenya, using stove monitoring data. Customers’ average PAYG LPG consumption was 0.97 kg/capita/month (11.6 kg/capita/year) prior to COVID-19 lockdown. Despite adverse economic impacts of the lockdown, 95% of households continued using PAYG LPG, and consumption increased to 1.22 kg/capita/month (March-June 2020). Daily cooking events using PAYG LPG increased by 60% (1.07 events/day (pre-lockdown) to 1.72 events/day (lockdown)). In contrast, among seven households purchasing full 6kg cylinder LPG in Eldoret, average days/month using LPG declined by 75% (17 to four days) during COVID-19 lockdown. Median PAYG LPG payment frequency doubled (from every 8 days to every 4 days) during lockdown, while average payment amount was nearly halved (336 Kenyan Shillings (KSh)/US$3.08 to 179 KSh/US$1.64).Interviewed customers reported numerous benefits of PAYG LPG beyond fuel affordability, including safety, time savings, cylinder delivery and user-friendliness. PAYG LPG helped sustain clean cooking during COVID-19 lockdown, possibly averting increases in polluting cooking fuel use and associated household air pollution exposures.Graphical AbstractHighlightsFirst study to report long-term cooking/spending patterns using PAYG LPG smart meter data95% of 301 active PAYG LPG customers in February 2020 continued to use the fuel during COVID-19 lockdownDaily cooking events using PAYG LPG increased by 60% during COVID-19 lockdownMedian payment frequency increased 50%, while single payment amount decreased 50% during lockdownThree-quarters of PAYG LPG households in this study were first time LPG users

Background/Aim. Esophageal Cancer (EC) is the most common cancer in Kenya with age standardised rates of 17.6 per 100,000 in both sexes, compared to 5.9 worldwide. Traditional risk factors (e.g. sm...

Epigenetic mechanisms such as aberrant DNA methylation (DNAme) are known to drive esophageal squamous cell carcinoma (ESCC), yet they remain poorly understood. Here, we studied tumor-specific DNAme in ESCC cases from nine high-incidence countries of Africa, Asia, and South America. Infinium MethylationEPIC array was performed on 108 tumors and 51 normal tissues adjacent to the tumors (NAT) in the discovery phase, and targeted pyrosequencing was performed on 132 tumors and 36 NAT in the replication phase. Top genes for replication were prioritized by weighting methylation results using RNA-sequencing data from The Cancer Genome Atlas and GTEx and validated by qPCR. Methylome analysis comparing tumor and NAT identified 6,796 differentially methylated positions (DMP) and 866 differential methylated regions (DMR), with a 30% methylation (Δβ) difference. The majority of identified DMPs and DMRs were hypermethylated in tumors, particularly in promoters and gene-body regions of genes involved in transcription activation. The top three prioritized genes for replication, PAX9, SIM2, and THSD4, had similar methylation differences in the discovery and replication sets. These genes were exclusively expressed in normal esophageal tissues in GTEx and downregulated in tumors. The specificity and sensitivity of these DNAme events in discriminating tumors from NAT were assessed. Our study identified novel, robust, and crucial tumor-specific DNAme events in ESCC tumors across several high-incidence populations of the world. Methylome changes identified in this study may serve as potential targets for biomarker discovery and warrant further functional characterization. Significance: This largest genome-wide DNA methylation study on ESCC from high-incidence populations of the world identifies functionally relevant and robust DNAme events that could serve as potential tumor-specific markers.

Project Summary The overall objective of the BIGPIC study was to utilize a transdisciplinary implementation research approach to address the challenge of reducing CVD risk in low-resource settings. The central hypothesis is: group medical visits integrated into microfinance groups will be effective and cost-effective in reducing CVD risk among individuals with diabetes and at increased risk for diabetes in western Kenya, and that the key modifiable CVD risk factor to be addressed is BP. We hypothesized that group medical visits and microfinance may each reduce CVD risk, but the integration of group medical visits and microfinance will yield the largest gains. We further hypothesized that changes in social network characteristics may mediate the impact of interventions on the primary outcome, and that baseline social network characteristics may moderate the impact of interventions. The goal of this qualitative data collection project was to identify the contextual factors, facilitators, and barriers that may impact integration of group medical visits and microfinance for CVD risk reduction. Methods: A combination of qualitative research methods were conducted: 1) baraza (traditional community gathering) form of inquiry; and 2) focus group discussions among individuals with diabetes or at increased risk for diabetes, microfinance group members, and rural health workers. Trained research staff members led the discussions using structured question guides. Content analysis was performed with Nvivo using deductive and inductive codes that were then grouped into themes. Results: Participants expressed interest in participating in microfinance and group medical visits, but cited several key challenges: 1) stigma of chronic disease, 2) earned skepticism of the health system, and 3) socio-economic fragility. Data Collection Overview We conducted 5 mabaraza and 16 FGDs. A total of 205 individuals (113 men and 92 women) participated in the mabaraza, while 162 individuals (57 men and 105 women) participated in the FGDs. As described in the project description, interviews and FGDs were organized and moderated by research team members, recorded and transcribed. They were also translated from Swahili to English, when applicable. The data repository contains representative excerpts from the transcripts. They are organized by code (including a definition), and labeled to provide information regarding sex of the participant (male or female), as well as the type of participant (patient, clinician, member of a microfinance group, or participant in a Baraza). Data Overview This project consists of qualitative data transcripts from interviews and focus group discussions (FGDs) conducted as part of the BIGPIC Study in order to assess factors impacting receptiveness to group medical visits and microfinance for non-communicable disease care in rural Kenya. Interviews and discussions were organized and moderated by research team members, recorded and transcribed. They were also translated from Swahili to English, when applicable. They are organized by code (including a definition), and labeled to provide information regarding sex of the participant (male or female), as well as the type of participant (patient, clinician, member of a microfinance group, or participant in a Baraza). Organization of Shared Data A table of representative excerpts sorted by code (including definition) is included. All codes are included. Each quote is labeled to provide information regarding sex of the participant (male or female), as well as the type of participant (patient, clinician, member of a microfinance group, or participant in a Baraza. Full transcripts of the interviews conducted cannot be shared because publicly sharing them would violate the agreement to which the participants consented.