Efficacy of a Single Oral Dose of Artesunate plus Sulfalene-Pyrimethamineversus Praziquantel in the Treatment of Schistosoma mansoni in Kenyan Children: An Open-Label, Randomized, Exploratory Trial.

Unlike praziquantel, artemisinin derivatives are effective against juvenile schistosome worms. We assessed the efficacy and safety of a single oral dose of artesunate plus sulfalene-pyrimethamine versus praziquantel in the treatment of Schistosoma mansoni. Seventy-three schoolchildren (aged 9-15 years) with confirmed S. mansoni infection in Rarieda, western Kenya, were randomly assigned to receive either a single oral dose of artesunate plus sulfalene-pyrimethamine (n = 39) or a single dose of praziquantel (n = 34). The cure and egg reduction rates at 4 weeks posttreatment were 69.4% (25/36) versus 80.6% (25/31) (P = 0.297) and 99.1% versus 97.5% (P = 0.607) in the artesunate plus sulfalene-pyrimethamine group versus praziquantel group, respectively. Fourteen children developed adverse events, and there were no serious adverse events. A single oral dose of artesunate plus sulfalene-pyrimethamine has efficacy comparable to that of praziquantel in the treatment of S. mansoni, but these results should be confirmed in larger randomized controlled trials.

SCHISTOACT: a protocol for an open-label, five-arm, non-inferiority, individually randomized controlled trial of the efficacy and safety of praziquantel plus artemisinin-based combinations in the treatment of Schistosoma mansoni infection.

BACKGROUND: Schistosomiasis control relies on praziquantel for preventive chemotherapy. Alternative drugs are needed for the treatment and control of schistosomiasis. Praziquantel is effective against adult schistosome worms but ineffective against larval stages of the parasite and cannot prevent re-infection or interrupt the transmission of infection. Continued reliance on praziquantel for wide-scale schistosomiasis control will likely accelerate the emergence of drug resistance. Artemisinin derivatives are effective against the juvenile stages but ineffective against adult worms. The SCHISTOACT study aimed to evaluate the efficacy and safety of praziquantel plus one of four artemisinin-based combinations in treating Schistosoma mansoni infection in Kenya. METHODS: The SCHISTOACT study is an open-label, head-to-head, five-arm, proof-of-concept, non-inferiority, individually randomized controlled trial with a follow-up of 12 weeks. A total of 540 primary school-aged children from the Mwea area, Kirinyaga County in central Kenya, diagnosed with S. mansoni infection (by Kato-Katz method) are randomly allocated (1:1:1:1:1) to a single dose of praziquantel plus a 3-day course of artesunate-sulfalene/pyrimethamine, or artesunate-amodiaquine, or artesunate plus mefloquine, or dihydroartemisinin-piperaquine, or praziquantel control arm. The primary endpoints are efficacy (cure rate, assessed by microscopy) and safety (adverse events) of each study arm 6 weeks after treatment. Secondary endpoints include cumulative cure rate, egg reduction rate, and re-infection 12 weeks after treatment. The non-inferiority margin is set at - 10 for the risk difference in cure rates between praziquantel and the combined treatment. DISCUSSION: This study assesses a strategy for repurposing artemisinin-based combination therapies (ACTs) for treating schistosomiasis. It adopts a head-to-head comparison of four different ACTs to test a non-inferiority hypothesis and to strengthen local capacity to conduct clinical trials for interventions against neglected tropical diseases. TRIAL REGISTRATION: Pan-African Clinical Trials Registry PACTR202001919442161 . Retrospectively registered on 6 January 2020.

Comparing travel behaviour characteristics and correlates between large and small Kenyan cities (Nairobi versus Kisumu).

Understanding urban travel behaviour is crucial for planning healthy and sustainable cities. Africa is urbanising at one of the fastest rates in the world and urgently needs this knowledge. However, the data and literature on urban travel behaviour, their correlates, and their variation across African cities are limited. We aimed to describe and compare travel behaviour characteristics and correlates of two Kenyan cities (Nairobi and Kisumu). We analysed data from 16,793 participants (10,000 households) in a 2013 Japan International Cooperation Agency (JICA) household travel survey in Nairobi and 5790 participants (2760 households) in a 2016 Institute for Transportation and Development Policy (ITDP) household travel survey in Kisumu. We used the Heckman selection model to explore correlations of travel duration by trip mode. The proportion of individuals reporting no trips was far higher in Kisumu (47% vs 5%). For participants with trips, the mean number [lower - upper quartiles] of daily trips was similar (Kisumu (2.2 [2-2] versus 2.4 [2-2] trips), but total daily travel durations were lower in Kisumu (65 [30-80] versus 116 [60-150] minutes). Walking was the most common trip mode in both cities (61% in Kisumu and 42% in Nairobi), followed by motorcycles (17%), matatus (minibuses) (11%), and cars (5%) in Kisumu; and matatus (28%), cars (12%) and buses (12%) in Nairobi. In both cities, females were less likely to make trips, and when they did, they travelled for shorter durations; people living in households with higher incomes were more likely to travel and did so for longer durations. Gender, income, occupation, and household vehicle ownership were associated differently with trip making, use of transport modes and daily travel times in cities. These findings illustrate marked differences in reported travel behaviour characteristics and correlates within the same country, indicating setting-dependent influences on travel behaviour. More sub-national data collection and harmonisation are needed to build a more nuanced understanding of patterns and drivers of travel behaviour in African cities.

Socioeconomic inequalities in food purchasing practices and expenditure patterns: Results from a cross-sectional household survey in western Kenya.

Introduction: Socioeconomic inequalities contribute to poor health. Inequitable access to diverse and healthy foods can be a risk factor for non-communicable diseases, especially in individuals of low socioeconomic status. We examined the extent of socioeconomic inequalities in food purchasing practices, expenditure, and consumption in a resource-poor setting in Kenya. Methods: We conducted a secondary analysis of baseline cross-sectional data from a natural experimental study with a sample size of 512 individuals from 376 households in western Kenya. Data were collected on household food sources, expenditure and food consumption. Household socioeconomic status (SES) was assessed using the multiple correspondence analysis (MCA) model. Concentration indices (Ci) and multivariable linear regression models were used to establish socioeconomic inequalities. Results: About half (47.9%) of individuals achieved a minimum level of dietary diversity with the majority coming from wealthier households. The two most consumed food groups were grains and roots (97.5%, n = 499) and dark green leafy vegetables (73.8%, n = 378), but these did not vary by SES. The consumption of dark green leafy vegetables was similar across wealth quantiles (Ci = 0.014, p = 0.314). Overall, the wealthier households spent significantly more money on food purchases with a median of USD 50 (IQR = 60) in a month compared to the poorest who spent a median of USD 40 (IQR = 40). Of all the sources of food, the highest amount was spent at open-air markets median of USD 20 (IQR = 30) and the expenditure did not vary significantly by SES (Ci = 0.4, p = 0.684). The higher the socioeconomic status the higher the total amount spent on food purchases. In multivariable regression analysis, household SES was a significant determinant of food expenditure [Adjusted coefficient = 6.09 (95%confidence interval CI = 2.19, 9.99)]. Conclusion: Wealthier households spent more money on food compared to the poorest households, especially on buying food at supermarkets. Individuals from the poorest households were dominant in eating grains and roots and less likely to consume a variety of food groups, including pulses, dairy, eggs and fruits, and vegetables. Individuals from the poorest households were also less likely to achieve adequate dietary diversity. Deliberate policies on diet and nutrition are required to address socioeconomic inequalities in food purchasing practices.

Foodscapes, finance, and faith: Multi-sectoral stakeholder perspectives on the local population health and wellbeing in an urbanizing area in Kenya.

Introduction: Rapid urbanization (growth of cities) can upset the local population's health and wellbeing by creating obesogenic environments which increase the burden of non-communicable diseases (NCDs). It is important to understand how stakeholders perceive the impact of urbanizing interventions (such as the construction of a new hypermarket) on the health and wellbeing of local populations. Because low- and middle-income countries (LMICs) lack the reliable infrastructure to mitigate the effects of obesogenic environments, so engaging stakeholders who influence dietary habits is one population-level strategy for reducing the burden of NCDs caused by newly built developments. Methods: We conducted key informant interviews with 36 stakeholders (25 regulatory and 11 local community stakeholders) from Kisumu and Homa Bay Counties of Western Kenya in June 2019. We collected stakeholders' perspectives on the impacts of a new Mall and supermarket in Kisumu, and existing supermarkets in Homa Bay on the health and wellbeing of local populations. Results: Through thematic discourse analysis, we noted that some stakeholders thought supermarkets enabled access to unhealthy food items despite these outlets being also reliable food sources for discerning shoppers. Others linked the changing physical environment to both an increase in pollution and different types of diseases. Stakeholders were unsure if the pricing and convenience of supermarkets would stop local populations from buying from their usual small-scale food vendors. The key finding of this study was that engaging relevant stakeholders as part of population health impact assessments of new developments in cities are important as it directs focus on health equity and prevention in instances of resource constraints. The findings highlight, also, that community members have a strong awareness of the potential for interventions that would improve the health and wellbeing of local populations.

Navigating the local foodscape: qualitative investigation of food retail and dietary preferences in Kisumu and Homa Bay Counties, western Kenya.

INTRODUCTION: Non-communicable diseases have risen markedly over the last decade. A phenomenon that was mainly endemic in high-income countries has now visibly encroached on low and middle-income settings. A major contributor to this is a shift towards unhealthy dietary behavior. This study aimed to examine the complex interplay between people's characteristics and the environment to understand how these influenced food choices and practices in Western Kenya. METHODS: This study used semi-structured guides to conduct in-depth interviews and focus group discussions with both male and female members of the community, across various socioeconomic groups, from Kisumu and Homa Bay Counties to further understand their perspectives on the influences of dietary behavior. Voice data was captured using digital voice recorders, transcribed verbatim, and translated to English. Data analysis adopted an exploratory and inductive analysis approach. Coded responses were analyzed using NVIVO 12 PRO software. RESULTS: Intrapersonal levels of influence included: Age, the nutritional value of food, occupation, perceived satiety of some foods as opposed to others, religion, and medical reasons. The majority of the participants mentioned location as the main source of influence at the community level reflected by the regional staple foodscape. Others include seasonality of produce, social pressure, and availability of food in the market. Pricing of food and distance to food markets was mentioned as the major macro-level influence. This was followed by an increase in population and road infrastructure. CONCLUSION: This study demonstrated that understanding dietary preferences are complex. Future interventions should not only consider intrapersonal and interpersonal influences when aiming to promote healthy eating among communities but also need to target the community and macro environments. This means that nutrition promotion strategies should focus on multiple levels of influence that broaden options for interventions. However, government interventions in addressing food access, affordability, and marketing remain essential to any significant change.

Review of 2022 WHO guidelines on the control and elimination of schistosomiasis.

Schistosomiasis is a helminthiasis infecting approximately 250 million people worldwide. In 2001, the World Health Assembly (WHA) 54.19 resolution defined a new global strategy for control of schistosomiasis through preventive chemotherapy programmes. This resolution culminated in the 2006 WHO guidelines that recommended empirical treatment by mass drug administration with praziquantel, predominately to school-aged children in endemic settings at regular intervals. Since then, school-based and community-based preventive chemotherapy programmes have been scaled-up, reducing schistosomiasis-associated morbidity. Over the past 15 years, new scientific evidence-combined with a more ambitious goal of eliminating schistosomiasis and an increase in the global donated supply of praziquantel-has highlighted the need to update public health guidance worldwide. In February, 2022, WHO published new guidelines with six recommendations to update the global public health strategy against schistosomiasis, including expansion of preventive chemotherapy eligibility from the predominant group of school-aged children to all age groups (2 years and older), lowering the prevalence threshold for annual preventive chemotherapy, and increasing the frequency of treatment. This Review, written by the 2018-2022 Schistosomiasis Guidelines Development Group and its international partners, presents a summary of the new WHO guideline recommendations for schistosomiasis along with their historical context, supporting evidence, implications for public health implementation, and future research needs.

Comparison of household socioeconomic status classification methods and effects on risk estimation: lessons from a natural experimental study, Kisumu, Western Kenya.

INTRODUCTION: Low household socioeconomic status is associated with unhealthy behaviours including poor diet and adverse health outcomes. Different methods leading to variations in SES classification has the potential to generate spurious research findings or misinform policy. In low and middle-income countries, there are additional complexities in defining household SES, a need for fieldwork to be conducted efficiently, and a dearth of information on how classification could impact estimation of disease risk. METHODS: Using cross-sectional data from 200 households in Kisumu County, Western Kenya, we compared three approaches of classifying households into low, middle, or high SES: fieldworkers (FWs), Community Health Volunteers (CHVs), and a Multiple Correspondence Analysis econometric model (MCA). We estimated the sensitivity, specificity, inter-rater reliability and misclassification of the three methods using MCA as a comparator. We applied an unadjusted generalized linear model to determine prevalence ratios to assess the association of household SES status with a self-reported diagnosis of diabetes or hypertension for one household member. RESULTS: Compared with MCA, FWs successfully classified 21.7% (95%CI = 14.4%-31.4%) of low SES households, 32.8% (95%CI = 23.2-44.3) of middle SES households, and no high SES households. CHVs successfully classified 22.5% (95%CI = 14.5%-33.1%) of low SES households, 32.8% (95%CI = 23.2%-44.3%) of middle SES households, and no high SES households. The level of agreement in SES classification was similar between FWs and CHVs but poor compared to MCA, particularly for high SES. None of the three methods differed in estimating the risk of hypertension or diabetes. CONCLUSIONS: FW and CHV assessments are community-driven methods for SES classification. Compared to MCA, these approaches appeared biased towards low or middle SES households and not sensitive to high household SES. The three methods did not differ in risk estimation for diabetes and hypertension. A mix of approaches and further evaluation to refine SES classification methodology is recommended.

Efficacy of 3-day low dose quinine plus clindamycin versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children (CLINDAQUINE): an open-label randomized trial.

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.

Adolescent Levers for a Diet and Physical Activity Intervention Across Socioecological Levels in Kenya, South Africa, Cameroon, and Jamaica: Mixed Methods Study Protocol.

BACKGROUND: The increasing burden of noncommunicable diseases that are prevalent in low- and middle-income countries (LMICs) is largely attributed to modifiable behavioral risk factors such as unhealthy diets and insufficient physical activity (PA). The adolescent stage, defined as 10 to 24 years of age, is an important formative phase of life and offers an opportunity to reduce the risk of noncommunicable diseases across the life course and for future generations. OBJECTIVE: The aim of this paper is to describe a protocol for a study using a convergent mixed methods design to explore exposures in the household, neighborhood, school, and the journey from home to school that may influence diet and PA behaviors in adolescents from LMICs. METHODS: Male and female adolescents (n≥150) aged between 13 and 24 years will be recruited from selected high schools or households in project site countries to ensure the socioeconomic diversity of perspectives and experiences at the individual, home, and neighborhood levels. The project will be conducted at 5 sites in 4 countries: Kenya, Cameroon, Jamaica, and South Africa (Cape Town and Johannesburg). Data on anthropometric measures, food intake, and PA knowledge and behavior will be collected using self-report questionnaires. In addition, a small number of learners (n=30-45) from each site will be selected as citizen scientists to capture data (photographs, audio notes, text, and geolocations) on their lived experiences in relation to food and PA in their homes, the journey to and from school, and the school and neighborhood environments using a mobile app, and for objective PA measurements. In-depth interviews will be conducted with the citizen scientists and their caregivers to explore household experiences and determinants of food intake and foodways, as well as the PA of household members. RESULTS: The study described in this protocol paper was primarily funded through a UK National Institute for Health Research grant in 2017 and approved by the relevant institutional ethics review boards in the country sites (South Africa, Cameroun, and Jamaica in 2019, and Kenya in 2020). As of December 23, 2020, we had completed data collection from adolescents (n≥150) in all the country sites, except Kenya, and data collection for the subgroup (n=30-45) is ongoing. Data analysis is ongoing and the output of findings from the study described in this protocol is expected to be published by 2022. CONCLUSIONS: This project protocol contributes to research that focuses on adolescents and the socioecological determinants of food intake and PA in LMIC settings. It includes innovative methodologies to interrogate and map the contexts of these determinants and will generate much-needed data to understand the multilevel system of factors that can be leveraged through upstream and downstream strategies and interventions to improve health outcomes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/26739.

Cross-Sectional Association of Food Source with Food Insecurity, Dietary Diversity and Body Mass Index in Western Kenya.

The triple burden of malnutrition in many low- and middle-income countries (LMICs) is partly a result of changing food environments and a shift from traditional diets to high-calorie Western-style diets. Exploring the relationship between food sources and food- and nutrition-related outcomes is important to understanding how changes in food environments may affect nutrition in LMICs. This study examined associations of household food source with household food insecurity, individual dietary diversity and individual body mass index in Western Kenya. Interview-administered questionnaire and anthropometric data from 493 adults living in 376 randomly-selected households were collected in 2019. Adjusted regression analyses were used to assess the association of food source with measures of food insecurity, dietary diversity and body mass index. Notably, participants that reported rearing domesticated animals for consumption ('own livestock') had lower odds of moderate or severe household food insecurity (odds ratio (OR) = 0.29 (95% CI: 0.09, 0.96)) and those that reported buying food from supermarkets had lower odds of moderate or severe household food insecurity (borderline significant, OR = 0.37 (95% CI: 0.14, 1.00)), increased dietary diversity scores (Poisson coefficient = 0.17 (95% CI: 0.10, 0.24)) and higher odds of achieving minimum dietary diversity (OR = 2.84 (95% CI: 1.79, 4.49)). Our findings provide insight into the relationship between food environments, dietary patterns and nutrition in Kenya, and suggest that interventions that influence household food source may impact the malnutrition burden in this context.

Impacts of a New Supermarket on Dietary Behavior and the Local Foodscape in Kisumu, Kenya: Protocol for a Mixed Methods, Natural Experimental Study.

BACKGROUND: Access to healthy food is considered a key determinant of dietary behavior, and there is mixed evidence that living near a supermarket is associated with a healthier diet. In Africa, supermarkets may contribute to the nutrition transition by offering both healthy and unhealthy foods and by replacing traditional food sellers. In Kisumu, Kenya, a planned hypermarket (ie, a supermarket combined with a department store) will form the basis for a natural experimental evaluation. OBJECTIVE: The aim of this study is to explore the impacts of a new hypermarket on food shopping practices, dietary behaviors, physical activity patterns, and body composition among local residents and to identify concurrent changes in the local foodscape. We also aim to explore how impacts and associations vary by socioeconomic status. METHODS: We employ a mixed methods, longitudinal study design. Two study areas were defined: the hypermarket intervention area (ie, Kisumu) and a comparison area with no hypermarket (ie, Homabay). The study is comprised of 4 pieces of primary data collection: a quantitative household survey with local residents, a qualitative study consisting of focus group discussions with local residents and semistructured interviews with government and private sector stakeholders, an audit of the local foodscape using on-the-ground data collection, and an intercept survey of shoppers in the hypermarket. Assessments will be undertaken at baseline and approximately 1 year after the hypermarket opens. RESULTS: Baseline assessments were conducted from March 2019 to June 2019. From a total sampling frame of 400 households, we recruited 376 of these households, giving an overall response rate of 94.0%. The household survey was completed by 516 individuals within these households. Across the two study areas, 8 focus groups and 44 stakeholder interviews were conducted, and 1920 food outlets were geocoded. CONCLUSIONS: This study aims to further the understanding of the relationship between food retail and dietary behaviors in Kenya. Baseline assessments for the study have been completed. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/17814.

The global diet and activity research (GDAR) network: a global public health partnership to address upstream NCD risk factors in urban low and middle-income contexts.

BACKGROUND: Non-communicable diseases (NCDs) are the leading cause of death globally. While upstream approaches to tackle NCD risk factors of poor quality diets and physical inactivity have been trialled in high income countries (HICs), there is little evidence from low and middle-income countries (LMICs) that bear a disproportionate NCD burden. Sub-Saharan Africa and the Caribbean are therefore the focus regions for a novel global health partnership to address upstream determinants of NCDs. PARTNERSHIP: The Global Diet and Activity research Network (GDAR Network) was formed in July 2017 with funding from the UK National Institute for Health Research (NIHR) Global Health Research Units and Groups Programme. We describe the GDAR Network as a case example and a potential model for research generation and capacity strengthening for others committed to addressing the upstream determinants of NCDs in LMICs. We highlight the dual equity targets of research generation and capacity strengthening in the description of the four work packages. The work packages focus on learning from the past through identifying evidence and policy gaps and priorities, understanding the present through adolescent lived experiences of healthy eating and physical activity, and co-designing future interventions with non-academic stakeholders. CONCLUSION: We present five lessons learned to date from the GDAR Network activities that can benefit other global health research partnerships. We close with a summary of the GDAR Network contribution to cultivating sustainable capacity strengthening and cutting-edge policy-relevant research as a beacon to exemplify the need for such collaborative groups.

Implications of COVID-19 control measures for diet and physical activity, and lessons for addressing other pandemics facing rapidly urbanising countries.

At the time of writing, it is unclear how the COVID-19 pandemic will play out in rapidly urbanising regions of the world. In these regions, the realities of large overcrowded informal settlements, a high burden of infectious and non-communicable diseases, as well as malnutrition and precarity of livelihoods, have raised added concerns about the potential impact of the COVID-19 pandemic in these contexts. COVID-19 infection control measures have been shown to have some effects in slowing down the progress of the pandemic, effectively buying time to prepare the healthcare system. However, there has been less of a focus on the indirect impacts of these measures on health behaviours and the consequent health risks, particularly in the most vulnerable. In this current debate piece, focusing on two of the four risk factors that contribute to >80% of the NCD burden, we consider the possible ways that the restrictions put in place to control the pandemic, have the potential to impact on dietary and physical activity behaviours and their determinants. By considering mitigation responses implemented by governments in several LMIC cities, we identify key lessons that highlight the potential of economic, political, food and built environment sectors, mobilised during the pandemic, to retain health as a priority beyond the context of pandemic response. Such whole-of society approaches are feasible and necessary to support equitable healthy eating and active living required to address other epidemics and to lower the baseline need for healthcare in the long term.

Obstructive Sleep Apnea Awareness among Primary Care Physicians in Africa.

Rationale: Obstructive sleep apnea (OSA) is a significant health problem among adults and children globally, resulting in decreased quality of life and increased costs of healthcare. For optimal clinical care, primary care physicians should be familiar with OSA and confident in their ability to screen, diagnose, and manage this condition.Objectives: To assess the knowledge, attitudes, and practices of primary care physicians in Kenya, Nigeria, and South Africa regarding OSA in adults and children.Methods: We conducted a multicenter cross-sectional survey in Kenya (Nairobi), Nigeria (Edo State), and South Africa (Cape Town) between April 2016 and July 2017. At least 40 participants were randomly selected from a register of primary care physicians at each site. Potential participants were contacted to receive online/paper-based, validated OSA Knowledge and Attitudes (OSAKA) and OSAKA in Children (OSAKA-KIDS) questionnaires related to adults and children, respectively. The median percentage knowledge scores and proportions of favorable attitude were computed and current diagnostic and referral practices were documented.Results: The median OSAKA knowledge scores were 83.3% (interquartile range [IQR], 77.8-88.9), 66.7% (IQR, 55.6-77.8), and 61.1% (IQR, 55.6-77.8) among South African, Kenyan, and Nigerian physicians, respectively. For OSAKA-KIDS, the median knowledge scores were 61.1% (IQR, 50.0-72.2), 64.2% (IQR, 35.3-93.2), and 58.3% (IQR, 44.4-66.7) among South African, Kenyan, and Nigerian physicians, respectively. Most physicians (90-94%) considered adult and pediatric OSA very/extremely important. Fewer physicians agreed/strongly agreed that they were confident about OSA diagnosis (55%), management (25%), and continuous positive airway pressure (18%) use in adults. Even fewer physicians agreed/strongly agreed that they were confident about pediatric OSA diagnosis (35%), management (21%), and continuous positive airway pressure use (18%). South African physicians mainly prescribed polysomnography (51%) and overnight oximetry (22%), whereas 49% of Nigerian physicians and 65% of Kenyan physicians commonly requested lateral cervical radiography.Conclusions: Primary care physicians in South Africa, Nigeria, and Kenya considered OSA to be important but had modest knowledge about OSA in adults and children, and had a low perceived confidence in adult and pediatric management. Focused educational interventions during undergraduate training and continuing professional development programs may improve primary physicians' knowledge about OSA and its diagnosis and management.

Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa.

BACKGROUND: In 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa. METHODS: Using data on the anti-infectivity efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0.15-0.4 mg PQ base/kg for children aged 1-5 years and 0.15-0.5 mg PQ base/kg for individuals aged ≥6 years (therapeutic indices 2.7 and 3.3, respectively). We chose 1.25 mg PQ base for infants aged 6-11 months because they have the highest rate of baseline anaemia and the highest risks of AHA and CSA. We modelled an anthropometric database of 661,979 African individuals aged ≥6 months (549,127 healthy individuals, 28,466 malaria patients and 84,386 individuals with other infections/illnesses) by the Box-Cox transformation power exponential and tested PQ doses of 1-15 mg base, selecting dosing groups based on calculated mg/kg PQ doses. RESULTS: From the Box-Cox transformation power exponential model, five age categories were selected: (i) 6-11 months (n = 39,886, 6.03%), (ii) 1-5 years (n = 261,036, 45.46%), (iii) 6-9 years (n = 20,770, 3.14%), (iv) 10-14 years (n = 12,155, 1.84%) and (v) ≥15 years (n = 328,132, 49.57%) to receive 1.25, 2.5, 5, 7.5 and 15 mg PQ base for corresponding median (1st and 99th centiles) mg/kg PQ base of: (i) 0.16 (0.12-0.25), (ii) 0.21 (0.13-0.37), (iii) 0.25 (0.16-0.38), (iv) 0.26 (0.15-0.38) and (v) 0.27 (0.17-0.40). The proportions of individuals predicted to receive optimal therapeutic PQ doses were: 73.2 (29,180/39,886), 93.7 (244,537/261,036), 99.6 (20,690/20,770), 99.4 (12,086/12,155) and 99.8% (327,620/328,132), respectively. CONCLUSIONS: We plan to test the safety of this age-based dosing regimen in a large randomised placebo-controlled trial (ISRCTN11594437) of uncomplicated falciparum malaria in G6PDd African children aged 0.5 - 11 years. If the regimen is safe and demonstrates adequate pharmacokinetics, it should be used to support malaria elimination.

High and Heterogeneous Prevalence of Asymptomatic and Sub-microscopic Malaria Infections on Islands in Lake Victoria, Kenya.

Kenya is intensifying its national efforts in malaria control to achieve malaria elimination. Detailed characterization of malaria infection among populations living in the areas where the disease is endemic in Kenya is a crucial priority, especially for planning and evaluating future malaria elimination strategy. This study aimed to investigate the distribution and extent of malaria infection on islands in Lake Victoria of Kenya to aid in designing new interventions for malaria elimination. Five cross-sectional surveys were conducted between January 2012 and August 2014 on four islands (Mfangano, Takawiri, Kibuogi and Ngodhe) in Lake Victoria and a coastal mainland (Ungoye). Malaria prevalence varied significantly among settings: highest in Ungoye, followed by the large island of Mfangano and lowest in the three remaining small islands. Of the 3867 malaria infections detected by PCR, 91.8% were asymptomatic, 50.3% were sub-microscopic, of which 94% were also asymptomatic. We observed geographical differences and age dependency in both proportion of sub-microscopic infections and asymptomatic parasite carriage. Our findings highlighted the local heterogeneity in malaria prevalence on islands and a coastal area in Lake Victoria, and provided support for the inclusion of mass drug administration as a component of the intervention package to eliminate malaria on islands.

Tuberculosis and latent tuberculosis infection among healthcare workers in Kisumu, Kenya.

OBJECTIVE: To assess prevalence and occupational risk factors of latent TB infection and history of TB disease ascribed to work in a healthcare setting in western Kenya. METHODS: We conducted a cross-sectional survey among healthcare workers in western Kenya in 2013. They were recruited from dispensaries, health centres and hospitals that offer both TB and HIV services. School workers from the health facilities' catchment communities were randomly selected to serve as the community comparison group. Latent TB infection was diagnosed by tuberculin skin testing. HIV status of participants was assessed. Using a logistic regression model, we determined the adjusted odds of latent TB infection among healthcare workers compared to school workers; and among healthcare workers only, we assessed work-related risk factors for latent TB infection. RESULTS: We enrolled 1005 healthcare workers and 411 school workers. Approximately 60% of both groups were female. A total of 22% of 958 healthcare workers and 12% of 392 school workers tested HIV positive. Prevalence of self-reported history of TB disease was 7.4% among healthcare workers and 3.6% among school workers. Prevalence of latent TB infection was 60% among healthcare workers and 48% among school workers. Adjusted odds of latent TB infection were 1.5 times higher among healthcare workers than school workers (95% confidence interval 1.2-2.0). Healthcare workers at all three facility types had similar prevalence of latent TB infection (P = 0.72), but increasing years of employment was associated with increased odds of LTBI (P < 0.01). CONCLUSION: Healthcare workers at facilities in western Kenya which offer TB and HIV services are at increased risk of latent TB infection, and the risk is similar across facility types. Implementation of WHO-recommended TB infection control measures are urgently needed in health facilities to protect healthcare workers.

Fixed dose artesunate amodiaquine - a phase IIb, randomized comparative trial with non-fixed artesunate amodiaquine.

BACKGROUND: Pharmacokinetic (PK) and pharmacodynamic (PD) data are limited for artesunate (AS) and amodiaquine (AQ) in uncomplicated Plasmodium falciparum. METHODS: From 2007-8, 54 P. falciparum-infected, Kenyan adults were assigned randomly fixed dose (FD) ASAQ (n = 26) or non-fixed (NF) ASAQ (n = 28). Total doses were 600 mg AS (both arms) + 1,620 mg (FD) or 1,836 mg (NF)AQ. Follow-up extended over 28 days. PK data were collected for AS, dihydroartemisinin (DHA), AS + DHA combined as DHA equivalents (DHAeq), AQ, desethylamodiaquine (DAQ),and their relationships assessed against the PD collected data consisting of parasitological efficacy, adverse events (AEs), and the Bazett's corrected QTinterval (QTcB). RESULTS: Mean AUC 0-72 of dihydroartemisinin equivalents (DHAeq) when administered as a fixed dose (FD) compared to NF dose were similar: 24.2 ±4.6 vs 26.4±6.9 µmol*h/L (p = 0.68) Parasite clearance rates were also similar after 24 hrs: 17/25 (68%) vs 18/28(64.3%) (p = 0.86),as well as at 48 hrs: 25/8 (100%)vs 26 (92.9%)/28 (p = 0.49). Mean FD vs NF DAQ AUC0-28 were 27.6±3.19 vs 32.7±5.53 mg*h/L (p = 0.0005). Two PCR-proven new infections occurred on Day (D) 28 for estimated, in vivo, DAQ minimum inhibitory concentrations of 15.2 and 27.5 ng/mL. Combining the FD and NF arms, the mean QTcB at D2+4 hrs increased significantly (p = 0.0059) vs baseline: 420 vs410 ms (∆ = 9.02 (95% confidence interval 2.72-15.31 ms), explained by falling heart rates, increasing DAQ concentrations and female sex in a general linear mixed effects model. Ten of 108 (9.26%) AEs (5/arm) reported by 37/54 (68.5%) patients were possibly or probably drug related. Severe, asymptomatic neutropaenia developed in 2/47 (4.25%) patients on D28: 574/µL (vsD0: 5,075/µL), and 777/µL (vsD0: 3,778/µL). CONCLUSIONS: Tolerability of both formulations was good. For QTcB, a parameter for ECG modifications, increases were modest and due to rising DAQ concentrations and falling heart rates as malaria resolved. Rapid parasite clearance rates and no resistant infections suggest effective pharmacokinetics of both formulations.