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Abstract Access to safe drinking water sources and appropriate sanitation facilities remains a dream in low and middle-income countries including South Africa. This study identified the origin of faecal pollution by using quantitative polymerase chain reaction (qPCR) targeting host-specific Bacteroidales genetic markers to track the distribution of human-specific (BacHum) and animal-specific (cattle—BacCow, chicken—Cytb, pig—Pig-2-Bac, dog—BacCan) markers in water sources used by rural communities of the Vhembe District Municipality (VDM). Results revealed the prevalence of BacHum, BacCow, and BacCan in all surface water sources in Thulamela Local Municipality (TLM) and Collins Chabane Local Municipality (CLM) during wet (100%) and dry seasons (50–75%). Cytb was not detected in untreated spring water in TLM and CLM, and Pig-2-Bac was not detected in untreated hand-dug well water in TLM during both seasons. Household-level analysis detected Cytb (28.8% wet, 17.5% dry), BacHum (34.4% wet, 25% dry for Pig-2-Bac) in stored untreated spring water in CLM, and Cytb (42.9% wet, 28.5% dry) in untreated hand-dug well water in TLM. Despite differences in detection frequencies of host-specific Bacteroidales, the study highlights the public health concern of faecal pollution in rural VDM households.

Background Tuberculosis (TB) is a leading cause of death worldwide with over 90% of reported cases occurring in low- and middle-income countries (LMICs). Pre-treatment loss to follow-up (PTLFU) is a key contributor to TB mortality and infection transmission. Objectives We performed a scoping review to map available evidence on interventions to reduce PTLFU in adults with pulmonary TB, identify gaps in existing knowledge, and develop a conceptual framework to guide intervention implementation. Methods We searched eight electronic databases up to February 6 2024, medRxiv for pre-prints, and reference lists of included studies. Two review authors independently selected studies and extracted data using a predesigned form. We analysed data descriptively, presented findings in a narrative summary and developed a conceptual framework based on the Practical, Robust Implementation, and Sustainability Model to map the factors for effective intervention implementation. Results We reviewed 1262 records and included 17 studies. Most studies were randomized controlled trials (8/17, 47%). Intervention barriers included stigma and inadequate resources; enablers included mobile phones and TB testing and results on the same day. We identified eight interventions that reduced PTLFU: treatment support groups; mobile notifications; community health workers; integrated HIV/TB services; Xpert MTB/RIF as the initial diagnostic test; computer-aided detection with chest radiography screening; active linkage to care; and multi-component strategies. Conclusion Given the variation of healthcare settings, TB programs should consider contextual factors such as user acceptability, political commitment, resources, and infrastructure before adopting an intervention. Future research should utilize qualitative study designs, be people-centred, and include social and economic factors affecting PTLFU.

Key Clinical Message A 3 ‐year‐old boy presented with a forehead nodular mass, which was excised and confirmed histologically as Juvenile Xanthogranulomma (JXG). It affects children with a predilection for the head and neck region. A relatively rare, benign, histiocytic proliferative cutaneous disorder with a potential for malignancy. A prompt and wide resection is recommended.

Background Vaccination is an important public health intervention, but not everyone benefits equally. Biological, social and structural factors render some communities vulnerable and unable to secure optimal health benefits from vaccination programmes. This drives health inequity and undermines wider vaccine impact by allowing the persistence of non-immune communities as foci for recurrent disease outbreaks. The NIHR Global Health Research Group on Vaccines for vulnerable people in Africa (VAnguard) aims to understand how biological, social, and structural factors interact to impair vaccine impact in vulnerable African communities. Methods The VAnguard project will be implemented through three thematic work packages (1-3) and four cross-cutting work packages (4-7). Work package 1 will investigate the biological drivers and mechanisms of population differences in vaccine responses. Work package 2 will support the understanding of how structural, social and biological determinants of vaccine response interrelate to determine vaccine impact. Work package 3 will synthesise data and lead analyses to develop, model and test community-based integrated strategies to optimise vaccine access, uptake and effectiveness. Work package 4 will plan and implement field investigations (community survey and qualitative studies (with support of work package 2) to explore structural, social & biological determinants impairing vaccine impact. Work package 5 will collaborate with work packages 1-4, to engage communities in designing interventions that aim to directly optimise vaccine impact through a process of co-learning and co-creation between them and the researchers. Work package 6 will build capacity for, and a culture of, consultative, collaborative multidisciplinary vaccine research in East Africa. Work package 7 will support the overall project management and governance. Following the project inception on the 1st of September 2022, project launch was held in November 2022. Conclusion Results from this project will contribute to the development of integrated strategies that will optimise vaccine benefits and drive health equity.

Introduction Invasive non-typhoidal Salmonellosis (iNTS) is mainly caused by Salmonella enterica serovars Typhimurium and Enteritidis and is estimated to result in 77 500 deaths per year, disproportionately affecting children under 5 years of age in sub-Saharan Africa. Invasive non-typhoidal Salmonellae serovars are increasingly acquiring resistance to first-line antibiotics, thus an effective vaccine would be a valuable tool in reducing morbidity and mortality from infection. While NTS livestock vaccines are in wide use, no licensed vaccines exist for use in humans. Here, a first-in-human study of a novel vaccine (iNTS-GMMA) containing S. Typhimurium and S. Enteritidis Generalised Modules for Membrane Antigens (GMMA) outer membrane vesicles is presented.Method and analysis The Salmonella Vaccine Study in Oxford is a randomised placebo-controlled participant-observer blind phase I study of the iNTS-GMMA vaccine. Healthy adult volunteers will be randomised to receive three intramuscular injections of the iNTS-GMMA vaccine, containing equal quantities of S. Typhimurium and S. Enteritidis GMMA particles adsorbed on Alhydrogel, or an Alhydrogel placebo at 0, 2 and 6 months. Participants will be sequentially enrolled into three groups: group 1, 1:1 randomisation to low dose iNTS-GMMA vaccine or placebo; group 2, 1:1 randomisation to full dose iNTS-GMMA vaccine or placebo; group 3, 2:1 randomisation to full dose or lower dose (dependant on DSMC reviews of groups 1 and 2) iNTS-GMMA vaccine or placebo.The primary objective is safety and tolerability of the vaccine. The secondary objective is immunogenicity as measured by O-antigen based ELISA. Further exploratory objectives will characterise the expanded human immune profile.Ethics and dissemination Ethical approval for this study has been obtained from the South Central—Oxford A Research Ethics Committee (Ethics REF:22/SC/0059). Appropriate documentation and regulatory approvals have been acquired. Results will be disseminated via peer-reviewed articles and conferences.Trial registration number EudraCT Number: 2020-000510-14.

Key Clinical Message This case highlights the need for thorough clinical examination to rule out Takayasu arteritis (TA) as a cause of stroke in a young asymptomatic East‐African male. Available clinical management guidelines should guide management of TA patients. Abstract We present a case of a young, previously asymptomatic East‐African Black male presenting with large territory ischemic infarct at first diagnosis of TA. To our knowledge, this is the first published report of a male patient in East Africa with a stroke as the first presentation of TA.

Abstract Outdoor biting by anopheline mosquitoes is one of the contributors to residual malaria transmission, but the profile of vectors driving this phenomenon is not well understood. Here, we studied the bionomics and genetically characterized populations of An. gambiae and An. funestus complexes trapped outdoors in three selected dryland areas including Kerio Valley, Nguruman and Rabai in Kenya. We observed a higher abundance of Anopheles funestus group members (n = 639, 90.6%) compared to those of the An. gambiae complex (n = 66, 9.4%) with An. longipalpis C as the dominant vector species with a Plasmodium falciparum sporozoite rate (Pfsp) of 5.2% (19/362). The known malaria vectors including An. funestus s.s. (8.7%, 2/23), An. gambiae (14.3%, 2/14), An. rivulorum (14.1%, 9/64), An. arabiensis (1.9%, 1/52) occurred in low densities and displayed high Pfsp rates, which varied with the site. Additionally, six cryptic species found associated with the An. funestus group harbored Pf sporozoites (cumulative Pfsp rate = 7.2%, 13/181). We detected low frequency of resistant 119F-GSTe2 alleles in An. funestus s.s. (15.6%) and An. longipalpis C (3.1%) in Kerio Valley only. Evidence of outdoor activity, emergence of novel and divergent vectors and detection of mutations conferring metabolic resistance to pyrethroid/DDT could contribute to residual malaria transmission posing a threat to effective malaria control.

The mango cultivar ‘Apple’ is an important fruitcrop in Kenya, but it is highly susceptible to russeting. The objective was to establish whether lenticels predispose cv. ‘Apple’ mango to russeting. Fruit mass and surface area increased in a sigmoidal pattern with time. The frequency of lenticels per unit surface area decreased during development. The number of lenticels per fruit was constant. Lenticels were most frequent in the apex region and least common in the cheek and nak (ventral) regions. The cheek region also had lenticels with the largest core areas, whereas the lenticel core areas in the apex region were significantly smaller. Microscopy revealed stomata became covered over with wax deposits at 33 days after full bloom (DAFB). By 78 DAFB, periderm had formed beneath the pore. At 110 and 161 DAFB, cracks had developed and the periderm had extended tangentially and radially. The presence of lenticels increased the strain released upon excision of an epidermal segment, further strain releases occurred subsequently upon isolation of the cuticle and on extraction of the cuticular waxes. The number of lenticels per unit surface area was negatively correlated with the fruit surface area (r2 = 0.62 **), but not affected by fruit size. Mango cv. ‘Apple’ had fewer, larger lenticels and more russet, compared with ‘Ngowe’, ‘Kitovu’ or ‘Tommy Atkins’ mango. In cv. ‘Apple’, the lowest lenticel frequency, the largest lenticels and the most russeting occurred at a growing site at the highest altitude, with the highest rainfall and the lowest temperature. Moisture exposure of the fruit surface resulted in enlarged lenticels and more microcracking of the cuticle. Our results establish that russeting in ‘Apple’ mango is initiated at lenticels and is exacerbated if lenticels are exposed to moisture.

Abstract Background Progressive pseudorheumatoid dysplasia is a rare, autosomal recessively inherited, noninflammatory musculoskeletal disorder caused by mutations occurring in the WNT1-inducible signaling pathway protein 3 gene. Joint cartilage is the primary site of involvement, leading to arthralgia, joint stiffness, contractures, enlargement of the epiphyses and metaphysis of the hand joints, spinal abnormalities, short stature, early osteoarthritis, and osteoporosis. Juvenile idiopathic arthritis is the most common chronic rheumatic disease in childhood and has unknown etiology. Clinical features of progressive pseudorheumatoid dysplasia resemble those of juvenile idiopathic arthritis. Patients with progressive pseudorheumatoid dysplasia are usually misdiagnosed as having juvenile idiopathic arthritis. Case presentation A 13-year-old Yemeni female presented to the rheumatology clinic with a history of joint pains, bone pains, and bone deformity for 7 years. Weight and height were below the third percentiles. There was no tender swelling of metacarpophalangeal and interphalangeal joints, and she presented with scoliosis. Radiographs of the hands revealed the widening of the epiphyses. Progressive pseudorheumatoid dysplasia was suspected, and genetic testing for WNT1-inducible signaling pathway protein 1, 2, and 3 was requested with these findings. A homozygous, likely pathogenic variant was identified in the WNT1-inducible signaling pathway protein 3 gene, which confirmed our diagnosis. Conclusion Progressive pseudorheumatoid dysplasia is a rare form of spondyloepimetaphyseal dysplasia and is clinically misdiagnosed as juvenile idiopathic arthritis. It is crucial to consider progressive pseudorheumatoid dysplasia, especially in patients with standard inflammatory markers who are being followed up for juvenile idiopathic arthritis and not improving with antirheumatic intervention.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb), remains a significant global health issue, with high morbidity and mortality rates. The emergence of drug-resistant strains, particularly multidrug-resistant TB (MDR-TB), poses difficult challenges to TB control efforts. This comprehensive review and meta-analysis investigated the prevalence of and molecular insights into isoniazid (INH) and rifampicin (RIF) resistance-conferring mutations in M. tb isolates from South Africa. Through systematic search and analysis of 11 relevant studies, we determined the prevalence of gene mutations associated with RIF and INH resistance, such as rpoB, katG, and inhA. The findings demonstrated a high prevalence of specific mutations, including S450L in rpoB, and S315T, which are linked to resistance against RIF and INH, respectively. These results contribute to the understanding of drug resistance mechanisms and provide valuable insights for the development of targeted interventions against drug-resistant TB.

Objectives The accuracy of bioelectrical impedance analysis (BIA) depends on population-specific prediction equations and there is no population-specific equation for predicting fat-free mass (FFM) in Malawian adolescents. This study aimed at determining the agreement between FFM measured by deuterium oxide dilution technique (the reference) and FFM by BIA; and propose BIA-based prediction equations to estimate FFM for Malawian adolescents.Design This was a cross-sectional study.Setting The study was conducted in Blantyre, MalawiParticipants 186 Malawian adolescents aged between 10 and 18 years were included in this study. Body composition was estimated by both the BodyStat BIA analyser and the deuterium oxide dilution method.Results BIA inbuilt equation underestimated FFM compared with deuterium oxide dilution (p=0.039). The new prediction equation for FFM (kg)=−4.316+ 0.425* height2(cm)/resistance (Ω)+1.287* sex (male=1, female=0)+0.307*age(years)+0.344* weight(kg)+0.019*reactance(Ω) yielded an R2 of 0.926. The equation for total body water (TBW) (kg)=−2.152 + 0.328*height2(cm)/resistance (Ω) 0.910*sex (male=1, female=0)+0.307 *age (years)+0.249*weight(kg)+0.015*reactance(Ω) yielded an R2 of 0.922. The Bland-Altman plot illustrated a good level of concordance between the FFM and TBW predicted by the new equations and the values derived using deuterium dilution method.Conclusions The new BIA prediction equations for estimating FFM and TBW could be used to assess with very good accuracy and precision the body composition of Malawian and adolescents with similar characteristics.

Background Physical activity (PA) is associated with numerous health benefits among children and youth. However, few studies have examined how active transportation (AT) and device-based measures of PA vary within and between countries in sub-Saharan Africa. Purpose This cross-sectional study sought to investigate the prevalence and correlates of AT and device-measured PA among children living in urban, peri-urban and rural areas in three African countries representing Eastern, Western and Southern regions of Africa. Methods 3,205 participants (53.3% girls; 46.7% boys) aged 10–12 years were recruited in Kenya, Nigeria and Mozambique. Data were collected using a child questionnaire, a parent/guardian questionnaire and PiezoRx® pedometers. ANCOVA and binary logistic regression analyses were used to examine the correlates of AT and PA while controlling for gender, age, parent education and vehicle ownership. Results Participants accumulated an average of 45.6±23.5 min/day of moderate-to-vigorous physical activity (MVPA) and 11,215±4,273 steps/day. Kenyan and Mozambican children were significantly more active than their Nigerian counterparts (pConclusions Majority of children engaged in AT, but still failed to meet MVPA recommendations. Most correlates of AT and PA were country-specific, suggesting that strategies to encourage both behaviours should be informed by local evidence.

Introduction Tenofovir Disoproxil Fumarate (TDF) is the most widely used Anti-Retroviral Therapy (ART) drug due to its potency, safety profile and World Health Organization (WHO) recommendation. TDF causes proximal tubular renal dysfunction (PTRD) leading to Fanconi syndrome, acute kidney injury and chronic kidney disease. Modest rates (2–4%) of TDF related toxicity based on estimated Glomerular Filtration Rate (GFR) have been described, while TDF-induced PTRD has been reported to be 22%. TDF toxicity is more likely among African patients, it is reversible and TDF may be renal dosed in patients with dysfunction. The objective of this study was to assess proximal tubular renal dysfunction, global renal function, and their determinants among patients on TDF versus TDF-sparing regimen. Methods This was a cross-sectional study among people living with HIV/AIDS (PLWHA) attending the Academic Model Providing Access to Healthcare (AMPATH) program. The primary outcome of interest in this study was PTRD while the secondary outcome of interest was estimated GFR. PTRD was defined as any two of beta-2 microglobulin in urine, metabolic acidosis, normoglycemic glucosuria and fractional excretion of phosphate. Student’s t-test, chi-square and their non-parametric equivalents were used to test for statistical significance. Univariate and multivariate logistic regression analysis was carried out. Results A total of 516 participants were included in the final analysis, 261 on TDF while 255 were on TDF-sparing regimens. The mean (SD) age of all participants was 41.5 (12.6) years with majority being female (60.3%). The proportion of PTRD was 10.0% versus 3.1% in the TDF compared to TDF-sparing group (PConclusion There was significant PTRD in the TDF compared to TDF-sparing group without significant difference in estimated GFR. The clinical significance of these findings may not be clear in the short term.

BackgroundLike many countries in sub-Saharan Africa, Kenya has experienced rapid urbanization in recent years. Despite the distinct socioeconomic and environmental differences, few studies have examined the adherence to movement guidelines in urban and rural areas. This cross-sectional study aimed at examining compliance to the 24-hour movement guidelines and their correlates among children from urban and rural Kenya.MethodChildren (n = 539) aged 11.1 ± 0.8 years (52% female) were recruited from 8 urban and 8 rural private and public schools in Kenya. Physical activity (PA) and sleep duration were estimated using 24-h raw data from wrist-worn accelerometers. Screen time (ST) and potential correlates were self- reported. Multi-level logistic regression was applied to identify correlates of adherence to combined and individual movement guidelines.ResultsCompliance with the combined movement guidelines was low overall (7%), and higher among rural (10%) than urban (5%) children. Seventy-six percent of rural children met the individual PA guidelines compared to 60% urban children while more rural children also met sleep guidelines (27% vs 14%). The odds of meeting the combined movement guidelines reduced with age (OR = 0.55, 95% CI = 0.35-0.87, p = 0.01), was greater among those who could swim (OR = 3.27, 95% CI = 1.09-9.83, p = 0.04), and among those who did not engage in ST before school (OR = 4.40, 95% CI = 1.81-10.68, pConclusionsPrevalence of meeting movement guidelines among Kenyan children is low and of greatest concern in urban areas. Several correlates were identified, particularly influential were features of the school day, School is thus a significant setting to promote a healthy balance between sleep, sedentary time, and PA.

Background: Equitable access to health services can be constrained in countries where private practitioners make up a large portion of primary care providers. Expanding purchasing arrangements has helped many countries integrate private providers into government-supported payment schemes, reducing financial barriers to care. However, private providers often must go through an onerous accreditation process to enroll in these schemes. The difficulties of this process are exacerbated where health policy is changed often and low-level bureaucrats must navigate these shifts at their own discretion. This paper analyzes one initiative to increase private provider accreditation with social health insurance (SHI) in Kenya by creating an intermediary between providers and “street-level” SHI bureaucrats. Methods: This paper draws on 126 semi-structured interviews about SHI accreditation experience with private providers who were members of a franchise network in Kenya. It also draws on four focus group discussions conducted with franchise representatives who provided accreditation support to the providers and served as liaisons between the franchised providers and local SHI offices. There was a total of 20 participants across all four focus groups. Results: In a governance environment where regulations are weak and impermanent, street-level bureaucrats often created an accreditation process that was inconsistent and opaque. Support from the implementing organizations increased communication between SHI officials and providers, which clarified rules and increased providers’ confidence in the system. The intermediaries also reduced bureaucrats’ ability to apply regulations at will and helped to standardize the accreditation process for both providers and bureaucrats. Conclusions: We conclude that intermediary organizations can mitigate institutional weaknesses and facilitate process efficiency. However, intermediaries only have a temporary role to play where there is potential to: 1) directly increase private providers’ power in a complex regulatory system; 2) reform the system itself to be more responsive to the limitations of on-the-ground implementation.

BackgroundAdolescence is a sensitive time for girls' sexual and reproductive health (SRH), as biological changes occur concurrently with heightening pressures for sexual activity. In western Kenya, adolescent girls are vulnerable to acquiring sexually transmitted infections (STIs), such as HIV and herpes simplex virus type 2 (HSV-2), and to becoming pregnant prior to reaching adulthood. This study examines associations between individual, household, and partner-related risk factors and the prevalence of sex, adolescent pregnancy, HIV, and HSV-2.Methods and findingsWe report baseline findings among 4,138 girls attending secondary school who were enrolled between 2017 and 2018 in the Cups or Cash for Girls (CCG) cluster randomized controlled trial in Siaya County, rural western Kenya. Laboratory confirmed biomarkers and survey data were utilized to assess the effects of girls' individual, household, and partner characteristics on the main outcome measures (adolescent reported sex, prior pregnancy, HIV, and HSV-2) through generalized linear model (GLM) analysis. Complete data were available for 3,998 girls (97%) with median age 17.1 years (interquartile range [IQR] 16.3 to 18.0 years); 17.2% were HSV-2 seropositive (n = 686) and 1.7% tested positive for HIV (n = 66). Sexual activity was reported by 27.3% girls (n = 1,090), of whom 12.2% had been pregnant (n = 133). After adjustment, orphanhood (adjusted risk ratio [aRR] 2.81, 95% confidence interval [CI] 1.18 to 6.71, p-value [p] = 0.020), low body mass index (BMI) (aRR 2.07; CI: 1.00 to 4.30, p = 0.051), and age (aRR 1.34, 1.18 to 1.53, p < 0.001) were all associated with HIV infection. Girls reporting light menstrual bleeding (aRR 2.42, 1.22 to 4.79, p = 0.012) for fewer than 3 days (aRR 2.81, 1.16 to 6.82, p = 0.023) were over twice as likely to have HIV. Early menarche (aRR 2.05, 1.33 to 3.17, p = 0.001) was associated with adolescent pregnancy and HSV-2-seropositive girls reported higher rates of pregnancy (aRR 1.62, CI: 1.16 to 2.27, p = 0.005). High BMI was associated with HSV-2 (aRR 1.24, 1.05 to 1.46, p = 0.010) and sexual activity (aRR 1.14, 1.02 to 1.28, p = 0.016). High levels of harassment were detected in the cohort (41.2%); being touched indecently conveyed the strongest association related to reported sexual activity (aRR 2.52, 2.26 to 2.81, p < 0.001). Study limitations include the cross-sectional design of the study, which informs on the SRH burdens found in this population but limits causal interpretation of associations, and the self-reported exposure ascertainment, which may have led to possible underreporting of risk factors, most notably prior sexual activity.ConclusionsOur findings indicate that adolescent girls attending school in Kenya face frequent harassment for sex and are at high risk of pregnancy and HSV-2, with girls experiencing early menarche particularly vulnerable. Targeted interventions, such as earlier sexual education programs, are warranted to address their vulnerability to SRH harms.Trial registrationClinicalTrials.gov NCT03051789.

Abstract Non-polio enteroviruses are emerging viruses known to cause outbreaks of polio-like infections in different parts of the world with several cases already reported in Asia Pacific, Europe and in United States of America. These outbreaks normally result in overstretching of health facilities as well as death in children under the age of five. Most of these infections are usually self-limiting except for the neurological complications associated with human enterovirus A 71 (EV-A71). The infection dynamics of these viruses have not been fully understood, with most inferences made from previous studies conducted with poliovirus. Non-poliovirus enteroviral infections are responsible for major outbreaks of hand, foot and mouth disease (HFMD) often associated with neurological complications and severe respiratory diseases. The myriad of disease presentations observed so far in children calls for an urgent need to fully elucidate the replication processes of these viruses. There are concerted efforts from different research groups to fully map out the role of human host factors in the replication cycle of these viral infections. Understanding the interaction between viral proteins and human host factors will unravel important insights on the lifecycle of this groups of viruses. This review provides the latest update on the interplay between human host factors/processes and non-polio enteroviruses (NPEV). We focus on the interactions involved in viral attachment, entry, internalization, uncoating, replication, virion assembly and eventual egress of the NPEV from the infected cells. We emphasize on the virus- human host interplay and highlight existing knowledge gaps that needs further studies. Understanding the NPEV-human host factors interactions will be key in the design and development of vaccines as well as antivirals against enteroviral infections. Dissecting the role of human host factors during NPEV infection cycle will provide a clear picture of how NPEVs usurp the human cellular processes to establish an efficient infection. This will be a boost to the drug and vaccine development against enteroviruses which will be key in control and eventual elimination of the viral infections.

HIV-related stigma is a frequently cited barrier to HIV testing and care engagement. A nuanced understanding of HIV-related stigma is critical for developing stigma-reduction interventions to optimize HIV-related outcomes. This qualitative study documented HIV-related stigma across eight communities in east Africa during the baseline year of a large HIV test-and-treat trial (SEARCH, NCT: 01864603), prior to implementation of widespread community HIV testing campaigns and efforts to link individuals with HIV to care and treatment. Findings revealed experiences of enacted, internalized and anticipated stigma that were highly gendered, and more pronounced in communities with lower HIV prevalence; women, overwhelmingly, both held and were targets of stigmatizing attitudes about HIV. Past experiences with enacted stigma included acts of segregation, verbal discrimination, physical violence, humiliation and rejection. Narratives among women, in particular, revealed acute internalized stigma including feelings of worthlessness, shame, embarrassment, and these resulted in anxiety and depression, including suicidality among a small number of women. Anticipated stigma included fears of marital dissolution, verbal and physical abuse, gossip and public ridicule. Anticipated stigma was especially salient for women who held internalized stigma and who had experienced enacted stigma from their partners. Anticipated stigma led to care avoidance, care-seeking at remote facilities, and hiding of HIV medications. Interventions aimed at reducing individual and community-level forms of stigma may be needed to improve the lives of PLHIV and fully realize the promise of test-and-treat strategies.

Introduction Environmental enteropathy (EE) is suspected to be a cause of growth faltering in children with sustained exposure to enteric pathogens, typically in resource-limited settings. A major hindrance to EE research is the lack of sensitive, non-invasive biomarkers. Current biomarkers measure intestinal permeability and inflammation, but not the functional capacity of the gut. Australian researchers have demonstrated proof of concept for an EE breath test based on using naturally 13C-enriched sucrose, derived from maize, to assay intestinal sucrase activity, a digestive enzyme that is impaired in villus blunting. Here, we describe a coordinated research project to optimise, validate and evaluate the usability of a breath test protocol based on highly enriched 13C-sucrose to quantify physiological dysfunction in EE in relevant target populations.Methods and analysis We use the 13C-sucrose breath test (13C-SBT) to evaluate intestinal sucrase activity in two phases. First, an optimisation and validation phase will (1) confirm that a 13C-SBT using highly enriched sucrose tracers reports similar information to the naturally enriched 13C-SBT; (2) examine the dose–response relationship of the test to an intestinal sucrase inhibitor; (3) validate the 13C-SBT in paediatric coeliac disease (4) validate the highly enriched 13C-SBT against EE defined by biopsy in adults and (5) validate the 13C-SBT against EE defined by the urinary lactulose:rhamnose ratio (LR) among children in Peru. Second, a cross-sectional study will be conducted in six resource-limited countries (Bangladesh, India, Jamaica, Kenya, Peru and Zambia) to test the usability of the optimised 13C-SBT to assess EE among 600 children aged 12–15 months old.Ethics and dissemination Ethical approval will be obtained from each participating study site. By working as a consortium, the test, if shown to be informative of EE, will demonstrate strong evidence for utility across diverse, low-income and middle-income country paediatric populations.Trial registration number NCT04109352; Pre-results.

The Plasmodium falciparum protein VAR2CSA allows infected erythrocytes to accumulate within the placenta, inducing pathology and poor birth outcomes. Multiple exposures to placental malaria (PM) induce partial immunity against VAR2CSA, making it a promising vaccine candidate. However, the extent to which VAR2CSA genetic diversity contributes to immune evasion and virulence remains poorly understood. The deep sequencing of the var2csa DBL3X domain in placental blood from forty-nine primigravid and multigravid women living in malaria-endemic western Kenya revealed numerous unique sequences within individuals in association with chronic PM but not gravidity. Additional analysis unveiled four distinct sequence types that were variably present in mixed proportions amongst the study population. An analysis of the abundance of each of these sequence types revealed that one was inversely related to infant gestational age, another was inversely related to placental parasitemia, and a third was associated with chronic PM. The categorization of women according to the type to which their dominant sequence belonged resulted in the segregation of types as a function of gravidity: two types predominated in multigravidae whereas the other two predominated in primigravidae. The univariate logistic regression analysis of sequence type dominance further revealed that gravidity, maternal age, placental parasitemia, and hemozoin burden (within maternal leukocytes), reported a lack of antimalarial drug use, and infant gestational age and birth weight influenced the odds of membership in one or more of these sequence predominance groups. Cumulatively, these results show that unique var2csa sequences differentially appear in women with different PM exposure histories and segregate to types independently associated with maternal factors, infection parameters, and birth outcomes. The association of some var2csa sequence types with indicators of pathogenesis should motivate vaccine efforts to further identify and target VAR2CSA epitopes associated with maternal morbidity and poor birth outcomes.

INTRODUCTION: The burden of chronic kidney disease (CKD) is increasing worldwide. Few studies in low and low-middle income countries have estimated the prevalence of CKD. We aimed to estimate prevalence and factors associated with CKD among medical inpatients at the largest referral hospital in Kenya. METHODS: we conducted a cross-sectional study among medical inpatients at the Kenyatta National Hospital. We used systematic random sampling and collected demographic information, behavioural risk factors, medical history, underlying conditions, laboratory and imaging workup using a structured questionnaire. We estimated glomerular filtration rate (GFR) in ml/min/1.73m2 classified into 5 stages; G1 (? 90), G2 (60-89), G3a (45-59), G3b (30-44), G4 (15-29) and G5 (15, or treated by dialysis/renal transplant). Ethical approval was obtained from Kenyatta National Hospital/University of Nairobi ethics committee (P510/09/2017). We estimated prevalence of CKD and used logistic regression to determine factors independently associated with CKD diagnosis. RESULTS: we interviewed 306 inpatients; median age 40.0 years (IQR 24.0), 162 (52.9%) were male, 155(50.7%) rural residents. CKD prevalence was 118 patients (38.6%, 95% CI 33.3-44.1); median age 42.5 years (IQR 28.0), 74 (62.7%) were male, 64 (54.2%) rural residents. Respondents with CKD were older than those without (difference 4.4 years, 95% CI 3.7-8.4 years, P = 0.032). Fifty two (44.1%) of the patients had stage G2, 17 (14.4%) had end-stage renal disease; 64(54.2%) had haemoglobin ? 8g/dl while 33 (28.0%) had hyponatremia. Male sex (aOR 2.63, 95% CI 1.49-4.63), history of anaemia (aOR 1.80, 95% CI 1.02-3.19), proteinuria (aOR 5.16, 95% CI 2.09-12.74), hematuria (aOR 7.68, 95% CI 2.37-24.86), hypertension (aOR 2.71, 95% CI 1.53-4.80) and herbal medications use (aOR 1.97, 95% CI 1.07-3.64) were independently associated with CKD. CONCLUSION: burden of CKD was high among this inpatient population. Haematuria and proteinuria can aid CKD diagnosis. Public awareness on health hazards of herbal medication use is necessary.

Introduction Previous research demonstrated that substance use continues to be one of the most complex and prevalent problems among African, Caribbean and Black (ACB) people. A number of studies were conducted to characterise substance use patterns in this population. To our knowledge, this is the first known review in Canada characterising substance use disorders on ACB people.This scoping review seeks to answer the following research questions: What characterises substance use disorders among ACB people in Canada? What are the different types and prevalence of substance use among ACB people in Canada? Do ACB people in Canada use more than one substance? What factors are associated with substance use among ACB people in Canada? What are the health and social impacts of substance use in ACB people in Canada?Methods and analyses This study will use the methodological framework for scoping reviews developed by Arksey and O’Malley. We will search electronic bibliographic databases including Ovid MEDLINE, PsycINFO and CINAHL. We will limit our search to English articles published between 2000and2019. In addition, we will conduct a grey literature search. Two investigators will independently screen citations and full-text articles. Our findings will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for scoping reviews guidelines. We will provide a descriptive summary of the studies and summarise the findings with respect to the outcomes and report any gaps that might require further investigation.Ethics and dissemination Our proposed study does not involve human participants; therefore, research ethics approval is not required. This study will provide evidence that will inform the development of strategies for appropriate interventions, as well as policy and further research. The results will be disseminated through publications in open access peer-reviewed journals, presentations at scientific meetings and to the lay public.

Rakhi Karwa and colleagues discuss a program in which peer navigators support care for people with HIV at a Kenyan hospital.

Most humans have pre-existing immunity to influenza viruses. In this study, volunteers (ages of 18-85 years) were vaccinated with split, inactivated Fluzone™ influenza vaccine in four consecutive influenza seasons from 2013 to 2016 seasons. The impact of repeated vaccination on breadth and durability of antibodies was assessed as a result of vaccine strain changes. Total IgG anti-hemagglutinin (HA) binding antibodies and hemagglutination-inhibition (HAI) activity increased in all age groups against both influenza A HA components in the vaccine post-vaccination (day 21). However, younger subjects maintained seroprotective titers to the vaccine strains, which resulted in higher seroconversion rates in the elderly, since the HAI titers in elderly subjects were more likely to decline prior to the next season. Young subjects had significant HAI activity against historical, as well as contemporary H1 and H3 vaccine strains from the mid-1980s to present. In contrast, elderly subjects had HAI activity to H1 strains from all years, but were more likely to have HAI activity to older strains from 1918-1950s. They also had a more restricted HAI profile against H3 viruses compared to young subjects recognizing H3N2 influenza viruses from the mid-2000s to present. Vaccine recipients were then categorized by whether subjects seroconverted from a seronegative or seropositive pre-vaccination state. Regardless of age, immunological recall or 'back-boosting' to antigenically related strains were associated with seroconversion to the vaccine strain. Overall, both younger and older people have the ability to mount a breadth of immune responses following influenza vaccination. This report describes how imprinting exposure differs across age groups, influences antibody cross-reactivity to past hemagglutinin antigenic variants, and shapes immune responses elicited by current split inactivated influenza vaccines. Understanding how current influenza vaccines are influenced by pre-existing immunity in people of different ages is critical for designing the next-generation of 'universal' or broadly-protective influenza vaccines.

Melatonin is rhythmically secreted by both the pineal gland and retina in a circadian fashion, with its peak synthesis occurring during the night. Once synthesized, melatonin exerts its effects by binding to two specific G-protein coupled receptors-melatonin receptor type 1(MT1) and melatonin receptor type 2(MT2). Recent studies suggest the involvement of MT1 and MT2 in the regulation of glucose homeostasis; however the ability of melatonin signaling to impart timing cues on glucose metabolism remains poorly understood. Here we report that the removal of MT1 or MT2 in mice abolishes the daily rhythm in blood glucose levels. Interestingly, removal of melatonin receptors produced small effects on the rhythmic expression patterns of clock genes within skeletal muscle, liver, and adipose tissue. Taken together, our data suggest that the loss of the daily rhythm in blood glucose observed in MT1(-/-) and MT2(-/-) mice does not occur as a consequence of 'disrupted' clocks within insulin sensitive tissues. Finally our results highlight a diurnal contribution of melatonin receptor signaling in the daily regulation of blood glucose levels.

The SNARC effect refers to an association of numbers and spatial properties of responses that is commonly thought to be amodal and independent of stimulus notation. We tested for a horizontal SNARC effect using Arabic digits, simple-form Chinese characters and Chinese hand signs in participants from Mainland China. We found a horizontal SNARC effect in all notations. This is the first time that a horizontal SNARC effect has been demonstrated in Chinese characters and Chinese hand signs. We tested for the SNARC effect in two experiments (parity judgement and magnitude judgement). The parity judgement task yielded clear, consistent SNARC effects in all notations, whereas results were more mixed in magnitude judgement. Both Chinese characters and Chinese hand signs are represented non-symbolically for low numbers and symbolically for higher numbers, allowing us to contrast within the same notation the effects of heavily learned non-symbolic vs. symbolic representation on the processing of numbers. In addition to finding a horizontal SNARC effect, we also found a robust numerical distance effect in all notations. This is particularly interesting as it persisted when participants reported using purely visual features to solve the task, thereby suggesting that numbers were processed semantically even when the task could be solved without the semantic information.

In numerous psychological experiments, participants classify stimuli by pressing response keys. According to Lakens, Schneider, Jostmann, and Schubert (2011), classification performance is affected by physical distance between response keys--indicating a cognitive tendency to represent categories in spatial code. However, previous evidence for a key distance effect (KDE) from a color-naming Stroop task is inconclusive as to whether: (a) key separation automatically leads to an internal spatial representation of non-spatial stimulus characteristics in participants, or if the KDE rather depends on physical spatial characteristics of the stimulus configuration; (b) the KDE attenuates the Stroop interference effect. We therefore first adopted the original Stroop task in Experiment 1, confirming that wider key distance facilitated responses, but did not modulate the Stroop effect as was previously found. In Experiments 2 and 3 we controlled potential mediator variables in the original design. When we did not display instructions about stimulus-response mappings, thereby removing the unintended spatial context from the Stroop stimuli, no KDE emerged. Presenting the instructions at a central position in Experiment 4 confirmed that key separation alone is not sufficient for a KDE, but correspondence between spatial configurations of stimuli and responses is also necessary. Evidence indicates that the KDE on Stroop performance is due to known mechanisms of stimulus-response compatibility and response discriminability. The KDE does, however, not demonstrate a general disposition to represent any stimulus in spatial code.