TCR sequencing paired with massively parallel 3' RNA-seq reveals clonotypic T cell signatures.

High-throughput 3' single-cell RNA-sequencing (scRNA-seq) allows cost-effective, detailed characterization of individual immune cells from tissues. Current techniques, however, are limited in their ability to elucidate essential immune cell features, including variable sequences of T cell antigen receptors (TCRs) that confer antigen specificity. Here, we present a strategy that enables simultaneous analysis of TCR sequences and corresponding full transcriptomes from 3'-barcoded scRNA-seq samples. This approach is compatible with common 3' scRNA-seq methods, and adaptable to processed samples post hoc. We applied the technique to identify transcriptional signatures associated with T cells sharing common TCRs from immunized mice and from patients with food allergy. We observed preferential phenotypes among subsets of expanded clonotypes, including type 2 helper CD4+ T cell (TH2) states associated with food allergy. These results demonstrate the utility of our method when studying diseases in which clonotype-driven responses are critical to understanding the underlying biology.

Antimalarial activity assay of artesunate-3-chloro-4(4-chlorophenoxy) aniline in vitro and in mice models.

The global spread of multi-drug resistant P. falciparum, P. vivax, and P. malariae strains and absence of long-term effective vaccine makes chemotherapy the mainstay of malaria control strategies in endemic settings. The Mossman's assay and the Organization for Economic Co-operation and Development (OECD), 2001 guideline 423, were used to determine the cytotoxicity and acute oral toxicity of a novel hybrid drug, artesunate-3-Chloro-4(4-chlorophenoxy) aniline (ATSA), in vitro and in vivo, respectively. A modified Desjardins method was used to screen for antiplasmodial activity using P. falciparum (3D7 and W2) strains in vitro. The Peter's 4-day suppressive tests (4DTs) was used to evaluate the in vivo antimalaria activity using P. berghei ANKA strain, lumefantrine resistant (LuR), and piperaquine resistant (PQR) P. berghei lines. In silico prediction of absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles was assayed using PreADMET online prediction tool. The reference drug in all experiments was artesunate (ATS). Statistical significance between ATSA's activities in treated and control mice was evaluated by one-way analysis of variance (ANOVA). Results show that inhibitory concentrations-50 (IC50) of ATSA is 11.47 ± 1.3 (3D7) and 1.45 ± 0.26 (W2) against 4.66 ± 0.93 (3D7) and 0.60 ± 0.15 (W2) ng/ml of ATS with a selective index of 2180.91(3D7) and a therapeutic index (TI) of > 71). No mortalities were observed in acute oral toxicity assays and mean weight differences for test and controls were statistically insignificant (P > 0.05). The in vivo activity of ATSA was above 40% with effective dosage-50 (ED50) of 4.211, 2.601, and 3.875 mg/kg body weight against P. berghei ANKA, LuR, and PQR lines, respectively. The difference between treated and control mice was statistically significant (P < 0.05). ATSA has high intestinal absorption (HIA) > 95% and has medium human ether-a-go-go related gene (hERG) K+ channel inhibition risks. Preclinical and clinical studies on ATSA are recommended to evaluate its value in developing novel drugs for future management of multi-drug resistant malaria parasites.

Seroprevalence of Antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 Among Healthcare Workers in Kenya.

BACKGROUND: Few studies have assessed the seroprevalence of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among healthcare workers (HCWs) in Africa. We report findings from a survey among HCWs in 3 counties in Kenya. METHODS: We recruited 684 HCWs from Kilifi (rural), Busia (rural), and Nairobi (urban) counties. The serosurvey was conducted between 30 July and 4 December 2020. We tested for immunoglobulin G antibodies to SARS-CoV-2 spike protein, using enzyme-linked immunosorbent assay. Assay sensitivity and specificity were 92.7 (95% CI, 87.9-96.1) and 99.0% (95% CI, 98.1-99.5), respectively. We adjusted prevalence estimates, using bayesian modeling to account for assay performance. RESULTS: The crude overall seroprevalence was 19.7% (135 of 684). After adjustment for assay performance, seroprevalence was 20.8% (95% credible interval, 17.5%-24.4%). Seroprevalence varied significantly (P < .001) by site: 43.8% (95% credible interval, 35.8%-52.2%) in Nairobi, 12.6% (8.8%-17.1%) in Busia and 11.5% (7.2%-17.6%) in Kilifi. In a multivariable model controlling for age, sex, and site, professional cadre was not associated with differences in seroprevalence. CONCLUSION: These initial data demonstrate a high seroprevalence of antibodies to SARS-CoV-2 among HCWs in Kenya. There was significant variation in seroprevalence by region, but not by cadre.

Understanding the Potential Impact of Different Drug Properties on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission and Disease Burden: A Modelling Analysis.

BACKGROUND: The public health impact of the coronavirus disease 2019 (COVID-19) pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. METHODS: Using a mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. RESULTS: The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R = 1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalization) could have much greater benefits, particularly in resource-poor settings facing large epidemics. CONCLUSIONS: Advances in the treatment of COVID-19 to date have been focused on hospitalized-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

Genome-wide investigations reveal the population structure and selection signatures of Nigerian cattle adaptation in the sub-Saharan tropics.

BACKGROUND: Cattle are considered to be the most desirable livestock by small scale farmers. In Africa, although comprehensive genomic studies have been carried out on cattle, the genetic variations in indigenous cattle from Nigeria have not been fully explored. In this study, genome-wide analysis based on genotyping-by-sequencing (GBS) of 193 Nigerian cattle was used to reveal new insights on the history of West African cattle and their adaptation to the tropical African environment, particularly in sub-Saharan region.  RESULTS: The GBS data were evaluated against whole-genome sequencing (WGS) data and high rate of variant concordance between the two platforms was evident with high correlated genetic distance matrices genotyped by both methods suggestive of the reliability of GBS applicability in population genetics. The genetic structure of Nigerian cattle was observed to be homogenous and unique from other African cattle populations. Selection analysis for the genomic regions harboring imprints of adaptation revealed genes associated with immune responses, growth and reproduction, efficiency of feeds utilization, and heat tolerance. Our findings depict potential convergent adaptation between African cattle, dogs and humans with adaptive genes SPRY2 and ITGB1BP1 possibly involved in common physiological activities. CONCLUSION: The study presents unique genetic patterns of Nigerian cattle which provide new insights on the history of cattle in West Africa based on their population structure and the possibility of parallel adaptation between African cattle, dogs and humans in Africa which require further investigations.

Population Genomics Reveals Incipient Speciation, Introgression, and Adaptation in the African Mona Monkey (Cercopithecus mona).

Guenons (tribe Cercopithecini) are the most widely distributed nonhuman primate in the tropical forest belt of Africa and show considerable phenotypic, taxonomic, and ecological diversity. However, genomic information for most species within this group is still lacking. Here, we present a high-quality de novo genome (total 2.90 Gb, contig N50 equal to 22.7 Mb) of the mona monkey (Cercopithecus mona), together with genome resequencing data of 13 individuals sampled across Nigeria. Our results showed differentiation between populations from East and West of the Niger River ∼84 ka and potential ancient introgression in the East population from other mona group species. The PTPRK, FRAS1, BNC2, and EDN3 genes related to pigmentation displayed signals of introgression in the East population. Genomic scans suggest that immunity genes such as AKT3 and IL13 (possibly involved in simian immunodeficiency virus defense), and G6PD, a gene involved in malaria resistance, are under positive natural selection. Our study gives insights into differentiation, natural selection, and introgression in guenons.

Involvement of N-glycans in binding of Photorhabdus luminescens Tc toxin.

Photorhabdus luminescens Tc toxins are large tripartite ABC-type toxin complexes, composed of TcA, TcB and TcC proteins. Tc toxins are widespread and have shown a tropism for a variety of targets including insect, mammalian and human cells. However, their receptors and the specific mechanisms of uptake into target cells remain unknown. Here, we show that the TcA protein TcdA1 interacts with N-glycans, particularly Lewis X/Y antigens. This is confirmed using N-acetylglucosamine transferase I (Mgat1 gene product)-deficient Chinese hamster ovary (CHO) Lec1 cells, which are highly resistant to intoxication by the Tc toxin complex most likely due to the absence of complex N-glycans. Restoring Mgat1 gene activity, and hence complex N-glycan biosynthesis, recapitulated the sensitivity of these cells to the toxin. Exogenous addition of Lewis X trisaccharide partially inhibits intoxication in wild-type cells. Additionally, sialic acid also largely reduced binding of the Tc toxin. Moreover, proteolytic activation of TcdA1 alters glycan-binding and uptake into target cells. The data suggest that TcdA1-binding is most likely multivalent, and carbohydrates probably work cooperatively to facilitate binding and intoxication.

Fragmented landscapes affect honey bee colony strength at diverse spatial scales in agroecological landscapes in Kenya.

Landscape fragmentation and habitat loss at multiple scales directly affect species abundance, diversity, and productivity. There is a paucity of information about the effect of the landscape structure and diversity on honey bee colony strength in Africa. Here, we present new insights into the relationship between landscape metrics such as patch size, shape, connectivity, composition, and configuration and honey bee (Apis mellifera) colony strength characteristics. Remote-sensing-based landscape variables were linked to honey bee colony strength variables in a typical highly fragmented smallholder agroecological region in Kenya. We examined colonies in six sites with varying degrees of land degradation during the period from 2017 to 2018. Landscape structure was first mapped using medium resolution bitemporal Sentinel-1 and Sentinel-2 satellite imagery with an optimized random forest model. The influence of the surrounding landscape matrix was then constrained to two buffer distances, i.e., 1 km representing the local foraging scale and 2.5 km representing the wider foraging scale around each investigated apiary and for each of the six sites. The results of zero-inflated negative binomial regression with mixed effects showed that lower complexity of patch geometries represented by fractal dimension and reduced proportions of croplands were most influential at local foraging scales (1 km) from the apiary. In addition, higher proportions of woody vegetation and hedges resulted in higher colony strength at longer distances from the apiary (2.5 km). Honey bees in moderately degraded landscapes demonstrated the most consistently strong colonies throughout the study period. Efforts towards improving beekeeper livelihoods, through higher hive productivity, should target moderately degraded and heterogeneous landscapes, which provide forage from diverse land covers.

Feasibility and effectiveness of self-monitoring of blood glucose among insulin-dependent patients with type 2 diabetes: open randomized control trial in three rural districts in Rwanda.

BACKGROUND: The prevalence of type 2 diabetes in sub Saharan Africa (SSA) has been on the rise. Effective control of blood glucose is key towards reducing the risk of diabetes complications. Findings mainly from high-income countries have demonstrated the effectiveness of self-monitoring of blood-glucose (SMBG) in controlling blood glucose levels. However, there are limited studies describing the implementation of SMBG in rural SSA. This study explores the feasibility and effectiveness of implementing SMBG among patients diagnosed with insulin-dependent type 2 diabetes in rural Rwanda. METHODS: Participants were randomized into intervention (n = 42) and control (n = 38) groups. The intervention group received a glucose-meter, blood test-strips, log-book, waste management box and training on SMBG in addition to usual care. The control group continued with their usual care consisting of, routine monthly medical consultation and health education. The primary outcomes were adherence to the implementation of SMBG (testing schedule and recording data in the log-book) and change in hemoglobin A1c. Descriptive statistics and a paired t-test were used to analyze the primary outcomes. RESULTS: In both the intervention and control arms, majority of the participants were female (59.5% vs 52.6%) and married (71.4% vs 73.7%). Most had at most a primary level education (83.3% vs. 89.4%) and were farmers (54.8% vs. 50.0%). Among those in the intervention group, 63.4% showed good adherence to implementing SMBG based on the number of tests recorded in the glucose meter. Only 20.3% demonstrated accurate recording of the glucose level tests in log-books. The mean difference of the HbA1C from baseline to six months post-intervention was significantly better among the intervention group -0.94% (95% CI -1.46, -0.41) compared to the control group 0.73% (95% CI -0.09, 1.54) p < 0.001. CONCLUSION: Our study showed that among patients with insulin-dependent type 2 diabetes residing in rural Rwanda, SMBG was feasible and demonstrated positive outcomes in improving blood glucose control. However, there is need for strategies to enhance accuracy in recording blood glucose test results in the log-book. TRIAL REGISTRATION: The trial was registered retrospectively on the Pan African Clinical Trial Registry, on 17th May 2019. The registration number is PACTR201905538846394.

Vaccine protection against Zika virus from Brazil.

Zika virus (ZIKV) is a flavivirus that is responsible for the current epidemic in Brazil and the Americas. ZIKV has been causally associated with fetal microcephaly, intrauterine growth restriction, and other birth defects in both humans and mice. The rapid development of a safe and effective ZIKV vaccine is a global health priority, but very little is currently known about ZIKV immunology and mechanisms of immune protection. Here we show that a single immunization with a plasmid DNA vaccine or a purified inactivated virus vaccine provides complete protection in susceptible mice against challenge with a strain of ZIKV involved in the outbreak in northeast Brazil. This ZIKV strain has recently been shown to cross the placenta and to induce fetal microcephaly and other congenital malformations in mice. We produced DNA vaccines expressing ZIKV pre-membrane and envelope (prM-Env), as well as a series of deletion mutants. The prM-Env DNA vaccine, but not the deletion mutants, afforded complete protection against ZIKV, as measured by absence of detectable viraemia following challenge, and protective efficacy correlated with Env-specific antibody titers. Adoptive transfer of purified IgG from vaccinated mice conferred passive protection, and depletion of CD4 and CD8 T lymphocytes in vaccinated mice did not abrogate this protection. These data demonstrate that protection against ZIKV challenge can be achieved by single-shot subunit and inactivated virus vaccines in mice and that Env-specific antibody titers represent key immunologic correlates of protection. Our findings suggest that the development of a ZIKV vaccine for humans is likely to be achievable.

Ad26/MVA therapeutic vaccination with TLR7 stimulation in SIV-infected rhesus monkeys.

The development of immunologic interventions that can target the viral reservoir in HIV-1-infected individuals is a major goal of HIV-1 research. However, little evidence exists that the viral reservoir can be sufficiently targeted to improve virologic control following discontinuation of antiretroviral therapy. Here we show that therapeutic vaccination with Ad26/MVA (recombinant adenovirus serotype 26 (Ad26) prime, modified vaccinia Ankara (MVA) boost) and stimulation of TLR7 (Toll-like receptor 7) improves virologic control and delays viral rebound following discontinuation of antiretroviral therapy in SIV-infected rhesus monkeys that began antiretroviral therapy during acute infection. Therapeutic vaccination with Ad26/MVA resulted in a marked increase in the magnitude and breadth of SIV-specific cellular immune responses in virologically suppressed, SIV-infected monkeys. TLR7 agonist administration led to innate immune stimulation and cellular immune activation. The combination of Ad26/MVA vaccination and TLR7 stimulation resulted in decreased levels of viral DNA in lymph nodes and peripheral blood, and improved virologic control and delayed viral rebound following discontinuation of antiretroviral therapy. The breadth of cellular immune responses correlated inversely with set point viral loads and correlated directly with time to viral rebound. These data demonstrate the potential of therapeutic vaccination combined with innate immune stimulation as a strategy aimed at a functional cure for HIV-1 infection.

Prevalence and factors associated with caesarean section in Rwanda: a trend analysis of Rwanda demographic and health survey 2000 to 2019-20.

BACKGROUND: Caesarean section (CS) is an important medical intervention for reducing the risk of poor perinatal outcomes. However, CS trends in sub-Saharan Africa (SSA) continue to increase yet maternal and neonatal mortality and morbidity remain high. Rwanda, like many other countries in SSA, has shown an increasing trend in the use of CS. This study assessed the trends and factors associated with CS delivery in Rwanda over the past two decades. METHODS: We used nationally representative child datasets from the Rwanda Demographic and Health Survey 2000 to 2019-20. All births in the preceding 3 years to the survey were assessed for the mode of delivery. The participants' characteristics, trends and the prevalence of CS were analysed using frequencies and percentages. Unadjusted and adjusted logistic regression analyses were used to assess the factors associated with population and hospital-based CS in Rwanda for each of the surveys. RESULTS: The population-based rate of CS in Rwanda significantly increased from 2.2% (95% CI 1.8-2.6) in 2000 to 15.6% (95% CI 13.9-16.5) in 2019-20. Despite increasing in all health facilities over time, the rate of CS was about four times higher in private (60.6%) compared to public health facilities (15.4%) in 2019-20. The rates and odds of CS were disproportionately high among women of high socioeconomic groups, those who resided in Kigali city, had multiple pregnancies, and attended at least four antenatal care visits while the odds of CS were significantly lower among multiparous women and those who had female babies. CONCLUSION: Over the past two decades, the rate of CS use in Rwanda increased significantly at health facility and population level with high regional and socio-economic disparities. There is a need to examine the disparities in CS trends and developing tailored policy guidelines to ensure proper use of CS in Rwanda.

Schistosomiasis, soil transmitted helminthiasis, and malaria co-infections among women of reproductive age in rural communities of Kwale County, coastal Kenya.

BACKGROUND: Schistosoma haematobium, soil transmitted helminthes (STH), and malaria lead to a double burden in pregnancy that eventually leads to poor immunity, increased susceptibility to other infections, and poor pregnancy outcomes. Many studies have been carried out on pre-school and school aged children but very little has been done among the at risk adult population including women of reproductive age (WRA). Our current study sought to establish the risk factors and burden of co-infection with S. haematobium, STH, and Plasmodium sp. among WRA in Kwale County, Coastal Kenya. METHODS: A total of 534 WRA between the ages of 15-50 were enrolled in this cross-sectional study from four villages; Bilashaka and Mwaluphamba in Matuga sub-County, and Mwachinga and Dumbule in Kinango sub-County. Socio-demographic information was collected using a pre-tested standardized questionnaire. Parasitological examination was done using urine filtration method for Schistosoma haematobium, Kato Katz for STH (Ascaris lumbricoides, Hookworm, Trichuris trichiura), and standard slide microscopy for Plasmodium sp. Statistical analyses were carried out using STATA version 15.1. RESULTS: The overall prevalence of S. haematobium was 3.8% (95% CI: 2.6-5.4) while that for malaria was 4.9% (95% CI: 2.0-11.7). The prevalence of STH was 5.6% (95% CI: 2.8-11.3) with overall prevalence of 5.3% (95% CI: 2.5-10.9) for hookworm and 0.6% (95% CI: 0.2-1.9) for T. trichiura. The occurrence of co-infection was low and was recorded between S. haematobium and P. falciparum (0.6%), followed by S. haematobium and STH (0.4%). Among pregnant women, 2.6% had co-infection with S. haematobium and P. falciparum. Only 1.3% had co-infection with S. haematobium and hookworm or T. trichiura. Among non-pregnant women, co-infection with S. haematobium and P. falciparum was 0.2%. Similarly, co-infection with S. haematobium and hookworm or T. trichiura was 0.2%. Bed net ownership and usage among pregnant women was 87.8 and 96.6%, respectively. 66.3% of the women reported using improved water sources for drinking while 78.1% reported using improved sanitation facilities. CONCLUSION: The use of improved WASH activities might have contributed to the low prevalence of STHs and S. haematobium infections. Further, bed net ownership and usage might have resulted in the low prevalence of Plasmodium sp. infections observed.

'They can stigmatize you': a qualitative assessment of the influence of school factors on engagement in care and medication adherence among adolescents with HIV in Western Kenya.

School-related factors may influence retention in care and adherence to antiretroviral therapy (ART) among adolescents with human immunodeficiency virus (HIV). We analyzed data from in-depth interviews with 40 adolescents with HIV (aged 14 -19 years), 40 caregivers of adolescents with HIV, and 4 focus group discussions with healthcare workers to evaluate contextual factors affecting adherence to ART and clinic attendance among adolescents, with a focus on the school environment. Informed by Anderson's Model of Health Services Utilization, transcripts were systematically coded and synthesized to identify school-related themes. All groups identified the school environment as a critical barrier to engagement in HIV care and medication adherence for adolescents with HIV. Adolescent participants reported inflexible school schedules and disclosure to school staff as the biggest challenges adhering to clinic appointments and ART. Adolescents described experiencing stigma and discrimination by peers and school staff and would adjust when, where and how often they took ART to avoid inadvertent disclosure. Boarding school students faced challenges because they had limited private space or time. Caregivers were often instrumental in navigating school permissions, including identifying a treatment supporter among school staff. Additional research engaging school staff may guide interventions for schools to reduce stigma and improve adherence and retention.

α-Gal specific-IgE prevalence and levels in Ecuador and Kenya: Relation to diet, parasites, and IgG4.

BACKGROUND: IgE to α-Gal is a cause of mammalian meat allergy and has been linked to tick bites in North America, Australia, and Eurasia. Reports from the developing world indicate that α-Gal sensitization is prevalent but has been little investigated. OBJECTIVE: We sought evidence for the cause(s) of α-Gal sensitization and lack of reported meat allergy among children in less developed settings in Ecuador and Kenya. METHODS: IgE to α-Gal and total IgE were assessed in children from Ecuador (n = 599) and Kenya (n = 254) and compared with children with (n = 42) and without known (n = 63) mammalian meat allergy from the southeastern United States. Information on diet, potential risk factors, and helminth infections was available for children from Ecuador. IgG4 to α-Gal and antibodies to regionally representative parasites were assessed in a subset of children. RESULTS: In Ecuador (32%) and Kenya (54%), α-Gal specific IgE was prevalent, but levels were lower than in children with meat allergy from the United States. Sensitization was associated with rural living, antibody markers of Ascaris exposure, and total IgE, but not active infections with Ascaris or Trichuris species. In Ecuador, 87.5% reported consuming beef at least once per week, including 83.9% of those who had α-Gal specific IgE. Levels of α-Gal specific IgG4 were not high in Ecuador, but were greater than in children from the United States. CONCLUSIONS: These results suggest that in areas of the developing world with endemic parasitism, α-Gal sensitization is (1) common, (2) associated with Ascaris exposure, and (3) distinguished by a low percentage of specific/total IgE compared with individuals with meat allergy in the United States.

Comparison of measured and predicted mesiodistal tooth-widths of 13-17 years old Kenyans: a descriptive cross-sectional study to develop a new prediction equation for use in the mixed dentition in a Kenyan population.

BACKGROUND: The Tanaka and Johnson equation is commonly used in mixed dentition analysis. However, the analysis is based on  a Caucasian population making clinical decisions challenging when used in different ethnic groups. This study developed a prediction equation based on a Kenyan population. DESIGN: A descriptive cross-sectional study done in 68 13-17 years old Kenyans of African descent in two boarding secondary schools. Alginate impressions were taken, study models obtained, and mesiodistal tooth-widths measured on upper and lower study models from the first molar to the contralateral first molar. Descriptive statistics, paired t-tests and independent t-tests were conducted and Pearson product-moment correlation coefficients calculated (p < 0.05). RESULTS: The mean age was 13.78 years (SD ± 0.70), females were 59%. The mesiodistal tooth-widths of the permanent canines and premolars were different between males and females (p ˂ 0.1). The Tanaka and Johnston equation significantly under-estimated the mesiodistal tooth-widths of the permanent canines and premolars (p ˂ 0.05). The addition of lower first permanent molars to the permanent lower incisors provided higher correlation coefficients than the Tanaka Johnston equation. CONCLUSIONS: A new equation that includes the permanent lower incisors and first permanent molars as predictor teeth seems to be more suitable for mixed dentition analysis for this Kenyan population. A larger study is needed to validate these findings.

The Comoros Show the Earliest Austronesian Gene Flow into the Swahili Corridor.

At the dawn of the second millennium, the expansion of the Indian Ocean trading network aligned with the emergence of an outward-oriented community along the East African coast to create a cosmopolitan cultural and trading zone known as the Swahili Corridor. On the basis of analyses of new genome-wide genotyping data and uniparental data in 276 individuals from coastal Kenya and the Comoros islands, along with large-scale genetic datasets from the Indian Ocean rim, we reconstruct historical population dynamics to show that the Swahili Corridor is largely an eastern Bantu genetic continuum. Limited gene flows from the Middle East can be seen in Swahili and Comorian populations at dates corresponding to historically documented contacts. However, the main admixture event in southern insular populations, particularly Comorian and Malagasy groups, occurred with individuals from Island Southeast Asia as early as the 8th century, reflecting an earlier dispersal from this region. Remarkably, our results support recent archaeological and linguistic evidence-based suggestions that the Comoros archipelago was the earliest location of contact between Austronesian and African populations in the Swahili Corridor.

Strengthening community and stakeholder participation in the implementation of integrated vector management for malaria control in western Kenya: a case study.

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

Long lasting insecticidal mosquito nets (LLINs) ownership, use and coverage following mass distribution campaign in Lake Victoria basin, Western Kenya.

BACKGROUND: Long-lasting insecticidal nets (LLINs) are the most widely used malaria prevention and control intervention in Africa. However, their effectiveness may vary depending on their local geographic coverage, ownership and use at household level. This study aimed at assessing LLINs ownership and use following mass distribution campaign in western Kenya. METHODS: A cross-sectional study was conducted in November 2017. A total of 160 households were randomly selected from 16 villages. Structured questionnaires were used to collect data on households' knowledge on malaria, LLINs ownership, utilization and their perceived benefits. Data was analyzed using IBM Statistical Package for Social Sciences (SPSS) version 21 for windows. Variables were presented as proportions and associations between variables tested using Pearson's chi-square test. RESULTS: Malaria was reported to be the most frequently occurring disease (87.5%) in the area. Children under 5 years of age were reported to be at higher risks of malaria infection (28.6%). Around 31% of the respondents reported to have at least one member of the household sick with malaria a week before the interview. Commonly cited signs and symptoms of malaria were; fever (24.1%), headache (17.7%), vomiting (14.5%) feeling cold (12.6%) and loss of appetite (10%). There were 382 reported LLINs among 753 occupants in the 160 households surveyed. The average LLIN ownership was 2.4 nets per household and 1.97 persons per LLIN. Among the surveyed households, 96.9% owned at least one LLIN and 64.1% owned at least one LLIN for every two people. Among those who owned LLINs, 98.1% reported using them the previous night. Ownership per household ranged from 0 to 6 with a mean of 2.39. More than three quarter of the nets were acquired through free mass distribution campaigns and 80% were acquired less than 6 months prior to the survey. CONCLUSION: Despite high net coverage and use, a number of households experienced malaria episodes in the study area. There is need to investigate the likelihood of outdoor malaria transmission and assess the physical integrity of the existing LLINs and their insecticidal effectiveness in protecting household members against malaria.

Expansion of the CD4+ effector T-cell repertoire characterizes peanut-allergic patients with heightened clinical sensitivity.

BACKGROUND: Individuals with peanut allergy range in clinical sensitivity: some can consume grams of peanut before experiencing any symptoms, whereas others suffer systemic reactions to 10 mg or less. Current diagnostic testing only partially predicts this clinical heterogeneity. OBJECTIVE: We sought to identify characteristics of the peanut-specific CD4+ T-cell response in peanut-allergic patients that correlate with high clinical sensitivity. METHODS: We studied the T-cell receptor ß-chain (TCRß) usage and phenotypes of peanut-activated, CD154+ CD4+ memory T cells using fluorescence-activated cell sorting, TCRß sequencing, and RNA-Seq, in reactive and hyporeactive patients who were stratified by clinical sensitivity. RESULTS: TCRß analysis of the CD154+ and CD154- fractions revealed more than 6000 complementarity determining region 3 sequences and motifs that were significantly enriched in the activated cells and 17% of the sequences were shared between peanut-allergic individuals, suggesting strong convergent selection of peanut-specific clones. These clones were more numerous among the reactive patients, and this expansion was identified within effector, but not regulatory T-cell populations. The transcriptional profile of CD154+ T cells in the reactive group skewed toward a polarized TH2 effector phenotype, and expression of TH2 cytokines strongly correlated with peanut-specific IgE levels. There were, however, also non-TH2-related differences in phenotype. Furthermore, the ratio of peanut-specific clones in the effector versus regulatory T-cell compartment, which distinguished the clinical groups, was independent of specific IgE concentration. CONCLUSIONS: Expansion of the peanut-specific effector T-cell repertoire is correlated with clinical sensitivity, and this observation may be useful to inform our assessment of disease phenotype and to monitor disease longitudinally.