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High exposure to malaria vector bites despite high use of bednets in a setting of seasonal malaria in southwestern Mali: the urgent need for outdoor vector control strategies.
Get PDFBACKGROUND: Early evening and outdoor biting by vector mosquitoes undermines the effectiveness of insecticide-treated nets (ITNs), as users of nets are exposed to vector biting whilst not under a net, both outdoors and indoors. This study assessed exposure to malaria vector bites amongst users and non-users of ITNs in southwestern Mali. METHODS: Using cross-sectional household survey data of human behaviour and malaria infection prevalence, along with mosquito human landing catch (HLC) data collected in 30 separate communities, the average number of Anopheles gambiae sensu lato (s.l.) mosquito bites per person per night (bppn) received outdoors and indoors were estimated for each survey respondent. The proportion of bites that were not preventable by using a net, the relative contributions of outdoor and indoor residual biting, and the risk factors for exposure to vector bites were estimated. RESULTS: Despite very high use of nets (93.2%), malaria infection prevalence was 34% overall. A large proportion of respondents (78%) reported being outdoors at 8 pm, but by midnight, 98% were indoors. Net users were exposed to indoor biting for 1 h, on average, between going indoors and going to bed. For 91%, the net used was an ITN. Human biting rates peaked between 2 and 4 am, when most people (90%) were in bed. Individuals using a net received 11.2 bppn in total, of which 7.1 bppn (63%) occurred outdoors. Those not using a net received almost 10 times the number of bites indoors as net users (38.4 bppn versus 4.0 bppn). The total number of bites received by net users was about one third the total number of bites received by non-net users, indicating the proportion of bites not preventable by use of a net alone. Risk factors for biting exposure included not using a net, going indoors late, location near the river and age over 15 years. CONCLUSIONS: ITNs substantially reduce exposure to indoor biting, but in this setting, net users still received a large number of Anopheles mosquito bites, giving rise to high malaria infection prevalence despite near-universal net use. Most residual biting occurred outdoors, but about a third still occurred with individuals indoors before going under a net. Effective interventions that reduce residual outdoor and indoor biting are necessary to reduce the high malaria burden in settings like southwestern Mali
Validation and Evaluation of Lateral Flow Tests for the Detection of Antimicrobial Residues on Poultry Feathers.
Get PDFPersistence of antimicrobial drugs (AMDs) administered to poultry is longer in feathers than in edible tissues. Hence, poultry feathers are a suitable matrix to investigate historical exposure contributing to antimicrobial resistance, since current detection methods are either non-specific or highly technical and costly. Here we present an analysis of the performance of lateral flow test (LFT) panels in the detection of five AMD classes, namely sulfonamides, tetracyclines, beta-lactams, quinolones, and aminoglycosides, on chicken feather samples. The limit of detection (LOD) of eight AMD substances was determined between 4.7 μg/kg for enrofloxacin and 700 μg/kg for streptomycin. The performance of feather LFT was evaluated for four AMD classes against the reference method (LC-MS/MS). From 79 samples collected from the field, LFT test specificity ranged from 0.63 (quinolones) to 0.95 (tetracyclines). Test sensitivity ranged from 0.15 (beta-lactams) to 0.78 (quinolones and tetracyclines). LFT testing had the greatest discriminatory power for tetracyclines (specificity 0.95 and sensitivity 0.78). LFT had similar test characteristics for sulfonamides and quinolones and performed poorly for beta-lactams. Poor recovery rates (< 15%) were observed in neomycin, kanamycin, and ampicillin. These methods are suitable for preliminarily screening tetracyclines, sulfonamides, and quinolones, with recommendations for further extraction protocols
The impact of enhancing nutrition and antenatal infection treatment on birth outcomes in Amhara, Ethiopia: a pragmatic factorial, cluster-randomised clinical effectiveness study.
Get PDFINTRODUCTION: We aimed to determine the impact of antenatal interventions to optimise maternal nutrition and infection management on birth outcomes in Ethiopia. METHODS: We conducted a pragmatic, open-label, 2×2 factorial randomised clinical effectiveness study among pregnant women enrolled <24 weeks gestation in 12 rural health centres in Amhara, Ethiopia. Eligible health centres were randomised to deliver an enhanced nutrition package (ENP) (iron-folic acid, iodised salt and targeted micronutrient fortified balanced energy protein (BEP) supplementation for undernourished women) or routine nutrition care (iron-folic acid only). Individual women were randomised to receive an enhanced infection management package (EIMP) (genitourinary tract infection screening-treatment and enhanced deworming) or routine infection care (syndromic management). The primary outcomes were birth weight and length; secondary outcomes were gestational age, preterm delivery, small-for-gestational-age, low birth weight, stillbirth, newborn weight-for-age and length-for-age z-scores, newborn head circumference, and maternal anemia. Analysis was intention to treat. RESULTS: From August 2020 to December 2021, 2392 women were randomised (604 ENP+EIMP, 600 ENP alone, 593 EIMP alone and 595 neither package) and followed until June 2022, with 2170 pregnancy outcomes analysed (565 ENP+EIMP, 549 ENP, 525 EIMP, 531 neither). In the ENP arm, 427 (36%) women were eligible for BEP and consumed on average 74 days. The prevalence of genitourinary tract infection was low (4.9%), while parasitic stool infections were common (31%). There was no difference in birth weight (ENP vs not-ENP: adjusted mean difference -4 g (-83 to 75); EIMP vs not-EIMP: 18 g (-35 to 70); ENP+EIMP vs neither: 14 g (-81 to 109)) or birth length (ENP: -0.3 cm (-1.1 to 0.5); EIMP: 0.2 cm (-0.1 to 0.5); ENP+EIMP: -0.1 cm (-1.2 to 1.1)) between study arms. In the ENP+EIMP group, the stillbirth rate was lower compared with the arm receiving neither package (7.1/1000 vs 24.7/1000 births; adjusted relative risk: 0.29 (0.09 to 0.94)). The packages did not significantly affect other secondary outcomes. CONCLUSIONS: In this pragmatic study implemented within the Ethiopian health system, enhanced nutrition and infection packages did not affect birth weight or length. While stillbirth rates were lower in the group receiving both packages, these findings need to be supported by additional studies. TRIAL REGISTRATION NUMBER: ISRCTN15116516
The impact of adverse weather events on cockroaches and flies, and the possible effects on disease.
No full textClimate change is associated with an increase in adverse weather events such as heatwaves, drought, hurricanes and typhoons, floods and wildfires. These extreme weather events can disrupt public health infrastructure and can be detrimental to hygiene and sanitation practices, leading to knock-on effects on populations of vectors associated with disease transmission. Both the frequency and intensity of climate-related adverse weather events are predicted to increase, likely resulting in changes to vector dynamics and vector-human interactions, leading to an increased risk of disease transmission. Yet, a gap exists in our knowledge of the impact of these events on hygiene and associated pest-borne diseases. A growing body of research connects two groups of pests (domestic flies and cockroaches) that are linked with poor hygiene and sanitary conditions to mechanical disease transmission. We present a review of these specific vectors' population biology and behaviour, links with hygiene and sanitation and how pest populations and public health could be affected by adverse weather events. There is evidence that increased temperatures, extreme rainfall and flooding events are most likely to be associated with increased fly and cockroach populations and changes in the behaviour or activity of these insects, which could exacerbate the risks of disease transmission. Warmer temperatures accelerate their rates of reproduction, while heavy rainfall and flooding disrupt their habitats, driving them indoors. Other factors like habitat destruction, breakdown in healthcare system infrastructure, population displacement and altered pesticide use following an extreme weather event are predicted to influence insect populations and provide opportunities for increased human -pest contact. We highlight research gaps and provide recommendations for the improvement of current domestic and professional pest control products and strategies that might be employed to mitigate the impacts of adverse weather events on hygiene-related pests in a changing world
A new method for detecting mixed Mycobacterium tuberculosis infection and reconstructing constituent strains provides insights into transmission.
Get PDFBACKGROUND: Mixed infection with multiple strains of the same pathogen in a single host can present clinical and analytical challenges. Whole genome sequence (WGS) data can identify signals of multiple strains in samples, though the precision of previous methods can be improved. Here, we present MixInfect2, a new tool to accurately detect mixed samples from Mycobacterium tuberculosis short-read WGS data. We then evaluate three approaches for reconstructing the underlying mixed constituent strain sequences. This allows these samples to be included in downstream analysis to gain insights into the epidemiology and transmission of mixed infections. METHODS: We employed a Gaussian mixture model to cluster allele frequencies at mixed sites (hSNPs) in each sample to identify signals of multiple strains. Building upon our previous tool, MixInfect, we increased the accuracy of classifying in vitro mixed samples through multiple improvements to the bioinformatic pipeline. Major and minor proportion constituent strains were reconstructed using three approaches and assessed by comparing the estimated sequence to the known constituent strain sequence. Lastly, mixed infections in a real-world Mycobacterium tuberculosis population from Moldova were detected with MixInfect2 and clusters of recent transmission that included major and minor constituent strains were built. RESULTS: All 36/36 in vitro mixed and 12/12 non-mixed samples were correctly classified with MixInfect2, and major strain proportions were estimated with high accuracy (within 3% of the true strain proportion), outperforming previous tools. Reconstructed major strain sequences closely matched the true constituent sequence by taking the allele at the highest frequency at hSNPs, while the best-performing approach to reconstruct the minor proportion strain sequence was identifying the closest non-mixed isolate in the same population, though no approach was effective when the minor strain proportion was at 5%. Finally, fewer mixed infections were identified in Moldova than previous estimates (6.6% vs 17.4%) and we found multiple instances where the constituent strains of mixed samples were present in transmission clusters. CONCLUSIONS: MixInfect2 accurately detects samples with evidence of mixed infection from short-read WGS data and provides an excellent estimate of the mixture proportions. While there are limitations in reconstructing the constituent strain sequences of mixed samples, we present recommendations for the best approach to include these isolates in further analyses
WASH and learn: a scoping review of health, education and gender equity outcomes of school-based water, sanitation and hygiene in low-income and middle-income countries.
Get PDFSchool-age children in low-income and middle-income countries (LMICs) face health and educational challenges due to inadequate water, sanitation and hygiene (WASH) in schools (WinS). Evidence for the impact of WinS interventions is limited and inconsistent, and previous systematic reviews have faced challenges in synthesising data due to varied interventions, study designs and outcome measures, although most do not examine this variability in more detail. This scoping review identified 83 experimental studies from 33 LMICs measuring a primary or secondary health or educational outcome among pupils, published up to November 2023, using a systematic search of seven databases and searching of reference lists of previous systematic reviews and included articles. These included 65 studies (78%) not included in previous WinS reviews and encompassed 313 intervention effects across 14 outcome domains. Interventions comprised an array of WASH technologies and approaches, often combining infrastructure and behaviour change methods and frequently integrated with other school-based initiatives like deworming. 36 studies (43%) measured only behavioural or knowledge outcomes. Our comprehensive inventory of study outcomes identified 158 unique outcome measures, with 72% measured in exactly one study. Common outcomes included parasitic infections, anthropometric measures and school absence, but approaches to measurement varied widely even for similar outcomes. Only 7% of results were disaggregated by gender, limiting assessment of differential impacts. Our findings underscore the need for standardised outcome measures in WinS research incorporating a complete definition of the assessment and aggregation approach, greater attention to gender-specific impacts, and further exploration of modalities and functions of WinS interventions alongside novel meta-analysis methods to disentangle effects of diverse intervention components
Analysis insights to support the use of wastewater and environmental surveillance data for infectious diseases and pandemic preparedness.
Get PDFWastewater-based epidemiology is the detection of pathogens from sewage systems and the interpretation of these data to improve public health. Its use has increased in scope since 2020, when it was demonstrated that SARS-CoV-2 RNA could be successfully extracted from the wastewater of affected populations. In this Perspective we provide an overview of recent advances in pathogen detection within wastewater, propose a framework for identifying the utility of wastewater sampling for pathogen detection and suggest areas where analytics require development. Ensuring that both data collection and analysis are tailored towards key questions at different stages of an epidemic will improve the inference made. For analyses to be useful we require methods to determine the absence of infection, early detection of infection, reliably estimate epidemic trajectories and prevalence, and detect novel variants without reliance on consensus sequences. This research area has included many innovations that have improved the interpretation of collected data and we are optimistic that innovation will continue in the future
Safety and broad immunogenicity of HIVconsvX conserved mosaic candidate T-cell vaccines vectored by ChAdOx1 and MVA in HIV-CORE 006: a double-blind, randomised, placebo-controlled phase 1 trial in healthy adults living without HIV-1 in eastern and southern Africa.
Get PDFBACKGROUND: Even within the context of antiretroviral treatment and prevention, an HIV-1 vaccine remains the best strategy for ending the HIV/AIDS epidemic. A vaccine is particularly needed in sub-Saharan Africa, where HIV-1 greatly affects people's lives and economy. Here, we aimed to assess the safety and immunogenicity of candidate T-cell vaccines in African populations. METHODS: HIV-CORE 006 was a double-blind, randomised, placebo-controlled phase 1 trial conducted across four clinical research centres in Uganda, Kenya, and Zambia. Eligible participants were not pregnant, were living without HIV-1 or HIV-2, had a low likelihood of acquiring HIV-1, were aged 18-50 years, fully comprehended the purpose and details of this study as outlined in the participant information sheet, and passed an assessment of understanding before providing written informed consent. Participants were randomly assigned (9:2) to receive either a vaccine regimen or a placebo. The vaccine was administered as ChAdOx1.tHIVconsv1 (C1) followed by MVA.tHIVconsv3 (M3) and MVA.tHIVconsv4 (M4) in regimen C1-M3M4. The first primary outcome was the vaccines' safety assessment, assessed in all participants who received at least one vaccine or placebo dose. The second primary outcome evaluated the C1-M3M4 regimen's induction of HIVconsvX-specific T-cell responses by assessing the proportion of vaccine recipients who responded to the vaccination, assessed in all participants who received all doses of vaccine or placebo as per protocol. This study is registered with ClinicalTrials.gov, NCT04553016, and the Pan-African Clinical Trials Registry PACTR202006495409011, and is now closed. FINDINGS: Between July 15, 2021, and Nov 2, 2022, 89 healthy adults living without HIV-1 were randomly assigned, with 88 receiving either the vaccine (n=72) or placebo (n=16). Of these 88 participants, 57 (65%) were male and 31 (35%) were female. The C1, M3, and M4 vaccine components were well tolerated and induced HIVconsvX-specific responses in 70 (99%) of the 71 participants who completed all vaccine doses. Vaccine-elicited T cells peaked at a median of 2310 (IQR 1080-4480) IFN-γ spot-forming units per 106 peripheral blood mononuclear cells and recognised a median of eight (five to ten) of ten peptide pools spanning the HIVconsvX immunogen. The total frequencies of elicited T cells decreased 4·6 times over a 40-week follow-up period compared with the peak responses. Upon antigenic re-exposure, T cells proliferated, exhibited multiple effector functions, and inhibited HIV-1 representatives from clades A, B, C, and D. INTERPRETATION: Results from key sub-Saharan African populations supported the safety of the vaccine regimen previously shown in the first-in-human trial in the UK. The induction of T cells and their characteristics encourage vaccine integration into HIV-1 cure strategies, which could inform HIV-1 prevention efforts. FUNDING: The European and Developing Countries Clinical Trials Partnership
HIV status alters immune cell infiltration and activation profile in women with breast cancer.
Get PDFThe breast cancer (BC)-related mortality is higher and the immunity is altered in women living with HIV (WLWH) compared to HIV-negative women. Therefore, tumor samples of 296 black BC patients from South Africa and Namibia with known age, HIV status, tumor stage, hormone receptor and HER2 status and overall survival (OS) are analyzed for components of the tumor microenvironment (TME). WLWH (n = 117), either with suppressed viral activity (HR = 1.25) or with immune suppression (HR = 2.04), have a shorter OS. HIV status is associated with increased numbers of CD8+ T cells in the TME compared to HIV-negative patients; no correlation is found with CD4+ T cell numbers in the blood. Moreover, an increased expression of CD276/B7-H3 and a more pronounced IFN-γ signaling in the tumors are found in WLWH, independent of age, stage, and BC subtypes. In conclusion, altered T cell composition and CD276 expression in WLWH may contribute to inferior survival and can be used for targeted treatment
Genome-wide association study identifying novel risk variants associated with glycaemic traits in the continental African AWI-Gen cohort.
Get PDFAIMS/HYPOTHESIS: Glycaemic traits such as high fasting glucose levels and insulin resistance are positively associated with the risk of type 2 diabetes and other cardiometabolic diseases. Genetic association studies have identified hundreds of associations for each glycaemic trait, yet very few studies have involved continental African populations. We report the results of genome-wide association studies (GWASs) in a pan-African cohort for four glycaemic traits, namely fasting glucose, fasting insulin, insulin resistance (HOMA-IR) and beta cell function (HOMA-B), which are quantitative variables that affect the risk of developing type 2 diabetes. METHODS: GWASs for the four traits were conducted in approximately 10,000 individuals from the Africa Wits-INDEPTH Partnership for Genomics Studies (AWI-Gen) cohort, with participants from Burkina Faso, Ghana, Kenya and South Africa. Association testing was performed using linear mixed models implemented in BOLT-LMM, with age, sex, BMI and principal components as covariates. Replication, fine mapping and functional annotation were performed using standard approaches. RESULTS: We identified a novel signal (rs574173815) in the intron of the ankyrin repeat domain 33B (ANKRD33B) gene associated with fasting glucose, and a novel signal (rs114029796) in the intronic region of the WD repeat domain 7 (WDR7) gene associated with fasting insulin. SNPs in WDR7 have been shown to be associated with type 2 diabetes. A variant (rs74806991) in the intron of ADAM metallopeptidase with thrombospondin type 1 motif 16 (ADAMTS16) and another variant (rs6506934) in the β-1,4-galactosyltransferase 6 gene (B4GALT6) are associated with HOMA-IR. Both ADAMTS16 and B4GALT6 are implicated in the development of type 2 diabetes. In addition, our study replicated several well-established fasting glucose signals in the GCK-YTK6, SLC2A2 and THORLNC gene regions. CONCLUSIONS/INTERPRETATION: Our findings highlight the importance of performing GWASs for glycaemic traits in under-represented populations, especially continental African populations, to discover novel associated variants and broaden our knowledge of the genetic aetiology of glycaemic traits. The limited replication of well-known signals in this study hints at the possibility of a unique genetic architecture of these traits in African populations. DATA AVAILABILITY: The dataset used in this study is available in the European Genome-Phenome Archive (EGA) database ( https://ega-archive.org/ ) under study accession code EGAS00001002482. The phenotype dataset accession code is EGAD00001006425 and the genotype dataset accession code is EGAD00010001996. The availability of these datasets is subject to controlled access by the Data and Biospecimen Access Committee of the H3Africa Consortium. GWAS summary statistics are accessible through the NHGRI-EBI GWAS Catalog ( https://www.ebi.ac.uk/gwas/ )