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Development of a dynamical model to enhance understanding of epidemiology of schistosomiasis in school-aged-children
Get PDFSchool-aged-children are most vulnerable to schistosomiasis as exemplified by age-prevalence profiles although current understanding of these patterns needs improvement. Using epidemiological data from the southern shoreline of Lake Malawi, we investigated the dynamics of Schistosoma transmission and the main determinants of Schistosoma infection risk using a transmission dynamic model, considering urogenital and intestinal schistosomiasis respectively. Specifically, we assessed whether the proximity of primary schools to the immediate shoreline was a major geospatial and epidemiological determinant. Cross-sectional parasitology and malacological data previously collected and analysed was used, including age-infection profiles and interpolated predicted snail distributions for the southern part of Lake Malawi shoreline. A disease SEIRS ordinary differential equation model was created, and an observation prevalence model was formed using a binomial sampling distribution using the already published dataset. An optimisation using L-BFGS-B algorithm with upper/lower bounded box constraints was carried out to calibrate the model to find the best parameter values for each infection state transition given the disease model and dataset. The aim was to recapture the age-structure dynamics shown in the observation model representing the already published age-infection profiles. Concerning intestinal schistosomiasis, the best model for Biomphalaria sp. was the use of a single transmission rate for all the school’s and no spatial effect. By contrast, for urogenital schistosomiasis, the best model for Bulinus spp. was found when using an independent transmission rate for each school and no spatial effect. There was some evidence that we were able to capture the age-structured dynamics of infection in SAC despite the expected outcome differing to statistical output due to sparse data. Within our study area, we found there was no significant effect on SAC exposure to Schistosoma infection risk based on school distance from the shoreline. Further, there was heterogeneity between schools in transmission rates estimated, although these did not have significantly different confidence intervals. However, schools considered in our study were all relatively close to cercaria infested shorelines. Further studies using a longitudinal cohort study could improve understanding of Schistosoma infection dynamics and allow for improved control method application.</p
Schistosomiasis amongst adolescent boys in non-lakeshore southern Malawi: Investigating local risk-factors within a nested community-based cross-sectional survey
Get PDFBACKGROUND: Schistosomiasis is endemic to Malawi, where preventive chemotherapy by mass drug administration (MDA) has been the foundational public health strategy for over a decade. Despite ongoing control, our understanding of the contemporary epidemiology of schistosomiasis in rural Malawi is limited to infrequent school-based surveys, typically lacking evidence from community-based surveys particularly within non-lakeshore upland communities who may be perceived to be at lower risk. #METHODS: Between July and August 2022, we conducted a cross-sectional parasitological survey amongst a community-representative sub-sample of boys aged 10-15 years who had been randomly selected and recruited to the DeWorm3 endline survey in Namwera, Mangochi District. A total of 306 participants from 38 communities were assessed for S. mansoni by duplicate Kato-Katz thick smears. Of these, 243 (79.4%) subsequently provided a urine sample to be assessed by filtration for S. haematobium and 238 (77.8%) responded to a risk-factor questionnaire. A parallel malacological survey of eight locally important water contact sites was conducted. RESULTS: The overall prevalence of egg-patent schistosomiasis was 50.6% (95% CI 44.2-57.1). The prevalence of S. haematobium was 47.7% (95% CI 41.3-54.2), of which 37.9% (n=44) were heavy intensity infections whereas the prevalence of S. mansoni was 6.5% (95% CI 4.0-9.9), with one moderate intensity infection (0.3%). There was strong evidence of a positive association between detected S. haematobium infection and reporting "red urine" (p<0.001) and 'bilharzia' (p=0.005). Biomphalaria spp. were found at two sites while Bulinus spp. were found at five sites. CONCLUSION: Despite multiple years of MDA at reportedly high coverage, we observed a high egg-patent prevalence with high prevalence of heavy intensity infections amongst boys aged 10-15 years. This evidences engrained and ongoing transmission requiring additional efforts to gain and sustain effective control. Our findings highlight the importance of epidemiological monitoring alongside a schistosomiasis control programme, particularly in areas historically perceived to be at lower risk.</p
Conflicting perspectives on what constitutes fair compensation and benefits among research stakeholders in Malawi
Get PDFBackground: International ethics guidelines such as the Council for International Organizations of Medical Science (CIOMS) recommend that research participants must be compensated for their time, travel, and inconveniences. However, there is continued debate on what constitutes fair compensation and benefits for research participants. We conducted a qualitative study and sought views of various research stakeholders on what they considered as appropriate compensation and benefits for study participation in Malawi. Methods: We employed a qualitative study design and conducted 10 focus group discussions (FGD) with frontline researchers, community leaders, research participants, study decliners and Community Advisory Group (CAG) members from medical research projects conducted in rural and urban Malawi. We also conducted 17 in-depth interviews (IDI) with researchers, ethics committee members and District Health Officers. Thematic and framework analysis was used to interpret the results. Results: Our findings showed that ethics review committee members, researchers and frontline researchers had a common understanding of compensation, informed by available literature. On the other hand, some community members understood that compensation was given due to harm resulting from study participation while others indicated that intended study benefits were not visible to the community. Our study participants also expressed concerns that offering unequal compensation based on study design, procedures and risks had the potential to make some individuals feel devalued if they received lower payment amounts compared to others. Conclusion: This study revealed conflicting perspectives on compensation and benefits among research stakeholders. While stakeholders involved in conducting research had a shared understanding of compensation as reimbursement for time and costs, some community members viewed it as redress for harm. The disconnect suggests unequal access to information about research ethics among research stakeholders. Varying compensation based on study procedures also raised concerns over perceived inequalities and feelings of being devalued. These results suggest a need for consensus-building through inclusive stakeholder engagement and open dialogue to co-design guidelines that balance individual reimbursement and community benefits to advance ethical research practices centered on respect for participants.</p
Reductions in development assistance for health funding threaten decades of progress in Africa
Get PDFCountries across Africa face health crises driven by aid cuts, shifting demography, and infectious and environmental threats. Renewed public health strategies, smarter investment, and stronger surveillance can help, but reversing funding cuts is vital.</p
COVID-19 diagnosis within five days of symptoms onset among healthcare workers in Malawi; Non-randomized control trial of self-testing using Ag-RDTs
Get PDFEfficient and sustainable models of Corona Virus Disease of 2019 (COVID‑19) screening among healthcare workers (HCWs) such as self‑testing are essential for averting transmission within and outside health care facilities. We compared the number of confirmed early COVID‑19 positive diagnoses (defined as COVID‑19 cases diagnosed within five days of symptoms onset) among HCW in self‑testing arm using Antigen Rapid Diagnostic Test kits (Ag‑RDT) and standard of care arm (SOC) who were offered COVID‑19 testing if they presented at the clinic with any COVID‑19 symptoms. Twelve primary healthcare facilities in Blantyre, Malawi, were purposively allocated (1:1) aiming for geographical and size balance in a 2‑arm non‑randomised cluster trial (ISRCTN: 17596113), available from https:// doi.org/10.1186/ISRCTN17596113. Arm‑1 was SOC and Arm‑2 was COVID 19 self‑testing (C19ST). HCWs in the C19ST arm had twice‑weekly COVID‑19 Ag‑RDT self‑testing. The primary outcome compared by arm the harmonic mean number of early COVID‑19 positive diagnoses among HCWs. Analysis was by intention‑to‑treat using cluster‑level summaries and t‑test, with adjustment for imbalance. Participa‑ tion was 99.8% among eligible HCWs across all facilities (1081/1083). Of the 1081 participating, 612 (56.6%) and 469 (43.4%) were in SOC and C19ST arm, respec‑ tively. Mean age was 35.5y (sd: 9.3); 183/612 (29.9%) in SOC were male, compared to 166/469 (35.3%) in C19ST; overall prior vaccination was 80.0% with no difference between SOC, (81.5%) and C19ST (78.0%). Follow‑up at exit (12 weeks) was high (SOC: [94%]; C19ST: [87.6%]) and a harmonic mean of 1 and 4 HCWs had early COVID‑19 diagnosis in SOC and C19ST arms, respectively. COVID‑19 self‑testing using Ag‑RDTs provided a safe, quick, and reliable model for identifying early‑onset symptomatic and asymptomatic COVID‑19 positive HCW. Self‑testing was feasible to integrate for routine screening among HCW potentially reducing disruption to health services. This model has potential for wide scale up programmatically especially in resource‑constrained settings.</p
Transitioning to people-centred antimicrobial resistance surveillance
No full textAntimicrobial resistance (AMR) is a growing global health threat, and many public health surveillance programmes rely on blood cultures as a means to track this process. Blood cultures are diagnostic tests taken from patients with suspected sepsis or bloodstream infections, where timely results can be lifesaving. When blood culture-based AMR surveillance is instituted for global AMR monitoring, these investments might not realise their full potential in supporting patient care if their role as a diagnostic is not optimised, creating the risk that local hospitals see little benefit from surveillance activities and making such programmes less sustainable. We argue that blood cultures should be viewed first and foremost as a key diagnostic tool to guide patient care. By ensuring that local hospitals can use and act on their own data, we can both improve outcomes for patients and strengthen global AMR surveillance efforts.</p
Impact and cost-effectiveness of the community-led AMETHIST intervention among female sex workers in Zimbabwe
Get PDFFemale sex workers (FSW) face high HIV risk of HIV transmission and acquisition. The AMETHIST (“Adapted Microplanning: Eliminating Transmissible HIV In Sex Transactions”) trial enhanced Zimbabwe’s Key Populations (KP) programme by providing targeted, community-based support for FSW. We used the HIV Synthesis Model to assess its long-term impact and cost-effectiveness. Given USAID’s major role in funding, we also evaluated the effects of ending US support on the KP programme. We modelled a KP programme from 2010. From 2024 we compared (i) continuation of KP programme to (ii) continuation of KP programme + ‘AMETHIST’ intervention. We assessed HIV outcomes in 2030 and conducted cost-effectiveness analysis over a 50 year time horizon. Similar analyses were undertaken comparing continuation of the current KP programme to discontinuation. Here we show that AMETHIST had greater positive impact than the KP programme alone; a higher proportion of FSW tested for HIV in the past year, were diagnosed, on ART and had undetectable viral loads compared to the KP programme alone. Disability adjusted life years were averted with AMETHIST and it was cost-saving within 15 years. Continuing the current KP programme was also cost-saving compared to discontinuation of the KP programme
Reductions in development assistance for health funding threaten decades of progress in Africa
Get PDFCountries across Africa face health crises driven by aid cuts, shifting demography, and infectious and environmental threats. Renewed public health strategies, smarter investment, and stronger surveillance can help, but reversing funding cuts is vital.</p
An evaluation of screening methods for the detection of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in environmental samples from healthcare settings
Get PDFAbstractAimsExtended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) infections are increasingly problematic, leading to worse treatment outcomes and higher healthcare expenditure. This study evaluated laboratory workflows for the detection of ESBL-E in healthcare environments. We aimed to optimise workflows for organism yield, detection accuracy and practical feasibility to support future surveillance and transmission studies, which are needed to inform targeted interventions to interrupt the spread of drug-resistant organisms.Methods and ResultsWe sampled sinks, toilets, shower drains, shower heads, and high-touch surfaces, within six healthcare facilities in Liverpool, UK. We then assessed recovery of ESBL-producing Escherichia coli (ESBL-Ec) and Klebsiella pneumoniae (ESBL-Kp) using two swab types (foam and polyester), two pre-enrichment broths (Buffered Peptone Water and Tryptic Soy Broth), two incubation times (4 and 18 hours) and four selective agars (CHROMagar ESBL, cefotaxime-supplemented MacConkey, Membrane Lactose Glucuronide Agar and Simmons Citrate Agar with Inositol).Pre-enrichment for 18 hours significantly increased recovery of third-generation cephalosporin resistant Gram-negatives, compared to 4 hours. The choice of selective agar impacted the number of ESBL-Ec and ESBL-Kp detected and the number of samples requiring additional species confirmation. We found CHROMagar ESBL and cefotaxime-supplemented Membrane Lactose Glucuronide Agar performed best overall, demonstrating the highest yield and detection accuracy (i.e. colour of colonies matched their confirmed species) of ESBL-Ec and ESBL-Kp.ConclusionsPre-enrichment for 18 hours in Buffered Peptone Water, followed by plating onto cefotaxime-supplemented Membrane Lactose Glucuronide Agar, was the most effective screening method in our context, having a high detection efficacy, whilst maintaining a scalable and accessible cost
Transmission of extended spectrum β-lactamase-producing Escherichia coli and antimicrobial resistance gene flow across One Health compartments in eastern Africa: a whole-genome sequence analysis from a prospective cohort study
Get PDFBackground The One Health paradigm considers interdependence of human, animal, and environmental health. However, there is little evidence from high-income countries to support the importance of a One Health approach to addressing spread of antimicrobial resistance (AMR). Given AMR is a global threat, understanding how the close interactions of humans with animals and the environment in low-income settings affect the spread of AMR is important. We aimed to investigate diversity and transmission of extended spectrum β-lactamase (ESBL)-producing Escherichia coli across household-linked One Health compartments using genomic data. Methods: We sequenced whole genomes of ESBL-producing E coli isolates from humans, animals, and the environment from a prospective, longitudinal cohort study conducted in Malawi (April 29, 2019, to Dec 3, 2020) and Uganda (July 16, 2020, to Aug 6, 2021). In the cohort study, 259 households were enrolled at baseline in Malawi and 92 in Uganda from a mix of urban, peri-urban, and rural areas. Households were followed up at months 1, 3, and 6 in Malawi and at months 1, 2, and 4 in Uganda. Samples collected at each visit included human and animal stool, environmental samples from hand-contact areas, food, and water, and broader environmental samples such as river water. Samples were cultured in buffered peptone water and then ESBL chromogenic agar to isolate ESBL-producing E coli . ESBL-producing E coli isolates underwent whole-genome sequencing. We performed phylogenetic analyses, and in-silico multi-locus sequence typing, characterised AMR determinants and linked genotypes with sample location, ecological source, and other covariates. We performed fine-scale single nucleotide polymorphism (SNP) and network analysis to infer strain and plasmid transmission across ecological compartments. The primary outcome was colonisation with ESBL-producing E coli . Secondary outcomes were genomic clusters and ESBL genomic determinants within and between One Health compartments. Findings: We found high diversity of ESBL-producing E coli , with 170 sequence types and 166 genomic clusters identified from 2344 genomes, including 1814 genomes from Malawi (907 human, 221 animal, and 686 environmental) and 530 genomes from Uganda (380 human, 147 animal, and three environmental). Sequence type (ST)131 dominated in Malawi (209 [11·5%] of 1814 genomes), and ST10 dominated in Uganda (45 [8·5%] of 530 genomes). Common ESBL genes bla CTX−M−15 (1604 [68·4%] of 2344 genomes) and bla CTX−M−27 (336 [14·3%] of 2344 genomes) were carried on a complex network of 55 and 30 different plasmids. This diversity of plasmids presented multiple pathways for dissemination and revealed high force of selection. Phylogenetic analyses revealed common intermixing of isolates between humans, animals, and the environment. SNP transmission analysis revealed ecologically overlapping clusters, suggesting ESBL-producing E coli co-circulation both within and between compartments with frequent spillover events. Applying a five-SNP threshold, we inferred 463 human–environment transmission events, 146 human–animal events, and 142 animal–environment events. Interpretation Our work suggests that a One Health approach is crucial to addressing AMR in eastern Africa. Improving water, sanitation, and hygiene systems will create a safer environment, reduce spillovers of AMR bacteria between compartments, and eventually reduce AMR reservoirs in the environment and in animals.<p/