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Stakeholder Interviews to Inform Best Practice for Public Facing COVID-19 Wastewater Dashboards.
Get PDFBACKGROUND: Wastewater (WW) -based epidemiology is the detection of pathogens and chemicals from wastewater, typically sewage systems. Its use gained popularity during the COVID-19 pandemic as a rapid and non-invasive way to assess infection prevalence in a population. Public facing dashboards for SARS-CoV-2 were developed in response to the discovery that RNA biomarkers were being shed in faeces before symptoms. However, there is not a standard template or guidance for countries to follow. The aim of this research is to reflect on how currently available dashboards evolved during the pandemic and identify suitable content and rationale from these experiences. METHODS: Interviews were carried out with implementers and users of dashboards for SARS-CoV-2 WW data across Europe and North America. The interviews addressed commonalities and inconsistencies in displaying epidemiological data of SARS-CoV-2, clinical parameters of COVID-19, data on variants, and data transparency. RESULTS: The thematic analysis identified WW dashboard elements that can facilitate standardization, or at least interoperability. These elements emphasise communication among developers under the same organization, open access for identified stakeholders, and data summarized with a time-intensive graphic analysis through normalizing at least by population. Simultaneous communication of clinical surveillance is recommended. More research is needed on flow and faecal indicators for normalization of WW data, and on the analysis and representation of variants. DISCUSSION: WW dashboard development between 2020-2023 provided a 'real-time' iterative process of data representation, and several recommendations have been identified. Communication of data through dashboards has the potential to support early warning systems for infectious diseases
Global socioeconomic inequalities in vaccination coverage, supply, and confidence.
Get PDFSustainable Development Goal (SDG) adopted in 2015 aim to reduce inequalities and achieve universal health coverage, including access to essential vaccines for all. Using data from WHO, the Vaccine Confidence Project™, World Bank, and UNDP, we analyzed between-country inequalities in coverage of four vaccines (DTP1, DTP3, MCV1, and POL3), vaccine stock-outs, and vaccine confidence. Economic- and education-related inequalities in coverage (measured by the concentration index) declined from 2015 to 2019, increased in 2020, peaked in 2021, and have declined again since 2022. Inequalities increased continuously in the Region of the Americas. Over 2015-2022, 94 countries/territories reported at least one national level DTP-containing vaccine stock-out. Countries/territories with higher income or education attainment showed lower vaccine confidence. Our study underscores the decrease of inequalities in vaccination coverage following the SDG adoption in most regions, and emphasizes the need to address vaccine stock-outs and strength the vaccine confidence
Willingness to pay for a second pair of near-vision glasses: a cross-sectional study in a rural North Indian population.
Get PDFPURPOSE: There is an enormous unmet need for near vision correction with glasses. The cost and lack of felt need are important barriers. This study, which was conducted among a rural population of northern India, was designed to assess whether the short-term use of a pair of near-vision glasses can increase the desirability for individuals to procure subsequent pairs and to further assess the willingness to pay thresholds. METHODS: This study followed a quasi-experimental design. Uncorrected presbyopes were given near vision glasses at their doorstep, to carry out their chosen near work task for half- an- hour (this use of glasses was referred to as 'experience' for the purpose of this study). They were then referred to nearby vision centres to procure glasses. This 'experience' given was used as a proxy for having used the first pair. At the vision centre, glasses were offered at no cost, for Indian Rupees 75 (US1.20) in the first, second and third phases of the study, respectively. The usual price at which near-vision glasses were otherwise available in the region was Indian Rupees150 (US0.90 and at $1.20 respectively. The difference between these three phases was statistically significant (p < 0.001). Uptake was found to be increase with need for increasing lens power (p < 0.01) and especially among those who reported the 'experience' as 'very good' or 'excellent'(p < 0.001). Uptake decreased with increasing age (p < 0.01). Differences in uptake between sexes and between those with or without the availability of a mode of transport in their household were not found to be significant. CONCLUSION: Having experience with the first pair of near-vision glasses can increase desirability of procuring subsequent pairs. Offering the second pair at a reduced price can increase the uptake substantially in this setting, suggesting that active outreach to correct near vision in tandem with accessible and affordable marketplaces for reading glasses could provide a viable solution to scale near vision correction
An exploration of current and future vector-borne disease threats and opportunities for change.
Get PDFVector-borne diseases, including dengue, threaten the health and livelihoods of over 80% of the world's population, particularly in tropical and subtropical regions. Environmental, ecological, climatic, and socio-economic factors are expected to drive increased transmission, emphasizing the need to identify key threats and prioritize strategies for control. We examined drivers, challenges and potential solutions with global experts, using Brazil and India as case studies. Both countries face rapid population growth, unplanned urbanization and increased exposure to animal reservoirs alongside unique surveillance and control challenges. We advocate for improvements in surveillance systems and capacity, investment in sustainable vector control tools, leveraging of artificial intelligence for outbreak prediction, and fostering public-private partnerships to develop innovative interventions. A multifaceted approach, combining community-led initiatives with advanced technologies, is essential to reducing the burden of vector-borne diseases and preventing future epidemics
Multi-ancestry genome-wide association study of topiramate's effects on heavy alcohol use.
Get PDFBACKGROUND: Topiramate reduces alcohol consumption in individuals who drink heavily. Candidate gene studies aimed at identifying genetic variants that predict topiramate's effects on drinking have yielded inconsistent findings. To identify genetic variation associated with treatment response, we conducted a genome-wide association study (GWAS) among participants in the Million Veteran Program (MVP) who initiated topiramate treatment. METHODS: Using electronic health records, we identified individuals who were dispensed topiramate for at least 60 days for any indication (i.e., the index event). Alcohol consumption was assessed using Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) scores during the year prior to topiramate exposure (pre index) and at least 60 days after initiating topiramate but within 6 months of drug discontinuation (post index). The final GWAS sample included 8386 individuals who reported alcohol consumption (i.e., AUDIT-C score > 0) during the preceding year. We calculated polygenic scores (PGS) for topiramate treatment response in the Yale-Penn sample (n = 10,275) and examined associations with 692 phenotypes using a phenome-wide association study. RESULTS: In the cross-ancestry GWAS meta-analysis, 35 loci had suggestive associations, though none reached genome-wide significance. Topiramate response PGS had nominally significant associations with lower rates of alcohol-related liver disease, older age at alcohol use disorder diagnosis, and higher frequency of alcohol use. CONCLUSIONS: Although no loci reached genome-wide significance, the suggestive variants identified in the cross-ancestry meta-analysis are promising candidates for future investigation. Larger studies are needed to identify significant genetic predictors of topiramate response and advance precision medicine strategies for treating AUD
Tools and challenges in the use of routine clinical data for antimicrobial resistance surveillance.
Get PDFRoutine clinical microbiology data are widely used for antimicrobial resistance (AMR) surveillance, but data availability and quality vary. In this Perspective, we explore the technical challenges of utilising routine data to inform action at various levels, and summarise emerging open-source technical solutions for hospital-level data collection, aggregation, and sharing. We highlight a need for agreed-upon data standards, and tools that support both facility-level and public health surveillance
Genetic characterization of Haemophilus ducreyi from non-genital skin lesions in Cameroon.
Get PDFBACKGROUND: Haemophilus ducreyi, traditionally recognized as the etiological agent of chancroid, a genital ulcer disease, is increasingly being identified as a significant cause of cutaneous ulcers in yaws-endemic regions across the South Pacific, Southeast Asia, and Sub-Saharan Africa. Despite its clinical relevance, this pathogen remains poorly characterized, and comprehensive genetic tools for analyzing isolate relationships are still lacking. METHODS: In this study, we present a follow-up of our previous research and developed a multilocus sequence typing (MLST) approach based on six of the seven loci from the Haemophilus influenzae MLST scheme and applied it to 82 primary clinical samples, previously confirmed to contain H. ducreyi, without culture. We also performed whole-genome sequencing (WGS) and antibiotic susceptibility testing on four cultured isolates obtained from cutaneous ulcers in yaws endemic health districts of Cameroon. RESULTS: Antibiotic susceptibility testing of H. ducreyi cultured isolates revealed sensitivity to all tested antibiotics, including ceftriaxone, azithromycin, and ciprofloxacin. MLST analysis, using data extracted from WGS and directly from clinical samples, identified 38 complete profiles across the six loci (34 from direct samples and four from cultured isolates), identifying 14 distinct sequence types (STs). BURST analysis of the six MLST genes grouped the STs into two distinct clonal complexes. An additional, polymorphism was observed in the ftsI gene, which encodes the penicillin-binding protein 3. CONCLUSIONS: This study highlights the need for genetic typing of H. ducreyi strains circulating in the yaws-endemic regions of Cameroon. The developed MLST scheme offered effective strain discrimination and provided valuable insights into their genetic relationships in these areas
Household clustering and seasonal genetic variation of Plasmodium falciparum at the community-level in The Gambia
Get PDFUnderstanding the genetic diversity and transmission dynamics of
Plasmodium falciparum
, the causative agent of malaria, is crucial for effective control and elimination efforts. In some endemic regions, malaria is highly seasonal with no or little transmission during up to 8 mo, yet little is known about how seasonality affects the parasite population genetics. Here, we conducted a longitudinal study over 2.5 y on 1516 participants in the Upper River Region of The Gambia. With 425
P. falciparum
genetic barcodes genotyped from asymptomatic infections, we developed an identity by descent (IBD) based pipeline and validated its accuracy against 199 parasite genomes sequenced from the same isolates. Genetic relatedness between isolates revealed a very low inbreeding level, suggesting continuous recombination among parasites rather than the dominance of specific strains. However, isolates from the same household were sixfold more likely to be genetically related compared to those from other villages, suggesting close transmission links within households. Seasonal variation also influenced parasite genetics, with most differentiation occurring during the transition from the low transmission season to the subsequent high transmission season. Yet chronic infections presented exceptions, including one individual who had a continuous infection by the same parasite genotype for at least 18 mo. Our findings highlight the burden of asymptomatic chronic malaria carriers and the importance of characterizing the parasite genetic population at the community-level. Most importantly, ‘reactive’ approaches for malaria elimination should not be limited to acute malaria cases but be broadened to households of asymptomatic carriers
Pharmacokinetic-pharmacodynamic modeling of benznidazole and its antitrypanosomal activity in a murine model of chronic Chagas disease.
Get PDFBACKGROUND: There is an urgent need for improved treatments for Chagas disease, a neglected tropical infection caused by the protozoan parasite Trypanosoma cruzi. Benznidazole, the first line therapy, has severe limitations such as poor tolerability and variable efficacy in the chronic stage of infection. To optimize dosing regimens, a better understanding of the pharmacokinetic/pharmacodynamic (PK/PD) relationship for benznidazole is crucial. This study aimed to characterize the population pharmacokinetic properties of benznidazole in mice and investigate the relationship between exposure and antitrypanosomal activity in T. cruzi infected mice. METHODOLOGY/PRINCIPAL FINDINGS: Antitrypanosomal activity was assessed in 118 BALB/c mice with chronic-stage T. cruzi infection, utilizing highly sensitive in vivo bioluminescence imaging (BLI). Benznidazole was administered at doses ranging from 10 to 100 mg/kg for 5-20 days. The pharmacokinetic properties of benznidazole were evaluated in 52 uninfected BALB/c mice using nonlinear mixed-effects modeling. The relationship between simulated benznidazole exposure and sterile parasitological cure in the BLI experiments was evaluated by logistic regression and partial least squares - discriminant analysis. Benznidazole pharmacokinetics in mice were well described by a one-compartment disposition model with first-order absorption, with higher doses associated with slower absorption. Univariate logistic regression revealed a significant correlation between drug exposure and the probability of parasitological cure. Total plasma exposure, time above IC90 and peak plasma concentration were all strongly associated with efficacy, provided that benznidazole was administered for at least 5 days. CONCLUSIONS/SIGNIFICANCE: This is the first study to successfully quantify the dose-response relationship for benznidazole in T. cruzi-infected mice using preclinical BLI data. Our results underscore the complexity of distinguishing PK/PD drivers of efficacy due to high collinearity between PK/PD index parameters, and we propose dose-fractionation studies for future research. Studying the PK/PD relationship using the BLI model provides valuable insights, aiding hypothesis generation through endpoint assessment of parasite infection
Household clustering and seasonal genetic variation of Plasmodium falciparum at the community-level in The Gambia.
Get PDFUnderstanding the genetic diversity and transmission dynamics of Plasmodium falciparum, the causative agent of malaria, is crucial for effective control and elimination efforts. In some endemic regions, malaria is highly seasonal with no or little transmission during up to 8 mo, yet little is known about how seasonality affects the parasite population genetics. Here, we conducted a longitudinal study over 2.5 y on 1516 participants in the Upper River Region of The Gambia. With 425 P. falciparum genetic barcodes genotyped from asymptomatic infections, we developed an identity by descent (IBD) based pipeline and validated its accuracy against 199 parasite genomes sequenced from the same isolates. Genetic relatedness between isolates revealed a very low inbreeding level, suggesting continuous recombination among parasites rather than the dominance of specific strains. However, isolates from the same household were sixfold more likely to be genetically related compared to those from other villages, suggesting close transmission links within households. Seasonal variation also influenced parasite genetics, with most differentiation occurring during the transition from the low transmission season to the subsequent high transmission season. Yet chronic infections presented exceptions, including one individual who had a continuous infection by the same parasite genotype for at least 18 mo. Our findings highlight the burden of asymptomatic chronic malaria carriers and the importance of characterizing the parasite genetic population at the community-level. Most importantly, 'reactive' approaches for malaria elimination should not be limited to acute malaria cases but be broadened to households of asymptomatic carriers