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teamNGS Balances Sensitivity for Viruses with Comprehensive Microbial Detection in Clinical Specimens.
Get PDFProbe-based capture represents a highly sensitive and cost-effective approach for overcoming host background and enriching viruses in metagenomic NGS (mNGS) libraries. Using clinical specimens collected globally from patients with fever or respiratory illness, we generated mNGS libraries by random priming and Nextera XT tagmentation, followed by target enrichment (teNGS) with Comprehensive Viral Research Panel (CVRP) probes. Capture pool sizes and total reads were optimized, and libraries were initially sequenced separately. Using only 3-4% of reads required for standard mNGS, teNGS achieved increased sensitivity, 100-10,000× increases in depth, and >50% genome coverage for pathogens with titers ≥ 1000 cp/mL. Application to >2000 clinical specimens from various matrices and to contrived samples containing viruses absent from the CVRP probe set enabled detection of diverse viral families and established a minimum 65% nucleotide identity for hybridization, respectively. To save time and resources, teNGS and mNGS libraries were then combined into one sequencing run: teamNGS. In addition to streamlining the workflow, teamNGS also improved genome recovery. Coupling methods maintain the sensitivity and coverage for viruses achieved by enrichment alone while also ensuring comprehensive recovery of non-viral microbes. teamNGS has the potential to improve patient management and lower the rates of unnecessary testing and antibiotic use
Higher promoter methylation of the Ubiquitin Associated and SH3 domain containing A (UBASH3A) gene is associated with T-lymphocyte ontogeny and reduced susceptibility to early-onset sepsis.
No full textWe investigated the genetic and epigenetic regulation of the UBASH3A gene and its association with early-onset sepsis. Using matched whole blood DNA methylation, gene expression, genotypes and immune cell counts from the EPIC-HIPC newborn cohort, we report promoter methylation was negatively correlated (Pearson's r = -0.5, p < 2.2×10-16) with ontogenetic changes in UBASH3A gene expression and circulating CD3+ T-cell numbers. Higher promoter methylation at birth was associated with lower UBASH3A expression and reduced early onset sepsis risk (OR = 0.26, p = 0.015). Genetic variation significantly influenced variations in baseline UBASH3A methylation (132 cis-meQTL, FDR < 0.05)
Effective communication and public engagement strategies to counter misinformation about infectious diseases.
Get PDFEffective communication and public engagement are essential components of infectious disease control, yet they remain underdeveloped in the field of immunology. This review explores how immunologists and scientists can contribute to countering misinformation and improving vaccine uptake through inclusive, culturally sensitive engagement. Drawing on historical and contemporary case studies, we examine how trust, cognitive biases, and community involvement shape public responses. We highlight the importance of co-produced messaging and the role of community champions in building trust, particularly among marginalized groups. Vaccine communication is analyzed through the lens of the five Cs: confidence, complacency, convenience, communication, and context. We discuss how demographic and structural barriers, historical mistrust, and politicization of health messaging contribute to declining vaccine uptake and propose tailored strategies to address these challenges. The final section focuses on data presentation as a core foundation of public communication, emphasizing that clarity, transparency, and ethical framing are critical to public understanding. We outline principles for designing trustworthy visuals, mitigating cognitive biases, and embedding context directly within graphics to prevent misinterpretation. Participatory approaches to data communication are shown to improve comprehension and trust, especially when co-developed with affected communities. Together, these domains-engagement, vaccine communication, and data presentation-form a foundation for resilient public health responses. By integrating immunological expertise with inclusive communication strategies, scientists can play a central role in fostering informed decision making and strengthening public cooperation in future outbreaks
Acceptability and preferences for dual-active ingredient long-lasting insecticidal nets in rural Tanzania: a mixed-methods study.
No full textBACKGROUND: The World Health Organization (WHO) recommends dual-active ingredient long-lasting insecticidal nets (dual-AI LLINs) for protection against malaria in areas with insecticide resistance. The effectiveness of LLINs, however, depends on user compliance, influenced by community perceptions of malaria, prevention methods, and the acceptability of LLINs. Understanding these factors is essential for the success of large-scale implementation.
METHODS: This study was part of the two cluster-randomized controlled trials (RCTs) evaluating the efficacy of dual-AI LLINs on malaria indicators in Muleba and Misungwi districts, Tanzania. Polyethylene and polyester rectangular LLINs were distributed in Muleba (Olyset Plus and Olyset Net) in 2015 and in Misungwi (Olyset Plus, Royal Guard, Interceptor G2, and Interceptor) in 2019. A mixed-methods approach was used to assess users' acceptability, preferences, and perceptions, and identifying barriers to consistent use. Quantitative data were collected from 14,475 households, while qualitative data came from 36 focus group discussions and 44 in-depth interviews. A thematic analysis was applied using a deductive approach, guided by the study's conceptual framework. Descriptive statistics were used for quantitative analysis.
RESULTS: LLIN usage and acceptability were influenced by their availability in the households, the physical integrity, side-effects, nuisance from mosquito bites and perceived malaria risk. Olyset Plus was slightly favoured over Olyset net in Muleba due to the perception that the insecticide had a stronger effect (72% vs 63%), p = 0.1395. In Misungwi, net acceptability, measured by the proportion reporting LLINs as no longer protective, varied significantly by net type at 24, 30, and 36 months (p < 0.0001). In Misungwi, Olyset Plus had the highest overall dissatisfaction (15.1%), followed by Royal Guard (12.0%) while Interceptor G2 and Interceptor had the lowest (7.0-7.6%). In Misungwi, 86% (2338/2736) preferred polyester nets over polyethylene due to better comfort and durability. Adverse effects (itching, skin irritation) were reported more frequently for Royal Guard and Interceptor (48-55%). Bed bug infestations were found in 19-29% of study nets, averaging 15 bugs/net, negatively influenced consistent use. LLIN repurposing was more common in Misungwi (35%) than Muleba (19%). Preferences skewed heavily toward blue (61% in Muleba vs 93% in Misungwi), rectangular LLINs (61% in Muleba vs 91% in Misungwi) in both sites.
CONCLUSION: Acceptability and sustained use of dual-AI LLINs are shaped by perceived efficacy, comfort, and net integrity, while barriers like bed bugs and skin irritation reduce use. Addressing non-target pest issues, targeting different groups of users with tailored education, and integrating user perception into LLIN procurement can enhance uptake and impact. It is recommended that manufacturers and policymakers consider these community-informed insights to guide the development and deployment of more acceptable LLINs
Mapping risks of health conditions in people with atopic eczema in English primary care and hospital data.
Get PDFAtopic eczema may be associated with multiple health conditions. Here, we systematically explore risks across the full health spectrum based on the International Classification of Diseases, assessing associations between eczema and 2058 ICD-10 codes, 1593 phecodes, and 201 Global Burden of Disease codes. In English primary care electronic health records (1997 - 2023) we identify cohorts of people with eczema (up to 3 million) and matched (by age, sex, general practice) comparators without eczema (up to 14 million). In up to 25 years of follow-up, we capture outcomes recorded during hospital admissions. People with eczema show higher rates of several outcomes across multiple organ systems. Among those followed up from eczema diagnosis in childhood, atopic/allergic conditions and infections account for most excess diagnoses. Consistent across cohorts and analyses, large relative risk increases are seen for inflammatory bowel conditions (e.g., K50 Crohn disease, crude hazard ratio 1.70 [1.63-1.77]) and eye diseases (e.g., H16 Keratitis, crude hazard ratio 1.71 [1.57-1.86]). We provide a dashboard to explore and browse the full range of results
Genome-wide analysis of genetic diversity in Anopheles darlingi from Rondônia State, Brazil.
No full textAnopheles darlingi is the primary malaria vector in Central and South America and is responsible for most malaria transmission in the Amazon region. In this study, we perform whole-genome analysis of individual An. darlingi mosquitoes to explore genomic diversity, signatures of selection, and insecticide resistance markers. We analysed wild-caught (n = 20) and colony-maintained (n = 8) mosquitoes from the State of Rondônia, Brazil. In total, 1.54 million high-quality single-nucleotide polymorphisms (SNPs) were identified. Population genomic analysis revealed genetic differentiation between the colony and wild populations. No SNPs previously associated with insecticide resistance were detected. However, several SNPs were observed in four genes commonly associated with insecticide resistance: ace1, rdl, gste2, and vgsc. Genes under directional selection were identified, but no clear selective sweeps were found using genome-wide selection scans. Gene duplications were identified in cytochrome P450 genes, which are known to metabolise pyrethroids. This study provides a detailed genetic profile of An. darlingi, highlighting genes potentially involved in insecticide resistance, and presents an analysis of signatures of selection based on WGS data for this species. Our findings identify markers in insecticide resistance-associated genes that warrant further investigation through phenotypic-genotypic assays
Stakeholder meeting report: Chikungunya virus – recent outbreaks, vaccine development and the way forward
Get PDFThe International Vaccine Institute and Gorgas Institute (Gorgas Memorial Institute for Health Studies) organized the first Chikungunya Global Meeting in Panama City, Panama on December 12–13, 2023. Experts represented eight countries: Brazil, Colombia, Dominican Republic, India, Kenya, Panama, Paraguay, and Thailand. The aim of this meeting was for stakeholders to discuss chikungunya disease burden, vaccine deployment strategies, regulatory challenges, and access issues. This meeting highlighted lessons learned from recent chikungunya outbreaks and perspectives on ways forward in chikungunya research. Specifically, the following topics were discussed in the meeting: (i) lessons from recent chikungunya outbreaks and regional perspectives, (ii) chikungunya research priorities, (iii) chikungunya vaccine development, (iv) regulatory approval and pathways, (v) vaccine access, financing, and procurement, (vi) ways forward through a chikungunya vaccine initiative, and (vii) chikungunya research on how to analyse protection and long-term memory. Experts called for investments in vaccine deployment and a better understanding of the long-term economic impacts of chikungunya. Going forward, the experts recommended creation of a global chikungunya vaccine initiative to coordinate research and generate evidence to inform prevention and control programmes of chikungunya outbreaks and introduction of chikungunya vaccination in high-burden settings and regions at risk of chikungunya outbreaks
Emergence of Acquired HIV Drug Resistance Among Individuals Receiving Dolutegravir-Based Antiretroviral Therapy in Uganda: A National Laboratory-Based Survey 2023.
Get PDFBACKGROUND: As dolutegravir (DTG)-based regimens (DBRs) become more widely used and patients remain on treatment longer, cases of virological failure remain rare. This study presents findings from the second annual round of acquired HIV drug resistance (HIVDR) surveillance in Uganda, among individuals with viral nonsuppression (≥1000 copies/mL) receiving DBRs for ≥9 months. The first round was conducted from February to April 2022.
METHODS: This nationally representative cross-sectional survey analyzed randomly selected remnant plasma and dried blood spot specimens collected between April and July 2023 from the Central Public Health Laboratories. Genotyping targeted the integrase, protease, and reverse transcriptase regions of the HIV-1 pol gene, resistance was analyzed using the Stanford HIVDR Database. Weighted HIVDR prevalence and 95% confidence intervals (CIs) were calculated for children (0-14 years) and adults (≥15 years).
RESULTS: Out of 857 specimens tested, 400 (46.7%) were from children and 457 (53.3%) from adults. Median ages were 11 years for children and 36 years for adults. Median time on DBRs was 1.9 years for children and 2.4 years for adults. Five hundred and fifty-nine (65.2%) specimens were successfully genotyped. The prevalence of DTG resistance was 10.1% (95% CI: 6.4%-13.9%) in children and 8.6% (95% CI: 3.9%-13.3%) in adult, higher than the first round with a prevalence of 6.6% (95% CI: 3.5%-9.6%) and 4.4% (95% CI: 0.7%-7.1%), respectively.
CONCLUSIONS: The increase in DTG resistance among both children and adults highlights the need to strengthen adherence and enhance early identification of individuals at risk of HIVDR through novel and existing programmatic interventions
Modelling excess mortality from non-communicable diseases during wartime: application to the Gaza Strip, occupied Palestinian territories.
Get PDFBACKGROUND: Patients with non-communicable diseases (NCDs) face multiple risks of excess mortality during wars. The Gaza Strip's health services have been severely disrupted by Israel's campaign since October 2023. We developed a modelling approach to project NCD excess mortality under three defined scenarios. METHODS: We projected excess mortality from cancer (lung, colorectal, and breast), cardiovascular disease, diabetes mellitus type 1 patients, and chronic kidney disease requiring haemodialysis from February 2024 to August 2024. We defined three scenarios of treatment coverage: (i) ceasefire, (ii) status quo, and (iii) escalation. We used pre-war incidence and prevalence data to probabilistically simulate deaths among patient cohorts exposed to varying time-dependent mortality depending on their treatment status. We subtracted the expected non-crisis mortality based on pre-war data to compute excess deaths. RESULTS: We projected 1,680, 2,480 and 2,680 excess deaths under the ceasefire, status quo and escalation scenarios, respectively, from February till August 2024, plus 1489 in the war's earlier phase. Most deaths were projected among individuals aged >50 years old and from ischaemic heart disease. CONCLUSION: To our knowledge this is the first attempt to project NCD mortality in a live war setting, demonstrating potential impacts on NCD burden, particularly due to cardiovascular causes. The model focusses only on a subset of NCDs and neglects the impact of the crisis on disease progression, thereby plausibly underestimating actual mortality. It could inform better humanitarian resource allocation and service planning but requires refinement and improved parameterisation
Decline in HIV prevalence among female sex workers in Zimbabwe between 2013 and 2023.
Get PDFHIV epidemic trends among female sex workers in sub-Saharan Africa are rarely known. We analysed HIV prevalence trends among 10,562 female sex workers aged 18-39 years, recruited through serial cross-sectional respondent-driven sampling surveys in 13 towns and 2 cities in Zimbabwe between 2013 and 2023. HIV prevalence remained stable from 2013 to 2016-2017 but declined significantly from 54.6% in 2016-2017 to 38.9% in 2021-2023 (cluster prevalence mean difference: 15.7%, prevalence ratio: 0.74; 95% CI: 0.68-0.79). This decline cannot be attributed to sampling bias or shifts in the characteristics of the female sex worker population. Mathematical modelling using the HIV Synthesis model and age cohort analysis also suggested lower HIV incidence in later years. While the availability of oral pre-exposure prophylaxis increased, there was little evidence of reduced risk behaviour over time. Increased treatment coverage among the male population likely contributed to the lower HIV incidence among female sex workers