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Journal articleSangkaew S, Tumviriyakul H, Cheranakhorn C, et al., 2024,
Unveiling post-COVID-19 syndrome: incidence, biomarkers, and clinical phenotypes in a Thai population
, BMC Infectious Diseases, Vol: 24, ISSN: 1471-2334BackgroundPost-COVID- 19 syndrome (PCS) significantly impacts the quality of life of survivors. There is, however, a lack of a standardized approach to PCS diagnosis and management. Our bidirectional cohort study aimed to estimate PCS incidence, identify risk factors and biomarkers, and classify clinical phenotypes for enhanced management to improve patient outcomes.MethodsA bidirectional prospective cohort study was conducted at five medical sites in Hatyai district in Songkhla Province, Thailand. Participants were randomly selected from among the survivors of COVID-19 aged≥18 years between May 15, 2022, and January 31, 2023. The selected participants underwent a scheduled outpatient visit for symptom and health assessments 12 to 16 weeks after the acute onset of infection, during which PCS was diagnosed and blood samples were collected for hematological, inflammatory, and serological tests. PCS was defined according to the World Health Organization criteria. Univariate and multiple logistic regression analyses were used to identify biomarkers associated with PCS. Moreover, three clustering methods (agglomerative hierarchical, divisive hierarchical, and K-means clustering) were applied, and internal validation metrics were used to determine clustering and similarities in phenotypes.FindingsA total of 300 survivors were enrolled in the study, 47% of whom developed PCS according to the World Health Organization (WHO) definition. In the sampled cohort, 66.3% were females, and 79.4% of them developed PCS (as compared to 54.7% of males, p-value <0.001). Comorbidities were present in 19% (57/300) of all patients, with 11% (18/159) in the group without PCS and 27.7% (39/141) in the group with PCS. The incidence of PCS varied depending on the criteria used and reached 13% when a quality of life indicator was added to the WHO definition. Common PCS symptoms were hair loss (22%) and fatigue (21%), while mental health symptoms were less frequent (insomnia 3%, dep
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Journal articleRhodes J, Jacobs J, Dennis EK, et al., 2024,
What makes Candida auris pan-drug resistant? Integrative insights from genomic, transcriptomic, and phenomic analysis of clinical strains resistant to all four major classes of antifungal drugs
, Antimicrobial Agents and Chemotherapy, Vol: 68, ISSN: 0066-4804The global epidemic of drug-resistant Candida auris continues unabated. The initial report on pan-drug resistant (PDR) C. auris strains in a hospitalized patient in New York was unprecedented. PDR C. auris showed both known and unique mutations in the prominent gene targets of azoles, amphotericin B, echinocandins, and flucytosine. However, the factors that allow C. auris to acquire pan-drug resistance are not known. Therefore, we conducted a genomic, transcriptomic, and phenomic analysis to better understand PDR C. auris. Among 1,570 genetic variants in drug-resistant C. auris, 299 were unique to PDR strains. The whole-genome sequencing results suggested perturbations in genes associated with nucleotide biosynthesis, mRNA processing, and nuclear export of mRNA. Whole transcriptome sequencing of PDR C. auris revealed two genes to be significantly differentially expressed—a DNA repair protein and DNA replication-dependent chromatin assembly factor 1. Of 59 novel transcripts, 12 transcripts had no known homology. We observed no fitness defects among multi-drug resistant (MDR) and PDR C. auris strains grown in nutrient-deficient or -enriched media at different temperatures. Phenotypic profiling revealed wider adaptability to nitrogenous nutrients and increased utilization of substrates critical in upper glycolysis and tricarboxylic acid cycle. Structural modeling of a 33-amino acid deletion in the gene for uracil phosphoribosyl transferase suggested an alternate route in C. auris to generate uracil monophosphate that does not accommodate 5-fluorouracil as a substrate. Overall, we find evidence of metabolic adaptations in MDR and PDR C. auris in response to antifungal drug lethality without deleterious fitness costs.
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Journal articleJaggi TK, Agarwal R, Tiew PY, et al., 2024,
Fungal Lung Disease.
, Eur Respir JFungal lung disease encompasses a wide spectrum of organisms and associated clinical conditions presenting a significant global health challenge with type and severity determined by underlying host immunity and infecting fungal strain. The most common group of diseases are associated with the filamentous fungus Aspergillus spp. and include allergic bronchopulmonary aspergillosis (ABPA), sensitization, aspergilloma, and chronic and invasive pulmonary aspergillosis. Fungal lung disease remains epidemiologically heterogenous and is influenced by geography, environment, and host comorbidities. Diagnostic modalities continue to evolve and now include novel molecular assays and biomarkers, however, persisting challenges include achieving rapid and accurate diagnosis, particularly in resource-limited settings and in differentiating fungal infection from other pulmonary conditions. Treatment strategies for fungal lung diseases rely mainly on antifungal agents, however, the emergence of drug-resistant strains poses a substantial global threat and adds complexity to existing therapeutic challenges. Emerging antifungal agents and increasing insight into lung mycobiome via may offer fresh and personalized approaches to diagnosis and treatment, while innovative methodologies are required to mitigate drug resistance and adverse effects of treatment. This state-of-the-art review describes the current landscape of fungal lung disease, highlighting key clinical insights, current challenges, and emerging approaches for its diagnosis and treatment.
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Journal articleVillaveces A, Chen Y, Tucker S, et al., 2024,
Orphanhood and caregiver death among children in the United States by all-cause mortality, 2000-2021
, Nature Medicine, ISSN: 1078-8956Deaths of parents and grandparent caregivers threaten child wellbeing due to losses of care, financial support, safety, and family stability, but are relatively unrecognised as a public health crisis. We used cause-specific vital statistics deaths registrations in a modelling approach to estimate the full magnitude of orphanhood incidence and prevalence among United States (U.S.) children aged 0-17 years between 2000-2021 by cause, child age and race \& ethnicity, sex of deceased parent, and state, and also accounted for grandparent caregiver loss using population survey data. In 2021, we estimate 2.91 million children (4.2% of children) had in their lifetime experienced prevalent orphanhood and caregiver death combined, with incidence increasing by 49.5% and prevalence by 7.9% since 2000. Populations disproportionately affected by orphanhood included 5.2% of all adolescents; 6.4% and 4.7% respectively of non-Hispanic American Indian/Alaska Native, and non-Hispanic Black children; and children in southern and eastern states. In 2021, drug overdose was the leading cause of orphanhood among non-Hispanic white children, but not among minoritised subgroups. Effective policies and programs to support nearly 3 million bereaved children are needed to reduce the acute and long-term negative effects of orphanhood.
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Journal articleWoodroffe R, Astley K, Barnecut R, et al., 2024,
Farmer-led badger vaccination in Cornwall: Epidemiological patterns and social perspectives
, People and Nature, Vol: 6, Pages: 1960-1973In the United Kingdom, the management of bovine tuberculosis (bTB) challenges the coexistence of people and wildlife. Control of this cattle disease is hindered by transmission of its causative agent, Mycobacterium bovis, between cattle and badgers Meles meles. Badger culling has formed an element of bTB control policy for decades, but current government policy envisions expanding badger vaccination. Farming leaders are sceptical, citing concerns that badger vaccination would be impractical and potentially ineffective. We report on a 4-year badger vaccination initiative in an 11 km2 area which, atypically, was initiated by local farmers, delivered by scientists and conservationists, and co-funded by all three. Participating landholders cited controversies around culling and a desire to support neighbours as their primary reasons for adopting vaccination. The number of badgers vaccinated per km2 (5.6 km−2 in 2019) exceeded the number culled on nearby land (2.9 km−2 in 2019), and the estimated proportion vaccinated (74%, 95% confidence interval [CI] 40%–137%) exceeded the 30% threshold predicted by models to be necessary to control M. bovis. Farmers were content with how vaccination was delivered, and felt that it built trust with wildlife professionals. The percentage of badgers testing positive for M. bovis declined from 16.0% (95% CI 4.5%–36.1%) at the start of vaccination to 0% (95% CI 0%–9.7%) in the final year. With neither replication nor unvaccinated controls, this small-scale case study does not demonstrate a causal link between badger vaccination and bTB epidemiology, but it does suggest that larger-scale evaluation of badger vaccination would be warranted. Farmers reported that their enthusiasm for badger vaccination had increased after participating for 4 years. They considered vaccination to have been effective, and good value for money, and wished to continue with it. Synthesis and applications: Although small-scale, this ca
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Journal articleAliaga-Samanez A, Romero D, Murray K, et al., 2024,
Climate change is aggravating dengue and yellow fever transmission risk
, Ecography, Vol: 2024, ISSN: 0906-7590Dengue and yellow fever have complex cycles, involving urban and sylvatic mosquitoes, and non-human primate hosts. To date, efforts to assess the effect of climate change on these diseases have neglected the combination of such crucial factors. Recent studies only considered urban vectors. This is the first study to include them together with sylvatic vectors and the distribution of primates to analyse the effect of climate change on these diseases. We used previously published models, based on machine learning algorithms and fuzzy logic, to identify areas where climatic favourability for the relevant transmission agents could change: 1) favourable areas for the circulation of the viruses due to the environment and to non-human primate distributions; 2) the favourability for urban and sylvatic vectors. We obtained projections of future transmission risk for two future periods and for each disease, and implemented uncertainty analyses to test for predictions reliability. Areas currently favourable for both diseases could keep being climatically favourable, while global favourability could increase a 7% for yellow fever and a 10% increase for dengue. Areas likely to be more affected in the future for dengue include West Africa, South Asia, the Gulf of Mexico, Central America and the Amazon basin. A possible spread of dengue could take place into Europe, the Mediterranean basin, the UK and Portugal; and, in Asia, into northern China. For yellow fever, climate could become more favourable in Central and Southeast Africa; India; and in north and southeast South America, including Brazil, Paraguay, Bolivia, Peru, Colombia and Venezuela. In Brazil, favourability for yellow fever will probably increase in the south, the west and the east. Areas where the transmission risk spread is consistent to the dispersal of vectors are highlighted in respect of areas where the expected spread is directly attributable to environmental changes. Both scenarios could involve different prev
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Journal articleSilhol R, Maheu-Giroux M, Soni N, et al., 2024,
The impact of past HIV interventions and diagnosis gaps on new HIV acquisitions, transmissions, and HIV-related deaths in Côte d’Ivoire, Mali, and Senegal
, AIDS, Vol: 38, Pages: 1783-1793, ISSN: 0269-9370Objectives: To estimate the epidemiological impact of past HIV interventions and the magnitude and contribution of undiagnosed HIV among different risk groups on new HIV acquisitions in Côte d’Ivoire, Mali and Senegal.Design: HIV transmission dynamic models among the overall population and key populations [female sex workers (FSW), their clients, and MSM].Methods: Models were independently parameterized and calibrated for each set of country-specific demographic, behavioural, and epidemiological data. We estimated the fraction of new HIV infections over 2012–2021 averted by condom use and antiretroviral therapy (ART) uptake among key population and nonkey population, the direct and indirect contribution of specific groups to new infections [transmission population-attributable fraction (tPAF)] over 2012–2021 due to prevention gaps, and the distribution of undiagnosed PWH by risk group in January 2022 and their tPAF over 2022–2031.Results: Condom use and ART may have averted 81–88% of new HIV infections over 2012–2021 across countries, mostly because of condom use by key population. The tPAF of all key populations combined over 2012–2021 varied between 27% (Côte d’Ivoire) and 79% (Senegal). Male key population (clients of FSW and MSM) contributed most to new infections (>60% in Mali and Senegal) owing to their higher HIV prevalence and larger prevention gaps. In 2022, men represented 56% of all PWH with an undiagnosed infection in Côte d’Ivoire (male key population = 15%), 46% in Mali (male key population = 23%), and 69% in Senegal (male key population = 55%). If HIV testing and ART initiation rates remain at current levels, 20% of new HIV infections could be due to undiagnosed key population PWH in Côte d’Ivoire over 2022–2031, 53% in Mali, and 65% in Senegal.Conclusion: Substantial HIV diagnosis gaps remain in Western Africa, especially among male key population. Addressing
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Journal articleMilne GC, Oettle RC, Whittaker C, et al., 2024,
Revisiting immunity vs. exposure in schistosomiasis: a mathematical modeling study of delayed concomitant immunity
, PNAS Nexus, Vol: 3, ISSN: 2752-6542The relative contributions of exposure vs. acquired immunity to the epidemiology of human schistosomiasis has been long debated. While there is considerable evidence that humans acquire partial immunity to infection, age- and sex-related contact patterns with water bodies contaminated with infectious cercarial schistosome larvae also contribute to typical epidemiological profiles of infection. Here, we develop a novel schistosome transmission model that incorporates both partially protective “delayed concomitant” acquired immunity—stimulated by dying worms—and host age- and sex-dependent patterns of exposure. We use a contemporary Bayesian approach to fit the model to historical individual data on exposure to infectious cercaria, eggs per gram of feces, and immunoglobulin E antibodies specific to Schistosoma mansoni Tegumental-Allergen-Like protein 1 collected from a highly endemic community in Uganda, estimating the relative contributions of exposure and acquired immunity. We find that model variants incorporating or omitting delayed concomitant immunity describe equally well the age- and sex-specific immunoepidemiological patterns observed before intervention and 18 months after treatment. Over longer time horizons, we find that acquired immunity creates subtle differences in immunoepidemiological profiles during routine mass drug administration that may confer resilience against elimination. We discuss our findings in the broader context of the immunoepidemiology of schistosomiasis.
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Journal articleMeyer-Rath G, Imai-Eaton JW, 2024,
Optimising HIV spending in eastern Europe and central Asia.
, Lancet HIV, Vol: 11, Pages: e654-e655 -
Journal articleBelcher RN, Murray KA, Reeves JP, et al., 2024,
Socioeconomic deprivation modifies green space and mental health associations: a within-person study
, Environment International, Vol: 192, ISSN: 0160-4120Living in an area with good availability and accessibility of residential green spaces such as parks, woodlands, and residential gardens can improve mental health and reduce the global disease burden. Unlike for physical health, it is not well understood if mental health and green space associations might be modified by local area deprivation. Existing evidence for this association comes from cross-sectional studies, widely considered vulnerable to confounding and bias. Individual time-invariant mental health status, personality, and other factors may result in positive effect modification on green space and mental health associations in more deprived areas. We use fixed-effects models that remove time-invariant confounding by calculating differences within-persons to eliminate this bias and add to the existing evidence. We modelled changes in mental health status, green space, and deprivation (relative to the within-person mean) within 54,666 individuals with a combined total of 300,710 mental health scores from one of the world’s largest panel surveys: “Understanding Society” in the UK. We found a positive effect of increasing residential green space on mental health and this was positively modified and intensified by area deprivation before and after adjusting for confounding. Our results support providing green space to protect against the negative impact of socioeconomic deprivation on health, particularly for those moving from a less deprived to a more deprived area.
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