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The Effects on the Growth of HIV-exposed Uninfected Infants of Initiating Dolutegravir-based Versus Efavirenz-based cART in Late Pregnancy (DolPHIN-2)
Get PDFBackground: In 2019, the World Health Organization (WHO) changed its recommendations for pregnant women living with HIV from efavirenz-based to dolutegravir-based therapy due to its superior efficacy, tolerability and resistance profile. Perinatal exposure to antiretrovirals may influence infant growth, but limited data exist on the effects of specific regimens over time. Aim: This study aimed to compare growth trajectories over the first 72 weeks of life among infants exposed to dolutegravir-based versus efavirenz-based therapy during late pregnancy. Methods: The DolPHIN-2 trial was a randomized, open-label trial conducted in South Africa and Uganda, researching the efficacy of dolutegravir-based versus efavirenz-based therapy in pregnant women living with HIV, initiating treatment in the third trimester. In this secondary analysis, we compared growth trajectories until 72 weeks postpartum between HIV-exposed uninfected infants perinatally exposed to dolutegravir-based versus efavirenz-based therapy. Measures of infant weight, length and head circumference were converted to WHO-defined weight-for-age, weight-for-length, length-for-age and head circumference-for-age Z-scores. Subsequently, Z-scores were compared across treatment arms, using linear mixed-effect models. Results: After exclusions, 232 infants remained (dolutegravir: n = 116; efavirenz: n = 116). In both crude models and models adjusted for study site and maternal height, length-for-age Z-scores were 0.277 units higher in the dolutegravir arm. No statistically significant impact of treatment was observed for other outcomes. In both study arms, a decline in mean length-for-age Z-scores occurred over the first 72 weeks, while mean weight-for-age Z-scores declined between weeks 48 and 72. Conclusion: Our data support the WHO in recommending dolutegravir-based therapy over efavirenz-based therapy in pregnant women living with HIV.</p
Notes on the threadworm Strongyloides fuelleborni (Nematoda: Strongyloididae) in vervet monkeys (Chlorocebus pygerythrus) and zoonotic strongyloidiasis in southern Malawi
Get PDFWe sought to ascertain whether zoonotic strongyloidiasis occurred in vervet monkeys (Chlorocebus pygerythrus), a non-human primate (NHP) species becoming increasingly common in Southern Malawi. Faecal collection took place in four locations: Nyala Park, a private wildlife reserve adjacent to a sugarcane plantation in Chikwawa District, and three public locations, each near tourist lodges in Mangochi District. Our sampling took place during July 2023, when 32 faecal samples were inspected with parasitological methods. After faecal culture, threadworm larvae were noted in both districts that were confirmed by molecular identification methods as Strongyloides fuelleborni, a first report for Malawi. Given the close spatial proximity of vervets with people, our findings affirm prior disease surveillance concerns of local zoonotic potential. We therefore encourage future targeted helminthological surveys for better local monitoring of strongyloidiasis in NHPs and people.</p
Costs and cost-effectiveness of integrated horizontal community health worker programmes in low- and middle-income countries (2015-2024):A scoping literature review
Get PDFBackground Community health workers (CHWs) play a vital role in delivering primary health care in low- and middle-income countries (LMICs), addressing multiple diseases through horizontal programmes. Despite their effectiveness, there is a US265 (range US148 (Ethiopia)-346 (US549)). The most commonly reported cost metric was the annual cost per capita, with a median of 0.29-$67.95). Sensitivity analyses were conducted in 29% of the scenarios, with six scenarios concluding CHW programmes were cost-effective. However, most did not conclude on cost-effectiveness or affordability, highlighting gaps in the evidence base. Service provision was the most frequently reported outcome, while cost per outcome and affordability were under-reported. Conclusions This review highlights gaps in the economic evaluation of horizontal CHW programmes, particularly in cost-effectiveness and affordability. More large-scale evaluations are needed to inform national health policies and support sustained investment in CHW programmes to strengthen health systems and address workforce shortages.</p
Comparison of the analytical and clinical sensitivities of 34 rapid antigen tests with prevalent SARS-CoV-2 variants of concern during the COVID-19 pandemic in the UK
Get PDFAntigen-detection rapid diagnostic tests (Ag-RDTs) have become a central pillar for the management of coronavirus disease worldwide due to their speed and ease of use and are now being developed for use in other emerging outbreaks. Like other viruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is subject to rapid mutation as it spreads, and new variants of concern (VOCs) emerge frequently, posing a significant challenge for the detection of newer, highly mutated variants. It is, therefore, important that the performance of Ag-RDTs is regularly evaluated, particularly in outbreak scenarios where rapid diagnostics are key to limiting disease spread. Here, we present a comprehensive evaluation of the analytical and clinical sensitivities of 34 commercially available Ag-RDTs with five SARS-CoV-2 VOCs, all of which were highly prevalent in the UK at various times between 2019 and 2023. This study highlights the importance of regular evaluation of the Ag-RDT performance, with several Ag-RDTs demonstrating a reduced performance with some VOCs. We conclude that a regular performance evaluation through our proposed pipeline, combined with a broad consensus approval threshold across global organizations, is essential to maintaining the effectiveness of Ag-RDTs as a disease management tool during outbreaks
Microscopic detection and genetic characterisation of schistosome eggs within cervicovaginal lavage sediments from cases of female genital schistosomiasis
Get PDFControl of female genital schistosomiasis (FGS) has gained significant international attention, driven in part, as a newly appreciated underlying aetiological risk factor for HIV, HPV and cervical dysplasia. Whilst diagnosis and clinical staging of FGS typically relies upon colposcopy, alternative methods of incrimination have grown, particularly upon application of PCR diagnostic assays that detect schistosome DNA within tissue biopsy, genital (self-)swab and/or cervicovaginal lavage (CVL). With regard to the latter, we present novel evidence that microscopy alone of CVL sediments can be sufficient to incriminate FGS and CVL sediment provides an original source of (viable) schistosome eggs and miracidia for later genetic analysis. Upon a pilot examination of 55 adult women from Malawi with previously proven urogenital schistosomiasis by egg-patent urine microscopy, 25.5% (95% CI = 14.7 - 39.0) were found to have schistosome eggs within CVL, with one woman having more than 50 eggs observed. After praziquantel treatments and upon re-examination one year later, the prevalence of egg-patent CVLs reduced to 14.5% (95% CI = 6.5 - 26.7) although the same woman again presented with more than 50 observable eggs. Molecular DNA analysis by real-time PCR of extracted DNA from CVL sediments and CVL hatched miracidia (and eggs) revealed the dominance of Schistosoma haematobium within the samples, noting a fifth with Schistosoma mattheei co-infections and the singular presence of a putative S. haematobium x mattheei hybrid miracidium. Viable schistosome eggs shed from cervicovaginal surfaces likely represent a minor environmental transmission route, thus promoting secure menstrual hygiene management is needed.</p
A machine learning approach for automated injuries classification on postmortem images
Get PDFThe application of Artificial Intelligence (AI) in forensic science offers new opportunities for the automated detection of injuries in postmortem analysis. This study focuses on the semantic segmentation of two significant types of injuries—bruises and abrasions. A dataset of postmortem injury images was collected, followed by the development of appropriate data preprocessing and annotation techniques to train and evaluate AI models. Three deep learning architectures—U-Net, FPN, and LinkNe—were implemented, using EfficientNetB3 and ResNet50 as backbone networks. An optimisation strategy was employed to enhance detection performance by incorporating a custom loss function alongside a combination of image transformation and class balancing techniques. Experimental results demonstrated high sensitivity (92.7%) and specificity (98.9%) for the best-performing model. These findings highlight the potential of AI-driven methods for automated and objective analysis of postmortem images in injury detection, laying the foundation for further research
Proof-of-concept of duplex MNAzyme assay for simultaneous detection of Candida auris and Candida spp. using synthetic DNA targets
Get PDFThe global emergence of Candida auris as a multidrug-resistant fungal pathogen presents significant challenges to healthcare systems, particularly in hospital settings. Rapid and accurate diagnostics are crucial for managing C. auris infections. This study presents a preliminary analytical evaluation of a duplex Multicomponent Nucleic Acid Enzyme (MNAzyme) assay designed to simultaneously detect C. auris and genus-wide Candida species using synthetic DNA targets. Target sequences were selected from the conserved D1/D2 region of the LSU rDNA locus, and melting temperature analysis confirmed distinct probe hybridisation profiles, with Substrate 2:PCO1 yielding a Tm of 45°C and Substrate 3:PCO4 at 26°C. The assay demonstrated specificity by differentiating C. auris from other Candida species through melting curve analysis. In reactions containing synthetic targets, probe– target binding disrupted probe–PCO hybrids, resulting in a marked reduction in melt peaks compared to no DNA controls (NDC). The duplex format allows multiplex detection within a single fluorescence channel, offering a potential advantage over conventional single-target assays. This proof-of-concept establishes a rapid, low-cost diagnostic platform with promising potential for future clinical application. Further validation using clinical and environmental samples is needed to support its broader utility in detecting fungal pathogens.</p
An investigation of female genital schistosomiasis and associated genital infections in southern Malawi
Get PDFUrogenital schistosomiasis caused by zoonotic or hybrid schistosome infection(s) is an emerging public health concern in Malawi and we describe a 1-year clinical sub-study with three inspection time-points for female genital schistosomiasis upon selecting 86 women with proven urogenital schistosomiasis. This sub-study was set within a broader 2-year longitudinal 'Hybridization in UroGenital Schistosomiasis (HUGS)' investigation. A detailed cervicovaginal examination with a portable colposcope was conducted, examining cervicovaginal lavage (CVL), cervical swabs, cervical biopsy and urine with traditional parasitological and molecular diagnostic methods. At baseline, overt FGS by colposcopy was 72.1%, 64.3% by CVL real-time PCR and 51.2% by both colposcopy and CVL-PCR, noting urine-microscopy could often be negative. Human papilloma virus was detected in 31.0%, with 8.3% also FGS positive by colposcopy and real-time PCR. Over the year, FGS prevalence by colposcopy increased by 32.7% during the study to 84.6%, homogenous yellow and grainy sandy patches being very common in the youngest 18-25 age group, where 51.9% were positive. FGS appears widespread locally and we discuss difficulties in its detection without invasive sampling. In addition to the presence of S. haematobium, S. mattheei was noted alongside key concurrent sexually transmitted infections. From our findings, we point out that improved prevention and management of FGS is required, foremost, better availability and regular accessibility to praziquantel treatment is needed. Furthermore, targeted health education, raised community awareness and dovetailing synergistic public health activities within Sexual and Reproductive Health services and local HIV/AIDS programmes could develop an appropriate holistic health intervention package.</p
Lung function and onset of cardiometabolic diseases in the longitudinal Burden of Obstructive Lung Disease study
Get PDFIntroduction.Previous population-based studies, mainly from high-income countries, have shown that a higher forced vital capacity (FVC) is associated with a lower risk of developing cardiometabolic diseases. The aim of this study was to assess the longitudinal association between spirometry measures and the onset of cardiometabolic diseases across sites in low-income, middle-income and high-income countries.Methods.The study population comprised 5916 individuals from 15 countries participating in the Burden of Obstructive Lung Disease baseline and follow-up assessments. Postbronchodilator forced expiratory volume in 1 s (FEV1), FVC and FEV1/FVC were measured at baseline. Participants who reported having doctor-diagnosed hypertension, diabetes, heart disease and stroke at follow-up but not at baseline were considered new cases of these diseases. The association between lung function and the onset of participant-reported cardiometabolic diseases was assessed in each site using regression models, and estimates were combined using random effects meta-analysis. Models were adjusted for sex, age, smoking, body mass index and educational level.Results.Participants with greater per cent predicted FVC were less likely to have new-onset diabetes (OR per 10%=0.91, 95% CI 0.84 to 0.99), heart disease (OR per 10%=0.86, 95% CI 0.80 to 0.92) and stroke (OR per 10%=0.81, 95% CI 0.73 to 0.89) during the follow-up period (mean±SD 9.5±3.6 years). A greater percentage of FEV1 was associated with a lower risk of onset of heart disease and stroke. No significant association was found between FEV1/FVC and onset of reported cardiometabolic diseases, except for a higher risk of diabetes (OR per 10%=1.21, 95% CI 1.08 to 1.35) in participants with higher FEV1/FVC.Conclusions.The findings of this study suggest that a low FVC is more important than a low FEV1/FVC as a risk factor for developing cardiometabolic diseases. The value of including FVC in risk score models to improve their precision in predicting the onset of cardiometabolic diseases should be explored.</p