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Perceptions of pre-exposure prophylaxis among sexually active adolescent girls and young women in Zimbabwe–A qualitative study
Get PDFAdolescent girls and young women (AGYW; aged 15–24 years) in Zimbabwe face high risk of contracting HIV. Despite proven effectiveness of Pre-Exposure Prophylaxis (PrEP), its uptake and continuation among AGYW is low. We aimed to explore views on PrEP, norms around sexual behaviour and how programs can improve PrEP uptake among this group. From December 2021 to March 2023 nine focus group discussions were held with 92 (8–12 per group) sexually active AGYW, purposively selected from programs offering sexual and reproductive health (SRH) services to AGYW in Harare, Mazowe and Matabeleland South. Discussions were participatory and analysed thematically. Participants were aged 16–24 years; 73% had attained some high school education, 9% had never tested for HIV and 70% never used PrEP. Across all groups there was recognition that AGYW are at risk of contracting HIV. Knowledge of PrEP varied, with AGYW enrolled in the national sex worker and SRH programs more knowledgeable than the rest. A recurrent theme was that PrEP was viewed as undesirable due to its association with anti-retroviral treatment and risky sexual behaviours. AGYW thought their parents and partners would find their use of PrEP unacceptable. Unmarried sexually active AGYW seemed the most vulnerable and at high risk of HIV acquisition. Issues identified as important for improving uptake and adherence included ensuring private, confidential and free services, education of parents and partners on SRH issues and friendly attitudes of health workers. Additionally, AGYW indicated preference for the long-acting PrEP formulations, viewed as convenient and more private. Despite the recognition of being at risk of HIV, HIV related stigma and concerns about being viewed as having risky sexual behavior prevent them from taking PrEP. There is need to design youth-friendly PrEP programs that uphold privacy & confidentiality, prevent stigma and minimize opposition from parents and partners.</p
One-year follow-up of survival and health-related quality of life in patients with medical conditions admitted acutely to hospital in Malawi and Tanzania
Get PDFMultimorbidity, defined as the coexistence of two or more long-term conditions, is a major public health issue. In southern and eastern Africa, limited access to primary care frequently results in delayed diagnosis and chronic disease decompensation with the need for acute hospital admission [1]. This report details 1-year survival and health-related quality of life (HRQoL) data in patients admitted acutely to hospitals in Malawi and Tanzania and follows on from our study that detailed the high prevalence of hypertension (44%); HIV (31%); and diabetes mellitus (27%) in patients admitted to hospital [2].We conducted this study in line with our published protocol [3] and with statistical methodology replicated from our multicentre cohort study [2]. Patients were categorised based on the number (none, one and two or more) of long-term conditions. The 1-year follow-up for all patients was completed in December 2024. We evaluated 1-year survival and HRQoL (where a score of 1 represents perfect health and a score of 0 represents death) in survivors using EQ5D-5l. We have provided an open access link to our database hosted at: https://publications.mlw.mw. The 1-year survival analysis for this study was performed in R (4.4.1; R Studio for Statistical Computing, Vienna, Austria) using the survival, survminer and ggplot2 packages and HRQoL analysis was conducted in Stata MP 18.0 (StataCorp, College Station, TX, USA)
Exceptional Visual-Opsin Coexpression and Phenotypic Diversity in Outer-Retinal Photoreceptors of Caenophidian Snakes
Get PDFSnakes are a valuable yet understudied taxon for investigating evolutionary adaptations in the vertebrate retina. They possess up to three visual pigments: a short-wavelength-sensitive opsin (SWS1), a medium/long-wavelength-sensitive opsin (LWS), and rhodopsin (RH1). Nocturnal snakes have duplex retinas containing both rod and cone photoreceptors, whereas diurnal caenophidian ("advanced") snakes exhibit simplex "all-cone" retinas, lacking morphologically typical rods. In this study, we analyzed photoreceptor morphology in the retinas of caenophidian snakes using high-resolution scanning electron microscopy (SEM) and examined visual-opsin expression patterns with immunohistochemistry (IHC). Our analyses revealed remarkable interspecific variability in visual-cell morphology. Light microscopy showed that in all sampled diurnal caenophidians, photoreceptors expressing RH1 exhibit a gross cone-like morphology. However, SEM analysis revealed a subset of photoreceptors with distinct features-thinner inner segments and rod-like synaptic terminals-suggesting they are transmuted, cone-like rods. In retinal sections from nocturnal caenophidian snakes, coexpression of the cone opsins SWS1 and LWS in individual cones was observed, whereas rhodopsin expression remained restricted to morphologically typical rods and showed no coexpression. In contrast, diurnal caenophidians commonly coexpress rhodopsin and SWS1 in single cones, with some instances of triple coexpression (SWS1, RH1, and LWS) in single cones. We evaluated the patterns of spatial distribution of RH1- and SWS1-expressing photoreceptors, as well as SWS1 + RH1 multiopsin cones, in wholemounted retinas of ten species. Our findings revealed considerable species-specific variation in photoreceptor density, topography, and opsin coexpression patterns. IHC results suggest that in some species, rhodopsin is not only expressed in transmuted, cone-like rods but may also be co-opted by UV/violet-sensitive (SWS1-expressing) cones. These findings underscore the exceptional diversity and adaptive innovation in snake visual systems. The unique features and striking interspecific differences in their photoreceptors highlight snakes as an outstanding taxon for studying vertebrate visual-system function and evolution.</p
Refugee integration in national health systems of low- and middle-income countries (LMICs): evidence synthesis and future research agenda
Get PDFThis paper reviews evidence on healthcare responses for refugees, documenting the different approaches and their effectiveness and impact in particular in relation to supporting integrating refugees into national health systems. The review adopted a purposeful, iterative approach, utilizing electronic databases, grey literature, and reference lists from relevant studies. A total of 167 studies, primarily from low- and middle-income countries (LMICs), focusing on refugees and forcibly displaced persons with empirical data, were included. The review highlights a substantial literature on refugee health and healthcare access, with well-covered areas including delivery models, access barriers, gaps in coverage, and specific health services such as psychosocial care, non-communicable diseases, mental health, and maternal and child health. However, less attention is given to integration models, health system responses, and their impact on system resilience and social cohesion. Few studies examine the costs, feasibility, or sustainability of integration models, and little research focuses on health system perspectives or comparative analyses. Moreover, the host health system's status, capacity, and needs are often underexplored. Some countries are particularly well-represented in studies, e.g. Turkey, Jordan, Lebanon, Bangladesh, Democratic Republic of Congo (DRC), and Uganda. There is however a paucity of data that would provide the basis for more quantitative or analytical evaluation from a systems perspective. This gap highlights the need for further research on effective integration models, their operational aspects, and their long-term impact on local health systems' resilience and sustainability. To support this research agenda, we propose a conceptual framework to provide analytic guidance for future research on healthcare responses for refugees and health system integration.</p
Prevalence of Social Frailty and Pre-Frailty in Asian Older Adults A Systematic Review and Meta-Analysis
Get PDFPURPOSE: To synthesize the pooled estimate of the overall incidence of social frailty (SF) and pre-frailty, as well as the prevalence of SF based on sex, country, participant type, and assessment tool used. METHOD: This systematic review and meta-analysis incorporated data from inception to December 2021 using six databases: PubMed, Embase, MEDLINE, CINAHL Plus, PsycINFO, and Cochrane Library. In addition to using a comprehensive set of medical subject headings and text phrases in Chinese and English, additional research was manually retrieved from reference lists. Calculations of the combined incidence of SF and pre-frailty were based on a random-effects model. Sources of heterogeneity were also verified through subgroup analysis. RESULTS: The literature search yielded 2,371 articles, with 17 articles included in the meta-analysis. The combined incidences of SF and pre-frailty were 18.9% (95% confidence interval [CI] [13.7, 24.1]) and 46.6% (95% CI [34.4, 58.7]), respectively. After subgroup analyses of SF, the combined prevalence was 21.6% (95% CI [12.9, 30.3]) in Japan, 19.4% (95% CI [13.2, 25.5]) among females, 25.1% (95% CI [9.1, 41.1]) with Makizako's 5-item SF questionnaire, and 66.5% (95% CI [63.9, 69.1]) among older adults with heart failure. CONCLUSION: SF and pre-frailty were prevalent in Asian older adults, especially in Japan, among females, with Makizako's 5-item SF questionnaire, and among older adults with heart failure.</p
Evaluating a novel multi-species vector control tool for humanitarian crises: the efficacy of attractive targeted sugar baits among forcibly displaced populations in Northern Nigeria
Get PDFBackground: Armed conflicts, natural disasters and forced population displacement have escalated dramatically since the 1990s. By mid-2024, the total number of people driven from their homes, often surviving in very harsh conditions for years, reached 122.6 million globally. In emergencies characterised by flimsy shelters, food insecurity, inadequate sanitation, poor access to health services and increased exposure to blood-feeding insects, diseases such as malaria, dengue and leishmaniasis cause high levels of morbidity and mortality. Conventional vector control interventions are inadequate in these settings due to operational and biological limitations. Novel vector control tools which are lightweight, easy to use and effective against multiple vector species are urgently needed to protect displaced populations. Methods: We conducted a 6-month, 2-arm community field trial in two internally displaced people camps in Maiduguri, Nigeria, to evaluate the entomological efficacy of attractive targeted sugar baits (ATSB). Monthly entomological monitoring measured changes in adult and immature vector density. Intervention acceptability was assessed using focus group discussions and a cross-sectional survey. To investigate environmental drivers of vector abundance, which might influence field outcomes, a hybrid approach of unsupervised and supervised machine learning regression models was developed using composite demographic, bioclimatic and ecological remote sensing data. Results: ATSB demonstrated a significant impact on indoor female Anopheles gambiae s.l. density (IRR: 0.140 [95% CI: 0.093–0.212]; p < 0.0001) and indoor blood-fed An. gambiae s.l. density (IRR: 0.0193 [95% credible interval: 0.0111–0.0356]). ATSB also significantly reduced indoor blood-fed Aedes aegypti (IRR: 0.0746 [95% credible intervals: 0.00884–0.502]). More than 97% of camp residents showed high levels of acceptance for ATSB, including willingness to pay. The strongest environmental predictors of An. gambiae s.l. occurrence were composite indices of vegetation water content, soil moisture, moist canopy, landcover diversity, urbanisation and normalised and enhanced vegetation index which together contributed to 73.5% of the final model. Conclusions: Field trial findings strongly support the use of ATSB to control sympatric malaria and dengue vector populations in humanitarian crises. Remote sensing analysis identified key drivers of An. gambiae s.l. occurrence providing a high-resolution environmental profile where ATSB achieved an entomological impact against multiple vector species.</p
Effect of Continuous High-Frequency Oscillation Therapy on Lung Aeration in Mechanically Ventilated Patients With Impaired Consciousness: A Multicenter Randomized Controlled Trial
Get PDFBACKGROUND: Atelectasis frequently occurs in patients with impaired consciousness who are being treated with invasive mechanical ventilation. It is mainly caused by secretion accumulation, which can lead to longer durations of ventilation and ICU stay. RESEARCH QUESTION: Does continuous high-frequency oscillation (CHFO) therapy improve lung aeration and reduce atelectasis in adults with impaired consciousness who are mechanically ventilated? STUDY DESIGN AND METHODS: This multicenter, single-blind, randomized controlled trial was conducted across 11 hospitals in China. Adult patients with impaired consciousness (Glasgow Coma Scale score </= 8) who required invasive mechanical ventilation were randomly assigned in a 1:1 ratio to either the CHFO or usual care group. The CHFO group received three to four sessions daily. The primary outcome was the percent change in nonaerated lung tissue, measured by CT scan, from baseline to day 5, as analyzed in the intention-to-treat population. RESULTS: From June 19, 2023, to July 2, 2024, a total of 80 patients were included in the intention-to-treat analysis. Five patients from each group were excluded from the primary analysis due to incomplete CT scans. On day 5, the decrease in nonaerated lung tissue was greater in the CHFO group (-51.3%; 95% CI -62.7 to -40.0) compared with the usual care group (-37.6%; 95% CI, -49.3 to -26.0), with a mean difference of -13.69% (95% CI, -24.86 to -2.52; P = .017). The CHFO group also had a higher number of ventilator-free days, a lower clinical pulmonary infection score, and a shorter ICU stay. No adverse events of interest were observed during the study. INTERPRETATION: In patients with impaired consciousness who are mechanically ventilated, 5 days of CHFO treatment significantly reduced nonaerated lung tissue. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry; No.: ChiCTR2300070988; https://www.chictr.org.cn
Polygenic viral factors enable efficient mosquito-borne transmission of African Zika virus
Get PDFZika virus (ZIKV) is a mosquito-borne flavivirus primarily transmitted among humans by Aedes aegypti. Over the past two decades, it has caused significant outbreaks associated with birth defects and neurological disorders. Phylogenetically, ZIKV consists of two main genotypes referred to as theAfrican and Asian lineages, each exhibiting distinct biological properties. African lineage strains are transmitted more efficiently by mosquitoes, but pinpointing the genetic basis of this difference has remained challenging. Here, we address this question by comparing recent African and Asian strains using chimeric viruses, in which segments of the parental genomes are swapped. Our results show that the structural genes from the African strain enhance viral internalization, while the non-structural genes improve genome replication and infectious particle production in mosquito cells. In vivo mosquito transmission is most significantly influenced by the structural genes, although no single viral gene alone determines this effect. Additionally, we develop a stochastic model of in vivo viral dynamics in mosquitoes that mirrors the observed patterns, suggesting that the primary difference between the African and Asian strains lies in their ability to traverse the mosquito salivary glands. Overall, our findings suggest that the polygenic nature of ZIKV transmissibility has prevented Asian lineage strains from achieving the same epidemic potential as African lineage strains, underscoring the importance of lineage-specific adaptive landscapes in shaping ZIKV evolution and emergence
Outcomes for delusional infestation in multidisciplinary clinics
Get PDFBackground Delusional infestation (DI) is a psycho-dermatological illness that often presents to dermatologists. Patients have fixed delusional beliefs that they are infested with living or nonliving pathogens that cause symptoms. Antipsychotic medication is the treatment of choice. Patient engagement is a challenge. Little is known about the best settings in which to treat DI. Objectives We examined outcomes for patients with DI referred to multidisciplinary clinics in the UK, comprising dermatologists or tropical medicine physicians paired with psychiatrists. Methods We used Clinical Global Impression scale (CGI-S) score changes as our main outcome parameter. We report average CGI-S score changes for all groups. We used independent t-tests and an Anova analysis to measure differences between those who had a planned discharge and those who were lost to follow-up (LTFU), separating each group between those who reported taking medication and those who did not. Results Records from 465 patients were reviewed: 94 (20.2%) patients had no CGI-S data points (12.0% did not attend; 8.2% missing data); 151 (32.5%) were followed up and had a planned discharge; 193 (41.5%) were lost to follow-up (LTFU) at some point, of whom 63 patients (13.5%) attended only once and had their last (only) observation carried forward. Of the 281 (60.4%) patients who attended the clinics at least twice, 108 (38.4%) had a response or remission (n = 69; 24.6%). The mean average CGI-S score change was –1.29, indicating clinically relevant improvement. Those who had a planned discharge and reported to have taken medication had an average CGI-S score change of –2.02, indicating significant improvement. Those who took medication but were LTFU had an average CGI-S change of –0.63 (just below clinically relevant improvement); those LTFU who did not take medication did not improve (CGI-S change –0.07). Conclusions Patients with DI who took medication did significantly better than those who did not. Patients who had a planned discharge did significantly better than those who were LTFU. Multidisciplinary clinics have good clinical outcomes for patients with DI, especially where patient engagement was reasonable.</p
Controlled human infection model (CHIM) inoculum production in Malawi using principles of good manufacturing practice
Get PDFBackground Controlled Human Infection Models (CHIM) are an important tool in biomedical research in which pathogens are inoculated into human volunteers to study pathogenesis and test vaccines or treatments. Production of CHIM inoculum, however, presents specific challenges in safety, reproducibility and replication of the desired dose. The principles of Good Manufacturing Practice (GMP) developed for production of medications can be applied to the preparation of CHIM inocula, but licensed GMP facilities are scarce in low resource settings. Methods We applied GMP principles to develop protocols for CHIM inocula production at Liverpool School of Tropical Medicine, UK and subsequently at Malawi-Liverpool Wellcome Programme, Malawi. We used published guidelines to evaluate these protocols and to advise selection, characterisation, manufacture, quality control and storage. We established in-house production of Streptococcus pneumoniae serotypes 3 and 6B for use in Experimental Human Pneumococcal Challenge models. Results The manufacturing process underwent regulatory review in both the UK and Malawi. CHIM inocula production in Malawi was approved by the National Health Sciences Research Committee after written and oral submission. We successfully implemented our procedure and manufactured batch lots of Streptococcus pneumoniae serotype 3 ( n = 2) and serotype 6B (n = 2). We safely, accurately and successfully inoculated participants in CHIM studies and achieved experimental human pneumococcal carriage with both serotype strains. Discussion CHIM inoculum manufacture of pneumococcus was feasible in Malawi. This allowed the Malawi scientific ecosystem to demonstrate scientific and regulatory autonomy as well as having the potential to improve operational efficiency compared to importation of challenge agents.</p