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Genetic diversity within Strongyloides fuelleborni: Mitochondrial genome analysis reveals a clear African and Asian division
Get PDFFollowing the recent report of strongyloidiasis caused by Strongyloides fuelleborni within a semi-captive colony of baboons in a UK safari park, we investigated the genetic relationships of this isolate with other Strongyloides isolates across the world. Whole genome sequence (WGS) data were generated with later phylogenetic analysis of mitochondrial (mt) cytochrome oxidase subunit 1 (cox1) and nuclear ribosomal 18S sequences against 300 published Strongyloides reference genotypes. The putative African origin of the UK S. fuelleborni was confirmed and full length mt genome sequences were assembled to facilitate a more detailed phylogenetic analysis of 14 mt coding regions against all available Strongyloides species. Our analyses demonstrated that the UK isolate represented a novel African lineage not previously described. Additional complete mt genomes were assembled for several individual UK safari park worms to reveal a slightly altered mt genome gene arrangement, allowing clear separation from Asian S. fuelleborni. Furthermore, these UK worms possessed expanded intergenic regions of unknown function that increase their mt genome size to approximately 24 kilobases (kb) as compared with some 16 kb for Asian S. fuelleborni; this may have arisen from unique populational founder and genetic drift effects set within the peculiar mixed species baboon and drill ancestry of this semi- captive primate colony. A maximum likelihood phylogeny constructed from 14 mitochondrial coding regions supported an evolutionary distinction between Asian and African S. fuelleborni, most likely supporting paraphyly.</p
Sub-optimal birth spacing and associated factors among mothers of children admitted to therapeutic feeding centers with severe acute malnutrition in Oda Bultum Woreda, Eastern Ethiopia:A cross-section study
Get PDFIntroduction: Although several strategies have been implemented, sub-optimal birth space continues to be a serious public health issue in Ethiopia. There is limited information regarding sub-optimal birth spacing among mothers of children with severe acute malnutrition in the study area. Thus, this study aimed to assess the magnitude of sub-optimal birth spacing and it is associated factors among mothers of children admitted to therapeutic feeding centers with severe acute malnutrition in Oda-Bultum Woreda, eastern Ethiopia. Methods: An institutional-based cross-sectional study was carried out among 404 randomly selected mothers of children admitted to therapeutic feeding center with severe acute malnutrition in Oda BultumWoreda, Eastern Ethiopia from October 5 to December 4, 2020. A pretested structured interviewer-administered questionnaire was used. The collected data were entered into EpiData version 3.1 and then exported to SPSS version 25 for analysis. Binary logistic regression was used to examine the association between suboptimal birth spacing and independent variables. A P-value < 0.05 was used to declare a statistical significance. Results: More than half of 213 (52.7%) of the study participants had sub-optimal birth spacing (<33 months). Rural residence (AOR: 1.87; 95% CI: 1.11 – 3.15), younger age at marriage (AOR: 2.92; 95%CI: 1.67––5.10), (AOR: 1.78; 95%CI: 1.07–2.95), not knowing the duration of optimal birth spacing (AOR: 4.12; 95%CI: 1.89–9.00), and shorter breastfeeding duration (AOR: 3.36, 95% CI: 2.09–5.39), and no formal education (AOR: 1.78; 95%CI: 1.07–2.95) were significantly associated with suboptimal birth spacing. Conclusion: In this study, slightly more than half mothers' whose of children with severe acute malnutrition had suboptimal birth spacing. Rural residence, lack of education, younger marital age, lack of knowledge of ideal birth space, and shorter breastfeeding duration were the identified factors that increase the odds of having sub-optimal birth spacing. To optimize birth spacing in the study area, strategies concerning young women and rural communities are recommended.</p
Prevalence of hepatitis B virus infection among pregnant women and cord blood hepatitis B surface antigen positive newborns in sub-Saharan Africa and South Asia
Get PDFBackground: Newborns infected with Hepatitis B Virus (HBV) are at risk of chronic liver disease and hepatocellular carcinoma. Objectives: This study investigated the prevalence of HBV infection among pregnant women and cord blood Hepatitis B surface antigen (HBsAg) positivity of their newborns in Bangladesh, Bhutan, India, Ethiopia, Mozambique, Kenya, Nigeria, Mali, and South Africa. Study design: Randomly selected paired maternal and cord blood samples (n = 101 each site) taken at delivery were tested for HBsAg and Hepatitis B extractable antigen (HBeAg) in the women using a chemiluminescent microparticle immunoassay. Similarly, cord blood sample of newborn was assessed for HBsAg reactivity. HBV DNA was quantified using the Xpert® HBV viral load assay, followed by genotyping. Results: The overall prevalence of maternal HBsAg positivity was 5.5 % (95 %CI: 0.4 %–7.1 %; n = 50/909). HBsAg positivity was higher in African countries (7.3 %; 95 %CI: 5.4 %–9.6 %; n = 44/606) compared to South Asian countries (2.0 %; 95 %CI: 0.8 %–4.3 %; n = 6/303; p = 0.002). Relative to South Africa, there were higher odds of HBsAg sero-positivity in women from Mozambique ((aOR): 7.7, 95 %CI: 1.6 %–37.8 %) and Mali (aOR: 5.7; 95 %CI: 1.1 %–29.7 %). The rate of HBsAg positivity in cord blood of babies born to HBsAg positive women was 28.0 % (95 %CI: 17.1 %–42.3 %; n = 14/50), including 31.8 % (95 %CI: 19.5–47.4 %; n = 14/44) in African countries. No cord blood HBsAg positivity was observed in South Asia. Genotypic analysis revealed HBV genotypes A (41.7 %) and E (58.3 %) were pre-dominant. Conclusion: The high rate of cord blood positivity (28.0 %) for HBsAg underscores the urgency of enhancing HBV prevention strategies to meet the World Health Organization's target of a 90 % reduction in new HBV infections by 2030.</p
Why do female sex workers disengage from targeted reproductive and sexual health services?: Experiences from the Sisters with a Voice programme in Zimbabwe
Get PDFBackgroundThe Sisters programme provides HIV and sexual and reproductive health services for female sex workers (FSW) in Zimbabwe. Many engage with these services only once, while others disengage after repeated visits. Little is known about reasons for disengagement and the extent of service needs after disengaging.MethodsProgramme staff used site- and age-stratified random sampling to identify 1,200 programme records of FSWs who attended one of four Sisters clinics at least once between January 2018 and June 2019, and had no evidence of a further visit before September 2020. Outreach workers attempted to contact these FSWs via home visits, phone tracing and contacting peer educators. We calculated the proportion of FSWs successfully contacted, the level of ongoing engagement in sex work, expressed unmet need for Sisters services and the proportion of FSWs who subsequently made a return visit to the programme. We explored sociodemographic factors associated with these outcomes.ResultsOf 1169 FSWs for whom contact was attempted, peer educators or others provided evidence in relation to 16 FSWs thought to have died. Of the 45% (504/1169) of FSWs who were successfully contacted, 37% (188/504) were no longer engaged in sex work, although 83% (156/188) reported that they were still in need of services. Reasons given for disengaging included having migrated (40%; 200/504); work commitments (16%; 79/504) and accessing services elsewhere (10%; 51/504). 62% of FSWs (313/504) said they were still active in sex work, among whom 23% (73/313) revisited the programme within 3 months of contact. FSWs living with HIV were less likely to re-engage with the programme (adjusted odds ratio 0.41, 95% CI 0.20–0.83). Age and site were associated with no longer being in sex work, while other factors showed no strong association.ConclusionsThese findings highlight the need for robust outreach and re-engagement strategies that accommodate the mobility and evolving circumstances of FSWs. In particular, programmes that promote peer-led, community-based microplanning—supported by integrated data management systems—can help address stigma, frequent relocation, and financial constraints that hinder continuous care. By tailoring services to both active and former FSWs, health systems can ensure that essential sexual and reproductive health services remain accessible, even when FSWs exit sex work. Such differentiated approaches ultimately strengthen continuity of care, reduce service gaps, and support broader public health goals by improving health equity and outcomes for this high-risk population
Protocol for the Redefining Maternal Anemia in Pregnancy and Postpartum (ReMAPP) study: A multisite, international, population-based cohort study to establish global hemoglobin thresholds for maternal anemia
Get PDFBackground. Anemia affects one in three pregnant women worldwide, with the greatest burden in South Asia and sub-Saharan Africa. During pregnancy, anemia has been linked to an increased risk of adverse maternal and neonatal health outcomes. Despite widespread recognition that anemia can complicate pregnancy, critical gaps persist in our understanding of the specific causes of maternal anemia and the cutoffs used to diagnose anemia in each trimester and in the postpartum period. Methods and analysis. The Redefining Maternal Anemia in Pregnancy and Postpartum (ReMAPP) study is a multisite, prospective, cohort study nested within the Pregnancy Risk, Infant Surveillance, and Measurement Alliance (PRISMA) Maternal and Newborn Health study. Research sites are located in Kenya, Ghana, Zambia, India, and Pakistan. Participants are up to 12,000 pregnant women who provide serial venous blood samples for hemoglobin assessment at five time points: at <20 weeks, 20 weeks, 28 weeks, and 36 weeks gestation and at six weeks postpartum. We will use two analytical approaches to estimate hemoglobin thresholds for defining anemia: (1) clinical decision limits for cutoffs in each trimester and at six weeks postpartum based on associations of hemoglobin levels with adverse maternal, fetal, and neonatal health outcomes and (2) reference limits for gestational-week-specific cutoffs and at six weeks postpartum for mild, moderate, and severe anemia based on tail statistical percentiles of hemoglobin values in a reference (i.e., clinically healthy) subpopulation. We will also conduct biomarker-intensive testing among a sub-sample of participants in each trimester to explore underlying contributing factors of maternal anemia. Ethics and dissemination. The study received local and national ethical approvals from all participating institutions. Findings from multisite analyses will be published among open-access, peer-reviewed journals and disseminated with local, national, and international partners. Strengths and limitations.• Novel study design to allow multiple analytical approaches (clinical decision limits and reference limits) in the same population to establish hemoglobin thresholds. • Use of gold standard methods and external quality assurance programs to ensure harmonized hemoglobin measurement across sites. • Inclusion of biomarker-intensive study arm to examine the etiology of anemia among pregnant women. • All data is contributed by populations historically underrepresented in research in low- and middle-income countries.</p
Neuronavigation-assisted stereotactic minimally invasive puncture with tenecteplase for the treatment of acute spontaneous deep intracerebral haemorrhage (NAS-TNK):Rationale and design of a multicentre randomised trial
Get PDFIntroduction: Minimally invasive puncture surgery followed by thrombolysis has been proven to be an effective approach for managing hypertensive intracerebral haemorrhage (ICH). Nevertheless, its impact on improving neurological outcomes remains controversial. The integration of neuronavigation-assisted stereotactic (NAS) technology will significantly help enhance the accuracy of catheter placement, while tenecteplase (TNK), a third-generation thrombolytic agent, offers stronger capabilities in breaking down platelet-rich clots and demonstrates increased fibrin selectivity, which could enhance the overall effectiveness of thrombolytic treatment. However, the efficacy and safety of combining NAS-assisted minimally invasive puncture with TNK (NAS-TNK) in reducing disability and mortality rates among patients with acute spontaneous deep ICH remain unknown. Aim: To describe the rationale and design of the NAS-TNK trial for the treatment of acute spontaneous deep ICH. Design: NAS-TNK is a randomised, open-label, outcome-blinded multicentre trial, involving 732 participants with acute basal ganglia or thalamic haemorrhage with a haematoma volume ranging from 20 to 50 mL. This study will evaluate the efficacy and safety of NAS-TNK, administered every 24 hours at a dose of 0.009 mg/mL of haematoma volume, compared with participants receiving standard medical care. Each patient will undergo follow-up evaluations for a period of 180 days. Study outcomes: The main measure of effectiveness is the percentage of participants achieving a modified Rankin Scale Score ranging from 0 to 3 at the 180-day mark. The primary safety outcome is the all-cause death at 30 days. Discussion and conclusion: The NAS-TNK study will help improve our understanding of the benefits of NAS-TNK in patients with acute spontaneous deep ICH.</p
Volatile pyrethroid spatial repellents for preventing mosquito bites: a systematic review and meta-analysis
Get PDFBackground: Volatile pyrethroid spatial repellents (VPSRs) can prevent mosquito-borne diseases including malaria and dengue fever, but the use of varied evaluation methods has resulted in a lack of clarity regarding their protective efficacy (PE) against contact with mosquitoes. This systematic review and meta-analysis consolidates the entomological evidence base on the PE of VPSRs against Anopheles, Aedes, and Culex mosquitoes and different test methods used. Methods: We identified studies completed between January 2000 and September 2023 by searching through databases, conference abstracts, and personal correspondences. Included studies were semi-field or field studies that measured the PE of VPSRs using human landing catch (HLC) of mosquito landings on human legs and/or mosquito trap density, the number of mosquitoes captured using traps per set time period, compared to control groups. The systematic review summarised study-level data using a generalised linear mixed model with random effects. The meta-analysis pooled individual mosquito-level data and weather data on temperature, humidity, and wind from satellites, analysing PE subgrouped by product format, active ingredient, mosquito capture method used, mosquito species, and indoor vs outdoor setting. Risk of bias was assessed using a SYRCLE tool adapted for mosquito studies. Additional studies published from October 2023 to July 2025 were summarised. PROSPERO registration: CRD42021268852. Findings: 58 eligible publications showed that VPSRs provided an average of 56% (95% CI 50, 62%) PE from mosquito bites. Meta-analysis of individual mosquito-level data from 50 (86%) of eligible studies involving 1,703,120 mosquitoes showed that PE was highest when measured using HLC, with similar results seen in semi-field (58%, 95% CI 54, 62%) and field studies (50%, 95% CI 40, 59%). Differences between indoor (54%, 95% CI 18, 68%) and outdoor settings (56%, 95% CI 51, 60%) were unclear. Species-level differences were observed with low PE seen in Anopheles funestus (31%, 95% CI 19, 43%); the potential for cross-resistance to solid-state pyrethroids is unclear. Efficacy was not sensitive to combined weather effects. Interpretation: VPSRs offer protection from contact with mosquitoes, with semi-field studies reflecting field data and species-level differences observed. HLC provided the best quality data. Additional field studies that evaluate outdoor protection in malaria-endemic settings are needed, especially in West African, South American, and Southeast Asian settings. Funding: National Institutes of Health (National Institute of Allergy and Infectious Diseases (K01AI156182)) and “Accelerate to Eliminate Malaria” program.</p
Pharmacokinetics of the inactive favipiravir metabolite, favipiravir hydroxide (M1), as a proxy for establishing metabolic activity in patients receiving intravenous favipiravir for treatment of SARS-CoV-2 infection
No full textBackground: Favipiravir (FVP) has demonstrated in vitro activity against several RNA viruses, and its use for treatment of high consequence infectious diseases (HCIDs) continues to be evaluated. FVP is primarily metabolized by aldehyde oxidase (AO) to the pharmacologically inactive, favipiravir hydroxide (M1). FVP has complex pharmacokinetics (PK), with auto-inhibition of AO by FVP leading to increased FVP concentrations in plasma over time. Interindividual variability is a hallmark of FVP PK, but the cause of this is undetermined. Here, we report M1 concentrations in plasma from patients hospitalized with COVID-19 enrolled on the AGILE CST-6 clinical trial.Methods: AGILE CST-6 is a phase I randomized, adaptive study to evaluate safety and efficacy of intravenous (IV) FVP for treatment of COVID-19. Patients with laboratory confirmed COVID-19 were randomized 2:1 to received IV FVP or standard of care (SoC). Four cohorts with six patients were enrolled, with escalating dose per cohort (600, 1200, 1800 and 2400 mg). Patients received IV FVP infusions for 1 h twice daily (BD) for 7 days. Plasma samples were collected on Days 1, 3 and 5 at 0–1 and 6–12 h post-completion of infusion. Extra samples were taken on Days 1 and 3 at pre-dose and 2–4 h post-completion of infusion. FVP and M1 (concentrations) in plasma were determined using validated LC–MS methods and concentrations expressed as ng/mL. PK parameters for M1 and FVP were derived using WinNonlin (Phoenix 64, v8.5). Fixed effect linear modelling of the data was performed using SPSS (IBM, v29.0.1).Results: A total of 153 samples were evaluable from 16 patients. M1 increased with dose but decreased from Days 1 to 5. Geometric mean (GM) Cmax [M1] were (600|1200|1800|2400 mg) 5873, 9706, 18 576, 25 868 ng/mL on Day 1; 4901, 6808, 10 311 and 12 475 ng/mL on Day 3 and 4275, 7021, 8701 and 15 185 ng/mL on Day 5. (FVP) Cmax were 16 481, 38 006, 52 044, 88 486 ng/mL on Day 1; 16 526, 61 907, 85 362 and 195 067 ng/mL on Day 3; and 23 461, 86 743, 115 781 and 202 676 ng/mL on Day 5. Median (range) M1:FVP ratios were 600 mg: 0.41 (0.06–0.75); 1200 mg: 0.18 (0.01–0.60); 1800 mg: 0.14 (0.05–0.81) and 2400 mg: 0.10 (0.04–0.46) and decreased from Days 1 to 5; M1:FVP ratios were Day 1: 0.42 (0.06–0.81), Day 3: 0.13 (0.01–0.66) and Day 5: 0.10 (0.02–0.48). Interindividual variability was high with %CV > 57%. Dose (94% lower FPV with 600 mg vs. 2400 mg; p < 0.001), M1:FVP ratio (33% decrease in FVP with increasing ratio; p < 0.001) and treatment day (60% decrease in FPV on Day 1 vs. Day 5) were independent, significant predictors of (FVP).Conclusion: M1 concentrations decrease as FVP plasma concentration increases—both with escalating dose and over treatment duration, indicating potential saturation of metabolic pathways and increased inhibition of AO (due to accumulation of FVP). High interindividual variability in M1:FVP suggests the presence of fast and slow metabolisers. (FVP) was independently predicted by dose, M1:FVP ratio and treatment day, highlighting the complex pharmacokinetic profile of FVP.<br/
Improved Speech Recognition in Adults With Conductive or Mixed Hearing Loss Using a Direct-to-Consumer Bone-Conduction Device: A Multiple Methods Intervention Study
Get PDFBackground: Hearing loss affects 20% of the global population, including 250 million experiencing chronic suppurative otitis media, which can present challenges for conventional hearing aids due to ear discharge. Although assistive technology for hearing is available in high-income settings, provision is poor in low-income settings due to high costs and low availability of audiology services, reaching approximately 3% of those who could benefit from it. Objective: This study aimed to evaluate the performance of a low-cost self-fitted direct-to-consumer bone-conduction headset for individuals with conductive or mixed hearing loss.Methods: We conducted a multiple methods study to test the efficacy and acceptability of this device using a purposive sample. Participants with a range of conductive and mixed hearing loss underwent speech-in-quiet speech audiometry with and without the device and took part in feedback interviews exploring their subjective impressions of the device. Results: In 33 participants, the device improved speech recognition in those with bone conduction thresholds <50 dB by a median of 11%, with larger air-bone gap associated with larger improvement. Participants rated the device positively on weight, style, and ease of use.Conclusions: This multiple methods study assessed the acceptability and efficacy of a low cost self-fitted bone-conduction device in adults. We found the device provides hearing benefit for those with conductive or mixed hearing loss (with bone conduction thresholds <50dB HL). Those with significant conductive hearing loss were measured to have their speech perception significantly improved. Participants had a mixed response to device aesthetics. Further studies should seek to establish if this type of device has effectiveness in real-world trials and which individuals are most likely to benefit. This low cost device could provide hearing benefits to millions of people without access to other devices. Product designers and clinical researchers should explore device optimization. Given the economic impacts of hearing loss across the globe, this style of self-fitted device could represent a paradigm shift in future assistive technology for hearing loss, in both high and low resource settings.</p
Did the WHO recognition of snakebite as a neglected tropical disease impact national NTD master plans in 15 African countries?
Get PDFIn 2018, the World Health Organization (WHO) acknowledged Snakebite Envenoming (SBE) as a Neglected Tropical Disease (NTD). The WHO set a target for 2030 to halve the number of snakebite victims and published a roadmap to assist affected countries with drafting national SBE policies. These national SBE policies define the course of action to reach country specific and global goals. In order to review the policy environment needed to reduce the burden, we studied if SBE policy was included in national NTD programmes and if it included the four WHO SBE policy aims and a vision for the integration of NTDs. National NTD masterplans were reviewed and combined with in-depth interviews focusing on stakeholders’ experience with the integration of SBE in NTD programmes, and the influence of the inclusion of SBE on the NTD list. Only 18 % (2 out of 11) of 2015–2020 NTD masterplans mentioned SBE whereas all twelve countries who published masterplans for 2020–2025 included SBE and the need for an integrated approach between NTD programmes. Information on the type of activities allowing integration or the organizational aspects of an integrated approach was often missing. The extent to which the core policy aims of the WHO SBE roadmap has been elaborated differs considerably from country to country. In the interviews, several stakeholders raised the importance of improving the quality of epidemiological data to convince policy makers of its importance, to base antivenom distribution and to facilitate overall policy making. The path of improvement that has been taken since the recognition of SBE as an NTD must be continued and benefits from a closer collaboration between policymakers, researchers and healthcare workers to reduce the evidence gap and, ultimately, to improve care.</p