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Genetic Mapping of Resistance: ddRADseq-Based QTL and Associated Polymorphism Conferring Resistance to Alpha-Cypermethrin in Anopheles funestus
Get PDFThe heavy reliance on pyrethroid-based interventions has largely driven insecticide resistance in malaria vectors, accelerating the spread of resistant strains, including resistant Anopheles funestus strains. The efficacy of insecticide-based interventions, especially insecticide-treated nets (ITNs), the cornerstone of malaria control and management, is threatened by the widespread occurrence of resistance, jeopardising malaria control efforts. Alpha-cypermethrin, a type II pyrethroid, is increasingly utilised in various ITN formulations, including those combined with piperonyl butoxide (PBO) and chlorfenapyr-based Interceptor G2 (IG2) nets, to enhance effectiveness against resistant mosquito populations. Therefore, understanding the molecular basis of resistance is essential to monitor and track resistance trends for an effective malaria control program. In this study, we identified a 1.4 Mb QTL on the telomeric end of the left arm of chromosome 2, conferring resistance to α-cypermethrin (rap1 QTL). Different crossing schemes and sequencing approaches were explored to determine the most effective strategy. Individual-based QTL mapping performed on segregating individuals from an isofemale family identified a QTL at the F7 generation. Higher recombination density relative to the physical genome in the F7 isofemale family, with a recombination every 240 kb, facilitated the detection of a QTL compared to the F2 family (335 kb/cM). Additionally, we exploited bulk segregant analysis (BSA) between susceptible and resistant phenotypes from the F7 isofemale family and an F7 mixed cross-family to perform cost-effective and rapid QTL-mapping discovery. The strongest signal in both independent BSA analyses overlaps with the rap1 QTL, further supporting its role in α-cypermethrin resistance. The known resistant alleles of the cytochrome P450 CYP6P9a and 6.5-kb structural variant within the rap1 QTL strongly correlate with survival to α-cypermethrin. In this study, we validated that previously developed DNA-based assays, originally designed to monitor permethrin resistance, are effective for tracking resistance to α-cypermethrin as well. Additionally, we identified candidate variants that can serve as reliable markers for monitoring α-cypermethrin resistance.</p
Evolving Through Challenges-Reflections from Intervention’s Editorial Board on the Financial Situation in the Humanitarian Sector
Get PDFWe introduce this 2025 Intervention collection of field reports, articles and personal reflections during a time of significant change, both within the journal and in the broader field of mental health and psychosocial support (MHPSS) in settings affected by conflict, displacement and other emergencies. The past year has brought about humanitarian crises that have been extremely distressing and have often had a profound impact on us, not only as professionals but also as individuals. Additionally, the increasing complexity of the global response to these crises has unfolded amid significant structural and financial challenges in our field. Despite all turmoil, Intervention journal remains committed to promoting co-learning, equitable collaboration, an inclusive evidence base and dialogue. We strongly believe that this is crucial to our mission, now more than ever
Conducting non-pandemic research during the COVID-19 pandemic
Get PDFThe COVID-19 pandemic presented unprecedented challenges to the conduct of non-pandemic research. The pandemic disrupted regulatory processes, strained health systems, and necessitated ethical recalibrations. This paper is a case study retrospectively examining the experience of conducting one non-pandemic clinical study of infant nutritional supplements in western Kenya between October 2020 and January 2024. The original study documents were reviewed to identify lessons learned, particularly those relevant to ethical and regulatory aspects of conducting non-pandemic research during a pandemic. A retrospective documentary case analysis was conducted using the archived ethics and regulatory submissions, feedback received during those submissions, study progress reports, meeting minutes, and relevant peer-reviewed literature. A framework analysis approach guided thematic coding, supported by independent dual review to ensure reliability (Cohen’s Kappa ≥0.6). Public health restrictions during the third pandemic wave, particularly at the main recruitment site, compounded delays. Adaptive measures included reduced physical contact, use of satellite recruitment centers, community engagement with Traditional Birth Attendants, and remote monitoring via digital platforms. Parallel submission to both the Ethics Review Committee and the Regulatory Authority notably expedited the overall turnaround time for approval of protocol amendments. Despite these challenges, the study achieved an impressive 91% follow-up completion rate, with 96% of scheduled home visits successfully carried out. This case study highlights how flexible, community-informed, and ethically responsive research practices can sustain clinical trials under adverse conditions. Strong stakeholder collaboration, open communication, and proactive risk mitigation were essential to maintaining study integrity and protecting participant welfare. These findings underscore the need for future research designs to embed contingency planning, community partnerships, and regulatory adaptability to ensure continuity and resilience for research conducted during public health emergencies.</p
“People here live in denial”: A qualitative study of the pervasive impact of stigma on asthma diagnosis and care in Kenya and Sudan
Get PDFEpidemiological studies show a global increase in asthma, straining healthcare systems in low- and middle-income countries. There are multiple barriers to accessing diagnosis and treatment in Sub-Saharan African countries like Kenya and Sudan such as healthcare infrastructure, diagnostic tools, healthcare workers’ capacities, and cost. Asthma can be well controlled using safe and cost-effective treatments such as inhalers. Stigma related to asthma negatively impacts treatment-seeking and adherence in higher-income settings, with limited information about such impacts in Sub-Saharan Africa. We conducted qualitative interviews and Focus Group Discussions in Kenya and Sudan to explore health systems aspects of diagnosis and management of chronic respiratory diseases. Participants included patients, primary care healthcare workers, hospitals, and community actors. Data were analysed through a framework approach; our initial analysis showed that asthma stigma was prevalent in both countries. Further analysis was using the Health, Stigma, and Discrimination Framework by Stangl. Negative perceptions about the aetiology and prognosis of asthma contribute to stigma. Anticipated, internalized stigma, and enacted stigma affects individuals with asthma, encouraging them to hide their symptoms and resist diagnosis. This contributes to delayed healthcare seeking and treatment uptake, impacting both individuals with asthma and health professionals. Overall, stigma exacerbates challenges in communicating diagnosis, managing the illness, and maintaining psychosocial health and well-being for those with asthma. Poor asthma control can exacerbate fear and stigma. Improving asthma control has the potential to reduce fear and positively influence community norms. The rollout of inhalers and spacers for asthma treatment should be accompanied by deliberate stigma reduction strategies and awareness raising at all levels of the system.</p
The Efficacy and Safety of Intra-Arterial Thrombolysis in Mechanical Thrombectomy: A Systematic Review and Meta-Analysis
No full textAbstract – Introduction: Intra-arterial thrombolysis (IAT) after mechanical thrombectomy (MT) may improve microvascular reperfusion and reduce disability in patients with ischemic stroke. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational cohort studies to investigate the efficacy and safety of MT combined with IAT for the treatment of acute ischemic stroke. Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science databases in all languages published from inception to May 30, 2025, using the search terms “stroke”, “thrombectomy”, “intra-arterial thrombolysis”. The primary efficacy outcome was excellent functional outcome (modified Rankin scale 0–1) at 90 days and the key safety outcomes were death and symptomatic intracerebral hemorrhage. Effect sizes were computed as risk ratio (RR) with random-effect or fixed-effect models. Results: Seven RCTs and 9 cohort studies with a total of 6, 258 patients met the inclusion criteria. The results of the RCTs indicated that for patients with large vessel occlusion stroke who were treated with MT and achieved successful recanalization, the subsequent administration of IAT significantly increased the chances of excellent functional outcome (mRS 0–1, RR: 1.24, 95% CI: 1.12–1.37, p < 0.0001) without increasing the risk of sICH or death. While cohort studies lacked excellent functional outcome rates, other endpoints were consistent with RCTs. The results of subgroup analysis suggested that, in patients who did not receive IVT before MT, the combination of MT and IAT significantly improved the likelihood of achieving excellent functional outcomes (RR: 1.17, 95% CI: 1.04–1.32). Conclusion: This systematic review and meta-analysis indicated that MT combined with IAT could lead to a higher opportunity of excellent functional outcome (mRS 0–1) than MT alone in acute stroke. Importantly, adding IAT was safe and did not increase the risk of symptomatic intracranial hemorrhage and death.</p
How do musculoskeletal disorders impact on quality of life in Tanzania? Results from a community-based survey
Get PDFObjectives There are little available data on the prevalence, economic and quality of life impacts of musculoskeletal disorders in sub-Saharan Africa. This lack of evidence is wholly disproportionate to the significant disability burden of musculoskeletal disorders as reported in high-income countries. Our research aimed to undertake an adequately powered study to identify, measure and value the health impact of musculoskeletal conditions in the Kilimanjaro region, Tanzania. Design A community-based cross-sectional survey was undertaken between January 2021 and September 2021. A two-stage cluster sampling with replacement and probability proportional to size was used to select a representative sample of the population. Setting The survey was conducted in 15 villages in the Hai District, Kilimanjaro region, Tanzania. Participants Economic and health-related quality of life (HRQOL) questionnaires were administered to a sample of residents (aged over 5 years old) in selected households (N=1050). There were a total of 594 respondents, of whom 153 had a confirmed musculoskeletal disorder and 441 matched controls. Almost three-quarters of those identified as having a musculoskeletal disorder were female and had an average age of 66 years. Primary and secondary outcome measures Questions on healthcare resource use, expenditure and quality of life were administered to all participants, with additional more detailed economic and quality of life questions administered to those who screened positive, indicating probable arthritis. Results There is a statistically significant reduction in HRQOL, on average 25% from a utility score of 0.862 (0.837, 0.886) to 0.636 (0.580, 0.692) for those identified as having a musculoskeletal disorder compared with those without. The attributes 'pain' and 'discomfort' were the major contributors to this reduction in HRQOL. Conclusions This research has revealed a significant impact of musculoskeletal conditions on HRQOL in the Hai district in Tanzania. The evidence will be used to guide clinical health practices, interventions design, service provisions and health promotion and awareness activities at institutional, regional and national levels.</p
Beyond malaria: can intermittent preventive treatment with sulphadoxine-pyrimethamine reduce the number of small vulnerable newborns globally?
Get PDFEfforts to reduce the global burden of small vulnerable newborns (SVNs) by scaling up existing preventive interventions must be complemented with new preventive approaches to achieve global targets. Intermittent preventive treatment with sulphadoxine-pyrimethamine (IPTp-SP) was originally designed to protect pregnant women from malaria infection, but appears to retain efficacy against low birthweight even when Plasmodium infection is absent or the parasite is highly resistant to sulphadoxine-pyrimethamine. This specific effect might occur through the antimicrobial activity of sulphadoxine-pyrimethamine against maternal genitourinary tract infections and pathogenic gut bacteria, direct effects on maternal gut physiology that might reverse environmental enteric dysfunction, or anti-inflammatory actions. Refining our understanding of the pathways underlying the protective efficacy of sulphadoxine-pyrimethamine will require mechanistic studies and placebo-controlled randomised trials of IPTp-SP in non-malarious settings. These studies will be crucial to confirm whether sulphadoxine-pyrimethamine could be considered for reducing the risk of SVNs in settings with high prevalence of SVNs and little or no malaria transmission.</p
Community engagement approaches and lessons learned: a case study of the PRECISE pregnancy cohort study in Kenya
No full textCommunity engagement (CE) has been recommended as an important ethical consideration for health research to enhance informed consent and exchange knowledge between researchers and community members. The purpose of this paper is to describe how CE was developed and delivered for the PRECISE prospective pregnancy cohort study in Kenya. PRECISE enrolled pregnant women in antenatal care, followed them up to the postpartum period, and collected data and biological samples to enable the study of placental disorders in sub-Saharan Africa. Initially CE was aimed at informing the community about the study, establishing community-wide acceptance of the research and addressing concerns about biological sample collection to facilitate participation in the study. CE later evolved to be a platform for mutual learning aiming to deepen the community’s understanding of research principles and informed consent and providing a feedback loop to researchers. We engaged diverse stakeholders including health workers and managers, local administrators, religious and traditional leaders, older women, pregnant women, non-pregnant women and men. We utilized a variety of CE approaches and tools adapting to the specific contextual factors at the study sites. Achievements included widespread understanding of informed consent and research principles, clarification of misconceptions, and dispelling of fears regarding biological sample collection. The relationship with the community was strengthened evidenced by frequent inquiries and active participation in CE activities and the research study. For effective CE, we recommend involvement of community members in the CE team and continuous and adaptive CE throughout the study period.</p
Acceptability and feasibility of integrating female genital schistosomiasis and sexual and reproductive health interventions in Kenya A demonstration study
No full textFemale genital schistosomiasis (FGS) is a neglected gynaecological condition that is a manifestation of chronic urogenital schistosomiasis. This disease has significant implications for the reproductive health and overall well-being of women and girls, especially in areas with limited access to water, sanitation, and hygiene (WASH). In Kenya, where urogenital schistosomiasis is endemic, the burden of FGS and how to best address it within existing sexual and reproductive health (SRH) services has not been fully explored. This mixed-methods study applied an implementation research approach to assess the feasibility and acceptability of integrating FGS services into routine SRH interventions across public health facilities in three high schistosomiasis endemic counties in Kenya. The intervention included implementing a minimum service package, between December 2023 and December 2024, encompassing health literacy, screening, diagnosis, and treatment. A total of 8,856 women were screened for FGS, with an overall estimated positivity rate of 27.7% (95% CI [26.7, 28.7]). A quantitative survey with a subset of 1,041 clients revealed high acceptability of integration 98.8% (95% CI [98, 99.3]). Integration enabled diagnosis and highlighted a hidden burden of FGS. Qualitative findings revealed significant gaps in knowledge and awareness, stigma-related barriers, and the absence of standardised indicators in the Kenya Health Information System (KHIS), which hampers effective data collection, reporting, and resource planning, including procurement of praziquantel. These findings show the urgent need for health system improvements, including the integration of standardised FGS indicators into the KHIS, to support surveillance, preparedness, and equitable resource distribution, the need for inclusion of FGS within medical training curricula, and for normative clinical guidance on FGS. The evidence supports scaling up FGS-SRH integration and positions MCH clinics and outreach programs as critical entry points.</p
Diagnostic accuracy of the WHO clinical staging system for detection of immunologically defined advanced HIV disease: A systematic review and meta-analysis
Get PDFIntroduction: People with advanced HIV disease face high risks of severe illness and death. CD4 testing enables timely diagnosis and appropriate care, yet access remains limited in many settings. This review investigated the diagnostic accuracy of the WHO clinical staging for identifying advanced HIV disease. Methods: We conducted a systematic review and meta-analysis of studies published between 1 January 1998 and 1 May 2024 that assessed both WHO clinical staging and CD4 counts in people living with HIV aged 5 years and older (PROSPERO: CRD42024558372). We pooled sensitivity and specificity estimates of WHO Stage 3/4 for detecting advanced HIV disease (CD4 <200 cells/μL) using bivariate random-effects meta-analysis. Risk of bias was assessed using QUADAS-2, and certainty of evidence was appraised using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). Results: Of 15,194 studies screened, 335 relevant studies were identified, from which 25 were included in evidence synthesis and 21 in the meta-analysis. Most studies were from the WHO African (19/25) and South-East Asian (5/25) regions. Risk of bias was moderate to high in 88% of studies, primarily due to issues with clinical staging assessment. Pooled sensitivity and specificity of WHO Stage 3/4 were 60.7% (95% CI: 48.0%–72.1%) and 72.4% (95% CI: 61.4%–81.3%), respectively. Specificity was significantly higher outside the African region (p < 0.001). In a population of 100,000 people living with HIV with 30% advanced HIV disease prevalence, WHO staging would miss 11,700 true advanced HIV disease cases and misclassify 19,600.Conclusions: WHO clinical staging alone shows low accuracy for detecting advanced HIV disease, risking both missed diagnoses and overtreatment. CD4 testing remains essential for accurately identifying and managing advanced HIV disease.</p