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Advancing approaches to identify young children at risk for post-discharge mortality: Protocol for a prospective observational cohort study in Western Kenya.
Get PDFIntroduction Childhood mortality rates following hospital discharge may outpace inpatient mortality rates in some sub-Saharan African settings. Broadly validated risk assessment tools and biomarkers to identify children at risk for post-discharge mortality (PDM) are lacking. Moreover, clinical diagnoses (eg, pneumonia, sepsis, etc.) that confer high risk of PDM share a common pathobiology that culminates in endothelial dysfunction. The objectives of this study are to (1) externally validate existing risk assessment tools for PDM at 60 days and (2) test the association between a marker of endothelial dysfunction (ie, the global arginine bioavailability ratio [GABR]) and 60-day PDM among young children. Methods and analysis This is a prospective, observational cohort study of neonates (aged 0–28 days, n=1000) and infants and children (aged 1–59 months, n=1000) consecutively discharged from two hospitals in Western Kenya (ie, Jaramogi Oginga Odinga Teaching and Referral Hospital [JOOTRH] and Siaya County Referral Hospital). Candidate variables for previously developed risk assessment tools identified through a systematic review and plasma samples will be collected on the day of hospital discharge. Caregivers of participants will receive telephone calls 30 days and 60 days following discharge to ascertain participants’ vital status. Test characteristics and area under the receiver operating characteristic curves will be calculated for each risk tool to determine their discriminatory value. Risk predictiveness and calibration of each tool will also be determined. Mean and median levels of GABR will be compared between cases and matched controls, and conditional logistic regression will be used to test the association between GABR and PDM. Ethics and dissemination This protocol has received clearance from the Kenya Medical Research Institute Scientific Ethics Review Unit, the JOOTRH Ethics Research Committee, and the Emory University institutional review board. Our results will be disseminated through scientific presentations at national and international conferences and peer-reviewed publications.</p
Investigating the Feasibility, Effectiveness and Implementation Processes of a Co-created Gender-Specific Intervention for Tuberculosis in Public Health Facilities in Uganda
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Comparative genomics of blood and faecal E. coli and K. pneumoniae isolates from neonates with bloodstream infections in Tanzania
No full textBloodstream infections (BSIs) are a major cause of hospitalisation and death for children under the age of five in sub-Saharan Africa, with Gram-negative bacteria such as Klebsiella pneumoniae and Escherichia coli among the most common causative agents. These bacteria usually colonise the human gastrointestinal (GI) tract, which has been identified as a reservoir for invasive infections into extra-intestinal environments such as the urinary tract and bloodstream. In this study we used comparative genomics to compare hybrid genome assemblies of blood and faecal bacterial isolates taken from the same patients (all neonates under 19 days old) to determine if the BSI associated isolates and the GI tract associated isolates were related. Multiple pairs of highly related E. coli and K. pneumoniae were found, suggesting that translocation between the GI tract and the bloodstream occurred in multiple cases of BSI. We also highlight key virulence genes and acquired mutations that are indicative of pathogenic strains capable of BSI. These findings expand our understanding of the Gram-negative bacteria involved in BSI pathogenicity and could help guide targeted interventions to prevent future BSI infections in neonates
Biologics in IgE-mediated food allergy: A systematic review and meta-analysis of interventional studies
Get PDFBackground and aims: IgE-mediated food allergy (FA) is a major healthcare problem, affecting millions of children and adults worldwide. FA management usually involves elimination diets; however, there is increasing interest in alternative strategies that enable individualized optimal approaches. Yet, there is little consensus on the optimal strategies for managing FA. This review aimed to evaluate the effectiveness and safety of biologics, including omalizumab (OMA), as monotherapy or in combination with oral immunotherapy (OIT), for FA management. Methods: A systematic review (SR) and meta-analysis (MA) was conducted, searching 10 international electronic databases (from their start to May 2024) for randomized controlled trials (RCTs) assessing biologics in FA patients. The outcomes were desensitization, increased tolerated dose of food allergens, sustained unresponsiveness, adverse events/reactions (ARs/AEs), quality of life (QoL) measures, immunological biomarkers, and cost-effectiveness. Data were pooled using random-effects model. The study quality was assessed by the Cochrane Risk of Bias. Results: We included 11 RCTs, 2 secondary reports from earlier RCTs and 2 US National Clinical Trials with 1010 participants in total. Nine RCTs were at low, 3 at moderate, and 1 at high risk of bias. Meta-analyses demonstrated that OMA significantly improved desensitization rates and increased food tolerance thresholds compared to placebo (risk ratio (RR) 2.035, 95% CI: 1.29 to 3.22 and RR 4.90, 95% CI 2.14 to 11.20, respectively.) OMA reduced the risk of food allergic reactions (RR 0.55, 95% CI 0.36 to 0.85) without significantly increasing skin (RR = 1.09, 95% CI 0.45 to 2.65) or other adverse or severe reactions. Immunologic outcomes showed decreased hypersensitivity, a lowered allergic and inflammatory response. QoL measures improved for patients and parents with multifood oral immunotherapy. However, no studies investigated the cost-effectiveness of biologics in FA management. Conclusions: Based on the existing literature and our SR and MA, OMA can be recommended for use in carefully selected patients with IgE-mediated food allergies as monotherapy. However, patient-specific factors need to be addressed to reduce the risk of food-induced allergic reactions. OMA in combination with oral immunotherapy is recommended for cow's milk allergy. For the other foods, it will be recommended based on the results of ongoing, large RCTs in the field of biologics for food allergy. In order to recommend a wider indication for use, more research is needed to evaluate optimal treatment durations, long-term outcomes, and cost-effectiveness.</p
Examining the emergence and implementation experience of Primary Health Care Networks (PCNs) in Kenya: a qualitative process evaluation
Get PDFBackground: Kenya has identified Primary Health Care Networks (PCNs) as a key reform to strengthen Primary Health Care (PHC) delivery and enacted the Primary Health Care Act of 2023 to support their implementation. PCNs were piloted in Kisumu and Garissa counties in 2020 and rolled out nationally in 2023. However, little is known about how PCNs are being implemented across diverse county contexts. This study examined the emergence and implementation experience of the PCN reform in Kenya. Methods: We used a cross-sectional qualitative process evaluation design. We collected data at the national level and in five purposefully selected counties, using in-depth interviews (n = 65) and document reviews, between February and June 2024. Participants included stakeholders from the national level (Ministry of Health, development and implementing partners, and the Council of Governors), county level (county health departments, sub-county managers, multi-disciplinary team (MDT) members, facility managers, and frontline health workers), and community level (community health committee chairs and community health workers). We reviewed policy documents and county reports on PCN implementation for document review. We analysed the data using a thematic approach. Results: The emergence of PCNs as a policy reform was motivated by a technocratic process that identified underlying challenges in PHC service delivery and proposed PCNs as a solution, as well as political interest and support that facilitated their adoption. The implementation effectiveness of PCNs varied across the study counties, with critical aspects of PCN design, such as the establishment of MDTs and the digitisation of PCNs, being inadequately implemented. The effectiveness of PCNs’ implementation may have been constrained by capacity gaps in key foundational aspects of PHC health systems, including financing, human resources, health commodities, and information systems. Moreover, the implementation effectiveness of PCNs may have been undermined by the limited integration of key health facility functions, including financing, human resource management, health commodity supply chains, information systems, and care coordination. Conclusion: Strengthening PCN implementation in Kenya requires investment in policy capacity to ensure effective implementation. The foundational aspects of PHC systems must be reinforced. The PCN design should be refined to enhance the integration and coordination of key health facility functions.</p
Understanding Resilience in UNRWA Health Response to the Syrian Crisis: Lessons from Causal Loop Analysis
Get PDFTowards elimination of genital schistosomiasis in Africa: Outlining strategic public health objectives and measures to protect future generations
Get PDFUrogenital schistosomiasis has two gender-specific manifestations, male genital schistosomiasis (MGS) and female genital schistosomiasis (FGS). The burdens of MGS and FGS are multifaceted, encompassing financial hardship, emotional and mental health problems and sometimes social stigmatisation. Given the pernicious nature of sequelae in the genitalia, managing these chronic health conditions is expensive, difficult and problematic in resource poor settings. Key challenges include lack of epidemiological data on the burden of MGS and FGS, inadequate knowledge among primary and auxiliary health care workers, leading to misdiagnosis, incorrect treatment administration, e.g. overuse of antibiotics, and a lack of appropriate point-of-care diagnostic equipment. Prevention of MGS and FGS is therefore more preferrable, however, current preventive programmes and chemotherapy campaigns offering praziquantel are becoming more resource constrained and in most endemic areas are not reaching at-risk adults (and adolescents), sufficiently. Furthermore, there are limited prospects for adequate access to treatment in pre-school children where infections can be first acquired. Therefore, we propose three key recommendations guiding movement towards elimination of schistosomiasis as a public health problem: scaling-up praziquantel treatment for other at-risk groups; developing a targeted One Health approach to reduce environmental transmission in both humans and animals; Multi-stakeholder collaboration and community engagement for effective implementation of Water Sanitation and Hygiene (WASH) components of disease control. Whilst maintaining a school-based approach is still foundational, targeted and sustainable expansion of preventive chemotherapy to other at-risk groups within communities is needed to secure real prospects in elimination of genital schistosomiasis as a public health problem in Africa.</p
Establishing the value of regional cooperation and a critical role for regional organisations in managing future health emergencies
Get PDFThe COVID-19 pandemic revealed the failures of global, multilateral cooperation to respond and adapt to health emergencies while observing the principles of solidarity and equity. This response has raised the question of whether the global architecture for health emergencies is fit for purpose. In this Health Policy, amid proposals to reform this architecture, we consider the potential value of regional cooperation and the role regional organisations might play in delivering effective and equitable solutions to the challenges posed by public health emergencies. Drawing on our multidisciplinary perspectives and diverse experience of geographical regions, we explore the value of regional cooperation, the role of regional organisations, where they could have the greatest impact, and the major factors affecting regional cooperation and regional organisations in managing public health emergencies. As the COVID-19 pandemic reshapes our approach to health emergencies, leveraging and integrating the capabilities of regional organisations will be crucial for improving preparedness and response efforts globally.</p
The duplicated cytochrome P450 CYP6P9a/b confers cross-resistance to a mitochondrial complex I inhibitor in the African malaria vector Anopheles funestus
Get PDFMetabolic resistance to pyrethroids driven by cytochrome P450s is threatening malaria control interventions and may provide cross-resistance to insecticides with unrelated modes of action. Here, we show that cytochrome P450 genes CYP6P9a/b associated with pyrethroid resistance in Anopheles funestus also confer cross-resistance to a novel mitochondrial complex I inhibitor insecticide, code-named Sherlock. Using standard bioassays (CDC bottle bioassays, WHO cone bioassays, and WHO tunnel tests), the Sherlock and pyrethroid insecticides were tested against pyrethroid-resistant An. gambiae s.s. (Nkolondom, Cameroon) and An. funestus s.s. (Mibellon, Cameroon) and FUMOZ-R). Molecular assays (genotyping of P450 markers and qRT-PCR expression) were performed to investigate the underlying resistance mechanisms and cross-resistance in An. funestus. Field sampled strains of An. gambiae s.s. and An. funestus s.s. from Cameroon were fully susceptible to Sherlock, whereas moderate resistance was observed in the FUMOZ-R An. funestus strain. Genotypic analysis of hybrid mosquitoes demonstrated a correlation between pyrethroid-resistance markers and reduced susceptibility to Sherlock. Individuals carrying one CYP6P9a_R allele had significantly higher odds of surviving exposure to Sherlock compared to those lacking this allele, as evidenced by CDC bottle bioassays (1xDC: OR = 5.3, CI = 2.7–9.8, p < 0.0001; 5xDC: OR = 18.6, CI = 7.8–46.4, p < 0.0001)), cone bioassays (OR = 5.1, CI = 2.7–9.8, p < 0.0001), and tunnel tests (OR = 6.6, CI = 3.4–12.6 p < 0.0001). qRT-PCR analysis revealed elevated expression of CYP6P9a in surviving hybrid mosquitoes exposed to Sherlock and permethrin, as observed in CDC bottle bioassays (1xDC: FC = 24.7; 5xDC: FC = 45.6; permethrin: FC = 35.4) and cone bioassays (FC = 9.8; FC = 4.8, respectively). These findings were consistent with the patterns of CYP6P9b and the 6.5 kb insertion. The L119F_GSTe2 pyrethroid resistance marker did not confer cross-resistance to Sherlock. These findings highlight the importance of considering cross-resistance patterns in the development and deployment of new insecticides for malaria vector control.</p