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Survival probability and under-five mortality predictors in Western Kenya between 2015 and 2020
Get PDFBackground information: Despite gains in reducing under-five mortality in Kenya from 52 to 41.6 deaths per 1000 live births between 2015 and 2022, the rate remains notably higher than the Sustainable Development Goal (SDG) 3 target of 25 deaths per 1000 by 2030. The impact of interventions on risk factors and socio-structural inequities have varied across regions, indicating potential effects of unaddressed issues. There is a need to further understand the key drivers of under-5 mortality in given contexts to help improve intervention effectiveness. Objective: To estimate the survival probability and determine predictors of under-five mortality in Siaya County. Methods: The study utilized secondary data from the Siaya Health Demographic Surveillance System from 2015 to 2020; semi-annual population-based longitudinal surveillance, and data analyzed in cohort design. We performed both descriptive and multivariable analyses. We used the Cox regression model to estimate survival probability and predictors of under-five mortality. We employed an adjusted hazard ratio (AHR) to measure association. Significance was declared at p < 0.0. Results: There were 24,452 live births in the study period with 1,540 (6.3%) children dying before their fifth birthday. The cumulative survival probability among children under five was 92% with children of younger age being at increased risk of death. In Cox multivariable analysis, the risk of under-five mortality increased with decreasing maternal education (aHR 1.93; 95%CI1.19, 3.10) and number of Antenatal Clinic (ANC) visits (aHR 2.1; 95%CI 1.14, 1.62). Delivery at home/way to the hospital (aHR 1.51; 95% CI 1.29, 1.77); Maternal age less than 18 years (aHR 1.34; 95% CI 1.11, 1.62); no latrine (aHR 1.22; 95% CI 1.04, 1.43) and male gender were associated with reduced survival. Conclusion: Under-five mortality in Siaya was 63/1000 live births, which is higher than the national average of 41.6/1000 live births. Gender, maternal education, number of ANC visits, maternal age, delivery in hospital, and availability of toilets at home were the main predictors of under-five mortality. These observations reinforce the need to target multiple components at the community and institutional levels to reduce childhood mortality. Such interventions may target increasing uptake of preventive healthcare and education attainment.</p
Exploring the interactions of Wolbachia pipientis & Usutu virus within British mosquito species.
No full textReactivation of multi-drug resistant tuberculosis following allogeneic stem cell transplantation in a UK centre
Get PDFBackground: Current data indicate a rising incidence of tuberculosis in the UK, affecting both UK-born and non-UK-born individuals. Although infrequent, reactivation of TB post-stem cell transplantation can be devastating. Due to limitations and paucity of available data, there is currently no evidence-based strategy for screening and prophylaxis as part of transplant work-up. Case Report: A 44-year old female of Filipino origin underwent chemotherapy treatment of an intermediate risk acute myeloid leukaemia (AML) in a UK centre. She was treated multiply for persistent fevers associated with new inflammatory changes in the right upper lung, although chest radiograph at diagnosis was normal. The patient was not screened for latent tuberculosis on entry to the UK, falling outside current age criteria for inclusion. Extensive investigation for tuberculosis was undertaken, with collaboration between haematology and infection teams, yielding negative results. The patient was therefore empirically treated for invasive fungal infection. In first complete remission, an allogenic stem cell transplant was performed. Throughout, the patient experienced unremitting high-grade fevers, treated with both antifungal and antibacterial agents. Computerised tomography showed a peri-hilar mass, with mediastinal and hilar lymphadenopathy. A spontaneous sputum sample later became smear positive for alcohol acid fast bacilli, confirmed with bronchoalveolar lavage the same week. Whole genome sequencing identified multi-drug resistance. A slow but steady clinical improvement was seen with anti-tuberculous treatment, with no evidence of AML recurrence to date. Conclusion: A multi-disciplinary team approach resulted in a favourable outcome, highlighting the value of an integrated approach to diagnosis and management of reactivation. Going forward, further research is crucial to forming evidence-based guidelines for latent tuberculosis screening and prophylaxis in stem cell transplant. Co-development of research with experts in higher burden settings, and a collaborative approach to guideline development, are essential to addressing the potential impact of changing epidemiology on clinical practice.</p
The role of informal health providers in the management of neglected tropical diseases in Liberia: A participatory investigation
Get PDFBackgroundInformal health providers (e.g. traditional and faith healers) are the first point of contact for many persons affected by skin Neglected Tropical Diseases (NTDs) due to varying beliefs and perceptions, yet, they are typically not considered within interventions designed to support persons affected. Despite this neglect, most informal providers are already using their existing roles within communities to support persons affected with care. We sought to investigate the role of informal providers in the management of NTDs in Liberia using participatory approaches to understand and identify ways to improve equitable and effective care for people affected by skin NTDs.MethodsQualitative and participatory data were collected from two purposively selected counties in Liberia: Grand Gedeh and Lofa. Key informant interviews (6), photovoice (16), and vignettes (32) with traditional and faith healers and informal drug sellers sought to understand their roles in providing care for people affected by skin NTDs. Analysis was conducted using a thematic framework approach.FindingsHealth beliefs influenced care seeking from informal providers and/or biomedical care. Informal providers provide persons affected with holistic support, including physical, psychosocial, spiritual, social and financial. This care, based on their respective underlying health beliefs and cultural norms, is driven by perceptions of poor quality of the formal or biomedical health system. During care provision, traditional and faith healers emphasised referring persons affected to the health facility as part of their roles.ConclusionUnderstanding the roles of informal providers in the management of skin NTDs is important in reducing the burden of NTDs. Informal providers are trusted by their communities and seen as a primary contact to provide care. They expressed willingness to collaborate with the formal health system. Training them on identification and referral, and basic psychosocial support would enhance early referral and collaboration between formal and informal health systems
Prospective characterisation of drug-resistant bloodstream infections in Africa and Asia (ACORN2): a surveillance network assessment
Get PDFBackground Antimicrobial resistance (AMR) is a major global health threat, but there is scarcity of laboratory surveillance data linked to clinical information to determine burden and inform interventions, especially from low-income and middle-income countries. The ACORN2 study sought to address this through prospective case-based surveillance in 19 hospitals across Africa and Asia to characterise drug-resistant infections by origin, clinical syndrome, patient age, outcome, and geographical location. Methods Patients were enrolled on selected wards and clinical data were collected daily for community-acquired infections (CAIs). Point prevalence surveys for hospital-acquired infections (HAIs) were conducted weekly. Mortality was assessed at discharge and after 28 days. Linked microbiology data were extracted from local laboratory databases. Primary descriptive analyses focused on WHO Global Antimicrobial Resistance and Use Surveillance System pathogen (target organism) bloodstream infections (BSIs). Comparisons were adjusted for clustering by site using random effects models. Findings Over 31 months, 41 907 infections were characterised from 41 032 admissions. Two-thirds were children (19 351; 47·2%) or neonates (6649; 16·2%). There were marked differences in pathogen incidence and antibiotic resistance when clinical infections were stratified by patient age category and infection origin (CAI/HAI). The highest rates of target organism AMR BSI were third-generation cephalosporin-resistant (3GC-R) Escherichia coli (718·56/100 000 blood cultured infection episodes), meticillin-resistant Staphylococcus aureus (586·89/100 000 blood cultured infection episodes), and 3GC-R Klebsiella pneumoniae (364·92/100 000 blood cultured infection episodes). In-hospital mortality was 13·1% (166/1265) in patients with target organism BSI versus 6·2% (1357/21 845) in those with negative blood cultures, p<0·0001. Interpretation ACORN2 has shown practical implementation of collecting linked clinical-laboratory AMR data in low-income and middle-income countries and identified a significant burden of WHO GLASS BSI. Adoption of the ACORN2 approach at scale might enhance use of diagnostic microbiology and improve the volume of clinical data included in national and global AMR surveillance datasets. </p
A CRITICAL REFLECTION WITH PEOPLE ON HOW URBAN DEVELOPMENT-INDUCED DISPLACEMENT AND RELOCATION PROCESS INFLUENCE THE WELLBEING OF PEOPLE RESETTLED FROM INFORMAL SETTLEMENTS IN AHMEDABAD, INDIA.
No full textNanobody-based recombinant antivenom for cobra, mamba and rinkhals bites
Get PDFEach year, snakebite envenoming claims thousands of lives and causes severe injury to victims across sub-Saharan Africa, many of whom depend on antivenoms derived from animal plasma as their sole treatment option1. Traditional antivenoms are expensive, can cause adverse immunological reactions, offer limited efficacy against local tissue damage and are often ineffective against all medically relevant snake species2. There is thus an urgent unmet medical need for innovation in snakebite envenoming therapy. However, developing broad-spectrum treatments is highly challenging owing to the vast diversity of venomous snakes and the complex and variable composition of their venoms3. Here we addressed this challenge by immunizing an alpaca and a llama with the venoms of 18 different snakes, including mambas, cobras and a rinkhals, constructing phage display libraries, and identifying high-affinity broadly neutralizing nanobodies. We combined eight of these nanobodies into a defined oligoclonal mixture, resulting in an experimental polyvalent recombinant antivenom that was capable of neutralizing seven toxin families or subfamilies. This antivenom effectively prevented venom-induced lethality in vivo across 17 African elapid snake species and markedly reduced venom-induced dermonecrosis for all tested cytotoxic venoms. The recombinant antivenom performed better than a currently used plasma-derived antivenom and therefore shows considerable promise for comprehensive, continent-wide protection against snakebites by all medically relevant African elapids.</p
Must Epidemiologically Impactful Vector Control Interventions Disrupt Mosquito Population Structure? A Case Study of a Cluster-Randomised Controlled Trial
Get PDFLarge epidemiological impacts resulting from disease vector control interventions are typically associated with significant disruption of vector populations. While vector density is a frequently measured response, impacts on demography and connectivity are suspected but rarely quantified. We analysed low-coverage whole-genome sequence data of 893 Anopheles gambiae mosquitoes collected between 2014 and 2015 during a cluster-randomized control trial (cRCT) in Burkina Faso to compare a pyrethroid-only net (ITN) with a pyrethroid-pyriproxyfen (ITN-PPF) net. Despite reductions of clinical malaria by 12% and vector density by 22% in the ITN-PPF arm, we found no significant changes in An. gambiae population genetic structure or diversity. We found remarkably low population differentiation and a lack of discernible clustering by treatment, time, or space. Nucleotide diversity and inbreeding coefficient remained stable between treatments, and genome-wide scans showed no putative signatures of selection between trial arms. These results show that ITN-PPF did not alter An. gambiae genetic structure, possibly due to large, vagile populations in West Africa. More widely, this is the first evidence that epidemiologically meaningful reductions in vector density may not impact genetic diversity or connectivity and challenges what constitutes adequate vector control in large populations.</p
Asthma: epidemiology, risk factors, and opportunities for prevention and treatment
Get PDFAsthma is characterised by variable airflow obstruction and is associated with symptoms of cough, wheeze, and dyspnoea, and with airway inflammation and hyperresponsiveness. There are approximately 300 million people with asthma worldwide. Despite a current plateau, the burden of this disease is likely to increase due to population growth, urbanisation, and ageing. Disease onset is associated with low birthweight, preterm birth, viral infections, in-utero passive smoke exposure, urbanisation, and occupational exposures. Obesity is associated with increased incidence and severity of asthma, whereas exposure to small allergen particles leads to severe disease. In adults and adolescents, inhaled corticosteroids in combination with formoterol (as anti-inflammatory reliever or as maintenance and anti-inflammatory reliever therapy) are widely recommended to control the symptoms of asthma. For children, low-dose inhaled corticosteroid is the preferred first-line treatment. Monotherapy with short-acting β-agonists is strongly discouraged. The WHO Global Action Plan for the Prevention and Control of Non-communicable Diseases includes availability of affordable combination inhalers for asthma. Co-ordinated national asthma policies, ensuring access to inhalers, have resulted in fewer hospitalisations and school and work absences. Future asthma prevalence could be reduced by good maternal and infant care, with reduction in premature births and reduction in infant respiratory infections, and by reduction in obesity at all ages.</p
A high-throughput assay to measure antibodies that block adhesion of Plasmodium falciparum infected erythrocytes to chondroitin sulfate A.
Get PDFPlacental malaria due to Plasmodium falciparum ( Pf ) is associated with adverse pregnancy outcomes. Infected erythrocytes (IEs) bind to placental chondroitin sulfate A (CSA) and antibodies that inhibit this adhesion are a potential correlate of protection. We developed a simplified adhesion inhibition assay that uses diaminofluorene to measure haemoglobin release from IEs bound to CSA. Using hyperimmune plasma, the assay demonstrated concentration-dependent inhibition of CSA adhesion. Assay performance was consistent over time with strong reproducibility ( r = 0.82), and results correlated with a published assay ( r = 0.53). In 466 Malawian pregnant women (321 P. falciparum -infected and 145 uninfected at first antenatal visit), adhesion inhibitory antibodies were significantly higher in mid-pregnancy in infected multigravidae (46.3 % IQR 23.2 %, 74.8 %) compared to infected primigravidae (9.7 % IQR 0 %, 29.3 %, p < 0.001) and in uninfected multigravidae (29.9 % IQR 8.6 %, 54.5 %) than uninfected primigravidae (15.6 % IQR 0 %, 36.4 %, p = 0.04). Similar, significant gravidity-dependent differences were observed at delivery in both infected and uninfected women. Between enrolment and delivery, changes in antibodies were similar in infected and uninfected women. Adhesion inhibitory antibodies protected against placental malaria. Of 162 women with infection at mid-pregnancy, 88 with no placental malaria had more adhesion inhibitory antibody (33.8 %, IQR 1.9 %, 63.2 %) than 74 with past placental malaria (12.5 %, IQR 0 %, 37.8 %; p = 0.002). This low cost, reproducible, and rapid high-throughput adhesion inhibition assay shows promise as a correlate of protection against placental malaria.</p