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Susceptibility of Anopheles gambiae s.l. to the neonicotinoid insecticide clothianidin in eighteen sites located along the south–north transect of Benin
Get PDFBackground:
The widespread resistance of malaria vectors to traditional neurotoxic insecticides has stimulated the search for new insecticide classes with novel modes of action. For that, the present study was designed to collect data on the susceptibility of field-collected Anopheles gambiae sensu lato (s.l.) to clothianidin, a neonicotinoid insecticide used in agriculture and that recently received WHO approval for use in indoor residual spraying.
Methods:
An. gambiae s.l. were collected as larvae and pupae from 18 sites located along the south–north transect of Benin, and reared to adulthood. Female mosquitoes aged 2–5 days were exposed to clothianidin-impregnated papers (2% weight by volume (w/v) of SumiShield™ 50WG dissolved in distilled water). Due to the delayed action of clothianidin, mortality was daily recorded over 7 days. Polymerase chain reaction was used to assess the molecular species composition in the An. gambiae s.l. complex and the frequency of knockdown resistance (kdr) and insensitive acetylcholinesterase (Ace-1R) mutations.
Results:
Mortality rates of field-collected An. gambiae s.l. were very high (≥98%) between 2- and 7-day post-exposure, indicating full susceptibility to clothianidin. Molecular species identification revealed the presence of An. coluzzii (53.7%), An. gambiae sensu stricto (s.s.) (42.5%), and An. arabiensis (3.8%) in the An. gambiae s.l. complex. kdr and Ace-1R mean frequencies were 84% (95% CI 82–86) and 3% (95% CI 2–4) in An. coluzzii, and 88% (95% CI 87–90) and 4% (95% CI 3–6) in An. gambiae s.s., respectively.
Conclusions:
Findings of the present study indicates that An. gambiae s.l. populations collected along the north–south transect of Benin remain susceptible to clothianidin. This broadens the portfolio of indoor residual spraying products that the national malaria control programme can deploy to better control pyrethroid-resistant populations of vectors
The state of vaccine confidence among the general public in Eastern Europe and Central Asia.
Get PDFBACKGROUND: The COVID-19 pandemic brought global attention to challenges vaccination programs face in relation to public confidence and exposed important differences in vaccine acceptance worldwide-prompting renewed emphasis on monitoring of vaccine confidence. Most studies in Europe focus on the 27 European Union (EU) countries, with sparse evidence among the broader WHO European Region. This study extend coverage of vaccine confidence surveillance where such research is limited.
METHODS: Members of the general public in North Macedonia, Bosnia and Herzegovina, Belarus, Armenia, Georgia, and Kazakhstan were surveyed between June and July of 2023 (n = 1000 per country) using the Vaccine Confidence Index (VCI) to measure confidence in the safety, importance, effectiveness of vaccines and their compatibility with personal beliefs. Levels of vaccine confidence for vaccines in general as well as for the measles-mumps-rubella (MMR), Human Papillomavirus (HPV), seasonal influenza (flu), and Covid-19 vaccine were assessed. Bi-variate logistic regressions explore the relationship between socio-demographic characteristics and vaccine confidence in each country.
RESULTS: Across the 6 countries, the average for overall vaccine confidence was 43.7 %, lower than the 2022 EU-27 average of 49.97 %. Confidence in vaccines in general was lowest in Kazakhstan (35.5 %) and highest in Georgia (51.8 %). Confidence in specific vaccines varied greatly between the study countries, as did the levels of each dimension of confidence (perceived importance, safety, effectiveness, and compatibility with religious beliefs) and how they contributed to shaping confidence between and within each country. Relationships between socio-demographic variables were country-specific, highlighting the complexity of vaccine confidence.
CONCLUSION: With limited vaccine confidence evidence in Eastern European and Central Asian countries, more research is needed to better understand vaccine confidence levels, drivers, and trends over time. This could help inform tailored interventions to improve confidence and acceptance of existing and new vaccines
Genetic insights into antimicrobial resistance and virulence characteristics of Salmonella enterica isolated from Nile tilapia sourced from retail markets in Thailand.
Get PDFBACKGROUND: Antimicrobial-resistant Salmonella enterica in aquaculture represents a significant public health concern due to its potential transmission through the food chain. Despite these concerns, there is a notable lack of comprehensive genomic characterization of S. enterica isolates from Nile tilapia in Thailand. This study aimed to evaluate the prevalence, antimicrobial resistance (AMR) profiles, and genetic diversity of S. enterica isolated from retail-sourced Nile tilapia (Oreochromis niloticus) between May and October 2023.
METHODS: A total of 714 Nile tilapia specimens comprising liver, kidney, meat, gill, mucus, lung, and intestine tissues were collected from fish purchased at retail markets in Thailand. Salmonella isolation and identification were performed using standard microbiological methods following ISO 6579-1:2017, and serotyping was conducted using the Kauffmann-White scheme. Antimicrobial susceptibility testing was carried out using the agar dilution method in accordance with CLSI guidelines. The whole genome sequencing was performed on 14 multidrug-resistant isolates using Illumina short-read technology to characterize their genetic resistance and virulence profiles.
RESULTS: The prevalence of S. enterica was 15.4%, with the highest rates observed in gill (40.9%) and mucus (26.5%) samples. Thirty-five serovars were identified, with Escanaba, Kentucky, and Othmarschen being the most frequently detected. Resistance to oxytetracycline (33.6%), tetracycline (16.0%), and ampicillin (12.8%) were prevalent, and 19.2% of isolates exhibited multidrug resistance (MDR). Although extended-spectrum beta-lactamase (ESBL)-producing isolates accounted for only 2.4%, concerns persist regarding their increasing global prevalence. WGS of 14 MDR isolates identified over 20 resistance genes, including blaTEM-1B, blaCTX-M-55, qnrS1, and tet(A), as well as efflux pump systems (mdsABC and mdtK) and various virulence factors.
CONCLUSIONS: These isolates were classified into nine sequence types (STs), several of which have been associated with human infections. The findings underscore the necessity of stringent antimicrobial regulations and improved aquaculture practices to mitigate AMR transmission and enhance food safety
Effects of deprescribing from inhaled corticosteroids in people with cystic fibrosis: protocol for a target trial emulation using the UK CF Registry.
Get PDFINTRODUCTION: Observational data are increasingly used to study and draw causal inferences about the effects of treatments. Target trial emulation (TTE) is a framework for mitigating biases in causal investigations through specification of an observational study, targeting a specific causal research question, based on a real or hypothetical randomised controlled trial. Investigations into the effects of treatment discontinuation are of growing interest and particularly relevant in cystic fibrosis (CF), where treatment burden is high and new transformative therapies are becoming widespread. We aim to use the TTE framework to investigate the effect of discontinuation of inhaled corticosteroids (ICS) on clinical outcomes in people with CF. Our observational emulation will be based on the CF WISE (Withdrawal of Inhaled Steroids Evaluation) trial (PMID:16556691).
METHODS AND ANALYSIS: Two study designs proposed for investigating treatment effects using observational data are the prevalent new-user design and the sequential trials design. Each design uses different but related methods to address similar causal questions; however, the comparability between them remains uncertain. We will conduct a population-based cohort study using data from the UK CF Registry between January 2016 and June 2018 and apply these designs. We will specify the target trial protocol for each study design. Estimates for the causal effects of discontinuing ICS will be obtained and compared with those from the CF-WISE trial.
ETHICS AND DISSEMINATION: This study has received approval from the UK CF Registry Research Committee for both the research and access to data. Ethical approval has also been granted by the LSHTM Ethics Committee. The UK CF Registry has NHS Research Ethics Committee approval (REC reference: 24/EE/0012). The findings from this project will be submitted to peer-reviewed journals and presented at academic conferences
Effective coverage of skilled birth attendance in Ethiopia: a population-based cross-sectional study.
No full textBACKGROUND: Skilled birth attendance is among the crucial maternal health interventions for maternal and neonatal mortality reduction. The availability of core components of services at healthcare facilities and the quality-of-service provision are essential for the effective utilization of skilled birth attendance. Effective coverage measures the availability of essential components at health facilities and the quality of care delivered. This study aimed to measure effective coverage of skilled birth attendance in Ethiopia. METHODS: We applied the cascade approach to measure effective coverage, focusing on four steps up to quality-adjusted coverage as a proxy for effective coverage of skilled birth attendance. To assess the structural quality of facilities, we used the PMA service delivery assessment data in 2019. Effective coverage was defined as the product of skilled birth attendance, facility readiness score, intervention coverage (proportion who received uterotonic injection), and a process quality score. RESULTS: The crude coverage for skilled delivery attendance was 54% (95%CI; 52, 56). The average level of facility readiness to provide skilled delivery service was 72%, ranging from 17% for private and non-governmental facilities to 88% for hospitals. The uterotonic injection coverage was 42% and the mean process quality for skilled delivery service was 46%. Based on the effective coverage cascade, the input-adjusted coverage was 38%, and the intervention-adjusted coverage was 16%, and the quality-adjusted coverage was 7%. Low level of facility readiness and low quality of service explain the low effective coverage of skilled delivery attendance. Apart from the overall low level of readiness, there was variability between different levels of facilities. Though the skilled delivery attendance coverage is improving, the low level of readiness, intervention provision, and poor process quality resulted in low effective coverage. The minimum level of readiness needs to be ensured at all levels of facilities to provide skilled delivery services. The minimum level of service readiness and quality of care need to be ensured at all facilities to provide skilled birth attendance
Invisible Pursuit: A Scoping Review of Global Policy for Continuity of Care of Vulnerable Infants Under 6 Months and Their Mothers in Low- and Middle-Income Countries.
Get PDFBACKGROUND/OBJECTIVES: Worldwide, millions of infants under 6 months are at increased risk of poor growth and development, illness, and death. We investigated the coherence of global policy characteristics, vulnerability, and continuity of care, which guides the care of vulnerable infants under 6 months and their mothers.
METHODS: We conducted a scoping review according to PRISMA-ScR guidance. We included English publications with no time limit, applicable to low- and middle-income countries, sourced through Google Scholar, contacts, WHO and UNICEF databases, global networks, and agency websites. The search was conducted from August 2023 to February 2024. We identified 34 documents for review. We categorised policies into guidelines, namely, WHO evidence-based recommendations and multi-source guidance documents with implementation details. We consolidated 49 vulnerability descriptors into 28 vulnerability factors and four sub-groups. We did not assess policy quality.
RESULTS: We found rich but fragmented global policy guidance. Multiple terminologies create superficial differences and mask important ones. Growth appraisal was mostly limited to nutrition-oriented guidance and was lacking in health-centric documents. Continuity of care lacked scope and depth. WHO policies are out of sync with each other and the latest evidence on mortality risk markers. WHO procedures need to accommodate non-UN documents to leverage existing guidance potential. A living policy system to manage evidence-to-policy processes and policy interactions is needed. The WHO-INTEGRATE evidence for decision frameworks could help country-led adaptations, system-sensitive global support, and WHO methodological development.
CONCLUSIONS: There are immediate opportunities for interdisciplinary policy cooperation. Action is urgently needed to secure coherent evidence-based policies for equitable and effective care
Cabotegravir and rilpivirine for treatment of HIV infection in Africa: week 96 results from the phase 3b randomized, open-label, noninferiority CARES trial.
Get PDFEvaluation of the durable efficacy and safety of long-acting injectable therapy for HIV is needed in African populations. In a multicenter, open-label phase 3b trial, 512 African adults with HIV-1, stable on first-line oral therapy, with screening plasma viral load (VL) <50 copies ml-1 and without past virologic failure were randomized (1:1) to continue oral therapy or switch to cabotegravir (600 mg) and rilpivirine (900 mg) intramuscular injections every 8 weeks (optional 4-week oral lead-in). VL was monitored every 24 weeks. Here the primary outcome for our analysis up to 96 weeks was VL <50 copies ml-1, using the Food and Drug Administration snapshot algorithm (noninferiority margin 10%) in the intention-to-treat exposed population. At 96 weeks, 247/255 (97%) in the long-acting group and 250/257 (97%) in the oral therapy group had VL <50 copies ml-1 (difference -0.4%; 95% confidence interval -3.1% to 2.0%), demonstrating noninferiority. Adverse events of severity grade ≥3 occurred in 41/255 (16%) in the long-acting group and in 22/257 (9%) in the oral therapy group, mostly considered unrelated to the study drug; only one treatment-related adverse event in the long-acting group led to a decision to discontinue treatment (injection-site abscess). Cabotegravir and rilpivirine long-acting therapy produced durable virologic suppression, met the prespecified noninferiority endpoint compared with oral therapy and demonstrated an acceptable safety and tolerability profile. Long-acting therapy may be considered for use in African treatment programs. PACTR registration: 202104874490818
Determinants of measles second-dose vaccine coverage in the Gambia - a secondary analysis of 2019 demographic and health survey data.
Get PDFBACKGROUND: Measles remains a leading cause of vaccine-preventable mortality in Africa, despite the availability of safe and effective vaccines. The World Health Organization recommends ≥95 % coverage with two doses of a measles-containing vaccine (MCV) to achieve elimination. In The Gambia, coverage with the second dose of measles containing vaccine (MCV2) remains below this target. Understanding the factors associated with sub-optimal MCV2 coverage in The Gambia is crucial for developing strategies to improve vaccine coverage.
METHODS: We conducted a secondary analysis of data from the 2019 Gambia Demographic and Health Survey to identify determinants of MCV2 vaccination among children aged 18-35 months (n = 1010). Multivariable logistic regression was used to assess associations between MCV2 vaccination status and child-, caregiver-, and household-level factors and interactions between these factors.
RESULTS: MCV2 coverage was 67.7 %. In multivariable analysis, completion of the recommended infant vaccine schedule in the first year of life was strongly associated with MCV2 uptake (adjusted odds ratio [aOR]: 7.75; 95 % CI: 3.98-15.12). Female children in urban areas had half the odds of vaccination compared to male children (aOR: 0.49; 95 % CI 0.31-0.78); while no significant difference was observed in rural areas (aOR: 0.92; 95 % CI; 0.60-1.39). Sex also modified the association between age and vaccination status. Among children aged 18-23 months, females had lower odds of vaccination compared to similarly aged males (aOR: 0.41; 95 % CI: 0.23-0.76) but the difference was not significant among children aged 24-35 months (aOR: 0.73; 95 % CI: 0.46-1.16).
CONCLUSION: MCV2 coverage in The Gambia remains below the elimination threshold. Interventions should focus on strengthening early-life immunization, addressing gender and urban-rural disparities, and encouraging timely vaccination before 2 years of age. These findings highlight the need for context-specific strategies to close immunization gaps in The Gambia and similar settings
Provider costs of professional COVID-19 rapid antigen testing in low-income settings.
Get PDFWorld Health Organization recommends antigen rapid diagnostic tests (RDT) as point of care tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in suspected outbreaks when polymerase-chain-reaction testing is not accessible; to trace the extent of outbreaks; and in areas with widespread community transmission. Annual economic costs were estimated for professional SARS-CoV-2 testing as part of several COVID-19 testing use cases in Malawi, Nigeria and Zimbabwe. Symptom screening and antigen-based RDT was implemented as part of a multi-country, Unitaid/STAR 3ACP (Africa, Asia, America COVID-19 Prevention) funded project (April 2022-June 2023). Testing services were provided through trained health providers in outpatient departments of primary care facilities (Malawi and Nigeria) and two primary non governmental organisation (NGO) use cases separately targeting key population (KP) and the general population in Zimbabwe. Combined financial expenditure analysis and on-site micro-costing took the provider/health system perspective in 2025 US9.73 (range across sites: 29.90) in Malawi, 11.64-US10.11 (209.09) and 10.76-521 (800) in Malawi; 202.66-1,125 ( 1,762) and 161-9.73 in Malawi, 10.70 and $9.79 in Zimbabwe. Integrating COVID-19 testing into existing sites can reach people at high risk of severe illness at a reasonable cost. For resource-limited settings where programmes are threatened by low fiscal space, costs might be reduced when scaling up, through greater spreading of startup and capital costs
Optimal anthropometric discharge criteria from treatment of wasting: meta-analysis of individual patient data from 34 studies.
Get PDFBACKGROUND: Community-based treatment of acute malnutrition saves lives, but recovered children remain at risk of relapse postdischarge. Strategies to reduce this risk may include modification of anthropometric discharge criteria.
OBJECTIVES: This study aims to compare the diagnostic accuracy of anthropometric indices to reduce postdischarge relapse risk.
METHODS: We searched PubMed from inception to June 2022. We included studies that enrolled children aged 0-59 mo successfully treated for severe or moderate acute malnutrition (SAM or MAM), assessed anthropometry at discharge, and had ≥1 follow-up assessment ≤6 mo postdischarge. Pooled sensitivity and specificity for anthropometric indices at discharge over multiple cutoffs were calculated using a bivariate mixed-effects model. Area under the pooled receiver operating curve (AUC) was estimated to measure diagnostic accuracy. "Pragmatic" cutoffs were defined as those maximizing AUC given both pooled sensitivity and pooled specificity ≥0.75. Primary outcomes were SAM relapse (SAM episode after successful SAM treatment: weight-for-height Z-score (WHZ) < -3, mid-upper arm circumference (MUAC) < 11.5 cm and/or edema) and MAM relapse (MAM episode after successful MAM treatment: -3 ≤ WHZ < -2 or 11.5 cm ≤ MUAC < 12.5 cm). Exposures were WHZ, MUAC, and weight-for-age Z-score (WAZ) at discharge.
RESULTS: We included 34 studies from 16 countries contributing 21,989 children. WHZ at discharge had a higher AUC in predicting lower SAM and MAM relapse risk than MUAC or WAZ at discharge. None of the cutoffs examined met the study definition of "pragmatic." The closest "pragmatic" cutoffs suggested that WHZ cutoffs of -1.4 and -1.8 or MUAC of 12.6 and 12.7 cm had the highest sensitivity and specificity in predicting lower SAM and MAM relapse risk.
CONCLUSIONS: Relapse risk is high after successful MAM/SAM treatment. Future research can consider optimization of anthropometric discharge criteria as a strategy to reduce postdischarge relapse risk, weighing the operational and financial tradeoffs associated with any modification.
This trial was registered at PROSPERO as CRD42022342009