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180-day efficacy of nirsevimab against hospitalisation for respiratory syncytial virus lower respiratory tract infections in infants (HARMONIE): a randomised, controlled, phase 3b trial
Get PDFBackground: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection and hospitalisations in infants worldwide. The primary analyses of HARMONIE showed that nirsevimab reduced infant hospitalisations due to RSV-associated lower respiratory tract infection through the RSV season. This analysis aims to evaluate nirsevimab's efficacy at 180 days after dosing, a period exceeding the typical 5-month RSV season. Methods: HARMONIE is an ongoing, open-label, parallel arm, randomised, controlled, phase 3b study conducted in France, Germany, and the UK. Infants aged 12 months or younger, born at a gestational age of at least 29 weeks, were randomly assigned (1:1) to receive either a single intramuscular dose of nirsevimab (50 mg for children <5 kg or 100 mg for children ≥5 kg) or standard care (without RSV prophylaxis) before or during their first RSV season. Randomisation was electronically done, stratified by country and age-group. The primary efficacy endpoint for this analysis was the incidence of hospitalisations due to RSV-associated lower respiratory tract infection up to 180 days after nirsevimab administration or randomisation in all randomised participants. Safety up to 365 days following nirsevimab administration was also assessed. This trial is ongoing and registered with ClinicalTrials.gov, number NCT05437510. Findings: Between Aug 8, 2022, and Feb 28, 2023, 8057 infants were randomly assigned to either the nirsevimab group (n=4038) or the standard care group (n=4019). The median age at randomisation was 4·00 months (IQR 1·0–7·0; range 0·0–12·0, and 4195 (52·1%) were male and 3862 (47·9%) were female. Up to 180 days, 12 (0·3%) of 4038 infants in the nirsevimab group and 68 (1·7%) of 4019 infants in the standard care group had been hospitalised for RSV-associated lower respiratory tract infection, corresponding to a nirsevimab efficacy of 82·7% (95% CI 67·8–91·5; p<0·0001). Most participants experienced grade 1 (2759 [68·7%] of 4016 in the nirsevimab group; 2696 [67·1%] of 4018 in the standard care group) or grade 2 (1447 [36·0%] of 4016 in the nirsevimab group; 1436 [35·7%] of 4018 in the standard care group) treatment-emergent adverse events, and no apparent safety concerns were raised up to 365 days after dosing. Interpretation: Nirsevimab offers consistent and sustained protection against hospitalisation due to RSV-associated lower respiratory tract infection for at least 6 months. This finding provides global health systems greater flexibility when implementing nirsevimab, providing substantial benefit in the ongoing effort to reduce the burden of infant RSV and the potential wider public health value. Funding: Sanofi and AstraZeneca.</p
Challenges and opportunities of human resource management activities for neglected tropical diseases in Liberia
Get PDFPeople affected by skin neglected tropical diseases (NTDs) are best cared for by a motivated, well-directed, competent and well-resourced health workforce. There is limited evidence about performance management for health workforce relating to NTD tasks. We explored human resource management relating to skin NTDs, with a focus on performance management. We carried out qualitative and participatory research with health workers across health systems levels in Liberia to explore experiences of caring for people with skin NTDs and views on optimal human resource management (HRM) practices. We conducted key informant interviews with national health systems policymakers (16) and county health workers (32); in-depth interviews with health workers (36); focus group discussions with health workers (4); and photovoice with 15 community health assistants and community health promoters, purposively selected for maximum variation. All interviews and FGDs were transcribed and analysed using thematic framework approach. We found health workers often have strong intrinsic motivation to care for people affected by skin NTDs. However, this is undermined by weak HRM structures particularly in geographic areas where integrated services for NTDs requiring case management have not yet rolled out. The main challenges described include: limited awareness of NTD-related roles, and mental health support provision role, particularly at facility level, gaps in knowledge and skills (how to identify, diagnose and manage skin NTDs), irregular supervision and limited resources to deliver care. Our findings have informed collaborative development of a bundle of HRM approaches to strengthen performance of health workers caring for patients with skin NTDs, including participatory training informed by adult learning-based approaches, supportive supervision, provision of job tasks, NTD manual and related tools, essential resource provision for community health assistants and promoters (CHAs and CHPs) and non-cash awards
Mapping and quantifying travel time to define health facility catchment areas in Blantyre city in Malawi
Get PDFBackground: Mapping health facility catchment areas is important for estimating the population that uses the health facility, as a denominator for capturing spatial patterns of disease burden across space. Mapping activities to generate catchment areas are expensive exercises and are often not repeated on a regular basis. Methods: In this work, we demonstrated the generation of facility catchment areas in Blantyre, Malawi using crowdsourced road data and open-source mapping tools. We also observed travel speeds associated with different means of transportation were made in five randomly selected residential communities within Blantyre city. AccessMod version 5.8 was used to process the generated data to quantify travel time and catchment areas of health facilities in Blantyre city. Results: When these catchments are compared with georeferenced patients originating communities (based on malaria records), an average of 90.3 percent of the patients come from communities within the generated catchments. Conclusions: The study suggests that crowdsourced data resources can be used for the delineation of catchment areas and this information can confidently be used in efforts to stratify the burden of diseases such as malaria.</p
The role of pharmacists in ensuring rational antibiotic therapy within the interdisciplinary team
Get PDFThe irrational use of antibiotics is one of the biggest threats to public health, as recently highlighted in the documents from the World Health Organization. It includes both the choice of an inappropriate drug, dose, form, or length of therapy for the patient, and a lack of attention to the global cost of treatment. One of the effects of excessive and irrational use of antibiotics worldwide is the increasing number of antibiotic-resistant microorganisms. The growing number of bacterial illnesses and deaths caused by this type of pathogens is of great significance, making the consequences of incorrect antibiotic use both medical and economic. In the rationalization of pharmacotherapy, the significant role of medical staff, including pharmacists, who have extensive knowledge in the field of antibiotic therapy, is emphasized. The main goal of the rational management of antimicrobial drugs should be to improve patient treatment outcomes and minimize the medical and economic consequences of antibiotic use. Antibiotic therapy rationalization programs are needed in all healthcare facilities, both in open care and in hospital settings. Educational interventions that target primary care physicians and physicians prescribing antibiotics in hospitals are necessary. Additionally, pharmacists, being the most accessible healthcare workers, can build awareness of rational antibiotic therapy among patients.</p
Guidance for conducting and evaluating serological surveys to assess interruption of yaws transmission in the context of an eradication target
Get PDFThis document provides a summary of guidance developed for national programmes on conducting serosurveys to assess yaws transmission status, with the objective of confirming yaws seroprevalence below 1% at each of three serosurveys over a period of 3–10 years after reporting the last case of active yaws in a region. It proposes active testing of children aged 1–5 years through population-based surveys and includes recommendations on survey design, sample size determination, sampling of primary sampling units (PSUs) within an evaluation unit, sampling of households within PSUs, integration with existing public health surveys, and follow-up protocols for positive results. Geospatial analysis and sustained surveillance are recommended for accurate assessment of whether transmission interruption has been achieved.</p
An exploratory study of context and factors shaping policies for integrated management of multimorbidity in Malawi
Get PDFBackground: Malawi faces a high burden of chronic diseases. There is an increasing prevalence of multimorbidity, where individuals experience the coexistence of two or more chronic communicable and noncommunicable diseases. International organizations such as the WHO call for policy reforms that embrace integrated disease management. Our study explored the policy environment and decisions directly relevant to the delivery of integrated multimorbidity care in Malawi. Methods: This was a cross-sectional qualitative study. We used a single case-study methodology combining two sources of data: a document review of policies published between 2000 and 2023 (N = 11) and key informant interviews with policymakers (N = 13). We used the policy triangle framework to examine the context in which the policies aimed at improving management of multimorbidity were formulated, the actors involved, the policy process and the contents of the policies. Additionally, we identified barriers to the implementation of these policies. Results: Malawi advocates for integrated health promotion, screening, treatment and management of chronic conditions across key policies, with a bias towards noncommunicable disease (NCD) + NCD and NCD + human immunodeficiency virus (HIV) integration. Integrated disease management was seen as a tool to accelerate achieving global and local goals such as the Sustainable Development Goals and universal health coverage. However, the formulation and implementation of these policies have been challenged by several factors including unclear burden of multimorbidity, donor-driven priorities through vertical disease funding and inadequate number and training of healthcare workers to manage multimorbidity. Conclusions: We suggest that the timely provision of resources, creation of guidelines for multimorbidity management, building clinicians’ capacity and harmonization of donor–government goals should accompany policy rollout for integrated multimorbidity management.</p
Significant variations in tolerance to clothianidin and pirimiphos-methyl in Anopheles gambiae and Anopheles funestus populations during a dramatic malaria resurgence despite sustained indoor residual spraying in Uganda
Get PDFBackground: A dramatic malaria resurgence occurred in areas of Uganda between 2020 and 2022, coinciding with the switch to clothianidin-based formulations for indoor residual spraying. During the resurgence, Anopheles funestus sensu lato (s.l.) numbers increased more than those of Anopheles gambiae s.l., but when an alternative insecticide, pirimiphos-methyl, was reintroduced in 2023, both malaria cases and An. funestus mosquito density fell. Methods: In this study, we investigated possible causes of the resurgence by assessing (1) whether sufficient quantities of insecticide were sprayed, (2) the residual insecticide bio-efficacy against wild mosquitoes, and (3) the insecticide susceptibility of both key vector populations using standard test tube assays and wall cone assays. Results: In 2023, after adjusting for extraction efficiency, 70–80% of the houses had optimal residual concentrations of insecticides (clothianidin > 0.3g/m2; pirimiphos-methyl > 0.5g/m2), with significant variations between sampling rounds and wall types. Mud walls had the lowest residual concentration of insecticides, and the lowest observed mortality in wall cone assays, compared to burnt bricks with plaster/cement/paint. In the studies of residual bio-efficacy, by World Health Organization (WHO) definitions, An. funestus s.l. showed resistance to clothianidin (< 80% mortality) up to 11 months, and susceptibility to pirimiphos-methyl (> 90% mortality) when exposed to wall surfaces up to 7 months post-spray. In WHO tube tests, variations were observed in susceptibility to clothianidin in An. funestus s.l. populations using dose– and time–response assays (80–98% mortality). In 2022, An. gambiae s.l. was largely susceptible to the clothianidin-based formulation Sumishield (85–90% mortality), although the levels dropped slightly in 2023 (60–85% mortality), mainly in mud and pole houses. In contrast, An. gambiae s.l. was highly susceptible with mild tolerance to the pirimiphos-methyl-based formulation Actellic (~ 80% mortality), and time–response assays showed that An. gambiae s.l. populations had very low knockdown and mortality at lower exposure time compared to An. funestus s.l. Regression models showed a positive association between residual insecticide concentration (RIC) and mortality in houses sprayed with Sumishield but not Actellic houses. Conclusions: Despite the possible variations observed in spray operations, the study revealed that An. funestus s.l. exhibited a higher tolerance to clothianidin-based formulations compared to An. gambiae s.l., and this might have driven the malaria resurgence observed in Uganda. However, there are signals of An. gambiae s.l. resistance to pirimiphos-methyl, which will require further investigation and monitoring.</p
Carboprost versus Oxytocin as the first-line treatment of primary postpartum haemorrhage (COPE) protocol for a phase IV, double-blind, double-dummy, randomised controlled trial and economic analysis
Get PDFIntroduction Excessive bleeding after childbirth (postpartum haemorrhage, PPH) affects 5% of births and causes 75 000 maternal deaths worldwide annually. It is the leading cause of direct maternal deaths globally and continues to be a major cause of mortality in the UK. Oxytocin is the standard first-line treatment for atonic PPH. The PPH rate is increasing, and this may be partially related to the overuse of oxytocics in labour. Laboratory studies on myometrium suggest that repeated use of oxytocics leads to the saturation of oxytocin receptors and reduced therapeutic efficacy of oxytocin. Carboprost (a prostaglandin analogue) is usually reserved for second-line management of atonic PPH. A systematic review comparing the efficacy of carboprost and conventional uterotonics for PPH prophylaxis found that carboprost was associated with less blood loss, but around 15% of women experienced side effects. The study's aim is to compare intramuscular carboprost with intravenous oxytocin for the initial treatment of PPH. In addition, to assess the cost-effectiveness of both treatments, participants' views on the two treatments and the consent process. Methods and analysis COPE is a double-blind, double-dummy, randomised controlled trial that aims to recruit 2000 women (1:1 allocation, stratified by mode of birth) across 20 hospitals in the UK. Due to the emergency nature of PPH, COPE uses a research without prior consent (RWPC) model. Randomisation and treatment will occur if eligibility criteria are met once bleeding starts. Postnatal consent will be sought for disclosure of identifiable data and continued follow-up. Clinical efficacy outcomes will be collected at 24 and 48 hours or at hospital discharge, if sooner. Questionnaires will also be collected at 24 hours and 4 weeks postrandomisation. Cost-effectiveness will be based on the incremental cost per quality-adjusted life-year, calculated from the perspective of the NHS and personal social services. Ethics and dissemination This study has been approved by the Coventry and Warwickshire Research Ethics Committee (REC) (18/WM/0227) and the Health Research Authority. Results will be disseminated via peer-reviewed publications.</p
Epidemiological Study of Childhood Idiopathic Epilepsy from 1990 to 2021 at Global, Regional, and National Scales
Get PDFObjective: To address the long-term impact of childhood idiopathic epilepsy on health and families, and to provide epidemiological evidence for developing effective prevention and treatment strategies, this study aimed to explore the trends in incidence, deaths, and disability-adjusted life years (DALYs) of childhood idiopathic epilepsy globally and across regions from 1990 to 2021. Patients and Methods: This cross-sectional analysis utilized data from the 2021 Global Burden of Disease database, covering idiopathic epilepsy cases among children aged 0-14 years across 204 countries and regions. The study period was from September 15, 2024, to October 31, 2024. Key indicators included incidence, deaths (all-cause and specific), and DALYs, with trend analysis conducted using the exponential annual percentage change (EAPC). All analyses were stratified by region, country, gender, and sociodemographic index (SDI). Results: In 2021, there were 1,227,191 new cases of childhood idiopathic epilepsy globally (95% uncertainty interval [UI], 786,363-1,734,488). From 1990 to 2021, the total number of cases increased by 26.3% (95% UI, 6.8%-51.2%), with the incidence rising from 55.85 per 100,000 population to 60.998, and an EAPC of 0.2% (95% CI, 0.17-0.23). Deaths decreased by 29.5%, from 25,768 to 18,171, with the death rate dropping from 1.482 per 100,000 to 0.903 and an EAPC of −1.39% (95% CI, −1.48 to −1.3). DALYs decreased by 14.90%, reaching 3,564,497 in 2021 (95% UI, 2,700,944-4,753,410), with an EAPC of −0.94% (95% CI, −1.0 to −0.89). Low SDI regions bore the highest burden, with the highest death rate (1.459 per 100,000 in 2021). Regionally, tropical Latin America saw the fastest growth in incidence (EAPC 0.29), whereas Tajikistan had the highest death rate (2.766 per 100,000), and Taiwan Province of China had the highest DALY rate (99.718 per 100,000). Conclusion: Childhood idiopathic epilepsy remains a significant global health challenge, with an increasing incidence. Despite a decline in global deaths and DALYs, the disease burden in low SDI regions remains substantial. Understanding the epidemiological characteristics of childhood idiopathic epilepsy is critical for developing effective prevention and management strategies. The findings highlight the importance of targeted interventions in resource-limited settings to bridge the gap in treatment outcomes for childhood epilepsy globally.</p
Spatial distribution and population structure of the invasive Anopheles stephensi in Kenya from 2022 to 2024
Get PDFThis study analyzes the distribution, genetic diversity, and spread of Anopheles stephensi in Kenya following initial detection in December 2022. A total of 114 larval and 33 adult An. stephensi samples were confirmed in 7 of 18 surveyed counties majorly along transportation routes. Genetic analyses revealed three distinct genetic compositions with different levels of genetic diversity, suggesting multiple introductions into the country. The genetic composition of mosquitoes in most counties resembled southern Ethiopian populations, while those from Turkana showed a unique haplotype. A species distribution model predicts a more extensive range than currently observed, with low precipitation and minimal seasonal temperature variations as key factors influencing distribution. Challenges in adult sampling were noted, with larval sampling revealing co-occurrence with native Anopheles species. The findings have implications for surveillance and control strategies, emphasizing the need for continued monitoring, refined sampling techniques to inform bionomics, and cross-border collaboration.</p