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Optimizing insecticide deployment strategies to delay quantitative resistance in mosquito populations
Full text linkThe large-scale use of insecticides remains a cornerstone of malaria vector control, but its long-term effectiveness is undermined by the evolution of quantitative insecticide resistance (qIR) in mosquito populations. We develop and analyze a mathematical model to identify optimal deployment strategies for two insecticides that differ only in their relative efficacy against target mosquito populations. Resistance is represented as a continuous phenotypic trait influencing mosquito fecundity and mortality, and the model accounts for successive deployment periods. Our results show that when mutational variance is high, the optimal strategy is to deploy the most effective insecticide at full coverage, regardless of its relative efficacy or pre-deployment exposure history. By contrast, when mutational variance is low, optimal deployment requires a transient reduction in coverage during early periods, with a threshold effect driven by both relative efficacy and initial exposure rates. Crucially, we find that, under the hypothesis that the first insecticide is ineffective against mosquitoes, simultaneous use of both insecticides is rarely optimal. Instead, sequential deployment–using one insecticide until resistance reaches a critical threshold, followed by optimal use of the second–delays resistance evolution and improves long-term control. These findings provide a theoretical foundation for adaptive qIR management strategies aimed at prolonging the effectiveness of insecticides in malaria vector control.</p
Multiplex PCR to Differentiate Monkeypox Virus Clades
No full textWe designed a multiplex quantitative PCR to differentiate monkeypox virus clades. For clinical samples collected in the United Kingdom and Nigeria, sensitivity was 78% (95% CI 67.67%-86.14%) and specificity 94% (95% CI 80.84%-99.30%); for samples with cycle thresholds <35, sensitivity was 98% (95% CI 91.72%-99.96%) and specificity 94% (95% CI 80.84%-99.30%).</p
13-valent pneumococcal conjugate vaccine-induced B cells produce serotype 6B but not serotype 3 capsule-specific IgG antibodies in young Malawian adults
Full text linkPneumococcal conjugate vaccine (PCV13) introduction has reduced vaccine-type carriage and disease; however pneumococcal carriage persists at high rates particularly in high-transmission settings. Serotype 3 remains a particular problem in Malawi and globally, with high carriage rates, as well as strain resistance to antibiotics and antibody-mediated killing. We studied antibody and B cell responses to PCV13 in 65 healthy Malawian adults (18–40 years) taking part in a randomized controlled trial. Serum, nasal fluid, and PBMC samples were collected before and after vaccination. Anti-capsular IgG for serotypes 3 and 6B were measured by ELISA, and capsule-specific B cells were assessed by spectral flow cytometry. PCV13 increased both serum and mucosal IgG levels, and IgG+ B cells in blood for serotype 6B but not serotype 3. The poor immunogenicity of serotype 3 capsular polysaccharide in Malawian young adults highlights the need for alternative vaccines to address persistent serotype 3 carriage and disease.</p
Rehabilitation for individuals with post-tuberculosis lung disease
Full text linkTuberculosis (TB) continues to be a global clinical and public health threat, particularly in low- and middle-income countries. TB care has primarily been centred around timely diagnosis and expanding access to treatment. Post-TB lung disease (PTLD), characterised by persistent respiratory symptoms, functional impairment and structural lung changes, is highly prevalent among TB survivors, with a prevalence ranging from 40% to 90%. This requires an effort to evaluate TB survivors in need of further care at the end of anti-TB treatment, for consideration of pulmonary rehabilitation.This review provides an overview of the current evidence and best practices in pulmonary rehabilitation for PTLD. This article aims to bridge the gap between evidence and practice, supporting tailored, multidisciplinary approaches to pulmonary rehabilitation, building on the existing experiences and challenges from diverse settings. Furthermore, this review supports the ongoing educational efforts of healthcare professionals to reframe TB care, placing long-term health and patient wellbeing at the centre of post-TB management
Immune dysregulation through longitudinal lymphocyte trajectories and their clinical determinants in hospitalized COVID-19 patients
No full textObjective: Immune dysregulation plays a pivotal role in the pathophysiology of sepsis and COVID-19, with lymphopenia emerging as a consistent marker of severity and poor prognosis. However, most existing studies have assessed lymphocyte counts at isolated time points, limiting insights into their temporal behavior and prognostic value. The dynamics of lymphocyte recovery or persistence of lymphopenia remain largely unexplored in large populations, as well as the impact of adjunctive therapies such as corticosteroids. We hypothesized that the persistence or recovery of lymphopenia may be key to understanding disease progression and predicting outcomes. Using the multinational ISARIC cohort, we investigated longitudinal lymphocyte trajectories in hospitalized patients and the clinical determinants associated with their evolution over time. Methods: We conducted a multinational prospective observational cohort study using data from the ISARIC-WHO Clinical Characterization Protocol. Patients with confirmed SARS-CoV-2 infection and at least four lymphocyte measurements during the first 28 days of hospitalization were included. We analyzed lymphocyte trajectories, Cox regression survival analyses and multivariable linear regression modelling. We also applied multistate models and joint modeling to assess the association between lymphocyte trajectories and 28-day mortality, incorporating corticosteroid use as a time-varying covariate. Results: Of 945,317 screened patients, 231,933 hospitalized adults with confirmed COVID-19 and sufficient lymphocyte data were included, with 56.6% classified as lymphopenic. Lymphopenia was independently associated with higher rates of ICU admission, organ support, and in-hospital mortality (OR = 1.52, 95% CI 1.48–1.55), and lower absolute lymphocyte counts were strongly linked to worse survival in adjusted Cox models (HR = 1.33 per 1 × 10⁹ cells/L decrease, 95% CI 1.28–1.38). Multistate modeling revealed that lymphopenic patients had a significantly higher daily transition rate to death and a shorter duration in that immune state, while corticosteroid exposure was associated with an increased likelihood of entering and remaining in lymphopenia. Joint modeling identified age, sex, and corticosteroid use as significant predictors of lower lymphocyte trajectories over time, with distinct dynamics between survivors and non-survivors. Conclusion: Lymphopenia was common and strongly associated with worse outcomes in hospitalized COVID-19 patients, with impaired recovery particularly evident in those receiving corticosteroids. These findings highlight the value of lymphocyte monitoring to inform tailored immunomodulatory strategies in sepsis and severe viral infections.</p
Advancing functional and systemic integration of HIV prevention into public health systems
No full textThe global HIV response has delivered substantial progress, largely through vertical programmes that created parallel systems of financing, governance, and service delivery. Sustaining these gains requires embedding HIV prevention more fully within routine public health systems, particularly as external funding declines and health priorities evolve. This Series paper examines how the principal functions of HIV prevention-risk-based prioritisation, demand generation, quality service provision, and continuity of use-are grounded in long-standing public health principles and essential functions. By tracing these shared roots, we show that integration is not an abandonment of HIV prevention's distinctive achievements but an evolution towards more coherent and sustainable public health systems. Although integration moves HIV prevention beyond exceptionalist approaches, it should be understood as an advance that reinforces durability and equity rather than a compromise that dilutes past gains. Drawing on literature, expert consultations, and country experiences, we compare HIV prevention functions against frameworks, such as WHO's Essential Public Health Functions. This comparison highlights integration as a technically sound and conceptually coherent path and acknowledges the financial, political, and structural legacies of vertical programming. We conclude that system-level integration can sustain HIV outcomes and strengthen overall health system resilience.</p
Challenging gender norms through participatory action research: A cross-country study of women close-to-community healthcare providers in fragile settings
No full textBackgroundDespite their critical role in delivering health services in fragile settings, women close-to-community (CTC) health providers, often face marginalisation due to deep-rooted gender norms. This study explores how participatory action research (PAR) can support these women in addressing gendered power relations and enhancing their agency in two fragile contexts.MethodsThrough a PAR study with women CTC providers in Nepal and Lebanon, a community advocacy film was co-produced and disseminated in Nepal, and a grassroots “Working Women” support group was established in Lebanon. Thematic analysis was conducted to examine the PAR process and its outcomes using the community-based participatory research (CBPR) framework.FindingsWomen CTC providers in both countries shared experiences of being undervalued, limited agency, and gendered constraints. The PAR process enabled reflection on these challenges, build solidarity, and develop context-specific interventions. In Nepal, the film-making process enhanced their visibility, allowing them to challenge community perceptions and advocate for recognition. In Lebanon, the support group created peer networks of 200 refugee women and established childcare systems. Outcomes included increased confidence, community engagement, and policy dialogue. Barriers like legal insecurity, limited resources, and safeguarding risks limited transformative changes.ConclusionPAR can act as a powerful tool to challenge and address gender norms and enhance agency among marginalised women health workers in fragile contexts. However, without structural reforms, including legal recognition, fair remuneration, and institutional integration, such approaches limit change. This study contributes to feminist global health literature by showing both the potential and limits of PAR in promoting gender-responsive approaches within health systems and its potential transformative change
Remote ischaemic conditioning improves outcomes of ischaemic stroke treated by endovascular thrombectomy: the SERIC-EVT trial
Full text linkBACKGROUND AND AIMS: Even after endovascular thrombectomy, more than half of patients with acute large vessel occlusion stroke do not achieve favourable outcomes. This study aimed to assess the efficacy and safety of remote ischaemic conditioning (RIC), a promising neuroprotective treatment, in patients with acute ischaemic stroke who received endovascular thrombectomy. METHODS: This participant-blinded, randomized controlled clinical trial was conducted at 25 hospitals. Patients were randomized 1:1 to either the RIC (cuff pressure, 200 mmHg; twice daily for 7 days) or sham RIC (60 mmHg; same procedure) groups. The primary outcome was the proportion of patients with a modified Rankin Scale score of 0-2 on Day 90. The primary safety outcome was the proportion of patients with haemorrhagic transformation within 7 days. RESULTS: In total, 498 participants were recruited. Ten patients (2.0%) were excluded because they did not receive any intervention. Thus, 488 participants (244 in the RIC group and 244 in the sham RIC group) were included in the modified intention-to-treat analysis. At 90 days, 61.1% of the patients in the RIC group and 48.9% in the sham RIC group achieved a modified Rankin Scale score of 0-2 (unadjusted risk ratio 1.25, 95% confidence interval 1.06-1.47; P = .009). The proportion of patients with haemorrhagic transformation was 37.7% and 35.2% in the RIC and sham RIC groups, respectively. CONCLUSIONS: Among patients with acute ischaemic stroke who underwent endovascular thrombectomy, intervention with RIC for 7 days, compared with sham RIC, resulted in an improved functional outcome at 90 days
Pyronaridine-artesunate for treating uncomplicated Plasmodium falciparum malaria
No full textRATIONALE: The World Health Organization (WHO) recommends artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria. Concerns about artemisinin resistance have led to global initiatives to develop new partner drugs to protect artemisinin derivatives in ACT. Pyronaridine-artesunate (PY-AS) is a novel ACT first recommended by the WHO in 2022. OBJECTIVES: To evaluate the benefits of pyronaridine-artesunate compared to alternative ACTs for treating people with uncomplicated P falciparum malaria, and to evaluate the harms of pyronaridine-artesunate and other pyronaridine treatments compared to alternative treatments. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and LILACS. We also searched ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, and the ISRCTN registry for ongoing or recently completed trials. The date of the last search was 31 July 2024. ELIGIBILITY CRITERIA: For the efficacy analysis, we included randomized controlled trials (RCTs) of pyronaridine-artesunate for treating adults and children with uncomplicated P falciparum malaria compared to any other WHO-recommended ACT. For the safety analysis, we included RCTs that used pyronaridine alone or in combination with any other antimalarials. OUTCOMES: Our primary outcomes were treatment failure at days 28 and 42 (PCR-adjusted and -unadjusted), serious adverse events, adverse events leading to withdrawal from treatment, and elevated liver function tests. Secondary outcomes included early treatment failure, other adverse events, cost-effectiveness, feasibility, and acceptability. RISK OF BIAS: We used the Cochrane RoB 1 tool to assess bias in the RCTs. SYNTHESIS METHODS: Two review authors independently extracted all data and assessed the certainty of the evidence. We meta-analyzed data to calculate risk ratios (RRs) for treatment failures between comparisons, and for safety outcomes between and across comparisons. INCLUDED STUDIES: We included 15 studies (14 RCTs reporting safety and efficacy, 1 quasi-experimental study reporting acceptability and feasibility) with 7295 participants. For a separate safety analysis, we included 10 non-randomized studies (NRS) with 11,783 participants. SYNTHESIS OF RESULTS: Efficacy analysis (RCTs) We evaluated pyronaridine-artesunate versus the following. - Artemether-lumefantrine. Pyronaridine-artesunate probably performs better for PCR-adjusted failures at day 28 (RR 0.40, 95% confidence interval (CI) 0.19 to 0.85; 5 RCTs, 3213 participants; moderate-certainty evidence); for unadjusted failures at day 28 (RR 0.27, 95% CI 0.14 to 0.52; 5 RCTs, 3314 participants; moderate-certainty evidence); and for unadjusted failures at day 42 (RR 0.61, 95% CI 0.46 to 0.82; 4 RCTs, 3080 participants; moderate-certainty evidence). For PCR-adjusted failures at day 42, there is probably little or no difference between groups (RR 0.86, 95% CI 0.49 to 1.51; 4 RCTs, 2575 participants; moderate-certainty evidence). - Artesunate-amodiaquine. Pyronaridine-artesunate may perform better for PCR-adjusted failures at day 28 (RR 0.55, 95% CI 0.11 to 2.77; 1 RCT, 1245 participants; low-certainty evidence, CI crosses line of no effect); probably performs better for unadjusted failures at day 28 (RR 0.49, 95% CI 0.30 to 0.81; 1 RCT, 1257 participants; moderate-certainty evidence); may make little or no difference for PCR-adjusted failures at day 42 (RR 0.98, 95% CI 0.20 to 4.83; 1 RCT, 1091 participants; low-certainty evidence); and probably makes little or no difference for unadjusted failures at day 42 (RR 0.98, 95% CI 0.78 to 1.23; 1 RCT, 1235 participants; moderate-certainty evidence). - Artesunate-mefloquine. Pyronaridine-artesunate may perform better for PCR-adjusted failures at day 28 (RR 0.37, 95% CI 0.13 to 1.05; 1 RCT, 1117 participants; low-certainty evidence, CI crosses line of no effect); probably performs better for unadjusted failures at day 28 (RR 0.36, 95% CI 0.17 to 0.78; 1 RCT, 1120 participants; moderate-certainty evidence); may make little or no difference for unadjusted failures at day 42 (RR 0.84, 95% CI 0.54 to 1.31; 1 RCT, 1059 participants; low-certainty evidence); but may lead to higher PCR-adjusted failures at day 42 (RR 1.80, 95% CI 0.90 to 3.57; 1 RCT, 1037 participants; low-certainty evidence). Safety analysis in adults and children (RCTs) Pyronaridine-artesunate was associated with raised liver enzymes compared to other antimalarials: alanine aminotransferase (ALT) (RR 3.59, 95% CI 1.76 to 7.33; 8 RCTs, 6669 participants; high-certainty evidence) and aspartate transaminase (AST) (RR 2.22, 95% CI 1.12 to 4.41; 8 RCTs, 6669 participants; high-certainty evidence). There was no such effect with bilirubin (RR 1.03, 95% CI 0.49 to 2.18; 7 RCTs, 6384 participants; moderate-certainty evidence). There was one reported case in which raised ALT occurred with raised bilirubin. No study reported severe drug-induced liver injury. Safety analysis in pregnant women (RCTs) We do not know if malaria testing and treatment with pyronaridine-artesunate for positive cases resulted in any difference in serious adverse effects for pregnant women compared to intermittent preventive treatment with sulfadoxine-pyrimethamine (RR 0.57, 95% CI 0.28 to 1.15; 1 RCT, 250 participants; very-low certainty evidence). Acceptability and feasibility One study determined that the adherence rate to a three-day treatment with pyronaridine-artesunate in children aged under five years was 85.3%. Limited qualitative data suggests pyronaridine-artesunate is acceptable to patients and their carers. Certainty of the evidence and limitations The studies included in this review ranged between very low-certainty and high-certainty evidence, largely due to imprecision of the effect estimate with wide CIs, and indirectness, given that children under five years were under-represented (especially in Asia). We did not identify any evidence of cost-effectiveness. AUTHORS' CONCLUSIONS: Pyronaridine-artesunate was efficacious against uncomplicated P falciparum malaria; achieved a PCR-adjusted treatment failure rate of less than 8% at days 28 and 42; and may be at least as good as artesunate-amodiaquine and artesunate-mefloquine (based on 1 RCT per drug) and may be at least as good as, or better than, artemether-lumefantrine. Pyronaridine-artesunate increases the risk of episodes of abnormally raised ALT and AST compared to other studied therapeutics. FUNDING: Tilly Fox and the Cochrane Infectious Diseases Group editorial base were funded by UK aid from the UK Government for the benefit of low- and middle-income countries (project number 300342-104, ended 31 December 2024). The views expressed do not necessarily reflect the UK Government's official policies. REGISTRATION: Protocol and previous versions available via doi.org/10.1002/14651858.CD006404, doi.org/10.1002/14651858.CD006404.pub2, doi.org/10.1002/14651858.CD006404.pub3, doi.org/10.1002/14651858.CD006404.pub4.</p
Repeated biannual cross-sectional surveys in primary schools set baseline seasonal and spatial surveillance for malaria and schistosomiasis in the Shire Valley Transformation Programme (SVTP), Malawi
Full text linkControl of malaria and schistosomiasis among school children poses a key public health challenge in Chikwawa District, Malawi. Furthermore, anticipated environmental changes from the Shire Valley Transformation Programme (SVTP), a large-scale irrigation scheme, are expected to both alter transmission of malaria and schistosomiasis. To later inform future disease surveillance and appropriate control interventions, our study sought to establish comprehensive seasonal and spatial baseline epidemiological data. Four cross-sectional surveys were undertaken in 21 primary schools, covering two wet and two dry seasons. A total of 4176 children aged 7–13 years were examined using rapid diagnostic tests for malaria, urine reagent strips with egg-filtration microscopy for urogenital schistosomiasis, and urine-Circulating Cathodic Antigen (CCA) dipsticks for intestinal schistosomiasis. The overall prevalence was 10.8% (95% CI: 9.8–11.7%) for malaria, 36.5% (95% CI: 35.1–38.0%) for urogenital schistosomiasis, and 1.9% (95% CI: 1.5–2.4%) for intestinal schistosomiasis. Co-infection prevalence of malaria and urogenital schistosomiasis was 5.2% (95% CI: 4.5–5.9%). Macrohematuria was at 5.5% (95% CI: 4.8–6.2%) while microhematuria was at 26.2% (95% CI: 24.9–27.6%). Seasonal fluctuations were noted for malaria, whereas schistosomiasis was limited, although both diseases exhibited strong spatial heterogeneity. Alarmingly, malaria exceeded 25% and urogenital schistosomiasis surpassed 50% in certain schools, thus clearly demonstrating currently unmet public health needs. These are set to become further exacerbated by forthcoming SVTP-driven environmental change; hence, we provide critical evidence to guide the Malawi Ministry of Health in strengthening surveillance and preparing integrated disease control.</p