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Clinical morbidity of single or mixed schistosome species infection in two communities of southern Malawi
Get PDFAs part of a larger community-based epidemiological study entitled Hybridisation in Uro-Genital Schistosomiasis (HUGS), a parasite infection and clinical morbidity sub-study, implementing portable ultrasonography annually, was undertaken upon 701 participants from two communities in Mangochi and Nsanje Districts, southern Malawi. Our aim was to document the clinical morbidity a year after praziquantel treatment in those with previously proven human and/or zoonotic schistosomiasis, repeated a calendar year later after biannual praziquantel treatment. The median participant age was 12.0 years, with 293 (41.8%) having urinary Schistosoma haematobium egg-patent infections. Upon molecular analyses, these participants were co-infected with S. mansoni (29, 9.9%), S. mattheei (38, 13.0%), and six were infected with all three schistosome species occurring concurrently. A total of 166 participants (23.7%) had abnormal bladder wall thickness, 72 severely abnormal thickened bladder walls and 7 had bladder wall masses, among other abnormalities by ultrasonography. On the second annual follow-up, 203 participants were available (median age: 22.0 years), and of these, 27 (13.3%) presented with urinary S. haematobium egg-patent infections, with 2 (1.0%) having Schistosoma mansoni, 8 (3.9%) having Schistosoma mattheei and 2 with all species concurrently. Of these, only six participants (3.0%) had severely abnormal thickened bladder walls and other abnormalities. Overall, greater morbidity was observed in those with S. haematobium alone than in those with mixed species infections. 'This article is part of the Royal Society Science+ meeting issue 'Parasite evolution and impact in action: exploring the importance and control of hybrid schistosomes in Africa and beyond'.</p
Differential effects of dual and synergist-based insecticide-treated bed nets on pyrethroid resistance and L995F/S knockdown resistance mutation dynamics in Anopheles gambiae s.l. populations in south-western Burkina Faso
Get PDFBackground: The introduction of next-generation insecticide-treated nets (ITNs) in Burkina Faso aims to mitigate pyrethroid resistance in malaria vectors. This study evaluated the impact of different ITN types on phenotypic resistance and kdr mutation frequencies in Anopheles gambiae sensus lacto (s.l.) populations across three health districts over 3 years. Methods: Annual mosquito collections were conducted in Banfora (where pyrethroid–chlorfenapyr nets had been distributed), Gaoua (pyrethroid-only ITNs) and Orodara (pyrethroid–piperonyl butoxide [PBO] ITNs). Two populations were analysed: adult females collected directly from the field and those reared from field-collected larvae. World Health Organization (WHO) susceptibility bioassays measured 24-h mortality after exposure to 1×, 5× and 10× concentrations of deltamethrin and alphacypermethrin, with and without pre-exposure to piperonyl butoxide. Frequencies of kdr mutations L995F and L995S were determined by polymerase chain reaction (PCR). Results: High-intensity resistance was observed in each study district, with mortality consistently below 45% and not reaching WHO thresholds even at 10× doses. PBO increased mortality, indicating metabolic resistance, but failed to restore full susceptibility. L995F predominated across all districts, years and mosquito populations. L995S remained low and variable. Pyr-only nets were associated with rising L995F frequencies and lower mortality in resistance assays. Pyrethroid (Pyr)–chlorfenapyr (CFR) nets improved mortality in resistance assays without increasing kdr prevalence. Pyr–PBO nets showed partial and inconsistent efficacy, with mosquitoes having mixed patterns in resistance assays. Similar patterns between field and laboratory-reared populations were observed. Conclusions: ITN type strongly influenced resistance dynamics. Dual-active ingredient (AI) nets, particularly Pyr–CFR, appear more effective in managing resistance. Integrated resistance management combining ITN rotation, routine monitoring and complementary interventions is essential to preserve vector control efficacy.</p
Effectiveness of antenatal care delivery of intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine in the context of an integrated strategy with seasonal malaria chemoprevention in Mali and Burkina Faso
Get PDFBackground To improve uptake of intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP), a cluster-randomised implementation trial of ‘integrated IPTp-SP delivery’ through seasonal malaria chemoprevention (SMC) alongside antenatal care (ANC) was conducted in Mali and Burkina Faso. This nested study assessed ANC provider acceptability and feasibility of the integrated strategy and whether the training they received as part of the intervention (‘enhanced facilities’) improved IPTp-SP delivery effectiveness. Methods A cross-sectional survey was conducted in 20 trial facilities in each country (10 intervention/10 control) from November 2023 to January 2024, involving ANC exit interviews with pregnant women, facility audits and structured interviews with ANC providers. The primary outcome was the proportion of eligible pregnant women receiving IPTp-SP by directly observed therapy (DOT). Predictors of receiving IPTp-SP by DOT were estimated using mixed model logistic regression. ANC provider attitudes towards the integrated strategy were assessed using Likert scales. Results In Mali, 240 and 297 of 703women interviewed were eligible for SP in the intervention and control facilities, respectively, and 323 and 334 of 709women, respectively, interviewed in Burkina Faso. Delivery effectiveness of IPTp-SP was higher in the enhanced facilities in both Mali (79.2% (95% CI 74.0% to 84.3%) vs 68.7% (95% CI 63.4% to 73.9%), p=0.006) and Burkina Faso (52.3% (95% CI 46.9% to 57.8%) vs 28.7% (95% CI 23.9% to 33.6%), p<0.0001). Predictors of receiving IPTp-SP by DOT included attending a routine ANC visit in Mali, and gestational age, multiparity and a routine ANC visit in Burkina Faso. ANC providers interviewed in Mali (44) and Burkina Faso (41) thought that IPTp-SP delivery through SMC increased ANC attendance and reduced malaria cases, and that it was feasible and acceptable. Conclusions ANC provider training improved IPTp-SP delivery effectiveness, showing greater impact in Mali than in Burkina Faso. ANC providers found the integrated IPTp-SP strategy through ANC and SMC acceptable and feasible.</p
Costs and cost-effectiveness of community health worker programs on reproductive, maternal, newborn and child health in low- and middle-income countries (2015–2024): A scoping review
Get PDFCommunity Health Workers (CHWs) are vital in delivering primary health care in low- and middle-income countries (LMICs). To inform their broader rollout, this study updates a 2015 review, critically examining the costs, cost-effectiveness and affordability of reproductive, maternal, newborn and child health (RMNCH) CHW programs in LMICs. A scoping review was conducted using ten databases and grey literature, covering studies published between August 2015 and July 2024. Search terms related to “Community Health Workers” and “Economic Evaluations” were used. Studies were screened via Covidence software based on inclusion and exclusion criteria. Data on study methodology, costs, and outcomes were extracted, tabulated in Microsoft Excel, and analysed. Across 53 studies (21 about reproductive health, maternal and newborn care and 32 child health focused), covering 161 scenarios, the most common cost metrics for CHW-led interventions were cost per beneficiary (ranging from 1,547), cost per capita (ranging from 20.25), and cost per consultation (ranging from 52.91). Of 100 scenarios that assessed cost-effectiveness, the majority concluded CHWs were cost-effective, most frequently when compared against an alternative service or delivery modality, such as facility-based care, or the no-longer widely accepted threshold of a country’s gross domestic product per capita. Few studies assessed the affordability of CHW programs for government and/or partners. Evidence suggests that CHWs are often more cost-effective than alternative service or delivery modalities, particularly for child health. The evidence is however constrained by the heterogeneity of methods and reporting standards. To best guide future implementation of CHW programs, future research should focus on whether these interventions are affordable to governments and/or partners.</p
Extra-pulmonary TB: a comparison between migrants and populations born in a low-incidence country
Get PDFThe proportion of TB cases attributable to extra-pulmonary TB (EPTB) is increasing in high-income countries, including England. We sought to describe the burden of EPTB in East London, an area with a large migrant population and high TB incidence.A retrospective analysis of individuals with TB was conducted and compared to national data.1,262 patients were diagnosed with TB between 2016 and 2019. 52.7% had EPTB, 32.6% isolated pulmonary TB (PTB), and 14.7% concurrent disease. This compares to 43.8% of individuals nationally with isolated EPTB. In our cohort, of those with EPTB, 83.6% were non-UK-born (migrants). Multivariate analysis demonstrated that migrants had significantly higher odds of EPTB compared to UK-born individuals after adjusting for age and sex (adjusted odds ratio: 1.55, 95% confidence interval: 1.16–2.09, P = 0.003). Median time since entry to the UK among migrants who were diagnosed with EPTB was 11 years (interquartile range: 5–21). Treatment outcomes were worse in migrants with EPTB, mainly due to higher mortality.Our data reports a higher proportion of EPTB compared to national data. EPTB was more common in migrants than UK-born individuals.<p/
Drug-Coated Balloon Angioplasty vs Up-Front Stenting for De Novo CAD: 3-Year Follow-Up of REC-CAGEFREE I Trial
No full textBackground: Owing to the absence of a metallic scaffold, percutaneous coronary intervention (PCI) with drug-coated balloons (DCBs) may cause less chronic inflammation and potentially reduce late complications compared with drug-eluting stents (DES). However, in the REC-CAGEFREE I study, the strategy of DCB angioplasty with rescue stenting failed to achieve noninferiority to intended DES implantation for treating de novo lesions at 2 years. Objective: This study sought to investigate the 3-year outcomes of the REC-CAGEFREE I trial and assess the mid-term effects of DCBs compared with DES. Methods: REC-CAGEFREE I was an open-label, randomized, noninferiority trial conducted across 43 sites in China. After successful lesion predilation, 2,272 patients with de novo coronary artery disease (regardless of target vessel diameter) were randomly assigned (1:1) to paclitaxel-coated balloon angioplasty with the option of rescue stenting (DCB arm) vs up-front deployment of second-generation thin-strut sirolimus-eluting stents (DES arm). The primary outcome was the device-oriented composite endpoint (DOCE; including cardiovascular death, target vessel myocardial infarction [TV-MI], and clinically and physiologically indicated target lesion revascularization [CPI-TLR]) assessed in the intention-to-treat population. The extended follow-up is ongoing and will continue for up to 10 years. Results: From February 5, 2021, to May 1, 2022, 1,133 patients were randomly assigned to the DCB arm and 1,139 to the DES arm. The median diameter of devices was at 3.00 ± 0.46 mm. Rescue DES implantation after unsatisfactory DCB angioplasty was performed in 106 patients (9.4%). At 3 years, the DOCE occurred in 92 patients (8.2%) in the DCB arm and 56 (5.0%) in the DES arm (difference: 3.21%; 95% CI: 1.17%-5.26%; P = 0.002). Landmark analyses showed that the rates of difference in the DOCE at 0 to 1, 1 to 2, and 2 to 3 years were 1.69% (95% CI: 0.32%-3.06%), 1.10% (95% CI: −0.13% to 2.32%), and 0.58% (95% CI: −0.51% to 1.66%), respectively (Ptrend = 0.023). Conclusions: In patients with de novo coronary artery disease, DCB angioplasty with rescue stenting was associated with a higher rate of the DOCE compared with up-front DES implantation regarding the DOCE at 3 years.</p
“Now that the baby is out, I can be vaccinated” a qualitative study on COVID-19 vaccine hesitancy in pregnant women in Kilifi, Kenya
No full textCOVID-19 vaccines are safe and effective in pregnancy, but vaccine hesitancy limits uptake and effectiveness. This study explored COVID-19 vaccine hesitancy in pregnancy in Kilifi, coastal Kenya, to elicit reasons for vaccine hesitancy and acceptance, and to compile misconceptions around vaccination in pregnancy. Twenty-three in-depth interviews were conducted with pregnant women, mothers who had given birth in the previous 2 years and health workers (community health promoters, nurses, and supervisors). Data were analyzed using thematic template analysis based on the Vaccine Hesitancy Determinants Matrix. Concern about vaccine safety for the unborn baby was a major driver of hesitancy. Many pregnant women had limited knowledge of the potential benefits to the unborn baby, leading to postponing vaccination until after pregnancy. The initial government exclusion of pregnant women from vaccination led many to believe that vaccines were unsafe in pregnancy, long after the eligibility was revised. Aggressive promotion of the vaccine by the government was a source of mistrust and misconceptions. Integrating COVID-19 vaccination into routine antenatal care improved acceptance and development and dissemination of local guidelines boosted healthcare workers’ confidence in offering vaccines to pregnant women. Future rollouts of vaccines for pregnant women should consider vaccination within antenatal care clinics alongside other routine pregnancy vaccines to enhance vaccine acceptance.</p
Trimester-specific exposure to multiple heat indicators and adverse birth outcomes across four European countries
Get PDFThe health of pregnant women and their fetuses is increasingly challenged by abnormal heat events. Few studies have disentangled the trimester-specific effects of heat exposure during pregnancy on perinatal outcomes and examined potential differences across multiple heat indicators. This study included singleton births from multiple national and region registries across Europe: Sweden (2014-2019), Belgium (2012-2022), Italy (Lazio Region) (2001-2019), and Greece (1999-2021). We obtained 2-m air temperature, Universal Thermal Climate Index (UTCI), Wet Bulb Globe Temperature (WBGT), and Heat Index data from the ERA5 reanalysis dataset. Our study outcomes were preterm birth (PTB), stillbirth (SB), small for gestational age (SGA), and large for gestational age (LGA). Cox proportional hazard models, with gestational age as the underlying time scale, were applied to evaluate trimester-specific associations between multiple heat indicators and adverse birth outcomes. Country-specific estimates were then combined through meta-analyses. In total, 4,924,422 mother-child pairs were included in the analysis. An increase in mean temperature from the 75th to the 99th percentile in the third trimester was associated with PTB (HR = 1.51, 95% CI: 1.34-1.71), SB (HR = 1.54, 95% CI: 1.44-1.65), SGA (HR = 1.16, 95% CI: 1.11-1.20), and LGA (HR = 1.12, 95% CI: 1.07-1.17). Comparable associations were observed across heat indicators and countries for each trimester. Our findings suggest that the third trimester is a critical exposure window of vulnerability for heat during pregnancy. The comparable effect estimates among heat indicators highlight the usefulness of mean air temperature in Europe.</p
The effect of pneumococcal conjugate vaccine and pneumococcal polysaccharide vaccine on nasopharyngeal colonisation following human infection challenge with serotype 3 and serotype 6B (PREVENTING PNEUMO 2): a double-masked, randomised, controlled, phase 4 trial
Get PDFBackground Although evidence suggests some direct protection from the 13-valent pneumococcal conjugate vaccine (PCV13) against Streptococcus pneumoniae serotype 3 (Spn3), Spn3 remains a frequent cause of pneumococcal disease in the UK, potentially due to lower vaccine effect on colonisation, shorter duration of protection, or the emergence of more successful Spn3 clades. To test these hypotheses, we compared PCV13 and 23-valent pneumococcal polysaccharide vaccine (PPV23) protection against prevalent Spn3 clades. Additionally, we assessed the long-term protection offered by pneumococcal vaccines against colonisation using S pneumoniae serotype 6B (Spn6B), a serotype PCV13 protects against in the short term. Methods This double-masked, randomised, controlled, phase 4 trial recruited healthy participants aged 18–50 years in Liverpool, UK, and assigned them (2:1:2) to PCV13, PPV23, or placebo (0·9% NaCl). Participants assigned to the PPV23 group were challenged with clade Iα, and participants in PCV13 and placebo groups were subsequently randomly assigned to receive clade Iα or II Spn3. Nasal challenge with Spn3 was at 1 month and with Spn6B in a subgroup at 6 months after vaccination. Selection for this subgroup was conducted on a first-come-first-served basis, with participants who enrolled earliest being offered participation in both challenges. Recruitment for the second challenge was discontinued once the target number of participants was reached. The primary outcome was the acquisition risk of the challenge strain as detected by nasal wash culture at 2 days, 7 days, 14 days, or 23 days in the vaccine versus the placebo groups. The analysis was performed in a modified intention-to-treat population, defined as all participants who received vaccination, underwent challenge, and had at least one nasal wash sample collected after the challenge. Randomisation used a computer-generated schedule that only the unmasked team could access. The unmasked team performed vaccinations and did not perform the nasal challenges or nasal washes. The laboratory staff and participants were masked to the vaccination status. This study was prospectively registered with the EU Drug Regulating Authorities Clinical Trials Database, 2019-004742-15, the International Standard Randomised Controlled Trial Number registry, ISRCTN15728847, and ClinicalTrials.gov , NCT04974294 , and is complete. Findings This trial was conducted between July 28, 2021, and Oct 3, 2023. The analysis included 407 participants challenged with Spn3 and 243 challenged with Spn6B. 1 month after vaccination, PCV13 was associated with a non-significant reduction (16%) in Spn3 colonisation acquisition when considering both clades combined(84 [56%] of 153 participants in the PCV13 group vs 101 [65%] of 155 in the placebo group; relative risk 0·84, 95% CI 0·70–1·01; p=0·068). PCV13 was moderately protective (29%) against clade II (0·71, 0·54–0·91; p=0·0090) but was not protective against clade Iα (1·01, 0·77–1·32; p=0·95). No evidence of protection from PPV23 vaccination was found against clade Iα (0·84, 0·63–1·11; p=0·22). At 6 months, PCV13 showed a 60% relative risk reduction against Spn6B (0·40, 0·22–0·69; p=0·0020) with no evidence of protection from PPV23 (0·90, 0·60–1·34; p=0.60). There were no severe or life-threatening adverse events. Interpretation Our findings indicate partial direct protection by PCV13 against Spn3 colonisation acquisition, with differential protection against the clades and no protection by PPV23 against clade Iα. By contrast, PCV13 protected against Spn6B colonisation for at least 6 months. These findings align with epidemiological evidence, indicating that, although PCV13 vaccination against Spn6B offers sustained direct and indirect protection, its effect on Spn3 colonisation and therefore indirect protection is limited. Direct vaccination of at-risk adults might therefore be more appropriate than relying solely on herd immunity from paediatric programmes. The development of next-generation pneumococcal vaccines and further immunological analysis are needed to optimise protection against Spn3. </p
Early antiplatelet treatment for minor stroke following thrombolysis: the EAST trial
Get PDFBackground and AimsAntiplatelet treatment is recommended to start 24 h after intravenous thrombolysis due to concerns about haemorrhagic transformation. This study aimed to investigate the potential benefit of early antiplatelet after intravenous thrombolysis in minor stroke.MethodsA multicentre, double-blind, randomized trial was conducted in China between 7 August 2022 and 1 August 2024, to evaluate the efficacy and safety of early antiplatelet in acute ischaemic stroke patients presenting with mild neurological deficits, as indicated by a National Institutes of Health Stroke Scale (NIHSS) score of 0–5, who received intravenous thrombolysis. Patients were randomly assigned to receive either clopidogrel and aspirin or placebo within 6 h after intravenous thrombolysis. The primary endpoint was an excellent functional outcome at 90 days, indicated by a modified Rankin Scale (mRS) score of 0–1. Statistical analysis was based on a modified intention-to-treat population. Symptomatic intracranial haemorrhage, any intracranial haemorrhage, and major systemic bleeding were safety endpoints.ResultsThe primary endpoint was not met in this study. Of the randomly assigned 1022 patients, 995 patients were included in the modified intention-to-treat analysis (503 with early antiplatelet treatment and 492 with placebo). The primary endpoint occurred in 89.7% (451/503) of patients receiving early antiplatelet vs 89.6% (441/492) of those receiving placebo with no significant difference (odds ratio 1.00, 95% confidence interval .67–1.51, P = .99). Similar safety profiles were found between the two groups.ConclusionsAmong Chinese patients with acute minor ischaemic stroke who received intravenous thrombolysis, early antiplatelet treatment with clopidogrel plus aspirin was safe but did not improve already excellent functional outcome (mRS 0–1) at 90 days