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Association of mucosal neutrophil inflammation and cytokine responses with natural and experimental pneumococcal carriage in a randomised vaccine trial using experimental human pneumococcal carriage
Get PDFBackground: Mucosal inflammation is associated with increased nasal pneumococcal colonisation, but the specific mechanisms are not fully understood. We aimed to find innate immune factors associated with pneumococcal carriage using a controlled human infection model. Methods: Healthy Malawian adults participating in a randomised trial of pneumococcal conjugate vaccine (PCV13) were inoculated with one of three doses of Streptococcus pneumoniae 6B. We categorised the participants into 4 pneumococcal carriage outcome groups - no carriage; natural carriage; experimental carriage; and dual carriage. We then measured neutrophil to lymphocyte ratio (NLR) in nasal mucosa and cytokine levels in nasal lining fluid at 7 days before and 2, 7 and 14 days after inoculation. Findings: We found that 45 % of participants had no carriage, 35 % had natural carriage, 12 % experimental carriage and 8 % dual carriage. At 2- and 7-days post inoculation, all groups showed an increase in NLR compared to 7 days before inoculation, accompanied by small changes in cytokine levels. An early increase in NLR was associated with protection against experimental carriage while cytokines did not associate with carriage pattern. Conclusion: Nasal inoculation with S. pneumoniae 6B induced mild, mucosal inflammation but established carriage was not pro-inflammatory. This suggests that nasal inoculation as a vaccine strategy could be asymptomatic
Community-based snakebite risk mapping for resource prioritisation in Eastern Province, Rwanda
No full textBackground: Snakebite envenoming is a medical emergency that requires rapid access to essential medicines and well-trained personnel. In resource-poor countries, mapping snakebite incidence can help policymakers to make evidence-based decisions for resource prioritisation. This study aimed to characterise the spatial variation in snakebite risk, and in particular to identify areas of relatively high and low risk, in Eastern Province, Rwanda. Methods: Snakebite surveillance of people bitten in 2020 was conducted in Eastern Province through household visits and case verification. Geostatistical modelling and predictive mapping were applied to data from 617 villages in six districts to develop sector-level and district-level risk maps. Results: There were 1217 individuals bitten by snakes across six districts. The estimated population-weighted snakebite incidence in Eastern Province was 440 (95% predictive interval 421 to 460) cases per 100 000 people, corresponding to 13 500 (95% predictive interval 12 950 to 14 150) snakebite events per year. Two sectors in the southwest, Gashanda and Jarama, showed >1500 snakebite events per 100 000 annually. The lowest incidence was observed in the north. Conclusions: Considerable differences exist in snakebite risk between sectors in Eastern Province, with the highest risk concentrated in the southwest. Policymakers should consider prioritising resources related to snakebite prevention, essential medicines and health worker training in this region
Embedding treatment in stronger care systems
No full textA key lesson from the west Africa (2014–16) Ebola disease epidemic was that outbreak responses fail when they respond to patients through a narrow clinical lens without considering the broader community and social context of care. Here, in the second of two Series papers on the modern landscape of Ebola disease, we review progress made in the last decade to improve patient-centred care. Although the biosafety imperatives of treating Ebola disease remain, recent advances show how to mitigate these so that patients are cared for in a safe and dignified manner that encourages early treatment-seeking behaviour and provides support after the return of patients to their communities. We review advances in diagnostics, including faster Ebola disease detection via real-time RT-PCR, and consider design improvements in Ebola disease treatment units that enhance patient safety and dignity. We also review advances in care provision, such as the integration of palliative care and mobile communication into routine care, and address how greater access to research is possible through harmonised clinical trials. Finally, we discuss how strengthened community engagement and psychosocial programmes are addressing stigma and providing holistic support for survivors
How Can We Accelerate Maternal Vaccination Globally?
No full textNew maternal vaccines could reduce infant deaths at and after birth, especially in low- and middle-income countries. Work is underway to prepare for new maternal vaccines globally, and the Maternal Immunization Readiness Network for Africa and Asia will support in-country preparation in several low- and middle-income countries. However, the impact of new maternal vaccines will only be realized with supportive policy recommendations and sufficient financing for the development of maternal immunization platforms
Safety of RTS,S/AS01E malaria vaccine up to 1 year after the third dose in Ghana, Kenya, and Malawi (EPI-MAL-003): a phase 4 cohort event monitoring study: a phase 4 cohort event monitoring study
Get PDFBackground: RTS,S/AS01E has been successfully administered to over two million children since 2019 through the Malaria Vaccine Implementation Programme (MVIP). In this Article, we report the safety results of a study evaluating RTS,S/AS01E safety and effectiveness in real-world settings. Methods: EPI-MAL-003 is an ongoing phase 4 disease surveillance study with prospective cohort event monitoring and hospital-based surveillance, done in the setting of routine health-care practice in Ghana, Kenya, and Malawi and fully embedded in the MVIP. The study design was dependent on the cluster-randomised vaccine implementation. In active surveillance, we enrolled children younger than 18 months from exposed (where RTS,S/AS01E was offered) and unexposed clusters. The coprimary endpoints were the occurrence of predefined adverse events of special interest and aetiology-confirmed meningitis. We report primary and secondary safety results up to 1 year after the primary vaccine schedule (three doses). The study is registered with ClinicalTrials.gov, NCT03855995. Findings: The first participant was enrolled on March 21, 2019. The cutoff date for the current analysis was 1 year after the third RTS,S/AS01E dose for each participant. In total, 44 912 children (19 993 in Ghana, 11 990 in Kenya, and 12 929 in Malawi) were included in the analysis set for the cluster-randomised comparison: 22 508 from exposed clusters and 22 404 from unexposed clusters. Incidence rates (expressed per 100 000 person-years) for generalised convulsive seizures and intussusception were similar between vaccinated and unvaccinated children. Aetiology-confirmed meningitis was reported in two children: one case of bacterial meningitis due to Streptococcus pneumoniae in an RTS,S/AS01E-vaccinated child in the exposed clusters, and one case of viral meningitis due to human herpesvirus 6 in an unvaccinated child in the unexposed clusters. Both cases occurred within 12 months after vaccination in children in the cluster-design analysis set, leading to incidence rates of 4·1 (95% CI 0·1–23·0) per 100 000 person-years in RTS,S/AS01E-vaccinated children and 4·0 (0·1–22·6) per 100 000 person-years in unvaccinated children, and a country-adjusted incidence rate ratio (IRR) of 0·96 (95% CI 0·06–15·34; p=0·98). Cerebral malaria cases were reported for four (<0·1%) of 20 639 RTS,S/AS01E-vaccinated children in the exposed clusters and two (<0·1%) of 22 137 unvaccinated children in the unexposed clusters. These included three and two cases occurring within 12 months after the primary vaccination, in RTS,S/AS01E-vaccinated children and unvaccinated children, respectively (IRR 1·43, 95% CI 0·24–8·58, p=0·70). Incidence rates for all-cause mortality were 659·7 (95% CI 561·5–770·3) in vaccinated children versus 724·5 (622·3–838·8) in unvaccinated children, with similar incidence rates for boys and girls. Interpretation: We found no evidence of vaccination being associated with an increased risk of meningitis, cerebral malaria, or mortality among vaccinated children, and no new safety risks were identified. Funding: GSK
Systematic Review of Clinical Prediction Models for the Risk of Emergency Caesarean Births
No full textBackground: Globally, caesarean births (CB), including emergency caesareans births (EmCB), are rising. It is estimated that nearly a third of all births will be CB by 2030. Objectives: Identify and summarise the results from studies developing and validating prognostic multivariable models predicting the risk of EmCBs. Ultimately understanding the accuracy of their development, and whether they are operationalised for use in routine clinical practice. Search Strategy: Studies were identified using databases: MEDLINE, CINAHL, Cochrane Central and Scopus with a search strategy tailored to models predicting EmCBs. Selection Criteria: Prospective studies developing and validating clinical prediction models, with two or more covariates, to predict risk of EmCB. Data Collection and Analysis: Data were extracted onto a proforma using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). Results: In total, 8083 studies resulted in 56 unique prediction modelling studies and seven validating studies, with a total of 121 different predictors. Frequently occurring predictors included maternal height, maternal age, parity, BMI and gestational age. PROBAST highlighted 33 studies with low overall bias, and these all internally validated their model. Thirteen studies externally validated; only eight of these were graded an overall low risk of bias. Six models offered applications that could be readily used, but only one provided enough time to offer a planned caesarean birth (pCB). These well-refined models have not been recalibrated since development. Only one model, developed in a relatively low-risk population, with data collected a decade ago, remains useful at 36 weeks for arranging a pCB. Conclusion: To improve personalised clinical conversations, there is a pressing need for a model that accurately predicts the timely risk of an EmCB for women across diverse clinical backgrounds. Trial Registration: PROSPERO registration number: CRD42023384439
The Shock Effect: How U.S. Global Health Policy Shifts Reshape Health Systems and Research: How U.S. Global Health Policy Shifts Reshape Health Systems and Research
Get PDFThe United States (U.S.) has long played a central role in shaping global health governance, supporting United Nations agencies and funding vital programs and initiatives. However, recent political shifts, including, funding cuts, changing geopolitical priorities and a retreat from multilateralism, are threatening the stability of global health systems and research. This editorial examines the cascading consequences of these shifts, particularly for low- and middle-income countries (LMICs). The U.S. withdrawal is not just a budgetary adjustment, but a significant political disruption with unforeseen effects on global inequities. It also redirects research priorities towards security-driven agendas and undermines capacity-building efforts in LMICs. As the U.S. steps back, new actors will try to fill the vacuum, but the direction of this transition remains uncertain. Whether it paves the way for a more decentralised and equitable global health research ecosystem will depend on how global health stakeholders respond. Crucially, LMICs must seize this moment not only to replace lost funding, but to assert greater autonomy, reimagine health systems financing and build more sustainable, locally led models of research and policy leadership. This editorial calls for urgent diversification of funding sources, strengthened South-South collaborations and increased autonomy for LMICs in setting their own research priorities
A pilot investigation of bovine schistosomiasis on Unguja Island, Zanzibar, raises a new concern for elimination of urogenital schistosomiasis
Get PDFOur pilot parasitological investigation of cattle, supplemented with molecular DNA characterisation of encountered schistosomes, sheds first light upon bovine schistosomiasis on Unguja Island, Zanzibar. During February 2024, a total of 99 cattle were examined. Of these, 47 were exported animals from the Tanzanian mainland, designated for slaughter at two governmental abattoirs (Kisakasaka and Muwanda), and 52 were free-grazing animals sampled from four grazing locations within the island’s North and West-B regions. Upon visual inspection of 31 cattle carcasses at Kisakasaka for adult worms, the prevalence of bovine schistosomiasis was 51.6%; however, upon faecal miracidia hatching test (MHT) it was 80.6%. At Muwanda, only faecal MHT was used, finding a much lower prevalence of 12.5%. In free-grazing animals, the prevalence of bovine schistosomiasis by MHT was 0.0%. At Muwanda, the animal quarantine paddock was in disrepair, inclusive of a large pond now acting as a watering point. Here, numerous Bulinus forskalii sp. were found. Whilst no snails were observed to shed schistosome cercariae, molecular xenomonitoring did detect a pre-patent infection prevalence of 10.8%, with Schistosoma bovis firmly incriminated. Molecular DNA characterisation of adult schistosomes (n = 19) by real-time polymerase chain reaction (PCR) and high-resolution melt profiling, alongside DNA sequencing, also identified S. bovis, although two worms were putative S. bovis-S. mattheei hybrids. Atypical intrauterine eggs of S. bovis were noted upon microscopy of a worm pair. A broader screen of 92 miracidia confirmed S. bovis and three miracidia as S. bovis-S. mattheei hybrids. Contrasting with Pemba Island, Zanzibar, where autochthonous transmission of S. bovis can occur, bovine schistosomiasis on Unguja Island currently appears restricted to imported animals alone. However, the seminal detection of putative S. bovis-mattheei hybrids, alongside the current inadequate quarantine facilities at Muwanda, raises a new concern that such hybrid schistosomes may escape and enter the island’s hinterland. Should this happen, surveillance and control of urogenital schistosomiasis on Unguja would be compromised and further complicated. We therefore strongly recommend immediate repair and improved maintenance of governmental animal quarantine facilities. Future epidemiological surveys of imported cattle are now well justified, not only to better understand the full repertoire of hybrid schistosomes present but also to develop appropriate mitigating interventions.</p
Costs and cost-effectiveness of community health worker programs focussed on HIV, TB and malaria infectious diseases in low- and middle-income countries (2015–2024): A scoping literature review
Get PDFInfectious diseases remain a significant public health challenge in low- and middle-income countries (LMICs), with HIV, tuberculosis (TB), and malaria contributing significantly to morbidity and mortality. Community Health Workers (CHWs) play a pivotal role in addressing these diseases, yet evidence on the costs and cost-effectiveness of CHW-led interventions remains fragmented. We performed a scoping review, searching ten databases and the grey literature for original studies published between August 2015 and July 2024. Recognized search terms related to “Community Health Workers” and “Economic Evaluation(s)” in LMICs were utilized. Covidence software was employed to screen studies based on inclusion and exclusion criteria. Data on study methodology, costs and cost-related outcomes were then extracted, tabulated in a data-extraction form, and analysed using Microsoft Excel. Thirty-three studies representing 106 scenarios were included, predominantly from sub-Saharan Africa (61%). Over half the scenarios provide evidence about malaria (n = 59), followed by HIV (n = 31) and TB (n = 24). CHWs performed diverse roles, including delivering preventive education, case finding, diagnosis, treatment adherence support, counselling and referrals. The majority demonstrated that CHW programs were cost-effective compared to alternative service delivery models, most commonly facility-based care. These programs were particularly effective in improving treatment adherence and targeting high-priority populations. Costs per beneficiary ranged widely, from 26,556. This review highlights significant heterogeneity in methodologies and reporting, impeding comprehensive comparisons. Future research should emphasize standardized reporting, assess affordability, explore integrated CHW roles across multiple disease groups, and focus on generating evidence that supports priority-setting and resource allocation at the health system level.</p