69832 research outputs found
Sort by
Computationally designed haemagglutinin with nanocage plug-and-display elicits pan-H5 influenza vaccine responses.
Get PDFThe increasing spread of highly pathogenic avian influenza (HPAI) A/H5 viruses poses a pandemic threat. Circulating clade 2.3.4.4b viruses have demonstrated rapid transcontinental dissemination, extensive reassortment, epizootic spread and potential sustained mammal-to-mammal transmission, signifying a heightened risk of becoming a human pathogen of high consequence. A broadly protective, future-proof vaccine against multiple clades of H5 influenza is urgently needed for pandemic preparedness. Here, we combine two novel vaccine technologies to generate a Digitally Immune Optimised and Selected H5 antigen (DIOSvax-H5inter) displayed multivalently on the mi3 nanocage using the SpyTag003/SpyCatcher003 conjugation system. Mice immunized with DIOSvax-H5inter Homotypic Nanocages at low doses demonstrate potent, cross-clade neutralizing antibody and T cell responses against diverse H5 strains. DIOSvax-H5inter Homotypic Nanocages provide a scalable vaccine candidate with the potential for pan-H5 protection against drifted or newly emergent H5 strains. This World Health Organization preferred characteristic is essential for prospective strategic stockpiling in the pre-pandemic phase
Characteristics of malaria vector populations and transmission before a randomised controlled trial assessing the efficacy of next-generation insecticide-treated nets in Côte d'Ivoire.
Get PDFBACKGROUND: The World Health Organization (WHO) recommends mass distribution of insecticide-treated nets (ITNs) to prevent malaria transmission. Unfortunately, resistance to pyrethroids affects the efficacy of standard ITNs. To overcome this resistance and continue to protect the population, the WHO has recommended new types of ITNs that combine a pyrethroid insecticide with either a synergist (PBO) or a second insecticide, such as chlorfenapyr. This study examines the baseline characteristics of malaria vectors prior to the distribution of three types of insecticide-treated nets as part of a three-arm randomised controlled trial: Interceptor G2 (pyrethroid-chlorfenapyr), VEERALIN (pyrethroid-PBO), and MAGNet (pyrethroid only). METHODS: The study was carried out in 40 villages (grouped into 33 clusters) of Tiébissou district in central Côte d'Ivoire. To assess biting rate and biting behaviour, human landing catches were conducted hourly indoors and outdoors in six randomly selected houses in each cluster, starting at 18:00 and continuing until 08:00 the next morning. Adult mosquitoes collected were morphologically identified, and a subset of Anopheles gambiae sensu lato (s.l.) and An. funestus s.l. were speciated by quantitative PCR (qPCR). Plasmodium sporozoite infections were detected by qPCR to estimate infection rates. The entomological inoculation rate was calculated as the product of the mosquito biting rate and the sporozoite infection rate. RESULTS: Among the 10,698 mosquitoes collected, An. gambiae s.l. was the predominant species, accounting for 62.5% (n = 6683) of the catch, followed by An. funestus s.s., which accounted for 19.8% (n = 2120). Of the sub-sample of An. gambiae s.l. processed by PCR, 79.0% (n = 1291/1635) were An. coluzzii and the remaining were Anopheles gambiae s.s. Malaria vectors were highly aggressive, with an average of 14.8 bites/person/night for An. coluzzii, 2.0 b/p/n for An. gambiae s.s. and 5.4 b/p/n for An. funestus, representing an overall average of 22.2 b/p/n (95% CI 17.2-27.2 b/p/n). No significant difference was found in biting activity between indoor and outdoor environments (Z = -0.25, P = 0.803). Plasmodium sporozoite infection rate was 2.4% (95% CI 1.3-3.6%) for An. coluzzii, 1.5% (95% CI 0.3-2.6%) for An. gambiae s.s. and 2.7% (95% CI 1.2-4.3%) for An. funestus. The estimated overall entomological inoculation rate was 0.4 infected b/p/n (95% CI 0.3-0.6) and varied between 0.0 and 0.2 infective bites/person/night according to species. There was no difference observed in entomological infection rate (EIR) between capture locations (indoors versus outdoors; Z = 1.521, P = 0.128). CONCLUSIONS: This study shows that An. coluzzii and An. funestus were the main malaria vectors and showed similar biting patterns both indoors and outdoors. Anopheles funestus was found in high density in a limited number of villages. Malaria transmission was high despite universal distribution of pyrethroid-ITN in the district
Understanding the impact of the COVID-19 pandemic on households’ livelihoods in Zimbabwe: A qualitative study using the sustainable urban livelihood framework.
Get PDFBackground Pandemics such as COVID-19 affect lives in complex ways, disrupting economic activities and impacting livelihoods. The Sustainable Livelihoods Framework (SLF) helps us to understand these diverse effects beyond health impacts. We investigate the impact of the pandemic on the livelihoods of urban households in Zimbabwe. Methods We conducted a qualitative study utilizing an iteration of the SLF, the Sustainable Urban Livelihoods Framework (SULF), as our theoretical foundation for exploring urban living in Harare and Bulawayo, Zimbabwe. Between April and December 2021, we collected primary data through household surveys, focus group discussions, and interviews with the key informants. Following SULF, we performed hybrid deductive and inductive thematic analysis of the data. Results Households from various socioeconomic backgrounds have experienced notable negative effects owing to the COVID-19 pandemic. The pandemic and its related control measures, such as social distancing and lockdowns, have led to job losses, income reductions, food insecurity, and the illness or death of household members. Additionally, many individuals faced decreased access to essential health services and education, which are vital for maintaining their livelihoods. Those from lower socioeconomic backgrounds were particularly affected, struggling to sustain their livelihoods more than those from higher income brackets. Conclusions The disproportionate impact on low-income households highlights the lack of properly established social support systems stemming from the challenging political and economic conditions in Zimbabwe. While low- and middle-income countries should consider international policy recommendations, we advocate evidence-based policy decision making that carefully evaluates the effects of COVID-19 policies on health, livelihoods, and the wider economy.</ns3:p
Sustained natural immunity following SARS-CoV-2 infection against severe COVID-19 outcomes and symptomatic reinfection: analyses of national data for Brazil and Scotland.
Get PDFOBJECTIVES: SARS-CoV-2 infection provides protection against reinfection and severe COVID-19 disease; however, this protective effect may diminish over time. We assessed waning of natural immunity conferred by previous infection against severe disease and symptomatic reinfection in Brazil and Scotland. DESIGN: We undertook a test-negative design study and nested case-control analysis to estimate waning of natural immunity against severe COVID-19 outcomes and symptomatic reinfection using national linked datasets. We used logistic regression to estimate ORs with 95% CIs. A stratified analysis assessed immunity during the Omicron dominant period in Brazil. SETTING AND PARTICIPANTS: We included data from the adult populations of Brazil and Scotland from 1 June 2020 to 30 April 2022. OUTCOME MEASURES: Severe COVID-19 was defined as hospitalisation or death. Reinfection was defined as reverse-transcriptase PCR or rapid antigen test confirmed at least 120 days after primary infection. RESULTS: From Brazil, we included 30 881 873 tests and 1 301 665 severe COVID-19 outcomes, and from Scotland, we included 1 520 201 tests and 7988 severe COVID-19 outcomes. Against severe outcomes, sustained protection was observed for at least 12 months after primary SARS-CoV-2 infection with little evidence of waning: 12 months postprimary infection: Brazil OR 0.12 (95% CI 0.10 to 0.14), Scotland OR 0.03 (95% CI 0.02 to 0.04). For symptomatic reinfection, Brazilian data demonstrated evidence of waning in the 12 months following primary infection, although some residual protection remained beyond 12 months: 12 months postprimary infection: OR 0.42 (95% CI 0.40 to 0.43). The greatest reduction in risk of SARS-CoV-2 infection was in individuals with hybrid immunity (history of previous infection and vaccination), with sustained protection against severe outcomes at 12 months postprimary infection. During the Omicron dominant period in Brazil, odds of symptomatic reinfection were higher and increased more quickly over time when compared with the overall study period, although protection against severe outcomes was sustained at 12 months postprimary infection (whole study: OR 0.12 (95% CI 0.10 to 0.14); Omicron phase: OR 0.15 (95% CI 0.12 to 0.19)). CONCLUSION: Cross-national analyses demonstrate sustained protection against severe COVID-19 disease for at least 12 months following natural SARS-CoV-2 infection, with vaccination further enhancing protection. Protection against symptomatic reinfection was lower with evidence of waning, but there remained a protective effect beyond 12 months from primary infection
Prospective multicentre randomised controlled trial to assess the clinical effectiveness of the novel CirrhoCare digital therapeutic management system: a study protocol.
Get PDFINTRODUCTION: Liver cirrhosis accounts for over 10 000 deaths in the UK each year with a total loss of 60 000 quality-adjusted life-years. There is a substantial cost to the NHS of £4.5 billion, with new liver-related decompensation events accounting for the majority of this. Following an acute cirrhosis decompensating event, there is a significant risk of hospital readmission with 90-day readmission rates as high as 53%. Current care in the UK is reactive and patients are often only readmitted when they have presented acutely as an emergency with significant decompensation. METHODS AND ANALYSIS: CirrhoCare is a prospective, multicentre, randomised controlled trial comparing the CirrhoCare management system with standard-of-care for high-risk cirrhosis patients who have been discharged following an admission with acute decompensation. The CirrhoCare management system comprises a novel digital platform for use in a patient's home, designed to proactively detect the first signs of new decompensation in patients with established cirrhosis, discharged to the community. This enables a clinician to instigate early community-based care or, if needed, to triage the patient for hospital interventions.214 patients will be recruited to the CirrhoCare trial from at least 12 UK centres. Patients will be randomised on a 1:1 ratio allocation to the CirrhoCare Management System or standard of care. Participants who are randomised to CirrhoCare will receive a CirrhoCare health kit comprising a smart watch, smart phone with enabled SIM (Subscriber Identity Module) network card, blood pressure monitor, weighing scales and thermometer. Participants will take measurements every morning Monday to Friday and will be followed up for 90 days postdischarge.The primary objective of this study is to assess the clinical effectiveness of the CirrhoCare digital management system. We hypothesise that its early community-based intervention will reduce the number of unplanned hospital interventions and admissions and prevent liver-related complications when compared with standard-of-care management. ETHICS AND DISSEMINATION: CirrhoCare is a National Institute for Health and Care Research-funded study (NCT06223893). The study has UK Research Ethics Committee and Health Research Authority (HRA) approvals, with approval granted by the HRA and Health and Care Research Wales committee. The results of this study will be published in peer review journals, disseminated at international conferences as well as established Patient and Public Involvement and Engagement networks. TRIAL REGISTRATION NUMBER: ISRCTN11380842
Multiple Imputation of Missing Covariates When Using the Fine-Gray Model.
Get PDFThe Fine-Gray model for the subdistribution hazard is commonly used for estimating associations between covariates and competing risks outcomes. When there are missing values in the covariates included in a given model, researchers may wish to multiply impute them. Assuming interest lies in estimating the risk of only one of the competing events, this paper develops a substantive-model-compatible multiple imputation approach that exploits the parallels between the Fine-Gray model and the standard (single-event) Cox model. In the presence of right-censoring, this involves first imputing the potential censoring times for those failing from competing events, and thereafter imputing the missing covariates by leveraging methodology previously developed for the Cox model in the setting without competing risks. In a simulation study, we compared the proposed approach to alternative methods, such as imputing compatibly with cause-specific Cox models. The proposed method performed well (in terms of estimation of both subdistribution log hazard ratios and cumulative incidences) when data were generated assuming proportional subdistribution hazards, and performed satisfactorily when this assumption was not satisfied. The gain in efficiency compared to a complete-case analysis was demonstrated in both the simulation study and in an applied data example on competing outcomes following an allogeneic stem cell transplantation. For individual-specific cumulative incidence estimation, assuming proportionality on the correct scale at the analysis phase appears to be more important than correctly specifying the imputation procedure used to impute the missing covariates
Associations between Fecal Contamination of the Household Environment and Enteric Pathogen Detection in Children Living in Maputo, Mozambique.
Get PDFEnvironmental exposure to enteric pathogens is generally assessed using fecal indicators but relationships between markers of fecal contamination and actual exposure to enteric pathogens remain poorly characterized. We investigated whether Escherichia coli and two human fecal markers (HF183 and Mnif) in urban Mozambican household soil and drinking water were associated with detection of eight bacteria, three viruses, and three protozoa measured by multiplex reverse-transcription PCR and soil transmitted helminths assessed by microscopy in stool samples from children. We used mixed-effects logistic regression with marginal standardization to obtain a pooled estimate of the overall indicator-pathogen relationship while simultaneously estimating pathogen-specific associations that accounted for assessing multiple pathogens per sample. At least one pathogen was detected in 88% (169/192) of stool samples from children. Increasing drinking water E. coli gene concentration was associated with higher Ascaris prevalence, while human HF183 in drinking water was weakly associated with lower prevalence of the most common pathogens but was infrequently detected. No fecal marker in the soil was clearly associated with any pathogen. We did not find evidence to support human markers as reliable indicators of enteric pathogen carriage in a high-prevalence domestic setting and recommend targeting enteric pathogens directly
Signal Monitoring for Adverse Events Following Immunisation with COVID-19 Vaccines During the SARS-CoV-2 Pandemic: An Evaluation of the South African Surveillance System.
Get PDFINTRODUCTION: Monitoring of adverse events following immunisation (AEFI) is recommended for post-licensure surveillance. We investigated whether the South African surveillance system could detect signals of disproportionate reporting and whether these signals aligned with globally identified AEFI and adverse events of special interest (AESI) post-coronavirus disease-2019 (COVID-19) vaccination. METHODS: This retrospective pharmacovigilance study undertook disproportionality analysis of the National Department of Health AEFI database from the start of the COVID-19 vaccine rollout on 17 May 2021 to 31 December 2022. We complemented this with AEFI reports for vaccines not on the routine Expanded Programme on Immunisation schedule, to address potential masking of signals due to the high reporting rate of COVID-19 vaccine AEFI. RESULTS: During the study period, 3846 AEFI were reported for 37,537,009 doses of COVID-19 vaccines (BNT162b2 and Ad26.COV2.S) administered. The overall reporting rate was 10.2 per 100,000 doses, 18.1/100,000 and 7.9/100,000 for Ad26.COV2.S and BNT162b2, respectively. Comparison with other countries suggests underreporting. Disproportionate reporting signals were obtained for three and seven AEFI following BNT162b2 and Ad26.COV2.S vaccines, respectively. An additional three AEFI signals from Ad26.COV2.S emerged in the augmented dataset, indicating masking. All Ad26.COV2.S signals, and one BNT162b2 signal, appear in the vaccines' product information. Among nine AESI evaluated, myocarditis/pericarditis presented as a signal of disproportionate reporting following BNT162b2 vaccination. CONCLUSIONS: This study is one of the first from a lower-middle-income country, using a spontaneous reporting system for signal detection post-COVID-19 vaccination. Signals aligned with those reported globally. The study highlights the need to further investigate underreporting, masking, and system attributes for system strengthening
A Multiplex Serological Assay to Evaluate the Antibody Responses to a Set of Plasmodium falciparum Antigens and Their Protective Role Against Malaria in Children Aged 1.5 to 12 Years Living in a Highly Seasonal Malaria Transmission Area of Burkina Faso.
Get PDFBackground/Objectives: Understanding the seroepidemiology of P. falciparum antibody responses is essential for assessing the acquisition of natural immunity and may guide interventions that impact the acquisition of immunity against malaria in endemic areas. This study assessed the association between antigen-specific IgG responses and protection against P. falciparum infection in children from Burkina Faso. Methods: Children aged 1.5 to 12 years were followed using cross-sectional and longitudinal approaches. IgG responses to 16 P. falciparum antigens were measured using a multiplex assay and analyzed by age group and malaria infection status. Associations between antibody levels and clinical malaria risk were assessed using incidence rate ratios (IRRs), and predictive performance of antibody combinations was evaluated using ROC analysis. Results: IgG responses to AMA1, CSP, and MSP2 CH150 showed weak but significant positive correlation with age. Children aged 5-12 years had higher antibody levels than younger children aged 1.5-5 years. Uninfected children had higher levels of antibodies to EBA181 RIII-V, Rh5.1, and SEA1, while infected children had elevated AMA1 and MSP2 CH150. Anti-GLURP R2 and anti-Rh5.1 antibodies were associated with reduced malaria risk (adjusted IRR = 0.52 and 0.40, respectively). The antibody combination of AMA1, GLURP R2, and Etramp5 Ag1 showed the best predictive performance (AUC = 0.70). Conclusions: This study underlines the value of less-studied antibodies (Etramp5 Ag1, Rh5.1, HSP40 Ag1) for diagnosing and protecting against malaria, opening up prospects for the development of more effective tests and targeted vaccine approaches. The variability of responses according to age and infection status calls for further studies to optimize prevention strategies