Understanding the epidemiological parameters and transmission dynamics of Lassa fever, a significant public health threat in west Africa caused by the rodent-borne Lassa virus, is crucial for informing evidence-based interventions and outbreak response strategies. Therefore, our study aimed to collate and enhance understanding of the key epidemiological parameters of Lassa fever. We conducted a systematic review, searching PubMed and Web of Science for peer-reviewed studies published from database inception up to June 13, 2024, to compile and analyse key epidemiological parameters, mathematical models, and outbreaks of Lassa fever. English-language, peer-reviewed, original research articles were included if they reported on Lassa fever outbreak sizes, transmission models, viral evolution, transmission, natural history, severity, seroprevalence, or risk factors. Non-peer-reviewed literature was excluded. Data were extracted by two independent individuals from published literature, focusing on seroprevalence, transmissibility, epidemiological delays, and disease severity. We performed a meta-analysis to calculate pooled estimates of case-fatality ratios (CFRs) and the delay from symptom onset to hospital admission. This study is registered with PROSPERO (identifier number CRD42023393345). The database search returned 5614 potentially relevant studies, and a further 16 studies were identified from backward citation chaining. After de-duplication and exclusion, 193 publications met our inclusion criteria and provided 440 relevant parameter estimates in total. Although Lassa virus is endemic in west Africa, the spatiotemporal coverage of general-population seroprevalence estimates (ranging from 2·6% [6/232] to 58·2% [103/177]) was poor, highlighting the spatial uncertainty in Lassa fever risk. Similarly, only four basic reproduction number estimates (ranging from 1·13 to 1·40) were available. We estimated a pooled total random effect CFR of 33·5% (95% CI 25·8-42·2, I2=95%) and found potential variation in severity by geographical regions typically associated with specific Lassa virus lineages. We estimated a pooled total random effect mean symptom-onset-to-hospital-admission delay of 8·19 days (95% CI 7·31-9·06, I2=93%), but other epidemiological delays were poorly characterised in the existing literature. Our findings highlight the absence of empirical Lassa fever parameter estimates despite its high burden in west Africa. Improved surveillance approaches to capture mild cases in humans and to further cover rodent populations are needed to better understand Lassa fever transmission dynamics. Addressing these gaps is essential for developing accurate mathematical models and informing evidence-based interventions to mitigate the effect of Lassa fever on public health in endemic regions. UK Medical Research Council, National Institute for Health and Care Research, Academy of Medical Sciences, Wellcome, UK Department for Business, Energy, and Industrial Strategy, British Heart Foundation, Diabetes UK, Schmidt Foundation, Community Jameel, Royal Society, and Imperial College London. For the French translation of the abstract see Supplementary Materials section.

SummaryBackgroundInsecticide treated nets (ITNs) are the most important malaria prevention tool in Africa but the rise of pyrethroid resistance in mosquitoes is likely impeding control. WHO has recommended a novel pyrethroid–pyrrole ITN following evidence of epidemiological benefit in two cluster-randomised, controlled trials (CRTs). It remains unclear how effective more costly pyrethroid–pyrrole ITNs are compared with other tools, or whether they should be deployed when budgets are limited. We aimed to compare the epidemiological impact and cost-effectiveness of the mass distribution of pyrethroid–pyrrole ITNs relative to other ITNs over 3 years in different African settings.MethodsIn this individual-based malaria transmission dynamics modelling study we characterise the entomological impact of ITNs using data from a systematic review of experimental hut trials from across Africa. This African entomological data was used to inform an individual-based malaria transmission dynamics model, which was validated against CRT results from Benin and Tanzania. The full impact of new ITNs was quantified for trial sites and simulation was used to project impact in different settings which were included within an accessible interface (the Malaria Intervention Tool) to support National Malaria Programmes to explore how vector control tools and budgets could be allocated across regions to avert the most cases.FindingsThe model projects that distributing pyrethroid–pyrrole ITNs averted 65% (95% credible interval 48–74) of cases over 3 years in Tanzania, and 75% (28–93) in Benin. The model indicates that trials might have underestimated the benefits of switching ITNs by 12–16% over 3 years because participants stopped using trial-allocated nets. In moderate endemicity non-trial settings, pyrethroid–pyrrole ITNs are projected to reduce malaria prevalence by 25–60% and switching from pyrethroid-only ITNs is probably highly cost-effective in most locations given current prices, averting an additional 10–30% of cases.InterpretationThe benefit of pyrethroid–pyrrole ITNs varies by setting but is generally the most cost-effective indoor vector control intervention in Africa. National Malaria Programmes can strategise deployment to maximise impact. Entomological data could broadly predict epidemiological impact, although there are some inconsistencies, illustrating the challenge in capturing the dynamics across diverse settings.FundingUnitaid, Bill & Melinda Gates Foundation, the UK Medical Research Council, Wellcome Trust, and the UK Foreign, Commonwealth & Development Office.

The COVID-19 pandemic has underscored the beneficial impact of vaccines. It also highlighted the need for future investments to expedite an equitable vaccine distribution. The 100 Days Mission aims to develop and make available a new vaccine against a future pathogen with pandemic potential within 100 days of that pathogen threat being recognised. We assessed the value of this mission by estimating the impact that it could have had on the COVID-19 pandemic. Using a previously published model of SARS-CoV-2 transmission dynamics fitted to excess mortality during the COVID-19 pandemic, we projected scenarios for three different investment strategies: rapid development and manufacture of a vaccine, increasing manufacturing capacity to eliminate supply constraints, and strengthening health systems to enable faster vaccine roll-outs and global equity. Each scenario was compared against the observed COVID-19 pandemic to estimate the public health and health-economic impacts of each scenario. If countries implemented non-pharmaceutical interventions (NPIs) as they did historically, the 100 Days Mission could have averted an estimated 8·33 million deaths (95% credible interval [CrI] 7·70-8·68) globally, mostly in lower-middle income countries. This corresponds to a monetary saving of US$14·35 trillion (95% CrI 12·96-17·87) based on the value of statistical life-years saved. Investment in manufacturing and health systems further increases deaths averted to 11·01 million (95% CrI 10·60-11·49). Under an alternative scenario whereby NPIs are lifted earlier on the basis of vaccine coverage, the 100 Days Mission alone could have reduced restrictions by 12 600 days (95% CrI 12 300-13 100) globally while still averting 5·76 million deaths (95% CrI 4·91-6·81). Our findings show the value of the 100 Days Mission and how these can be amplified through improvements in manufacturing and health systems equity. However, these investments must be enhanced by prioritising a more equitable global vaccine distribution. Schmidt Science Fellowship in partnership with the Rhodes Trust, WHO, UK Medical Research Council, Coalition for Epidemic Preparedness Innovations.

SummaryBackgroundImmune responses induced by several important vaccines differ between populations, with reduced responses in low-income and rural settings compared with high-income and urban settings. BCG immunisation boosts immune responses to some unrelated vaccines in high-income populations. We aimed to test the hypothesis that BCG revaccination can enhance responses to unrelated vaccines in Ugandan schoolchildren.MethodsWe conducted an open-label, randomised controlled trial to compare the effects of BCG revaccination versus no BCG revaccination on the immunogenicity of subsequent unrelated vaccines among adolescents aged 13–17 years who are participants in an urban Ugandan birth cohort study, in which BCG vaccination was documented at birth. Participants were excluded if they had received any of the trial vaccines or related agents when aged 5 years or older. Computer-generated 1:1 randomisation was implemented in REDCap. Participants were excluded if they were concurrently enrolled in other trials; had a clinically significant history of immunodeficiency, or serious psychiatric conditions or moderate to severe acute illnesses; were taking immunosuppressive medications; had allergies to vaccine components, a predisposition towards developing keloid scarring; positive HIV tests or pregnancy tests; were female participants who were lactating; or if they planned to use investigational drugs, vaccines, blood products, or any combination thereof. Trial participants assigned to the BCG revaccination group received the live parenteral BCG-Russia vaccine (Serum Institute of India, Pune, India; 0·1 mL intradermally, right upper arm) at week 0. All participants received yellow fever vaccine (YF-17D; Sanofi Pasteur, Lyon, France; 0·5 mL intramuscularly, left upper arm), live oral typhoid vaccine (Ty21a; PaxVax, London, UK; one capsule per day taken for three alternate days), and quadrivalent virus-like particle human papillomavirus (HPV) vaccine (Merck, Rahway, NJ, USA; 0·5 mL intramuscularly, left upper arm) at week 4; and toxoid vaccines (tetanus–diphtheria; Serum Institute of India; 0·5 mL intramuscularly, left upper arm) and an HPV booster at week 28. An additional HPV vaccination at week 8 was provided to female participants older than 14 years who had not previously been vaccinated. The primary outcomes were yellow fever neutralising antibody titres at 4 weeks post-YF-17D vaccination, Salmonella enterica serovar Typhi (henceforth S Typhi) O-lipopolysaccharide (O:LPS)-specific IgG concentration at 4 weeks post-Ty21a vaccination, and HPV-16 and HPV-18 L1 protein-specific IgG concentration at 4 weeks post-HPV vaccination. Primary outcome assays were conducted at week 8, and at week 52 for tetanus–diphtheria. We conducted an intention-to-treat analysis comparing log-transformed outcomes between trial groups, with results back-transformed to geometric mean ratios (GMRs). The safety population comprised all randomly allocated participants. The trial was registered at the ISRCTN Registry (ISRCTN10482904) and is complete.FindingsBetween Aug 31 and Oct 12, 2020, we screened 376 potential participants for eligibility. We enrolled and randomly allocated 300 participants to the two groups (151 [50%] to the BCG group and 149 [50%] to the no BCG group). 178 (59%) of 300 participants were male and 122 (41%) were female. 142 (91%) of 151 participants in the BCG group and 139 (93%) of 149 in the no BCG group completed follow-up. There was no effect of BCG revaccination, compared with no BCG revaccination, on the response observed for any vaccine. Yellow fever plaque reduction neutralising reference tests (PRNT50) titres (the reciprocal of the last plasma dilution that reduced by 50%) had a GMR of 0·95 (95% CI 0·75–1·19; p=0·62) and PRNT90 (reciprocal of the last plasma dilution that reduced by 90%) had a GMR of 0·94 (0·74–1·19; p=0·60); IgG to S Typhi O:LPS was 0·99 (0·80–1·23; p=0·94); IgG to HPV-16 was 0·97 (0·69–1·35; p=0·85) and to HPV-18 was 1·03 (0·76–1·40; p=0·83); and toxoid-specific IgG for tetanus was 1·13 (0·87–1·47; p=0·36) and was 1·00 (0·87–1·16; p=0·97) for diphtheria. There were no serious adverse events in either group.InterpretationWe found no evidence that BCG revaccination is an effective strategy to improve immunogenicity of other vaccines in this low-income, urban setting.FundingUK Medical Research Council.TranslationFor the Luganda translation of the abstract see Supplementary Materials section.

SummaryRapid surveys or assessments offer the possibility to collect data in contexts where classic data collection is not feasible (such as health, humanitarian, or climate crises) and when evidence-based urgent action is needed to mitigate the effects of the crisis. Until the past 5 years, rapid surveys were not widely used by practitioners, researchers, or policy makers to measure the effect of crises on violence against women due to a paucity of empirical evidence on their safety and likely utility in such contexts. In recent years, and particularly during the COVID-19 global pandemic, UN Women led the piloting and implementation of such surveys in various countries. We use our experiences from this work and other studies to offer concrete decision-making guidance—in the form of a checklist—for whether to conduct rapid surveys on violence against women in crisis contexts, with consideration of their value, risks, and the minimum safeguards needed to implement this type of work.

Key population HIV programmes in sub-Saharan Africa require epidemiological information to ensure equitable and universal access to effective services. We aimed to consolidate and harmonise survey data among female sex workers, men who have sex with men, people who inject drugs, and transgender people to estimate key population size, HIV prevalence, and antiretroviral therapy (ART) coverage for countries in mainland sub-Saharan Africa. Key population size estimates, HIV prevalence, and ART coverage data from 39 sub-Saharan Africa countries between 2010 and 2023 were collated from existing databases and verified against source documents. We used Bayesian mixed-effects spatial regression to model urban key population size estimates as a proportion of the gender-matched, year-matched, and area-matched population aged 15-49 years. We modelled subnational key population HIV prevalence and ART coverage with age-matched, gender-matched, year-matched, and province-matched total population estimates as predictors. We extracted 2065 key population size data points, 1183 HIV prevalence data points, and 259 ART coverage data points. Across national urban populations, a median of 1·65% (IQR 1·35-1·91) of adult cisgender women were female sex workers, 0·89% (0·77-0·95) were men who have sex with men, 0·32% (0·31-0·34) were men who injected drugs, and 0·10% (0·06-0·12) were women who were transgender. HIV prevalence among key populations was, on average, four to six times higher than matched total population prevalence, and ART coverage was correlated with, but lower than, the total population ART coverage with wide heterogeneity in relative ART coverage across studies. Across sub-Saharan Africa, key populations were estimated as comprising 1·2% (95% credible interval 0·9-1·6) of the total population aged 15-49 years but 6·1% (4·5-8·2) of people living with HIV. Key populations in sub-Saharan Africa experience higher HIV prevalence and lower ART coverage, underscoring the need for focused prevention and treatment services. In 2024, limited data availability and heterogeneity constrain precise estimates for programming and monitoring trends. Strengthening key population surveys and routine data within national HIV strategic information systems would support more precise estimates. UNAIDS, Bill & Melinda Gates Foundation, and US National Institutes of Health.