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Journal articleParag KV, Thompson RN, 2024,
Host behaviour driven by awareness of infection risk amplifies the chance of superspreading events
, Journal of the Royal Society Interface, Vol: 21, ISSN: 1742-5662We demonstrate that heterogeneity in the perceived risks associated with infection within host populations amplifies chances of superspreading during the crucial early stages of epidemics. Under this behavioural model, individuals less concerned about dangers from infection are more likely to be infected and attend larger sized (riskier) events, where we assume event sizes remain unchanged. For directly transmitted diseases such as COVID-19, this leads to infections being introduced at rates above the population prevalence to those events most conducive to superspreading. We develop an interpretable, computational framework for evaluating within-event risks and derive a small-scale reproduction number measuring how the infections generated at an event depend on transmission heterogeneities and numbers of introductions. This generalizes previous frameworks and quantifies how event-scale patterns and population-level characteristics relate. As event duration and size grow, our reproduction number converges to the basic reproduction number. We illustrate that even moderate levels of heterogeneity in the perceived risks of infection substantially increase the likelihood of disproportionately large clusters of infections occurring at larger events, despite fixed overall disease prevalence. We show why collecting data linking host behaviour and event attendance is essential for accurately assessing the risks posed by invading pathogens in emerging stages of outbreaks.
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Journal articleMercy K, Youm E, Aliddeki D, et al., 2024,
The Looming Threat of Dengue Fever: The Africa Context.
, Open Forum Infect Dis, Vol: 11, ISSN: 2328-8957In Africa, compared to 2019, dengue infections have surged ninefold by December 2023, with over 270 000 cases and 753 deaths reported across 18 African Union (AU) Member States. This commentary synthesises the context of dengue outbreaks in Africa and provides recommendations for sustainable control. In 2023, 18 African Union Member States reported outbreaks of dengue, among which seven had ongoing armed conflicts. These countries were amongst the top 15 African countries contributing to the most displaced persons on the continent and accounted for 98% of all dengue cases reported in the continent in 2023. Climate change remains an important driver, both through the displacement of people and global warming. The continent continues to face several challenges in detection, reporting and management, such as the lack of local laboratory capacity, misclassification of dengue cases and lack of medical countermeasures. Solutions targeting the strengthening of cross-border surveillance and early warning systems using a multisectoral one-health approach, local research and development for therapeutics and diagnostics and community engagement empowering communities to protect themselves and understand the gravity of the threat could help curb the spread of the disease in Africa.
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Journal articleAliaga-Samanez A, Romero D, Murray K, et al., 2024,
Potential climate change effects on the distribution of urban and sylvatic dengue and yellow fever vectors.
, Pathog Glob Health, Vol: 118, Pages: 397-407Climate change may increase the risk of dengue and yellow fever transmission by urban and sylvatic mosquito vectors. Previous research primarily focused on Aedes aegypti and Aedes albopictus. However, dengue and yellow fever have a complex transmission cycle involving sylvatic vectors. Our aim was to analyze how the distribution of areas favorable to both urban and sylvatic vectors could be modified as a consequence of climate change. We projected, to future scenarios, baseline distribution models already published for these vectors based on the favorability function, and mapped the areas where mosquitoes' favorability could increase, decrease or remain stable in the near (2041-2060) and distant (2061-2080) future. Favorable areas for the presence of dengue and yellow fever vectors show little differences in the future compared to the baseline models, with changes being perceptible only at regional scales. The model projections predict dengue vectors expanding in West and Central Africa and in South-East Asia, reaching Borneo. Yellow fever vectors could spread in West and Central Africa and in the Amazon. In some locations of Europe, the models suggest a reestablishment of Ae. aegypti, while Ae. albopictus will continue to find new favorable areas. The results underline the need to focus more on vectors Ae. vittatus, Ae. luteocephalus and Ae. africanus in West and Central sub-Saharan Africa, especially Cameroon, Central Africa Republic, and northern Democratic Republic of Congo; and underscore the importance of enhancing entomological monitoring in areas where populations of often overlooked vectors may thrive as a result of climate changes.
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Journal articleHe J, Flaxman A, Imai-Eaton JW, et al., 2024,
Association between early sexual debut and new HIV infections among adolescents and young adults in 11 African countries
, AIDS and Behavior, Vol: 28, Pages: 2444-2453, ISSN: 1090-7165We investigated the association between early sexual debut and HIV infection among adolescents and young adults. Analyzing data from nationally representative Population-Based HIV Impact Assessment (PHIA) surveys in 11 African countries, the research employed a multivariate logistic regression model to assess the relationship between the early sexual debut and new HIV infections in the age group of 10–24 years. The results revealed a significant and robust association, indicating that young individuals who experienced early sexual debut were approximately 2.65 times more likely to contract HIV than those who did not, even after accounting for other variables. These findings align with prior research suggesting that early initiation of sexual activity may increase vulnerability to HIV infection due to factors such as biological susceptibility and risky behaviors like low condom use and multiple sexual partners. The implications of these findings for HIV prevention strategies are substantial, suggesting that interventions aimed at delaying sexual debut could be an effective component in reducing HIV risk for this population. Targeted sex education programs that address the risks of early sexual debut may play a pivotal role in these prevention efforts. By employing a comprehensive approach, there is a possibility to advance efforts towards ending AIDS by 2030.
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Journal articlePenn MJ, Scheidwasser N, Khurana MP, et al., 2024,
Phylo2Vec: a vector representation for binary trees.
, Syst BiolBinary phylogenetic trees inferred from biological data are central to understanding the shared history among evolutionary units. However, inferring the placement of latent nodes in a tree is computationally expensive. State-of-the-art methods rely on carefully designed heuristics for tree search, using different data structures for easy manipulation (e.g., classes in object-oriented programming languages) and readable representation of trees (e.g., Newick-format strings). Here, we present Phylo2Vec, a parsimonious encoding for phylogenetic trees that serves as a unified approach for both manipulating and representing phylogenetic trees. Phylo2Vec maps any binary tree with n leaves to a unique integer vector of length n - 1. The advantages of Phylo2Vec are fourfold: i) fast tree sampling, (ii) compressed tree representation compared to a Newick string, iii) quick and unambiguous verification if two binary trees are identical topologically, and iv) systematic ability to traverse tree space in very large or small jumps. As a proof of concept, we use Phylo2Vec for maximum likelihood inference on five real-world datasets and show that a simple hill-climbing-based optimisation scheme can efficiently traverse the vastness of tree space from a random to an optimal tree.
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Journal articleYang Q, Park SW, Saad-Roy CM, et al., 2024,
Assessing population-level target product profiles of universal human influenza A vaccines.
, Epidemics, Vol: 48Influenza A has two hemagglutinin groups, with stronger cross-immunity to reinfection within than between groups. Here, we explore the implications of this heterogeneity for proposed cross-protective influenza vaccines that may offer broad, but not universal, protection. While the development goal for the breadth of human influenza A vaccine is to provide cross-group protection, vaccines in current development stages may provide better protection against target groups than non-target groups. To evaluate vaccine formulation and strategies, we propose a novel perspective: a vaccine population-level target product profile (PTPP). Under this perspective, we use dynamical models to quantify the epidemiological impacts of future influenza A vaccines as a function of their properties. Our results show that the interplay of natural and vaccine-induced immunity could strongly affect seasonal subtype dynamics. A broadly protective bivalent vaccine could lower the incidence of both groups and achieve elimination with sufficient vaccination coverage. However, a univalent vaccine at low vaccination rates could permit a resurgence of the non-target group when the vaccine provides weaker immunity than natural infection. Moreover, as a proxy for pandemic simulation, we analyze the invasion of a variant that evades natural immunity. We find that a future vaccine providing sufficiently broad and long-lived cross-group protection at a sufficiently high vaccination rate, could prevent pandemic emergence and lower the pandemic burden. This study highlights that as well as effectiveness, breadth and duration should be considered in epidemiologically informed TPPs for future human influenza A vaccines.
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Journal articleSmith T, Mishra S, Dorigatti I, et al., 2024,
Differential responses of SARS-CoV-2 variants to environmental drivers during their selective sweeps
, Scientific Reports, Vol: 14, ISSN: 2045-2322Previous work has shown that environmental variables affect SARS-CoV-2 transmission, but it is unclear whether different strains show similar environmental responses. Here we leverage genetic data on the transmission of three (Alpha, Delta and Omicron BA.1) variants of SARS-CoV-2 throughout England, to unpick the roles that climate and public-health interventions play in the circulation of this virus. We find evidence for enhanced transmission of the virus in colder conditions in the first variant selective sweep (of Alpha, in winter), but limited evidence of an impact of climate in either the second (of Delta, in the summer, when vaccines were prevalent) or third sweep (of Omicron, in the winter, during a successful booster-vaccination campaign). We argue that the results for Alpha are to be expected if the impact of climate is non-linear: we find evidence of an asymptotic impact of temperature on the alpha variant transmission rate. That is, at lower temperatures, the influence of temperature on transmission is much higher than at warmer temperatures. As with the initial spread of SARS-CoV-2, however, the overwhelming majority of variation in disease transmission is explained by the intrinsic biology of the virus and public-health mitigation measures. Specifically, when vaccination rates are high, a major driver of the spread of a new variant is it’s ability to evade immunity, and any climate effects are secondary (as evidenced for Delta and Omicron). Climate alone cannot describe the transmission dynamics of emerging SARS-CoV-2 variants.
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Journal articleMangal T, Mohan S, Colbourn T, et al., 2024,
Assessing the impact of health system frailties on HIV and TB programmes: a modelling study in Malawi
, The Lancet Global Health, ISSN: 2214-109XBackgroundMalawi is progressing towards UNAIDS and WHO End TB targets to eliminate AIDS and TB. We assess the prospective impact of achieving these goals and the influence of consumables constraints.MethodsThe Thanzi la Onse model is an individual-based multi-disease simulation model which represents HIV and TB, alongside other diseases, and gates access to essential medicines according to empirical estimates of availability. The model integrates dynamic disease modelling with health system engagement behaviour, health system usage and capabilities (personnel and consumables). HIV and TB programme scale-up are projected until 2033. Findings With uninterrupted medical supplies, HIV and TB incidence could drop to 26 and 55 cases/100,000 person-years by 2033 (from 152 and 123 cases /100,000 person-years in 2023) with programme scale-up, averting 12.21 million DALYs. However, the impact is compromised by limited access to key medicines, resulting in 58,700 additional deaths (33,400 AIDS and 25,300 TB deaths) attributed to consumables stockouts. Eliminating HIV treatment stockouts could avert 12,100 deaths, and improved TB prevention access could prevent 5,600 deaths above those achieved through programme scale-up alone. Consumables stockouts strain the healthcare system, requiring 14.3 million extra patient-facing hours between 2023-2033, mostly from clinical staff. With enhanced screening, 80.9% of individuals could start TB treatment within two weeks of initial presentation if all required consumables were available, but only 57.0% with current levels of availability. InterpretationIgnoring frailties in the healthcare system, in particular the non-availability of consumables, in projections of HIV and TB scale-up may risk over-estimating potential health impacts and under-estimating required health system resources. Simultaneous health system strengthening alongside programme scale-up is crucial, which should yield greater benefits to population health while mitigat
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Journal articleOkiring J, Gonahasa S, Maiteki-Sebuguzi C, et al., 2024,
LLIN Evaluation in Uganda Project (LLINEUP): modelling the impact of COVID-19-related disruptions on delivery of long-lasting insecticidal nets on malaria indicators in Uganda
, Malaria Journal, Vol: 23, ISSN: 1475-2875BACKGROUND: Disruptions in malaria control due to COVID-19 mitigation measures were predicted to increase malaria morbidity and mortality in Africa substantially. In Uganda, long-lasting insecticidal nets (LLINs) are distributed nationwide every 3-4 years, but the 2020-2021 campaign was altered because of COVID-19 restrictions so that the timing of delivery of new nets was different from the original plans made by the National Malaria Control Programme. METHODS: A transmission dynamics modelling exercise was conducted to explore how the altered delivery of LLINs in 2020-2021 impacted malaria burden in Uganda. Data were available on the planned LLIN distribution schedule for 2020-2021, and the actual delivery. The transmission model was used to simulate 100 health sub-districts, and parameterized to match understanding of local mosquito bionomics, net use estimates, and seasonal patterns based on data collected in 2017-2019 during a cluster-randomized trial (LLINEUP). Two scenarios were compared; simulated LLIN distributions matching the actual delivery schedule, and a comparable scenario simulating LLIN distributions as originally planned. Model parameters were otherwise matched between simulations. RESULTS: Approximately 70% of the study population received LLINs later than scheduled in 2020-2021, although some areas received LLINs earlier than planned. The model indicates that malaria incidence in 2020 was substantially higher in areas that received LLINs late. In some areas, early distribution of LLINs appeared less effective than the original distribution schedule, possibly due to attrition of LLINs prior to transmission peaks, and waning LLIN efficacy after distribution. On average, the model simulations predicted broadly similar overall mean malaria incidence in 2021 and 2022. After accounting for differences in cluster population size and LLIN distribution dates, no substantial increase in malaria burden was detected. CONCLUSIONS: The model results sugge
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Journal articleKruger M, van Elsland S, Wainwright L, et al., 2024,
Outcome of retinoblastoma after implementation of national retinoblastoma treatment guidelines in South Africa
, JCO Global Oncology, ISSN: 2687-8941IntroductionRetinoblastoma, a curable childhood cancer, has been identified as a tracer cancer in the WHO Global Initiative for Childhood CancerAimTo document the outcomes of children with retinoblastoma in South Africa, treated as per the first prospective standard national treatment guidelines for childhood cancerin South Africa. Patients and methodsAll children diagnosed with retinoblastoma between 2012 and 2016 in five South African pediatric oncology units (POUs) were treated with a standard treatment based on the International Society of Pediatric Oncology-Pediatric Oncology in Developing Countries (SIOP-PODC) guidelines for high-income settings. Treatment included focaltherapy with/without chemotherapy, or enucleation, with/without chemotherapy, and orbital radiotherapy, depending on enucleated eye histology. The endpoint was survival at 24 months, using Kaplan Meier curves with log -rank (Mantel-Cox) and chi square (χ2) with respective p-values reported.ResultsA total of 178 children were included in the study; 68% presented with unilateral disease. Median age was 27 months (range 0-118 months) with male:female ratio of 1:0.75. Overall survival (OS) was 79% at 24 months with significant association with stage at diagnosis (p < 0.001) and older age over two years as opposed to under twoyears (p < 0.001). Causes of death were disease progression/relapses 90% (34/38), unknown causes 2% (1/38), while treatment abandonment was 1.7% (3/178).ConclusionEfficacy with national treatment guidelines was confirmed and feasibility of implementing standard national childhood cancer treatment guidelines documented, involving multidisciplinary teams in South Africa. Outcome was significantly associated with stage at diagnosis and age.
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