Azra C. Ghani

Blood-stage vaccines (BSVs) against malaria offer a promising avenue for reducing parasite burden and transmission, yet their efficacy is challenging to interpret across different trial phases. In this study we develop a simple mechanistic within-host mathematical model of Plasmodium falciparum asexual parasitaemia. We fit this model to individual-level data from the phase I/IIa RH5.1 trial and estimate the relationship between vaccine efficacy and RH5 antibody titres, enabling the quantitative prediction of vaccine-impact on public health outcomes. We show that small reductions in erythrocyte invasion rate can lead to substantial decreases in probability of exceeding parasitaemia thresholds and transmission potential. Our framework provides a flexible, biologically motivated method for interpreting early-phase trial data and can inform future trial design, vaccine evaluation and integration into broader malaria control strategies.

Malaria remains a major constraint on economic development, yet the mechanisms linking disease prevalence to macroeconomic outcomes are poorly understood. We examine the impact of malaria case incidence on total factor productivity, leveraging a panel dataset covering 30 malaria-endemic countries from 2000 to 2019. Using a novel shift–share instrumental variable that combines time-invariant sickle-cell trait (HbS) prevalence with time-varying climate shocks and Mendelian Randomisation, we address endogeneity in malaria exposure. Our findings show that 10\% increase in malaria incidence reduces TFP by 0.35–0.84\%, with the preferred shift--share IV estimate implying a 0.84\% decline. The implied annual GDP loss is \$2.1 trillion (2017 USD), and the benefit–cost ratio of eradication exceeds 200. Human capital depletion mediates roughly half of the total effect. These results highlight malaria eradication as a high-return development investment with substantial long-run productivity gains.

In 2024, mpox cases surged in the Democratic Republic of the Congo (DRC) with cross-border spread to Burundi. We developed a transmission-dynamic model calibrated against surveillance data to understand drivers in enzootic (Clade Ia) and non-enzootic (Clade Ib) areas, and the potential impact of vaccination. In non-enzootic areas we estimated that 58-84% of transmission occurred within sexual networks. MVA-BN vaccination of sex workers could have averted 91% (95% CrI 81%–98%) of infections in Sud Kivu (DRC) but only 35% (95% CrI 26%–47%) in Bujumbura (Burundi), due to later outbreak detection. In historically enzootic Equateur (DRC), ongoing zoonotic spillover best explained sustained incidence. There, pledged Lc18m8 vaccines could have averted 42% (95% CrI 40%–46%) of infections; prioritising children improved impact. Across all settings, doubling vaccine coverage by using a single dose of MVA-BN outperformed two-dose strategies. Timely detection and tailored vaccination strategies are critical to reducing mpox burden.

Since their first detection in 2010, Plasmodium falciparum malaria parasites lacking the P. falciparum histidine-rich protein 2 gene (pfhrp2) have been observed in 40 of 47 surveyed countries, as documented by the World Health Organization. These genetic deletions reduce detection by the most widely used rapid diagnostic tests, prompting three countries to switch to alternative diagnostics. However, manufacturing of alternative rapid diagnostic tests has not been scaled up and there are no World Health Organization-prequalified combination tests that use P. falciparum Plasmodium lactate dehydrogenase. The continuing spread of pfhrp2 and/or pfhrp3 (pfhrp2/3) deletions threatens malaria control, creating an emerging public health crisis. Here we use mathematical modeling informed by current pfhrp2/3 deletion prevalence and a literature review to assess the global risk of pfhrp2 /3 deletions. We identify ten priority countries for surveillance and predict that the primary spread in Africa will move southward from the Horn of Africa through East Africa within 20 years. Despite variation in modeled timelines due to uncertainty in model parameters, four countries yet to switch rapid diagnostic tests are consistently classified as high risk under a range of model assumptions. This updated model offers refined predictions to guide pfhrp2/3 policy and prioritize future surveillance efforts and innovation.

COVID-19 has underscored the need for more timely access to vaccines during future pandemics. This has motivated development of broad-spectrum vaccines providing protection against entire viral families, which could be stockpiled and deployed rapidly following detection. Using mathematical modelling, we assess the utility of a broadly protective sarbecovirus vaccine during a hypothetical SARS-X outbreak, for a range of implementation strategies including ring-vaccination, spatial-targeting and mass vaccination of high-risk groups. Broadly protective sarbecovirus vaccine ring- or spatial strategies alone are insufficient to contain epidemics driven by a SARS-CoV-2-like virus, but when paired with rapid isolation and quarantine, can achieve containment of a SARS-CoV-1-like virus. Where suppression fails, broadly protective sarbecovirus vaccine utilisation still reduces the effective reproduction number and slows epidemic growth - buying valuable time for health-system response and virus-specific vaccine development. Vaccination of high-risk populations with the broadly protective sarbecovirus vaccine ahead of virus-specific vaccine availability could reduce mortality and enable shorter and less stringent non-pharmaceutical interventions to be imposed; results are sensitive to vaccine properties (e.g., efficacy), health system capabilities (e.g. rollout speed) and timeline to virus-specific vaccine availability. Our modelling suggests that broadly protective sarbecovirus vaccine delivery to those aged 60+ years could have averted 21-78 % of COVID-19 deaths during the pandemic’s first year, depending on the size of the stockpile. Realising this potential impact will require investment in manufacturing, delivery capacity and equitable access ahead of future pandemics.

Background: The pre-erythrocytic malaria vaccine R21/Matrix-M is recommended for young children, who often bear the highest burden, in malaria endemic regions. However, the small proportion of the vaccine-eligible population and waning vaccine efficacy means that routine administration is unlikely to prevent all severe cases in older children who still experience significant disease burden and mortality. Given the anticipated wide availability of R21/Matrix-M, vaccinating older age groups may be warranted. Methods and Findings: Using a stochastic, individual-based transmission model of P. falciparum malaria, we estimate the impact of (1) a one-off catch-up campaign expanding the R21/Matrix-M vaccine-eligible population to a range of previously unvaccinated age groups between 6 months and 14 years, and (2) extra booster doses at 2, 5 and/or 10 years after the primary series in a range of transmission settings. We assume that the vaccine efficacy in older children is the same as in the standard target age group of 5–17-month-olds. Prioritising expansion of the vaccine-eligible population through either catch-up campaigns to children under 5 years or via extra booster doses in areas of moderate or high transmission is predicted to prevent more clinical and severe cases per dose in nearly all scenarios than prioritising routine vaccination in areas of low transmission. For example, boosters 5 years post primary series averted 9 (95% CrI 5-13) severe cases per 1000 doses in a perennial setting with 45% Pf PR _2-10 versus 5 (95% CrI 2-8) severe cases per 1000 doses in children receiving routine vaccination at 5% Pf PR _2-10 . Conclusion: Additional doses of R21/Matrix-M delivered through catch-up campaigns or via extra booster doses can provide additional benefits to routine administration, but the value varies by transmission and seasonality setting. Further empirical studies, especially on vaccine efficacy in older children, are warranted to inform future policy guidance for malaria vaccination implementation.

Gene drives are a promising means of malaria control with the potential to cause sustained reductions in transmission. In real environments, however, their impacts will depend on local ecological and epidemiological factors. We develop a data-driven model to investigate the impacts of gene drives that causes vector population suppression. We simulate gene drive releases in sixteen ~ 12,000 km² areas of west Africa that span variation in vector ecology and malaria prevalence, and estimate reductions in vector abundance, malaria prevalence and clinical cases. Average reductions in vector abundance ranged from 71.6–98.4% across areas, while impacts on malaria depended strongly on which vector species were targeted. When other new interventions including RTS,S vaccination and pyrethroid-PBO bednets were in place, at least 60% more clinical cases were averted when gene drives were added, demonstrating the benefits of integrated interventions. Our results show that different strategies for gene drive implementation may be required across different African settings.

COVID-19 has underscored the need for more timely access to vaccines during future pandemics. This has motivated development of broad-spectrum vaccines providing protection against viral families, which could be stockpiled ahead of an outbreak and deployed rapidly following detection. We use mathematical modelling to evaluate the utility of a broadly protective sarbecovirus vaccine (BPSV) during a hypothetical SARS-X outbreak, including ring-vaccination, spatial targeting and mass vaccination of high-risk populations. Our results show BPSV ring- or spatially-targeted vaccination strategies are unlikely to contain a SARS-CoV-2-like virus but could contain or slow the spread of a SARS-CoV-1-like virus. Vaccination of high-risk populations with the BPSV ahead of a virus-specific vaccine (VSV) becoming available could substantially reduce mortality. For a 250-day VSV development timeline, BPSV availability reduced infection-related deaths in our model by 54% on average, though exact impact depended on the non-pharmaceutical intervention (NPI) scenario considered. We further show that BPSV availability enables shorter and less stringent NPIs to be imposed whilst limiting disease burden to that observed in the VSV-only scenario, though results are sensitive to vaccine properties (e.g. efficacy), health system capabilities (e.g. vaccination rollout speed) and the assumed timeline to VSV availability. Our modelling suggests that availability of a BPSV for those aged 60+ years could have averted 40-65% of COVID-19 deaths during the pandemic’s first year, with exact impact depending on the size of the maintained stockpile. Our work highlights significant potential impact of a BPSV, but that achieving this depends on investment into health systems enabling rapid and equitable access during future SARS-X pandemics.

Gene drive technologies are a promising means of malaria control with the potential to cause widespread and sustained reductions in transmission. In real environments, however, gene drive impacts will depend on local ecological and epidemiological factors. We develop a data-driven model to investigate the impacts of a gene drive that causes vector population suppression. We apply the model to sixteen ∼12,000km ² areas of west Africa that span variation in vector ecology and malaria prevalence. We simulate gene drive releases targeting different vector species combinations, and estimate reductions in vector abundance, malaria prevalence and clinical cases in children. Average reductions in vector abundance ranged from 77.3%-99.1% across areas when the gene drive releases targeted all major vector species ( Anopheles gambiae , An. coluzzii , An. arabiensis, and An. funestus ). Impacts on malaria depended strongly on which vector species were targeted. Consistently strong impacts required releases targeting all vector species, which reduced prevalence by over 90% in all areas. When the major vector species An. gambiae and An. coluzzii were targeted, average reductions in prevalence ranged from no reduction to 72% across areas, and reductions in cumulative clinical cases ranged from zero to 57%. When other new interventions including RTS,S vaccination and pyrethroid-PBO bednets were in place, at least 60% more clinical cases were averted when gene drives were added, demonstrating the benefits of integrated interventions. Our results give new insights into the factors determining the impacts of gene drives on malaria across different African settings.