Publications

View details for DOI 10.1001/jamapediatrics.2025.3561

View details for PubMedID 41021249

Abstract

Schistosomiasis is a neglected disease caused by parasitic flatworms of the genus Schistosoma and affects more than 150 million people worldwide. Praziquantel, the drug used in public health control programmes, has minimal activity against juvenile schistosomes (within 6 weeks of infection) and imperfect cure rates. We aimed to model the population-level impact of hypothetical novel drug candidates, targeting both juvenile and adult schistosomes with various efficacies, across a range of baseline epidemiological settings.In this modelling study, we used a stochastic, individual-based mechanistic model of Schistosoma mansoni infection and simulated mass drug administration control programmes in diverse epidemiological environments. These programmes involved the administration, over a 5-year period at 75% coverage, of praziquantel (single-dose or two-dose regimens) or hypothetical novel drugs with various assumed efficacies against adult and juvenile schistosome parasites: novel drug A, with equivalent efficacy to praziquantel against adult schistosomes plus perfect (100%) efficacy against juvenile schistosomes; novel drug B, with higher efficacy than praziquantel against adult schistosomes and no activity against juveniles; and novel drug C, with higher efficacy than praziquantel against adult schistosomes plus perfect efficacy against juveniles. The outcomes were median observed S mansoni infection prevalence and infection intensity over time in simulated populations.In a simulated high-endemicity setting (baseline prevalence of S mansoni infection of 53%), modelled prevalence after a single treatment was 20·8% (uncertainty interval 15·8-23·6) for single-dose praziquantel, 17·8% (15·2-19·8) for two-dose praziquantel, 18·4% (13·4-21·4) for novel drug A, 16·0% (15·0-16·8) for novel drug B, and 13·4% (12·6-14·0) for novel drug C; at year 5, modelled prevalence was 14·6% (12·2-16·4) for single-dose praziquantel, 13·6% (11·6-14·6) for two-dose praziquantel, 11·8% (9·4-13·4) for novel drug A, 12·6% (11·6-13·4) for novel drug B, and 9·6% (9·0-10·4) for novel drug C. In a simulated low-endemicity setting (baseline prevalence 15%), modelled prevalence after a single treatment was 4·8% (3·6-5·8) for single-dose praziquantel, 4·2% (3·6-5·0) for two-dose praziquantel, 4·6% (3·2-5·4) for novel drug A, 4·0% (3·4-4·6) for novel drug B, and 3·6% (3·2-4·2) for novel drug C; at year 5, modelled prevalence was 3·0% (2·2-3·6) for single-dose praziquantel, 2·8% (2·2-3·4) for two-dose praziquantel, 2·6% (1·8-3·2) for novel drug A, 2·7% (2·2-3·2) for novel drug B, and 2·2% (1·8-2·6) for novel drug C.This study provides policy-relevant data that could help to guide the development and selection of novel drugs for schistosomiasis. Novel anthelmintic drugs that can kill both adult and juvenile schistosomes with higher efficacy than praziquantel could have some public health gains in control programmes for schistosomiasis, especially in high-burden settings. Novel drugs with increased efficacy against adult schistosomes are likely to have an initial and larger impact on disease control, whereas targeting juveniles could moderately improve longer-term control outcomes.US National Institutes of Health.

View details for DOI 10.1016/j.lanmic.2024.101065

View details for PubMedID 40412412

Abstract

Widespread childhood vaccination has eliminated many infectious diseases in the US. However, vaccination rates are declining, and there are ongoing policy debates to reduce the childhood vaccine schedule, which may risk reemergence of previously eliminated infectious diseases.To estimate the number of cases and complications in the US under scenarios of declining childhood vaccination for measles, rubella, poliomyelitis, and diphtheria.A simulation model was used to assess the importation and dynamic spread of vaccine-preventable infectious diseases across 50 US states and the District of Columbia. The model was parameterized with data on area-specific estimates for demography, population immunity, and infectious disease importation risk. The model evaluated scenarios with different vaccination rates over a 25-year period. Inputs for current childhood vaccination rates were based on 2004-2023 data.The primary outcomes were estimated cases of measles, rubella, poliomyelitis, and diphtheria in the US. The secondary outcomes were estimated rates of infection-related complications (postmeasles neurological sequelae, congenital rubella syndrome, paralytic poliomyelitis, hospitalization, and death) and the probability and timing for an infection to reestablish endemicity.At current state-level vaccination rates, the simulation model predicts measles may reestablish endemicity (83% of simulations; mean time of 20.9 years) with an estimated 851 300 cases (95% uncertainty interval [UI], 381 300 to 1.3 million cases) over 25 years. Under a scenario with a 10% decline in measles-mumps-rubella (MMR) vaccination, the model estimates 11.1 million (95% UI, 10.1-12.1 million) cases of measles over 25 years, whereas the model estimates only 5800 cases (95% UI, 3100-19 400 cases) with a 5% increase in MMR vaccination. Other vaccine-preventable diseases are unlikely to reestablish endemicity under current levels of vaccination. If routine childhood vaccination declined by 50%, the model predicts 51.2 million (95% UI, 49.7-52.5 million) cases of measles over a 25-year period, 9.9 million (95% UI, 6.4-13.0 million) cases of rubella, 4.3 million cases (95% UI, 4 cases to 21.5 million cases) of poliomyelitis, and 197 cases (95% UI, 1-1000 cases) of diphtheria. Under this scenario, the model predicts 51 200 cases (95% UI, 49 600-52 600 cases) with postmeasles neurological sequelae, 10 700 cases (95% UI, 6700-14 600 cases) of congenital rubella syndrome, 5400 cases (95% UI, 0-26 300 cases) of paralytic poliomyelitis, 10.3 million hospitalizations (95% UI, 9.9-10.5 million hospitalizations), and 159 200 deaths (95% UI, 151 200-164 700 deaths). In this scenario, measles became endemic at 4.9 years (95% UI, 4.3-5.6 years) and rubella became endemic at 18.1 years (95% UI, 17.0-19.6 years), whereas poliovirus returned to endemic levels in about half of simulations (56%) at an estimated 19.6 years (95% UI, 14.0-24.7 years). There was large variation across the US population.Based on estimates from this modeling study, declining childhood vaccination rates will increase the frequency and size of outbreaks of previously eliminated vaccine-preventable infections, eventually leading to their return to endemic levels. The timing and critical threshold for returning to endemicity will differ substantially by disease, with measles likely to be the first to return to endemic levels and may occur even under current vaccination levels without improved vaccine coverage and public health response. These findings support the need to continue routine childhood vaccination at high coverage to prevent resurgence of vaccine-preventable infectious diseases in the US.

View details for DOI 10.1001/jama.2025.6495

View details for PubMedID 40272967

Abstract

Early investigation revealed a reduced risk of SARS-CoV-2 infection among social contacts of COVID-19 vaccinated individuals, referred to as indirect protection. However, indirect protection from SARS-CoV-2 infection-acquired immunity and its comparative strength and durability to vaccine-derived indirect protection in the current epidemiologic context of high levels of vaccination, prior infection, and novel variants are not well characterized. Here, we show that both vaccine-derived and infection-acquired immunity independently yield indirect protection to close social contacts with key differences in their strength and waning. Analyzing anonymized SARS-CoV-2 surveillance data from 9,625 residents in California state prisons from December 2021 to December 2022, we find that vaccine-derived indirect protection against Omicron SARS-CoV-2 infection is strongest within three months of COVID-19 vaccination [30% (95% confidence interval: 20-38%)] with subsequent modest protection. Infection-acquired immunity provides 38% (24-50%) indirect protection for 6 months after SARS-CoV-2 infection, with moderate indirect protection persisting for over one year. Variant-targeted vaccines (bivalent formulation including Omicron subvariants BA.4/BA.5) confer strong indirect protection for at least three months [40% (3-63%)]. These results demonstrate that both vaccine-derived and infection-acquired immunity can reduce SARS-CoV-2 transmission which is important for understanding long-term transmission dynamics and can guide public health intervention, especially in high-risk environments such as prisons.

View details for DOI 10.1038/s41467-024-55029-9

View details for PubMedID 39881133

View details for PubMedCentralID 9799368

View details for DOI 10.1016/S1473-3099(24)00678-9

View details for PubMedID 39455239

Abstract

Strongyloidiasis is a soil-transmitted helminthiasis that is estimated to affect 300-600 million people across Asia, Africa, South and central America, and the Pacific. This neglected parasitic disease is most known for its ability to persist as a lifelong infection due to autoinfection and its risk of hyperinfection and disseminated disease during immunosuppression, which has a more than 60% case fatality. Despite the large global burden of strongyloidiasis, there have been no large-scale public health programmes or WHO guidelines directed towards its control and elimination. However, over the past decade, key scientific and policy changes along with requests from endemic countries have led to WHO incorporating strongyloidiasis into its 2021-30 roadmap and public health targets for control and elimination of neglected tropical diseases. In 2024, WHO published its first guideline on public health control of strongyloidiasis with a single recommendation: in endemic settings with a Strongyloides stercoralis infection prevalence of 5% or higher (measured either with Baermann or agar plate culture from stool specimens), WHO conditionally recommends mass drug administration with single-dose ivermectin (200 μg/kg; oral therapy) in all age groups from 5 years and older to reduce strongyloidiasis. This Review, written by the 2023-24 strongyloidiasis guidelines development group along with WHO colleagues and international experts, presents a summary of the recently published WHO guideline recommendation for strongyloidiasis, and the supporting evidence, considerations for public health implementation, and future research needs.

View details for DOI 10.1016/S1473-3099(24)00595-4

View details for PubMedID 39481419

Abstract

There is a public health need to understand how different frequencies of COVID-19 booster vaccines may mitigate the risk of severe COVID-19, while accounting for waning of protection and differential risk by age and immune status. By analyzing United States COVID-19 surveillance and seroprevalence data in a microsimulation model, here we show that more frequent COVID-19 booster vaccination (every 6-12 months) in older age groups and the immunocompromised population would effectively reduce the burden of severe COVID-19, while frequent boosters in the younger population may only provide modest benefit against severe disease. In persons 75+ years, the model estimated that annual boosters would reduce absolute annual risk of severe COVID-19 by 199 (uncertainty interval: 183-232) cases per 100,000 persons, compared to a one-time booster vaccination. In contrast, for persons 18-49 years, the model estimated that annual boosters would reduce this risk by 14 (10-19) cases per 100,000 persons. Those with prior infection had lower benefit of more frequent boosting, and immunocompromised persons had larger benefit. Scenarios with emerging variants with immune evasion increased the benefit of more frequent variant-targeted boosters. This study underscores the benefit of considering key risk factors to inform frequency of COVID-19 booster vaccines in public health guidance and ensuring at least annual boosters in high-risk populations.

View details for DOI 10.1038/s41467-024-45549-9

View details for PubMedID 38448400

View details for PubMedCentralID 10014083

Abstract

Schistosomiasis is a neglected tropical disease affecting over 150 million people. Hotspots of Schistosoma transmission-communities where infection prevalence does not decline adequately with mass drug administration-present a key challenge in eliminating schistosomiasis. Current approaches to identify hotspots require evaluation 2-5 y after a baseline survey and subsequent mass drug administration. Here, we develop statistical models to predict hotspots at baseline prior to treatment comparing three common hotspot definitions, using epidemiologic, survey-based, and remote sensing data. In a reanalysis of randomized trials in 589 communities in five endemic countries, a regression model predicts whether Schistosoma mansoni infection prevalence will exceed the WHO threshold of 10% in year 5 ("prevalence hotspot") with 86% sensitivity, 74% specificity, and 93% negative predictive value (NPV; assuming 30% hotspot prevalence), and a regression model for Schistosoma haematobium achieves 90% sensitivity, 90% specificity, and 96% NPV. A random forest model predicts whether S. mansoni moderate and heavy infection prevalence will exceed a public health goal of 1% in year 5 ("intensity hotspot") with 92% sensitivity, 79% specificity, and 96% NPV, and a boosted trees model for S. haematobium achieves 77% sensitivity, 95% specificity, and 91% NPV. Baseline prevalence is a top predictor in all models. Prediction is less accurate in countries not represented in training data and for a third hotspot definition based on relative prevalence reduction over time ("persistent hotspot"). These models may be a tool to prioritize high-risk communities for more frequent surveillance or intervention against schistosomiasis, but prediction of hotspots remains a challenge.

View details for DOI 10.1073/pnas.2315463120

View details for PubMedID 38181058

View details for DOI 10.1056/NEJMp2304716

View details for PubMedID 37602574