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EXPLORE IDM’S CURRENT RESEARCH PUBLICATIONS

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THE JOURNAL OF INFECTIOUS DISEASES

Mathematical modeling can be used to project the impact of mass vaccination on cholera transmission. Here, we discuss two examples for which indirect protection from mass vaccination needs to be considered. In the first, we show that non-vaccinees can be protected by mass vaccination campaigns. This additional benefit of indirect protection improves the cost-effectiveness of mass vaccination. In the second, we model the use of mass vaccination to eliminate cholera. In this case, a high population level of immunity, including contributions from infection and vaccination, is required to reach the “herd immunity” threshold needed to stop transmission and achieve elimination.

NATURE COMPUTATIONAL SCIENCE

Understanding the complex interplay between human behavior, disease transmission and non-pharmaceutical interventions during the COVID-19 pandemic could provide valuable insights with which to focus future public health efforts. Cell phone mobility data offer a modern measurement instrument to investigate human mobility and behavior at an unprecedented scale. We investigate aggregated and anonymized mobility data, which measure how populations at the census-block-group geographic scale stayed at home in California, Georgia, Texas and Washington from the beginning of the pandemic. Using manifold learning techniques, we show that a low-dimensional embedding enables the identification of patterns of mobility behavior that align with stay-at-home orders, correlate with socioeconomic factors, cluster geographically, reveal subpopulations that probably migrated out of urban areas and, importantly, link to COVID-19 case counts. The analysis and approach provide local epidemiologists a framework for interpreting mobility data and behavior to inform policy makers’ decision-making aimed at curbing the spread of COVID-19.

Jessica V. Ribado, Nancy J. Li, Elizabeth Thiele, Hil Lyons, James A. Cotton, Adam Weiss, Philippe Tchindebet Ouakou, Tchonfienet Moundai, Hubert Zirimwabagabo, Sarah Anne J. Guagliardo, Guillaume Chabot-Couture, Joshua L. Proctor 

PLOS NEGLECTED TROPICAL DISEASES

Background
Guinea worm (Dracunculus medinensis) was detected in Chad in 2010 after a supposed ten-year absence, posing a challenge to the global eradication effort. Initiation of a village-based surveillance system in 2012 revealed a substantial number of dogs infected with Guinea worm, raising questions about paratenic hosts and cross-species transmission.

Methodology/principal findings
We coupled genomic and surveillance case data from 2012-2018 to investigate the modes of transmission between dog and human hosts and the geographic connectivity of worms. Eighty-six variants across four genes in the mitochondrial genome identified 41 genetically distinct worm genotypes. Spatiotemporal modeling revealed worms with the same genotype (‘genetically identical’) were within a median range of 18.6 kilometers of each other, but largely within approximately 50 kilometers. Genetically identical worms varied in their degree of spatial clustering, suggesting there may be different factors that favor or constrain transmission. Each worm was surrounded by five to ten genetically distinct worms within a 50 kilometer radius. As expected, we observed a change in the genetic similarity distribution between pairs of worms using variants across the complete mitochondrial genome in an independent population.

Conclusions/significance
In the largest study linking genetic and surveillance data to date of Guinea worm cases in Chad, we show genetic identity and modeling can facilitate the understanding of local transmission. The co-occurrence of genetically non-identical worms in quantitatively identified transmission ranges highlights the necessity for genomic tools to link cases. The improved discrimination between pairs of worms from variants identified across the complete mitochondrial genome suggests that expanding the number of genomic markers could link cases at a finer scale. These results suggest that scaling up genomic surveillance for Guinea worm may provide additional value for programmatic decision-making critical for monitoring cases and intervention efficacy to achieve elimination.

Katy AM Gaythorpe, Kaja Abbas, John Huber, Andromachi Karachaliou, Niket Thakkar, Kim Woodruff, Xiang Li, Susy Echeverria-Londono, VIMC Working Group on COVID-19 Impact on Vaccine Preventable Disease, Matthew Ferrari, Michael L Jackson, Kevin McCarthy, T Alex Perkins, Caroline Trotter, Mark Jit

ELIFE

Background:
Childhood immunisation services have been disrupted by the COVID-19 pandemic. WHO recommends considering outbreak risk using epidemiological criteria when deciding whether to conduct preventive vaccination campaigns during the pandemic.

Methods:
We used two to three models per infection to estimate the health impact of 50% reduced routine vaccination coverage in 2020 and delay of campaign vaccination from 2020 to 2021 for measles vaccination in Bangladesh, Chad, Ethiopia, Kenya, Nigeria, and South Sudan, for meningococcal A vaccination in Burkina Faso, Chad, Niger, and Nigeria, and for yellow fever vaccination in the Democratic Republic of Congo, Ghana, and Nigeria. Our counterfactual comparative scenario was sustaining immunisation services at coverage projections made prior to COVID-19 (i.e. without any disruption).

Results:
Reduced routine vaccination coverage in 2020 without catch-up vaccination may lead to an increase in measles and yellow fever disease burden in the modelled countries. Delaying planned campaigns in Ethiopia and Nigeria by a year may significantly increase the risk of measles outbreaks (both countries did complete their supplementary immunisation activities (SIAs) planned for 2020). For yellow fever vaccination, delay in campaigns leads to a potential disease burden rise of >1 death per 100,000 people per year until the campaigns are implemented. For meningococcal A vaccination, short-term disruptions in 2020 are unlikely to have a significant impact due to the persistence of direct and indirect benefits from past introductory campaigns of the 1- to 29-year-old population, bolstered by inclusion of the vaccine into the routine immunisation schedule accompanied by further catch-up campaigns.

Conclusions:
The impact of COVID-19-related disruption to vaccination programs varies between infections and countries. Planning and implementation of campaigns should consider country and infection-specific epidemiological factors and local immunity gaps worsened by the COVID-19 pandemic when prioritising vaccines and strategies for catch-up vaccination.

Funding:
Bill and Melinda Gates Foundation and Gavi, the Vaccine Alliance.

Angela Devine, Katherine E. Battle, Niamh Meagher, Rosalind E. Howes, Saber Dini, Peter W. Gething, Julie A. Simpson, Ric N. Price, Yoel Lubell 

PLOS MEDICINE

Background

In 2017, an estimated 14 million cases of Plasmodium vivax malaria were reported from Asia, Central and South America, and the Horn of Africa. The clinical burden of vivax malaria is largely driven by its ability to form dormant liver stages (hypnozoites) that can reactivate to cause recurrent episodes of malaria. Elimination of both the blood and liver stages of the parasites (“radical cure”) is required to achieve a sustained clinical response and prevent ongoing transmission of the parasite. Novel treatment options and point-of-care diagnostics are now available to ensure that radical cure can be administered safely and effectively. We quantified the global economic cost of vivax malaria and estimated the potential cost benefit of a policy of radical cure after testing patients for glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Methods and findings

Estimates of the healthcare provider and household costs due to vivax malaria were collated and combined with national case estimates for 44 endemic countries in 2017. These provider and household costs were compared with those that would be incurred under 2 scenarios for radical cure following G6PD screening: (1) complete adherence following daily supervised primaquine therapy and (2) unsupervised treatment with an assumed 40% effectiveness. A probabilistic sensitivity analysis generated credible intervals (CrIs) for the estimates. Globally, the annual cost of vivax malaria was US$359 million (95% CrI: US$222 to 563 million), attributable to 14.2 million cases of vivax malaria in 2017. From a societal perspective, adopting a policy of G6PD deficiency screening and supervision of primaquine to all eligible patients would prevent 6.1 million cases and reduce the global cost of vivax malaria to US$266 million (95% CrI: US$161 to 415 million), although healthcare provider costs would increase by US$39 million. If perfect adherence could be achieved with a single visit, then the global cost would fall further to US$225 million, equivalent to $135 million in cost savings from the baseline global costs. A policy of unsupervised primaquine reduced the cost to US$342 million (95% CrI: US$209 to 532 million) while preventing 2.1 million cases. Limitations of the study include partial availability of country-level cost data and parameter uncertainty for the proportion of patients prescribed primaquine, patient adherence to a full course of primaquine, and effectiveness of primaquine when unsupervised.

Conclusions

Our modelling study highlights a substantial global economic burden of vivax malaria that could be reduced through investment in safe and effective radical cure achieved by routine screening for G6PD deficiency and supervision of treatment. Novel, low-cost interventions for improving adherence to primaquine to ensure effective radical cure and widespread access to screening for G6PD deficiency will be critical to achieving the timely global elimination of Pvivax.

Robyn M Stuart, Romesh G Abeysuriya, Cliff C Kerr, Dina Mistry, Dan J Klein, Richard T Gray, Margaret Hellard, Nick Scott

BMJ OPEN

Objectives The early stages of the COVID-19 pandemic illustrated that SARS-CoV-2, the virus that causes the disease, has the potential to spread exponentially. Therefore, as long as a substantial proportion of the population remains susceptible to infection, the potential for new epidemic waves persists even in settings with low numbers of active COVID-19 infections, unless sufficient countermeasures are in place. We aim to quantify vulnerability to resurgences in COVID-19 transmission under variations in the levels of testing, tracing and mask usage.

Setting The Australian state of New South Wales (NSW), a setting with prolonged low transmission, high mobility, non-universal mask usage and a well-functioning test-and-trace system.

Participants None (simulation study).

Results We find that the relative impact of masks is greatest when testing and tracing rates are lower and vice versa. Scenarios with very high testing rates (90% of people with symptoms, plus 90% of people with a known history of contact with a confirmed case) were estimated to lead to a robustly controlled epidemic. However, across comparable levels of mask uptake and contact tracing, the number of infections over this period was projected to be 2–3 times higher if the testing rate was 80% instead of 90%, 8–12 times higher if the testing rate was 65% or 30–50 times higher with a 50% testing rate. In reality, NSW diagnosed 254 locally acquired cases over this period, an outcome that had a moderate probability in the model (10%–18%) assuming low mask uptake (0%–25%), even in the presence of extremely high testing (90%) and near-perfect community contact tracing (75%–100%), and a considerably higher probability if testing or tracing were at lower levels.

Conclusions Our work suggests that testing, tracing and masks can all be effective means of controlling transmission. A multifaceted strategy that combines all three, alongside continued hygiene and distancing protocols, is likely to be the most robust means of controlling transmission of SARS-CoV-2.

SCIENCEDIRECT

The coronavirus disease 2019 (COVID-19) pandemic highlighted the importance of mathematical modeling in advising scientific bodies and informing public policy making. Modeling allows a flexible theoretical framework to be developed in which different scenarios around spread of diseases and strategies to prevent it can be explored. This work brings together perspectives on mathematical modeling of infectious diseases, highlights the different modeling frameworks that have been used for modeling COVID-19 and illustrates some of the models that our groups have developed and applied specifically for COVID-19. We discuss three models for COVID-19 spread: the modified Susceptible-Exposed-Infected-Recovered model that incorporates contact tracing (SEIR-TTI model) and describes the spread of COVID-19 among these population cohorts, the more detailed agent-based model called Covasim describing transmission between individuals, and the Rule-Based Model (RBM) which can be thought of as a combination of both. We showcase the key methodologies of these approaches, their differences as well as the ways in which they are interlinked. We illustrate their applicability to answer pertinent questions associated with the COVID-19 pandemic such as quantifying and forecasting the impacts of different test-trace-isolate (TTI) strategies.

Ben J Brintz, Benjamin Haaland, Joel Howard, Dennis L Chao, Joshua L Proctor, Ashraful I Khan, Sharia M Ahmed, Lindsay T Keegan, Tom Greene

ELIFE

Traditional clinical prediction models focus on parameters of the individual patient. For infectious diseases, sources external to the patient, including characteristics of prior patients and seasonal factors, may improve predictive performance. We describe the development of a predictive model that integrates multiple sources of data in a principled statistical framework using a post-test odds formulation. Our method enables electronic real-time updating and flexibility, such that components can be included or excluded according to data availability. We apply this method to the prediction of etiology of pediatric diarrhea, where 'pre-test’ epidemiologic data may be highly informative. Diarrhea has a high burden in low-resource settings, and antibiotics are often over-prescribed. We demonstrate that our integrative method outperforms traditional prediction in accurately identifying cases with a viral etiology, and show that its clinical application, especially when used with an additional diagnostic test, could result in a 61% reduction in inappropriately prescribed antibiotics.

Nick Scott, Anna Palmer, Dominic Delport, Romesh Abeysuriya, Robyn M Stuart, Cliff C Kerr, Dina Mistry, Daniel J Klein, Rachel Sacks‐Davis, Katie Heath, Samuel W Hainsworth, Alisa Pedrana, Mark Stoove, David Wilson and Margaret E Hellard

MJA

Objectives: To assess the risks associated with relaxing coronavirus disease 2019 (COVID‐19)‐related physical distancing restrictions and lockdown policies during a period of low viral transmission.

Design: Network‐based viral transmission risks in households, schools, workplaces, and a variety of community spaces and activities were simulated in an agent‐based model, Covasim.

Setting: The model was calibrated for a baseline scenario reflecting the epidemiological and policy environment in Victoria during March–May 2020, a period of low community viral transmission.

Intervention: Policy changes for easing COVID‐19‐related restrictions from May 2020 were simulated in the context of interventions that included testing, contact tracing (including with a smartphone app), and quarantine.

Main outcome measure: Increase in detected COVID‐19 cases following relaxation of restrictions.

Results: Policy changes that facilitate contact of individuals with large numbers of unknown people (eg, opening bars, increased public transport use) were associated with the greatest risk of COVID‐19 case numbers increasing; changes leading to smaller, structured gatherings with known contacts (eg, small social gatherings, opening schools) were associated with lower risks. In our model, the rise in case numbers following some policy changes was notable only two months after their implementation.

Conclusions: Removing several COVID‐19‐related restrictions within a short period of time should be undertaken with care, as the consequences may not be apparent for more than two months. Our findings support continuation of work from home policies (to reduce public transport use) and strategies that mitigate the risk associated with re‐opening of social venues.

Edinah Mudimu, Kathryn Peebles, Zindoga Mukandavire, Emily Nightingale, Monisha Sharma, Graham F. Medley, Daniel J. Klein, Katharine Kripke, Anna Bershteyn 

PLOS ONE

Background
Pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV and has the potential to significantly impact the HIV epidemic. Given limited resources for HIV prevention, identifying PrEP provision strategies that maximize impact is critical.

Methods
We used a stochastic individual-based network model to evaluate the direct (infections prevented among PrEP users) and indirect (infections prevented among non-PrEP users as a result of PrEP) benefits of PrEP, the person-years of PrEP required to prevent one HIV infection, and the community-level impact of providing PrEP to populations defined by gender and age in western Kenya and South Africa. We examined sensitivity of results to scale-up of antiretroviral therapy (ART) and voluntary medical male circumcision (VMMC) by comparing two scenarios: maintaining current coverage (“status quo”) and rapid scale-up to meet programmatic targets (“fast-track”).

Results
The community-level impact of PrEP was greatest among women aged 15–24 due to high incidence, while PrEP use among men aged 15–24 yielded the highest proportion of indirect infections prevented in the community. These indirect infections prevented continue to increase over time (western Kenya: 0.4–5.5 (status quo); 0.4–4.9 (fast-track); South Africa: 0.5–1.8 (status quo); 0.5–3.0 (fast-track)) relative to direct infections prevented among PrEP users. The number of person-years of PrEP needed to prevent one HIV infection was lower (59 western Kenya and 69 in South Africa in the status quo scenario; 201 western Kenya and 87 in South Africa in the fast-track scenario) when PrEP was provided only to women compared with only to men over time horizons of up to 5 years, as the indirect benefits of providing PrEP to men accrue in later years.

Conclusions
Providing PrEP to women aged 15–24 prevents the greatest number of HIV infections per person-year of PrEP, but PrEP provision for young men also provides indirect benefits to women and to the community overall. This finding supports existing policies that prioritize PrEP use for young women, while also illuminating the community-level benefits of PrEP availability for men when resources permit.