Publications

Modeling the efficacy of CRISPR gene drive for schistosomiasis control

Published in PLOS Neglected Tropical Diseases, 2022

Abstract: CRISPR gene drives could revolutionize the control of infectious diseases by accelerating the spread of engineered traits that limit parasite transmission in wild populations. Gene drive technology in mollusks has received little attention despite the role of freshwater snails as hosts of parasitic flukes causing 200 million annual cases of schistosomiasis. A successful drive in snails must overcome self-fertilization, a common feature of host snails which could prevents a drive’s spread. Here we developed a novel population genetic model accounting for snails’ mixed mating and population dynamics, susceptibility to parasite infection regulated by multiple alleles, fitness differences between genotypes, and a range of drive characteristics. We integrated this model with an epidemiological model of schistosomiasis transmission to show that a snail population modification drive targeting immunity to infection can be hindered by a variety of biological and ecological factors; yet under a range of conditions, disease reduction achieved by chemotherapy treatment of the human population can be maintained with a drive. Alone a drive modifying snail immunity could achieve significant disease reduction in humans several years after release. These results indicate that gene drives, in coordination with existing public health measures, may become a useful tool to reduce schistosomiasis burden in selected transmission settings with effective CRISPR construct design and evaluation of the genetic and ecological landscape.

Recommended citation: Grewelle RE, Perez-Saez J, Tycko J, Namigai EKO, Rickards CG, De Leo GA (2022) Modeling the efficacy of CRISPR gene drive for snail immunity on schistosomiasis control. PLoS Negl Trop Dis 16(10): e0010894. https://doi.org/10.1371/journal.pntd.0010894 http://chloerickards.github.io/files/Grewelle_2022.pdf

Environmental Persistence of the World’s Most Burdensome Infectious and Parasitic Diseases

Published in Frontiers in Public Health, 2022

Abstract: Humans live in complex socio-ecological systems where we interact with parasites and pathogens that spend time in abiotic and biotic environmental reservoirs (e.g., water, air, soil, other vertebrate hosts, vectors, intermediate hosts). Through a synthesis of published literature, we reviewed the life cycles and environmental persistence of 150 parasites and pathogens tracked by the World Health Organization’s Global Burden of Disease study. We used those data to derive the time spent in each component of a pathogen’s life cycle, including total time spent in humans versus all environmental stages. We found that nearly all infectious organisms were environmentally mediated to some degree, meaning that they spend time in reservoirs and can be transmitted from those reservoirs to human hosts. Correspondingly, many infectious diseases were primarily controlled through environmental interventions (e.g., vector control, water sanitation), whereas few (14%) were primarily controlled by integrated methods (i.e., combining medical and environmental interventions). Data on critical life history attributes for most of the 150 parasites and pathogens were difficult to find and often uncertain, potentially hampering efforts to predict disease dynamics and model interactions between life cycle time scales and infection control strategies. We hope that this synthetic review and associated database serve as a resource for understanding both common patterns among parasites and pathogens and important variability and uncertainty regarding particular infectious diseases. These insights can be used to improve systems-based approaches for controlling environmentally mediated diseases of humans in an era where the environment is rapidly changing.

Recommended citation: Hopkins SR, Jones IJ, Buck JC, LeBoa C, Kwong LH, Jacobsen K, Rickards C, Lund AJ, Nova N, MacDonald AJ, Lambert-Peck M, De Leo GA and Sokolow SH (2022) Environmental Persistence of the World's Most Burdensome Infectious and Parasitic Diseases. Front. Public Health 10:892366. doi: 10.3389/fpubh.2022.892366 http://chloerickards.github.io/files/Hopkins_2022.pdf

(Pre-print) Age-Stratified SARS-CoV-2 Infection Fatality Rates in New York City estimated from serological data

Published in medRxiv, 2020

Abstract: COVID-19 has killed hundreds of thousands of people in the US and >1 million globally. Estimating the age-specific infection fatality rate (IFR) of SARS-CoV-2 for different populations is crucial for assessing the fatality of COVID-19 and for appropriately allocating limited vaccine supplies to minimize mortality. We used data from a published serosurvey of 5946 individuals 18 years or older conducted April 19-28, 2020 with time series of COVID-19 confirmed cases and deaths for five age-classes from the New York City Department of Health and Mental Hygiene. We inferred age-specific IFRs using a Bayesian framework that accounted for the distribution of delay between infection and seroconversion and infection and death. New York City IFRs were higher for 18-44 year olds and 45-64 year olds (0.58%; 0.45%-0.75%) than Spanish, English, and Swiss populations, but IFRs for 75+ year olds were lower than for English populations and similar to Spanish and Swiss populations. These results suggest that the age-specific fatality of COVID-19 differs among developed countries and raises questions about factors underlying these differences.

Recommended citation: Rickards, C. G., & Kilpatrick, A. M. (2020). Age-Stratified SARS-CoV-2 Infection Fatality Rates in New York City estimated from serological data (p. 2020.10.16.20214023). medRxiv. https://doi.org/10.1101/2020.10.16.20214023 http://chloerickards.github.io/files/Rickards_2020.pdf

Global Assessment of Schistosomiasis Control Over the Past Century Shows Targeting the Snail Intermediate Host Works Best

Published in PLOS Neglected Tropical Diseases, 2016

Abstract: Schistosomiasis is a parasitic disease infecting more than 250 million people worldwide, with almost 800 million at risk. Over the past century, nations undertook schistosomiasis control programs, with outcomes varying from little effect to elimination. The biggest hope for elimination began about 40 years ago with the discovery of the antischistosomal drug praziquantel, after which snail control was seen as old fashioned. Here, we review control program outcomes over the past 100 years across all major schistosomiasis endemic zones, including Africa, Asia, and the Americas. We screened for differences in long-term schistosomiasis reductions among countries and found the most successful programs focused on transmission control (most often snail control, with or without engineering interventions), sometimes in tandem with praziquantel. Although praziquantel has important human-health benefits, our results suggest old-fashioned snail control has been the key to schistosomiasis elimination.

Recommended citation: Sokolow SH, Wood CL, Jones IJ, Swartz SJ, Lopez M, Hsieh MH, et al. (2016) Global Assessment of Schistosomiasis Control Over the Past Century Shows Targeting the Snail Intermediate Host Works Best. PLoS Negl Trop Dis 10(7): e0004794. https://doi.org/10.1371/journal.pntd.0004794 http://chloerickards.github.io/files/Sokolow_2016.pdf