Heterogeneous susceptibility to rotavirus infection and gastroenteritis in two birth cohort studies

Parameter estimation and epidemiological implications

Joseph A. Lewnard, Benjamin A. Lopman, Umesh D. Parashar, Aisleen Bennett, Naor Bar-Zeev, Nigel A. Cunliffe, Prasanna Samuel, M. Lourdes Guerrero, Guillermo Ruiz-Palacios, Gagandeep Kang, Virginia E. Pitzer

Research output: Contribution to journalArticle

Abstract

Cohort studies, randomized trials, and post-licensure studies have reported reduced natural and vaccine-derived protection against rotavirus gastroenteritis (RVGE) in low- and middle-income countries. While susceptibility of children to rotavirus is known to vary within and between settings, implications for estimation of immune protection are not well understood. We sought to re-estimate naturally-acquired protection against rotavirus infection and RVGE, and to understand how differences in susceptibility among children impacted estimates. We re-analyzed data from studies conducted in Mexico City, Mexico and Vellore, India. Cumulatively, 573 rotavirus-unvaccinated children experienced 1418 rotavirus infections and 371 episodes of RVGE over 17,636 child-months. We developed a model that characterized susceptibility to rotavirus infection and RVGE among children, accounting for aspects of the natural history of rotavirus and differences in transmission rates between settings. We tested whether model-generated susceptibility measurements were associated with demographic and anthropometric factors, and with the severity of RVGE symptoms. We identified greater variation in susceptibility to rotavirus infection and RVGE in Vellore than in Mexico City. In both cohorts, susceptibility to rotavirus infection and RVGE were associated with male sex, lower birth weight, lower maternal education, and having fewer siblings; within Vellore, susceptibility was also associated with lower socioeconomic status. Children who were more susceptible to rotavirus also experienced higher rates of rotavirus-negative diarrhea, and higher risk of moderate-to-severe symptoms when experiencing RVGE. Simulations suggested that discrepant estimates of naturally-acquired immunity against RVGE can be attributed, in part, to between-setting differences in susceptibility of children, but result primarily from the interaction of transmission rates with age-dependent risk for infections to cause RVGE. We found that more children in Vellore than in Mexico City belong to a high-risk group for rotavirus infection and RVGE, and demonstrate that unmeasured individual- and age-dependent susceptibility may influence estimates of naturally-acquired immune protection against RVGE.

Original languageEnglish (US)
Article numbere1007014
JournalPLoS computational biology
Volume15
Issue number7
DOIs
StatePublished - Jul 1 2019

Fingerprint

Rotavirus Infections
gastroenteritis
Cohort Study
Rotavirus
Gastroenteritis
cohort studies
Parameter estimation
Susceptibility
Infection
Parameter Estimation
Cohort Studies
Parturition
infection
Vaccines
Education
Mexico
Estimate
parameter estimation
Randomized Trial
Children

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Modeling and Simulation
  • Ecology
  • Molecular Biology
  • Genetics
  • Cellular and Molecular Neuroscience
  • Computational Theory and Mathematics

Cite this

Heterogeneous susceptibility to rotavirus infection and gastroenteritis in two birth cohort studies : Parameter estimation and epidemiological implications. / Lewnard, Joseph A.; Lopman, Benjamin A.; Parashar, Umesh D.; Bennett, Aisleen; Bar-Zeev, Naor; Cunliffe, Nigel A.; Samuel, Prasanna; Guerrero, M. Lourdes; Ruiz-Palacios, Guillermo; Kang, Gagandeep; Pitzer, Virginia E.

In: PLoS computational biology, Vol. 15, No. 7, e1007014, 01.07.2019.

Research output: Contribution to journalArticle

Lewnard, JA, Lopman, BA, Parashar, UD, Bennett, A, Bar-Zeev, N, Cunliffe, NA, Samuel, P, Guerrero, ML, Ruiz-Palacios, G, Kang, G & Pitzer, VE 2019, 'Heterogeneous susceptibility to rotavirus infection and gastroenteritis in two birth cohort studies: Parameter estimation and epidemiological implications', PLoS computational biology, vol. 15, no. 7, e1007014. https://doi.org/10.1371/journal.pcbi.1007014
Lewnard, Joseph A. ; Lopman, Benjamin A. ; Parashar, Umesh D. ; Bennett, Aisleen ; Bar-Zeev, Naor ; Cunliffe, Nigel A. ; Samuel, Prasanna ; Guerrero, M. Lourdes ; Ruiz-Palacios, Guillermo ; Kang, Gagandeep ; Pitzer, Virginia E. / Heterogeneous susceptibility to rotavirus infection and gastroenteritis in two birth cohort studies : Parameter estimation and epidemiological implications. In: PLoS computational biology. 2019 ; Vol. 15, No. 7.
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