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Heterogeneous susceptibility to rotavirus infection and gastroenteritis in two birth cohort studies: Parameter estimation and epidemiological implications.

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.

SUBMITTER: Lewnard JA

PROVIDER: S-EPMC6690553 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Heterogeneous susceptibility to rotavirus infection and gastroenteritis in two birth cohort studies: Parameter estimation and epidemiological implications.

Lewnard Joseph A JA Lopman Benjamin A BA Parashar Umesh D UD Bennett Aisleen A Bar-Zeev Naor N Cunliffe Nigel A NA Samuel Prasanna P Guerrero M Lourdes ML Ruiz-Palacios Guillermo G Kang Gagandeep G Pitzer Virginia E VE

PLoS computational biology 20190726 7

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 sus ...[more]

PMID: 31348775

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Project description:BACKGROUND:Rotavirus is a leading worldwide cause of acute gastroenteritis in young children. This retrospective hospital-based study assessed the burden of rotavirus gastroenteritis in children younger than 6 years in Japan. METHODS:Children admitted to eight hospitals for acute gastroenteritis between 2008 and 2009 were identified from hospital admission databases. Diagnosis of acute gastroenteritis/rotavirus gastroenteritis and hospital-acquired rotavirus gastroenteritis was confirmed based on either the International Classification of Diseases and Related Health Problems 10th revision (ICD10) codes (intestinal infectious diseases [AA00-AA09] and rotavirus gastroenteritis [A08.0]) or from rapid rotavirus diagnostic test results. RESULTS:Of 13,767 hospitalized children, 11.9% (1,644), 4.8% (665) and 0.6% (81) were diagnosed with acute gastroenteritis, rotavirus gastroenteritis and hospital-acquired rotavirus gastroenteritis, respectively. Among acute gastroenteritis hospitalizations, 40.5% (665/1,644; ICD10 and rapid test) and 57.7% (645/1,118; rapid test only) were confirmed as rotavirus positive. Of 1,563 children with community-acquired acute gastroenteritis, 584 (37.4%) cases were confirmed as rotavirus positive. The median durations of hospitalization for all and community-acquired rotavirus gastroenteritis were 5.0 days (range: 2.0-133.0 days) and 5.0 days (range: 2.0-34.0 days), respectively. Among rotavirus gastroenteritis hospitalizations, 12.2% (81/665) of cases were hospital-acquired and the median duration of hospitalization was 10.0 days (range: 2.0-133.0 days). The median duration of additional hospitalization due to hospital-acquired rotavirus gastroenteritis was 3.0 days (range: 0-14 days). The overall incidence rate of hospital-acquired rotavirus gastroenteritis was 1.0 per 1,000 children hospital-days. The number of rotavirus gastroenteritis cases peaked between February and May in both 2008 and 2009, and the highest number of cases was reported in March 2008 (21.8%; 145/665). The highest number of rotavirus gastroenteritis hospitalizations (24.1%; 160/665) was observed in children aged 12-18 months. The proportion of hospital-acquired rotavirus gastroenteritis was higher in children aged below 18 months as compared to children at least 18 months of age (0.94 [95% CI: 0.71-1.21] vs. 0.39 [95% CI: 0.25-0.58]) and for children hospitalized for at least 5 days compared to those hospitalized for less than 5 days (0.91 [95% CI: 0.72-1.14] vs. 0.15 [95% CI: 0.05-0.32]). CONCLUSIONS:Both community- and hospital-acquired rotavirus gastroenteritis are significant public health problems in Japan. Data from this study justify the need for the introduction and implementation of rotavirus vaccination in the Japanese national immunization program. TRIAL REGISTRATION:ClinicalTrials.gov, NCT01202201.

Project description:Group A rotavirus infections cause diarrhea in infants and primarily occur in winter. These viruses are characterized by the viral structural proteins VP7 (G subtypes) and VP4 (P subtypes). Current treatments employ vaccines combined with symptomatic treatments. Through a review of published papers from 2003-2013, which included articles, theses, dissertations and academic conference proceedings in PubMed and CNKI (China National Knowledge Infrastructure), we examined the epidemiological and clinical studies conducted in the 7 regional administrative geographical divisions of the People's Republic of China. Binning of the clinical studies provided a quantitative synthesis of the published incidences of rotavirus-positive numbers, the infection rates and the distributions of different subtypes in the provinces. In an investigation of the 32 provincial administrative regions from 1994-2013, the number of positive infections in children, primarily ≤5 years of age, was highest in Guangdong (187,000 cases), Zhejiang (133,000 cases) and Hubei (11,000 cases) Provinces; the provinces that displayed the highest positive rates were Henan (75.20%), Jilin (64.94%) and the Ningxia Hui Autonomous Region (60.16%). Furthermore, the virus, which causes diarrhea, can also infect adults. Statistics regarding the rotavirus subtypes indicated that the top 3 G-subtypes reported were G3 (8,509 cases), G1 (6,490 cases) and G2 (1,601 cases); the top 3 P-subtypes reported were P[8] (8,483 cases), P[4] (2,017 cases) and P[6] (740 cases). The majority of clinical treatments for these infections comprised a combination of Chinese traditional and Western medicines, together with nursing and the administration of a variety of oral liquids to relieve symptoms. The top 3 positive rates were identified in provinces at higher latitude, which confirms increases in humidity and ambient temperature reduce the rotavirus infection rate and the number of rotavirus infections tends to be highest under cool, dry conditions. However, the presence of rotavirus in low-latitude provinces likely indicates living habits, living environments, and education level influencethe precautions and vaccine utilization rate. The traditional subtypes are the rotavirus G- and P-subtypes, thus allowing for the development of vaccines. In China, the treatments that are primarily used to combat the infection are integrative medicines combining a variety of nursing and adjuvant therapies.

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Heterogeneous susceptibility to rotavirus infection and gastroenteritis in two birth cohort studies: Parameter estimation and epidemiological implications.

Publications

Heterogeneous susceptibility to rotavirus infection and gastroenteritis in two birth cohort studies: Parameter estimation and epidemiological implications.

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