Norovirus-associated Diarrhea and Asymptomatic Infection in Children Aged Under 4 Years: a Community-cohort Study in the Philippines

Overview

Journal IJID Reg

Date 2025 Jan 29

PMID 39877416

Authors

Chuyao Yu

Maria Carmen A Corpuz

Joseph M Bonifacio

Makiko Kishi

Takeaki Imamura

Yusuke Sayama

Mariko Saito-Obata

Clyde Dapat

Michiko Okamoto

Hitoshi Oshitani

Mayuko Saito

Affiliations

Soon will be listed here.

Abstract

Objectives: This study aimed to estimate the incidence of norovirus (NoV)-associated diarrhea and asymptomatic infections in children under 4 years of age and identify the genotypes of multiple NoV infections.

Methods: A community-based cohort study was conducted in Tarlac, Philippines. Children aged 0-2 years were followed up for 2 years. The prevalence and incidence rates of NoV-associated diarrhea and asymptomatic infections were calculated. Risk factors were assessed using the Cox proportional hazards model. The genotypes and immunotypes of repeated infections were tabulated.

Results: A total of 338 children aged 6208 child-months were analyzed. NoV was detected in 17.4% (84 of 527, 95% confidence interval [CI]: 12.7-19.7%) of diarrheal episodes and 10.8% (219 of 2031, 95% CI: 9.4-12.3%) of asymptomatic stool samples. The highest incidence of NoV-associated diarrhea occurred in children aged 6-11 months (2.31 per 100 child-months, 95% CI: 1.30-3.32) and 18-23 months (2.34 per 100 child-months, 95% CI: 1.57-3.12), whereas the highest incidence of asymptomatic NoV infection was observed in children aged 12-23 months (4.49 per 100 child-months, 95% CI: 3.41-5.56). Repeated NoV infections were detected between different genotypes, except in two children who had repeated NoV GI.3 and two children with GI.9 infections.

Conclusions: Children had the highest risk of NoV-associated diarrhea during their first year of life, whereas asymptomatic NoV infections persisted after the second year. Repeated NoV infections suggest genotype-specific immunity after NoV infection.

References

ORyan M, Lucero Y, Prado V, Santolaya M, Rabello M, Solis Y . Symptomatic and asymptomatic rotavirus and norovirus infections during infancy in a Chilean birth cohort. Pediatr Infect Dis J. 2009; 28(10):879-84. DOI: 10.1097/INF.0b013e3181a4bb60. View

Menon V, George S, Sarkar R, Giri S, Samuel P, Vivek R . Norovirus Gastroenteritis in a Birth Cohort in Southern India. PLoS One. 2016; 11(6):e0157007. PMC: 4902233. DOI: 10.1371/journal.pone.0157007. View

Chhabra P, de Graaf M, Parra G, Chan M, Green K, Martella V . Updated classification of norovirus genogroups and genotypes. J Gen Virol. 2019; 100(10):1393-1406. PMC: 7011714. DOI: 10.1099/jgv.0.001318. View

Platts-Mills J, Babji S, Bodhidatta L, Gratz J, Haque R, Havt A . Pathogen-specific burdens of community diarrhoea in developing countries: a multisite birth cohort study (MAL-ED). Lancet Glob Health. 2015; 3(9):e564-75. PMC: 7328884. DOI: 10.1016/S2214-109X(15)00151-5. View

de Onis M, Onyango A, Borghi E, Siyam A, Blossner M, Lutter C . Worldwide implementation of the WHO Child Growth Standards. Public Health Nutr. 2012; 15(9):1603-10. DOI: 10.1017/S136898001200105X. View

Qi R, Huang Y, Liu J, Sun Y, Sun X, Han H . Global Prevalence of Asymptomatic Norovirus Infection: A Meta-analysis. EClinicalMedicine. 2019; 2-3:50-58. PMC: 6537540. DOI: 10.1016/j.eclinm.2018.09.001. View

Chan M, Roy S, Bonifacio J, Zhang L, Chhabra P, Chan J . Detection of Norovirus Variant GII.4 Hong Kong in Asia and Europe, 2017-2019. Emerg Infect Dis. 2020; 27(1):289-293. PMC: 7774557. DOI: 10.3201/eid2701.203351. View

Kojima S, Kageyama T, Fukushi S, Hoshino F, Shinohara M, Uchida K . Genogroup-specific PCR primers for detection of Norwalk-like viruses. J Virol Methods. 2001; 100(1-2):107-14. DOI: 10.1016/s0166-0934(01)00404-9. View

Blackwelder W, Biswas K, Wu Y, Kotloff K, Farag T, Nasrin D . Statistical methods in the Global Enteric Multicenter Study (GEMS). Clin Infect Dis. 2012; 55 Suppl 4:S246-53. PMC: 3502316. DOI: 10.1093/cid/cis788. View

10.

Thanusuwannasak T, Puenpa J, Chuchaona W, Vongpunsawad S, Poovorawan Y . Emergence of multiple norovirus strains in Thailand, 2015-2017. Infect Genet Evol. 2018; 61:108-112. DOI: 10.1016/j.meegid.2018.03.021. View

11.

Kageyama T, Kojima S, Shinohara M, Uchida K, Fukushi S, Hoshino F . Broadly reactive and highly sensitive assay for Norwalk-like viruses based on real-time quantitative reverse transcription-PCR. J Clin Microbiol. 2003; 41(4):1548-57. PMC: 153860. DOI: 10.1128/JCM.41.4.1548-1557.2003. View

12.

Jin M, Wu S, Kong X, Xie H, Fu J, He Y . Norovirus Outbreak Surveillance, China, 2016-2018. Emerg Infect Dis. 2020; 26(3):437-445. PMC: 7045832. DOI: 10.3201/eid2603.191183. View

13.

Kroneman A, Vennema H, Deforche K, v d Avoort H, Penaranda S, Oberste M . An automated genotyping tool for enteroviruses and noroviruses. J Clin Virol. 2011; 51(2):121-5. DOI: 10.1016/j.jcv.2011.03.006. View

14.

Peng C, Tsai C, Lin T, Perng L, Kao M, Yang T . Molecular characterization of secretor type alpha(1, 2)-fucosyltransferase gene deficiency in the Philippine population. Ann Hematol. 1999; 78(10):463-7. DOI: 10.1007/s002770050599. View

15.

Vielot N, Reyes Y, Blette B, Gonzalez F, Toval-Ruiz C, Gutierrez L . First Episodes of Norovirus and Sapovirus Gastroenteritis Protect Against Subsequent Episodes in a Nicaraguan Birth Cohort. Epidemiology. 2022; 33(5):650-653. PMC: 9378628. DOI: 10.1097/EDE.0000000000001500. View

16.

Rouhani S, Penataro Yori P, Paredes Olortegui M, Siguas Salas M, Rengifo Trigoso D, Mondal D . Norovirus Infection and Acquired Immunity in 8 Countries: Results From the MAL-ED Study. Clin Infect Dis. 2016; 62(10):1210-7. PMC: 4845786. DOI: 10.1093/cid/ciw072. View

17.

. Estimates of global, regional, and national morbidity, mortality, and aetiologies of diarrhoeal diseases: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Infect Dis. 2017; 17(9):909-948. PMC: 5589208. DOI: 10.1016/S1473-3099(17)30276-1. View

18.

Safadi M, Riera-Montes M, Bravo L, Tangsathapornpong A, Lagos R, Thisyakorn U . The burden of norovirus disease in children: a multi-country study in Chile, Brazil, Thailand and the Philippines. Int J Infect Dis. 2021; 109:77-84. DOI: 10.1016/j.ijid.2021.06.037. View

19.

Lopman B, Trivedi T, Vicuna Y, Costantini V, Collins N, Gregoricus N . Norovirus Infection and Disease in an Ecuadorian Birth Cohort: Association of Certain Norovirus Genotypes With Host FUT2 Secretor Status. J Infect Dis. 2014; 211(11):1813-21. PMC: 4425937. DOI: 10.1093/infdis/jiu672. View

20.

Saito M, Goel-Apaza S, Espetia S, Velasquez D, Cabrera L, Loli S . Multiple norovirus infections in a birth cohort in a Peruvian Periurban community. Clin Infect Dis. 2013; 58(4):483-91. PMC: 3905757. DOI: 10.1093/cid/cit763. View