Burden, Clinical Characteristics, Risk Factors, and Seasonality of Adenovirus 40/41 Diarrhea in Children in Eight Low-Resource Settings

Godfrey Guga; Sarah Elwood; Caroline Kimathi; Gagandeep Kang; Margaret N Kosek; Aldo A M Lima; Pascal O Bessong; Amidou Samie; Rashidul Haque; Jose Paulo Leite; Ladaporn Bodhidatta; Najeeha Iqbal; Nicola Page; Ireen Kiwelu; Zulfiqar A Bhutta; Tahmeed Ahmed; Jie Liu; Elizabeth T Rogawski McQuade; Eric Houpt; James A Platts-Mills; Estomih R Mduma

doi:10.1093/ofid/ofac241

Burden, Clinical Characteristics, Risk Factors, and Seasonality of Adenovirus 40/41 Diarrhea in Children in Eight Low-Resource Settings

Open Forum Infect Dis. 2022 May 13;9(7):ofac241. doi: 10.1093/ofid/ofac241. eCollection 2022 Jul.

Authors

Godfrey Guga¹, Sarah Elwood², Caroline Kimathi¹, Gagandeep Kang³, Margaret N Kosek², Aldo A M Lima⁴, Pascal O Bessong⁵, Amidou Samie⁵, Rashidul Haque⁶, Jose Paulo Leite⁷, Ladaporn Bodhidatta⁸, Najeeha Iqbal⁹, Nicola Page¹⁰, Ireen Kiwelu¹¹, Zulfiqar A Bhutta⁹, Tahmeed Ahmed⁶, Jie Liu², Elizabeth T Rogawski McQuade¹², Eric Houpt², James A Platts-Mills², Estomih R Mduma¹

Affiliations

¹ Haydom Global Health Research Centre, Haydom, Tanzania.
² Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USA.
³ Christian Medical College, Vellore, India.
⁴ Federal University of Ceara, Fortaleza, Brazil.
⁵ University of Venda, Thohoyandou, South Africa.
⁶ International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.
⁷ Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil.
⁸ Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
⁹ Aga Khan University, Karachi, Pakistan.
¹⁰ National Institute for Communicable Diseases, Johannesburg, South Africa.
¹¹ Kilimanjaro Clinical Research Institute, Moshi, Tanzania.
¹² Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.

Abstract

Background: The application of molecular diagnostics has identified enteric group adenovirus serotypes 40 and 41 as important causes of diarrhea in children. However, many aspects of the epidemiology of adenovirus 40/41 diarrhea have not been described.

Methods: We used data from the 8-site Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project birth cohort study to describe site- and age-specific incidence, risk factors, clinical characteristics, and seasonality.

Results: The incidence of adenovirus 40/41 diarrhea was substantially higher by quantitative polymerase chain reaction than enzyme immunoassay and peaked at ∼30 episodes per 100 child-years in children aged 7-15 months, with substantial variation in incidence between sites. A significant burden was also seen in children 0-6 months of age, higher than other viral etiologies with the exception of rotavirus. Children with adenovirus 40/41 diarrhea were more likely to have a fever than children with norovirus, sapovirus, and astrovirus (adjusted odds ratio [aOR], 1.62; 95% CI, 1.16-2.26) but less likely than children with rotavirus (aOR, 0.66; 95% CI, 0.49-0.91). Exclusive breastfeeding was strongly protective against adenovirus 40/41 diarrhea (hazard ratio, 0.64; 95% CI, 0.48-0.85), but no other risk factors were identified. The seasonality of adenovirus 40/41 diarrhea varied substantially between sites and did not have clear associations with seasonal variations in temperature or rainfall.

Conclusions: This study supports the situation of adenovirus 40/41 as a pathogen of substantial importance, especially in infants. Fever was a distinguishing characteristic in comparison to other nonrotavirus viral etiologies, and promotion of exclusive breastfeeding may reduce the high observed burden in the first 6 months of life.

Keywords: adenovirus; children; diarrhea; qPCR; seasonality.