Primary and Repeated Respiratory Viral Infections Among Infants in Rural Nepal

Abstract

Background: Respiratory viruses cause significant morbidity and death in infants; 99% of such deaths occur in resource-limited settings. Risk factors for initial and repeated respiratory viral infections in young infants in resource-limited settings have not been well described.

Methods: From 2011 to 2014, a birth cohort of infants in rural Nepal was enrolled and followed with weekly household-based active surveillance for respiratory symptoms until 6 months of age. Respiratory illness was defined as having any of the following: fever, cough, wheeze, difficulty breathing, and/or a draining ear. We tested nasal swabs of infants with respiratory illness for multiple respiratory viruses by using a reverse transcription polymerase chain reaction assay. The risk of primary and repeated infections with the same virus was evaluated using Poisson regression.

Results: Of 3528 infants, 1726 (49%) had a primary infection, and 419 (12%) had a repeated infection. The incidences of respiratory viral infection in infants were 1816 per 1000 person-years for primary infections and 1204 per 1000 person-years for repeated infection with the same virus. Exposure to other children and male sex were each associated with an increased risk for primary infection (risk ratios, 1.13 [95% confidence interval (CI), 1.06-1.20] and 1.14 [95% CI, 1.02-1.27], respectively), whereas higher maternal education was associated with a decreased risk for both primary and repeated infections (risk ratio, 0.96 [95% CI, 0.95-0.98]). The incidence of subsequent infection did not change when previous infection with the same or another respiratory virus occurred. Illness duration and severity were not significantly different in the infants between the first and second episodes for any respiratory virus tested.

Conclusions: In infants in rural Nepal, repeated respiratory virus infections were frequent, and we found no decrease in illness severity with repeated infections and no evidence of replacement with another virus. Vaccine strategies and public health interventions that provide durable protection in the first 6 months of life could decrease the burden of repeated infections by multiple respiratory viruses, particularly in low-resource countries.

Keywords: RSV; coronavirus; infants; influenza virus; parainfluenza virus; respiratory viruses; rhinovirus.

Figure 1.

Respiratory viral infections in Nepal. Shown are the numbers of cases of infection caused by coronavirus (COV) and human rhinovirus (HRV) (A), respiratory syncytial virus (RSV), influenza virus (FLU), and human metapneumovirus (HMPV) (B), and parainfluenza viruses types 1 through 4 (HPIV1 through HPIV4) (C) per month from 2011 to 2014 in infants in Nepal. Note that the relatively lower number of infants born and enrolled between April and July 2011 accounts for the lower number of respiratory viruses detected during that time.

Figure 2.

Clinical characteristics of respiratory viral infections in infants with repeated infections. (A) Durations of respiratory illness in infants with repeated infections of respiratory syncytial virus (RSV), human metapneumovirus (HMPV), influenza virus (Flu), human parainfluenza virus (HPIV), human rhinovirus (HRV), and coronavirus (CoV) during the first and second episodes. Each point represents 1 infant. Episodes for which not enough clinical data were available to assign severity are not shown and were not included in the analysis. Closed circles denote the first infection; open circles denote the second infection. (B) Severity for the first and second HRV episodes in infants with repeated infections. The size of each bubble reflects the percentage of infants with repeated HRV infections. Severity scores were based on the World Health Organization Integrated Management of Childhood Illness disease criteria. A severity score of 1 through 4 was assigned on the basis of whether the infant had an upper respiratory tract infection, mild lower respiratory tract infection (LRTI), severe LRTI, or very severe LRTI, respectively. (C) Durations of the first and second HRV episodes in infants with repeated infections. Each point represents 1 infant.