Pathogen-Specific Burden of Outpatient Diarrhea in Infants in Nepal: A Multisite Prospective Case-Control Study

• Published in: Journal of the Pediatric Infectious Diseases Society Vol. 6; no. 3; pp. e75 - e85
• Main Authors: Cardemil, Cristina V, Sherchand, Jeevan B, Shrestha, Laxman, Sharma, Arun, Gary, Howard E, Estivariz, Concepcion F, Diez-Valcarce, Marta, Ward, M Leanne, Bowen, Michael D, Vinjé, Jan, Parashar, Umesh, Chu, Susan Y
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01-09-2017
• Subjects: Age Factors; Bacteria - isolation & purification; Bacterial Infections - epidemiology; Bacterial Infections - microbiology; Caliciviridae Infections - diagnosis; Caliciviridae Infections - epidemiology; Caliciviridae Infections - virology; Case-Control Studies; Diarrhea - diagnosis; Diarrhea - epidemiology; Diarrhea - microbiology; Diarrhea - virology; Feces - microbiology; Feces - virology; Female; Genotype; Health Facilities; Humans; Infant; Male; Molecular Epidemiology; Multiplex Polymerase Chain Reaction - methods; Nepal; Norovirus - genetics; Norovirus - isolation & purification; Outpatients; Polymerase Chain Reaction; Prospective Studies; Rotavirus - genetics; Rotavirus - isolation & purification; Rotavirus Infections - diagnosis; Rotavirus Infections - epidemiology; Rotavirus Infections - virology; Rotavirus Vaccines; norovirus; diarrhea; rotavirus; Nepal; Salmonella; Campylobacter
• ISSN: 2048-7193; 2048-7207
• DOI: 10.1093/jpids/pix009

Abstract
Background
Nonsevere diarrheal disease in Nepal represents a large burden of illness. Identification of the specific disease-causing pathogens will help target the appropriate control measures.
Methods
Infants aged 6 weeks to 12 months were recruited from 5 health facilities in eastern, central, and western Nepal between August 2012 and August 2013. The diarrhea arm included infants with mild or moderate diarrhea treatable in an outpatient setting; the nondiarrhea arm included healthy infants who presented for immunization visits or had a mild nondiarrheal illness. Stool samples were tested for 15 pathogens with a multiplex polymerase chain reaction (PCR) assay and real-time reverse-transcription (RT)-PCR assays for rotavirus and norovirus. Rotavirus- and norovirus-positive specimens were genotyped. We calculated attributable fractions (AFs) to estimate the pathogen-specific burden of diarrhea and adjusted for facility, age, stunting, wasting, and presence of other pathogens.
Results
We tested 307 diarrheal and 358 nondiarrheal specimens. Pathogens were detected more commonly in diarrheal specimens (164 of 307 [53.4%]) than in nondiarrheal specimens (113 of 358 [31.6%]) (P < .001). Rotavirus (AF, 23.9% [95% confidence interval (CI), 14.9%–32.8%]), Salmonella (AF, 12.4% [95% CI, 6.6%–17.8%]), and Campylobacter (AF, 5.6% [95% CI, 1.3%–9.8%]) contributed most to the burden of disease. In these diarrheal specimens, the most common genotypes for rotavirus were G12P[6] (27 of 82 [32.9%]) and G1P[8] (16 of 82 [19.5%]) and for norovirus were GII.4 Sydney (9 of 26 [34.6%]) and GII.7 (5 of 26 [19.2%]).
Conclusions
The results of this study indicate that the introduction of a rotavirus vaccine in Nepal will likely decrease outpatient diarrheal disease burden in infants younger than 1 year, but interventions to detect and target other pathogens, such as Salmonella and Campylobacter spp, should also be considered.