Volume 102, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Globally, diarrheal and respiratory infections are responsible for more than 24% of deaths in children aged less than 5 years. Historically, these disease entities have been studied separately; recent evidence suggests that preceding diarrheal disease may be a risk factor for subsequent respiratory illness. We used data from a community-based, prospective randomized trial of maternal influenza immunization of 3,693 pregnant women and their 3,646 infants conducted in rural Nepal from 2011 to 2014. A case-crossover design was used to determine whether the risk of respiratory infection in the 30 days following a diarrheal episode was increased compared with that 30 days prior. Diarrheal illness was a significant risk factor for subsequent respiratory illness in infants but not in women during pregnancy or in women up to six months postpartum. Diarrheal illness and respiratory infections remain important global sources of morbidity and mortality, and our study supports a causal relationship between them in infants.

[open-access] This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Liu L, Oza S, Hogan D, Perin J, Rudan I, Lawn JE, Cousens S, Mathers C, Black RE, , 2015. Global, regional, and national causes of child mortality in 2000–13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet 385: 430440. [Google Scholar]
  2. United Nations, 2015. Transforming Our World: the 2030 Agenda for Sustainable Development: UN General Assembly. New York, NY: United Nations. [Google Scholar]
  3. Ashraf S, Huque MH, Kenah E, Agboatwalla M, Luby SP, , 2013. Effect of recent diarrhoeal episodes on risk of pneumonia in children under the age of 5 years in Karachi, Pakistan. Int J Epidemiol 42: 194200. [Google Scholar]
  4. Leung DT, Das SK, Malek MA, Qadri F, Faruque AS, Chisti MJ, Ryan ET, , 2015. Concurrent pneumonia in children under 5 years of age presenting to a diarrheal hospital in Dhaka, Bangladesh. Am J Trop Med Hyg 93: 831835. [Google Scholar]
  5. Schmidt WP, Cairncross S, Barreto ML, Clasen T, Genser B, , 2009. Recent diarrhoeal illness and risk of lower respiratory infections in children under the age of 5 years. Int J Epidemiol 38: 766772. [Google Scholar]
  6. Walker CL, Perin J, Katz J, Tielsch JM, Black RE, , 2013. Diarrhea as a risk factor for acute lower respiratory tract infections among young children in low income settings. J Glob Health 3: 010402. [Google Scholar]
  7. Chisti MJ, Huq S, Das SK, Malek MA, Ahmed T, Faruque AS, Salam MA, , 2008. Predictors of severe illness in children under age five with concomitant infection with pneumonia and diarrhea at a large hospital in Dhaka, Bangladesh. Southeast Asian J Trop Med Public Health 39: 719727. [Google Scholar]
  8. Sachdev HP, Kumar S, Singh KK, Satyanarayana L, Puri RK, , 1991. Risk factors for fatal diarrhea in hospitalized children in India. J Pediatr Gastroenterol Nutr 12: 7681. [Google Scholar]
  9. McDermott MR, Bienenstock J, , 1979. Evidence for a common mucosal immunologic system. I. Migration of B immunoblasts into intestinal, respiratory, and genital tissues. J Immunol 122: 18921898. [Google Scholar]
  10. Mjosberg J, Rao A, , 2018. Lung inflammation originating in the gut. Science 359: 3637. [Google Scholar]
  11. Bingula R, Filaire M, Radosevic-Robin N, Bey M, Berthon JY, Bernalier-Donadille A, Vasson MP, Filaire E, , 2017. Desired turbulence? Gut-lung Axis, immunity, and lung cancer. J Oncol 2017: 5035371. [Google Scholar]
  12. Ichinohe T, Pang IK, Kumamoto Y, Peaper DR, Ho JH, Murray TS, Iwasaki A, , 2011. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc Natl Acad Sci USA 108: 53545359. [Google Scholar]
  13. Steinhoff MC, 2017. Year-round influenza immunisation during pregnancy in Nepal: a phase 4, randomised, placebo-controlled trial. Lancet Infect Dis 17: 981989. [Google Scholar]
  14. World Health Organization, 2018. Health Topics: Diarrhoea. Available at: http://www.who.int/topics/diarrhoea/en/. Accessed August 23, 2018. [Google Scholar]
  15. Dixon KE, , 1997. A comparison of case-crossover and case-control designs in a study of risk factors for hemorrhagic fever with renal syndrome. Epidemiology 8: 243246. [Google Scholar]
  16. Popkin BM, Adair L, Akin JS, Black R, Briscoe J, Flieger W, , 1990. Breast-feeding and diarrheal morbidity. Pediatrics 86: 874882. [Google Scholar]

Data & Media loading...

  • Received : 28 May 2019
  • Accepted : 23 Sep 2019
  • Published online : 25 Nov 2019

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error