Volume 88, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Enteric infections are associated with linear growth failure in children. To quantify the association between intestinal inflammation and linear growth failure three commercially available enzyme-linked immunosorbent assays (neopterin [NEO], alpha-anti-trypsin [AAT], and myeloperoxidase [MPO]) were performed in a structured sampling of asymptomatic stool from children under longitudinal surveillance for diarrheal illness in eight countries. Samples from 537 children contributed 1,169 AAT, 916 MPO, and 954 NEO test results that were significantly associated with linear growth. When combined to form a disease activity score, children with the highest score grew 1.08 cm less than children with the lowest score over the 6-month period following the tests after controlling for the incidence of diarrheal disease. This set of affordable non-invasive tests delineates those at risk of linear growth failure and may be used for the improved assessments of interventions to optimize growth during a critical period of early childhood.

[open-access] This is an Open Access article distributed under the terms of the American Society of Tropical Medicine and Hygiene's Re-use License which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Article metrics loading...

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

Full text loading...



  1. Black RE, Allen LH, Bhutta ZA, Caulfield LE, de Onis M, Ezzati M, Mathers C, Rivera J, , 2008. Maternal and child undernutrition: global and regional exposures and health consequences. Lancet 371: 243260.[Crossref] [Google Scholar]
  2. Victora CG, de Onis M, Hallal PC, Blossner M, Shrimpton R, , 2010. Worldwide timing of growth faltering: revisiting implications for interventions. Pediatrics 125: e473e480.[Crossref] [Google Scholar]
  3. Bhutta ZA, Ahmed T, Black RE, Cousens S, Dewey K, Giugliani E, Haider BA, Kirkwood B, Morris SS, Sachdev HP, Shekar M, , 2008. What works? Interventions for maternal and child undernutrition and survival. Lancet 371: 417440.[Crossref] [Google Scholar]
  4. Sullivan PB, Marsh MN, Mirakian R, Hill SM, Milla PJ, Neale G, , 1991. Chronic diarrhea and malnutrition–histology of the small intestinal lesion. J Pediatr Gastroenterol Nutr 12: 195203.[Crossref] [Google Scholar]
  5. Sullivan PB, Lunn PG, Northrop-Clewes C, Crowe PT, Marsh MN, Neale G, , 1992. Persistent diarrhea and malnutrition–the impact of treatment on small bowel structure and permeability. J Pediatr Gastroenterol Nutr 14: 208215.[Crossref] [Google Scholar]
  6. Campbell DI, Murch SH, Elia M, Sullivan PB, Sanyang MS, Jobarteh B, Lunn PG, , 2003. Chronic T cell-mediated enteropathy in rural west African children: relationship with nutritional status and small bowel function. Pediatr Res 54: 306311.[Crossref] [Google Scholar]
  7. Kelly P, Menzies I, Crane R, Zulu I, Nickols C, Feakins R, Mwansa J, Mudenda V, Katubulushi M, Greenwald S, Farthing M, , 2004. Responses of small intestinal architecture and function over time to environmental factors in a tropical population. Am J Trop Med Hyg 70: 412419. [Google Scholar]
  8. Lunn PG, Northrop-Clewes CA, Downes RM, , 1991. Intestinal permeability, mucosal injury, and growth faltering in Gambian infants. Lancet 338: 907910.[Crossref] [Google Scholar]
  9. Campbell DI, Elia M, Lunn PG, , 2003. Growth faltering in rural Gambian infants is associated with impaired small intestinal barrier function, leading to endotoxemia and systemic inflammation. J Nutr 133: 13321338. [Google Scholar]
  10. Campbell DI, Lunn PG, Elia M, , 2002. Age-related association of small intestinal mucosal enteropathy with nutritional status in rural Gambian children. Br J Nutr 88: 499505.[Crossref] [Google Scholar]
  11. Sharp HL, , 1976. The current status of alpha-1-antityrpsin, a protease inhibitor, in gastrointestinal disease. Gastroenterology 70: 611621. [Google Scholar]
  12. Crossley JR, Elliott RB, , 1977. Simple method for diagnosing protein-losing enteropathies. BMJ 1: 428429.[Crossref] [Google Scholar]
  13. Laine L, Garcia F, McGilligan K, Malinko A, Sinatra FR, Thomas DW, , 1993. Protein-losing enteropathy and hypoalbuminemia in AIDS. AIDS 7: 837840.[Crossref] [Google Scholar]
  14. Black RE, Levine MM, , 1991. Intestinal protein loss in shigellosis. Nutr Res 11: 12151220.[Crossref] [Google Scholar]
  15. Black RE, Brown KH, Becker S, , 1984. Effects of diarrhea associated with specific enteropathogens on the growth of children in rural Bangladesh. Pediatrics 73: 799805. [Google Scholar]
  16. Margreiter R, Fuchs D, Hausen A, Huber C, Reibnegger G, Spielberger M, Wachter H, , 1983. Neopterin as a new biochemical marker for diagnosis of allograft rejection. Experience based upon evaluation of 100 consecutive cases. Transplantation 36: 650653.[Crossref] [Google Scholar]
  17. Leohirun L, Thuvasethakul P, Sumethkul V, Pholcharoen T, Boonpucknavig V, , 1991. Urinary neopterin in patients with systemic lupus erythematosus. Clin Chem 37: 4750. [Google Scholar]
  18. Fuchs D, Granditsch G, Hausen A, Reibnegger G, Wachter H, , 1983. Urinary neopterin excretion in coeliac disease. Lancet 2: 463464.[Crossref] [Google Scholar]
  19. Campbell DI, McPhail G, Lunn PG, Elia M, Jeffries DJ, , 2004. Intestinal inflammation measured by fecal neopterin in Gambian children with enteropathy: association with growth failure, Giardia lamblia, and intestinal permeability. J Pediatr Gastroenterol Nutr 39: 153157.[Crossref] [Google Scholar]
  20. Dorosko SM, Mackenzie T, Connor RI, , 2008. Fecal calprotectin concentrations are higher in exclusively breastfed infants compared to those who are mixed-fed. Breastfeed Med 3: 117119.[Crossref] [Google Scholar]
  21. Saiki T, , 1998. Myeloperoxidase concentrations in the stool as a new parameter of inflammatory bowel disease. Kurume Med J 45: 6973.[Crossref] [Google Scholar]
  22. Victora CG, Adair L, Fall C, Hallal PC, Martorell R, Richter L, Sachdev HS, , 2008. Maternal and child undernutrition: consequences for adult health and human capital. Lancet 371: 340357.[Crossref] [Google Scholar]
  23. Beckmann G, Ruffer A, , 2000. Microbiology of the Intestine. Hannover: Schluttersche, 1446. [Google Scholar]
  24. Ledjeff E, Artner-Dworzak E, Witasek A, Fuchs D, Hausen A, , 2001. Neopterin concentrations in colon dialysate. Pteridines 12: 155160.[Crossref] [Google Scholar]
  25. Meyers S, Wolke A, Field SP, Feuer EJ, Johnson JW, Janowitz HD, , 1985. Fecal alpha 1-antitrypsin measurement: an indicator of Crohn's disease activity. Gastroenterology 89: 1318.[Crossref] [Google Scholar]
  26. Huber C, Batchelor JR, Fuchs D, Hausen A, Lang A, Niederwieser D, Reibnegger G, Swetly P, Troppmair J, Wachter H, , 1984. Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon-gamma. J Exp Med 160: 310316.[Crossref] [Google Scholar]

Data & Media loading...

Supplementary PDF

  • Received : 04 Sep 2012
  • Accepted : 13 Oct 2012
  • Published online : 06 Feb 2013

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