Enteropathy

The World Health Organization has set forth ambitious efforts to control, and where possible, eliminate the neglected tropical diseases (NTDs) that contribute to poverty and ‘‘impair the ability of those infected to achieve their full potential, both developmentally and socioeconomically’’ (1,2)].

Currently, there are still >700,000 deaths per year globally related to diarrheal diseases (3), and in addition, the frequency of diarrheal episodes has not declined but remains unacceptably high (4). Among the myriad pathogens causing diarrhea in low/middle-income countries, the protozoa Giardia lamblia (synonymous with G. intestinalis/G. duodenalis) and Cryptosporidium spp. are among the most commonly isolated (5). In the past few years, important lessons have learned that make imperative an emphasis on these ‘‘neglected enteric protozoa’’ (NEP) and other enteropathy associated pathogens. Therefore, it must be recognized that environmental enteropathy (EE) is likely both a common and complex disease, and that infections related to the development or exacerbation of environmental enteropathy deserve prioritization in disease control strategies. One significant hurdle to overcome is the challenge inherent in studying a disease process that otherwise requires endoscopy and tissue biopsy for diagnosis.

The pursuit for reliable noninvasive biomarkers of EE that are readily available and both sensitive and specific is crucial for determining the true prevalence of this condition, and for increasing our understanding of its underlying pathophysiology and disease modulators (i.e., differential effects from various pathogens and co-pathogen infections, nutritional status and micronutrient intake, host genetics/epigenetics, and microbiota). Studies are currently investigating several leading candidate biomarkers found to be elevated in children in low-income countries, including: markers of intestinal inflammation such as fecal myeloperoxidase (MPO), lactoferrin, and neopterin; serum alpha-1 anti-trypsin (A1AT), a marker of hyperpermeability and protein wasting; and serum endotoxin core antibody (EndoCAb), a marker of bacterial translocation and systemic immune activation. Clinical Investigations have identified that elevated fecal lactoferrin and EndoCAb are present in malnourished children and in certain enteric infections, and that malnourished children have increased lactulose:mannitol ratios (L:M) (5,6). A combination of these candidate biomarkers or novel approaches such as metabonomics are needed to begin to truly appreciate the global prevalence, spectrum, and impact of EE and the differential influence NEP and other pathogens have on its severity.

Reference:

Bartelt, L.A et al; ‘‘Barriers’’ to Child Development and Human Potential: The Case for including the ‘‘Neglected Enteric Protozoa’’ (NEP) and Other Enteropathy-Associated Pathogens in the NTDs. PLOS Neglected Tropical Diseases 2013, 7 (4): 1- 5.

Other references:

  1. Savioli LS, Daumerie D (2010) First WHO report on neglected tropical diseases: working to overcome the global impact of neglected tropical diseases. Geneva: World Health Organization. pp. 1–169.
  2. Savioli L, Smith H, Thompson A (2006) Giardia and Cryptosporidium join the ‘Neglected Diseases Initiative’. Trends Parasitol 22:203–208.
  3. Liu L, Johnson HL, Cousens S, Perin J, Scott S, Lawn JE, Rudan I, Campbell H, Cibulskis R, Li M, Mathers C, Black RE, Childh Health Epidemiology Reference Group of WHO and UNICEF. (2012) Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet 379 (9832): 2151–2161.
  4. Kosek M, Bern C, Guerrant RL (2003) The global burden of diarrhoeal disease, as estimated from studies published between 1992 and 2000. Bull World Health Organ 81: 197–204.
  5. Mondal D, Minak J, Alam M, Liu Y, Dai J, et al. (2012) Contribution of enteric infection, altered intestinal barrier function, and maternal malnutrition to infant malnutrition in Bangladesh. Clin Infect Dis 54: 185–192.
  6. Barboza Junior MS, Silva TM, Guerrant RL, Lima AA (1999) Measurement of intestinal permeability using mannitol and lactulose in children with diarrheal diseases. Braz J Med Biol Res 32: 1499–1504.

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