Enteropathies in the Developing World: Neglected Effects on Global Health

Prendergast, Andrew J.; Kelly, Paul

doi:10.4269/ajtmh.2012.11-0743

Cited by 237 publications

(263 citation statements)

References 75 publications

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“…Environmental enteric dysfunction (EED) -also referred to as 'environmental enteropathy' -is a subclinical disorder characterized by the flattening of intestinal villi, nutrient malabsorption, intestinal inflammation (including an influx of inflammatory cells into the lamina propria) and increased gut permeability [162,163]. These manifestations may begin to appear soon after birth: during a study in India, the majority of infants displayed some degree of villous blunting within the first 30 days of life [164].…”

Section: Environmental Enteric Dysfunctionmentioning

confidence: 99%

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

et al. 2017

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Oral vaccines are less immunogenic when given to infants in low-income compared with high-income countries, limiting their potential public health impact. Here, we review factors that might contribute to this phenomenon, including transplacental antibodies, breastfeeding, histo blood group antigens, enteric pathogens, malnutrition, microbiota dysbiosis and environmental enteropathy. We highlight several clear risk factors for vaccine failure, such as the inhibitory effect of enteroviruses on oral poliovirus vaccine. We also highlight the ambiguous and at times contradictory nature of the available evidence, which undoubtedly reflects the complex and interconnected nature of the factors involved. Mechanisms responsible for diminished immunogenicity may be specific to each oral vaccine. Interventions aiming to improve vaccine performance may need to reflect the diversity of these mechanisms. Enteric pathogens are a substantial threat to public health. This threat takes many forms, from the toxin-producing bacteria (e.g., Vibrio cholerae) and flagellated protozoa (e.g., Giardia lamblia) that colonize the mucosal surface of the small intestine to the enteroviruses that are capable of spreading via the bloodstream to the CNS, causing acute flaccid paralysis (e.g., poliovirus). Each year, enteric pathogens cause hundreds of millions of cases of diarrhea and approximately 800,000 deaths, the vast majority of which occur among children in low-income countries [1]. The most common causes of childhood diarrheal morbidity include rotavirus, Cryptosporidium, enterotoxigenic Escherichia coli and Shigella [2].Vaccines against enteric pathogens are important tools for mitigating this disease burden. Oral vaccines offer several distinct benefits compared with parenteral vaccines. They can be produced in large quantities at relatively low cost, are easy to administer and have the capacity to induce local immunity in the intestinal mucosa, thereby protecting vaccinated individuals against subsequent infection and -by blocking onward transmission -enhancing herd immunity [3,4]. Currently licensed oral vaccines include live-attenuated poliovirus vaccines containing one, two or three serotypes, live-attenuated rotavirus vaccines (Rotarix R , RotaTeq R , Lanzhou lamb rotavirus vaccine [China only] and Rotavac R [India only]), live-attenuated cholera vaccine (CVD 103-HgR or Vaxchora TM ), inactivated cholera vaccines (Dukoral R and Shanchol R ) and live-attenuated typhoid vaccine (Ty21a). Other oral vaccines are in development, including those against Shigella, enterotoxigenic E. coli, Campylobacter and Clostridium difficile, as well as several novel rotavirus vaccine candidates (including the human neonatal vaccine RV3-BB [5] and an oral bovine pentavalent vaccine [6]).Yet oral vaccines have an Achilles' heel -their immunogenicity and efficacy is impaired in low-income countries that experience the greatest burden of enteric disease (Box 1). For example, Rotarix has a 1-year protective efficacy against severe rotavirus-associated gas...

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Section: Environmental Enteric Dysfunctionmentioning

confidence: 99%

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

et al. 2017

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“…Scrimshaw et al [9] first described a vicious cycle of infection and undernutrition, whereby infections predispose to malnutrition, through reduced intake and absorption and diversion of nutrients away from growth, while malnutrition reduces immune function and increases the risk and/or severity of infections. Various iterations of this cycle have been proposed over the years, with more recent versions recognizing that subclinical infection, enteropathy, changes in the composition and function of the gut microbiota and systemic inflammation are likely to be important in the pathogenesis of malnutrition, in addition to overt infections [10][11][12]. Children hospitalized for severe acute malnutrition are extremely sick, with physiological dysfunction such as reduced respiratory muscle mass, impaired cardiac function and electrolyte disturbance, in addition to micronutrient deficiencies, inflammation, clinical infection and mucosal barrier breakdown.…”

Section: The Immunology Of Malnutritionmentioning

confidence: 99%

Malnutrition and vaccination in developing countries

Prendergast

2015

Phil. Trans. R. Soc. B

130

103

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Malnutrition contributes to an estimated 45% of deaths among children under 5 years of age in developing countries, predominantly due to infections. Malnourished children therefore stand to benefit hugely from vaccination, but malnutrition has been described as the most common immunodeficiency globally, suggesting that they may not be able to respond effectively to vaccines. The immunology of malnutrition remains poorly characterized, but is associated with impairments in mucosal barrier integrity, and innate and adaptive immune dysfunction. Despite this, the majority of malnourished children can mount a protective immune response following vaccination, although the timing, quality and duration of responses may be impaired. This paper reviews the evidence for vaccine immunogenicity in malnourished children, discusses the importance of vaccination in prevention of malnutrition and highlights evidence gaps in our current knowledge.

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“…Environmental enteropathy (EE) is a gut disorder that is prevalent among inhabitants of low-income countries living in environments with poor sanitation and hygiene [1][2][3][4][5][6][7]. Chronic exposure to faecal pathogens is hypothesized to cause inflammation and resultant structural changes in the small bowel, which ultimately result in functional changes.…”

Section: Introductionmentioning

confidence: 99%

“…These functional changes include gut barrier disruption, carbohydrate malabsorption and chronic inflammation, and are hypothesized to contribute to impaired gut immune function and oral vaccine failure, and ultimately growth faltering and impaired child development. This disease is thought to occur in otherwise asymptomatic individuals without evidence of overt diarrhoea [1][2][3]5]. The lack of both non-invasive tests to diagnose and effective interventions to prevent or treat EE has left a large knowledge gap.…”

Section: Introductionmentioning

confidence: 99%

Exploring the role of environmental enteropathy in malnutrition, infant development and oral vaccine response

Gilmartin

Petri

2015

Phil. Trans. R. Soc. B

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Environmental enteropathy (EE) is a poorly defined state of intestinal inflammation without overt diarrhoea that occurs in individuals exposed over time to poor sanitation and hygiene. It is characterized pathologically by small intestine villous blunting and inflammation. In children from low-income countries, it is implicated as a cause of malnutrition, oral vaccine failure and impaired cognitive development. Here we review the search for non-invasive biomarkers to measure EE non-invasively, and assess the current evidence linking EE to malnutrition, vaccine failure and neurocognitive development.

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Enteropathies in the Developing World: Neglected Effects on Global Health

Cited by 237 publications

References 75 publications

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

Malnutrition and vaccination in developing countries

Exploring the role of environmental enteropathy in malnutrition, infant development and oral vaccine response

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