The Association Between Fecal Biomarkers of Environmental Enteropathy and Rotavirus Vaccine Response in Nicaraguan Infants

Becker‐Dreps, Sylvia; Vílchez, Samuel; Bucardo, Filemón; Twitchell, Erica; Choi, Wan Suk; Hudgens, Michael G.; Pérez, J García; Yuan, Lijuan

doi:10.1097/inf.0000000000001457

Cited by 28 publications

(36 citation statements)

References 24 publications

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“…Responses to oral RV vaccine were associated with fecal markers of inflammation in Nicaragua. 82 Vaccine responses to oral RV vaccine were attenuated in children with malnutrition and diarrhea in Bangladesh, 83 but this was not found in an earlier study from Brazil and Venezuela. 84 More recently, the PROVIDE study demonstrated that OPV and RV vaccine responses were negatively impacted by EED, as measured by fecal biomarkers.…”

Section: Could Enteropathy Plausibly Explain Poor Oral Vaccine Responmentioning

confidence: 86%

Pathophysiology of environmental enteric dysfunction and its impact on oral vaccine efficacy

et al. 2018

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Environmental enteric dysfunction (EED) refers to a subclinical disorder of intestinal function common in tropical countries and in settings of poverty and economic disadvantage. The enteropathy that underlies this syndrome is characterized by mucosal inflammation and villus blunting mediated by T cell activation. Epithelial cell disruption and microbial translocation drive systemic inflammation. EED in young children is associated geographically with growth failure, malnutrition, and greatly impaired responses to oral vaccines, notably rotavirus and poliovirus vaccines. In this review, we describe the pathophysiology of EED and examine the evidence linking EED and oral vaccine failure. This evidence is far from conclusive. Although our understanding of EED is still sketchy, there is limited evidence of disturbed innate immunity, B cell disturbances including aggregation into lymphoid follicles, and autoantibody generation. Pathways of T cell activation and the possibility of dendritic cell anergy, which could help explain oral vaccine failure, require further work.

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Section: Could Enteropathy Plausibly Explain Poor Oral Vaccine Responmentioning

confidence: 86%

Pathophysiology of environmental enteric dysfunction and its impact on oral vaccine efficacy

et al. 2018

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“…In Ghana and Pakistan, the intestinal microbiome composition has been associated with diminished efficacy of the RV1 vaccine 121,122 , although the exact implications of this are unclear. Environmental enteropathy (a common disorder in children in some low-income countries that is associated with diminished gastrointestinal immunity) might also have a role in reduced vaccine effectiveness in developing countries 123 . Indeed, the presence of biomarkers of environmental enteropathy has been associated with diminished RV5 vaccine seroconversion in infants 123 .…”

Section: Diagnosis Screening and Preventionmentioning

confidence: 99%

“…Environmental enteropathy (a common disorder in children in some low-income countries that is associated with diminished gastrointestinal immunity) might also have a role in reduced vaccine effectiveness in developing countries 123 . Indeed, the presence of biomarkers of environmental enteropathy has been associated with diminished RV5 vaccine seroconversion in infants 123 . In addition, in low-income countries that administer the oral polio vaccine, co-administration of this vaccine with oral rotavirus vaccines reduces the immunogenicity of the rotavirus vaccines 124 .…”

Section: Diagnosis Screening and Preventionmentioning

confidence: 99%

Rotavirus infection

Crawford

Ramani

Tate

et al. 2017

Nat Rev Dis Primers

537

558

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Rotavirus infections are a leading cause of severe, dehydrating gastroenteritis in children <5 years of age. Despite the global introduction of vaccinations for rotavirus over a decade ago, rotavirus infections still result in >200,000 deaths annually, mostly in low-income countries. Rotavirus primarily infects enterocytes and induces diarrhoea through the destruction of absorptive enterocytes (leading to malabsorption), intestinal secretion stimulated by rotavirus non-structural protein 4 and activation of the enteric nervous system. In addition, rotavirus infections can lead to antigenaemia (which is associated with more severe manifestations of acute gastroenteritis) and viraemia, and rotavirus can replicate in systemic sites, although this is limited. Reinfections with rotavirus are common throughout life, although the disease severity is reduced with repeat infections. The immune correlates of protection against rotavirus reinfection and recovery from infection are poorly understood, although rotavirus-specific immunoglobulin A has a role in both aspects. The management of rotavirus infection focuses on the prevention and treatment of dehydration, although the use of antiviral and anti-emetic drugs can be indicated in some cases.

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“…Owing to the invasive nature of intestinal biopsies, studies of EED have tended to rely on serum and fecal biomarkers, such as those indicative of small bowel bacterial overgrowth (e.g., hydrogen breath test), gut inflammation (e.g., fecal calprotectin and myeloperoxidase), microbial translocation (e.g., serum EndoCab) and mucosal permeability (e.g., lactulose/mannitol test). To date, the study of these biomarkers has failed to yield any consistent associations between EED and oral vaccine performance [28,98,[170][171][172][173], as discussed in detail elsewhere [Church et al, In Preparation].…”

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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The Association Between Fecal Biomarkers of Environmental Enteropathy and Rotavirus Vaccine Response in Nicaraguan Infants

Abstract: We found an association between biomarkers of EE and seroconversion to the first dose of RV5. It is possible that interventions that prevent or ameliorate EE may also improve oral rotavirus vaccine response.

Cited by 28 publications

References 24 publications

Pathophysiology of environmental enteric dysfunction and its impact on oral vaccine efficacy

Pathophysiology of environmental enteric dysfunction and its impact on oral vaccine efficacy

Rotavirus infection

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

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