Environmental Enteropathy, Oral Vaccine Failure and Growth Faltering in Infants in Bangladesh

Naylor, Caitlin; Lu, Miao; Haque, Rashidul; Mondal, Dinesh; Buonomo, Erica L.; Nayak, Uma; Mychaleckyj, Josyf C.; Kirkpatrick, Beth D.; Colgate, Ross; Carmolli, Marya P.; Dickson, Dorothy M.; Klis, Fiona van der; Weldon, William C.; Oberste, M. Steven; Jennie, Z.; Petri, William A.

doi:10.1016/j.ebiom.2015.09.036

Cited by 221 publications

(303 citation statements)

References 31 publications

(33 reference statements)

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“…[65], [98], [108], [135], [171], [196] [67], [133][134][135], [198][199][200][201] [8], [181], [182], [201], [203], [204] [28], [92], [93], [128], [131], [137], [138], [140], [130], [131], [157], [202] [ [43][44][45], [49], [61][62][63][64][65][66][67][68][69][70], [197] [ [155][156][157] [28], [98], [170][171][172]…”

Section: Conclusion and Future Perspectiveunclassified

“…It is possible that the ubiquitous nature of EED in developing countries is partly responsible for this. Indeed, in several of the studies that have examined the potential association between EED and oral vaccine outcome, the majority of infants displayed elevated levels for at least one inflammatory biomarker compared with those observed in high-income countries, and it would therefore be possible to classify nearly all vaccine recipients as having some degree of EED [28,171]. In such populations, EED may contribute to oral vaccine failure despite the absence of consistent correlations between individual biomarkers and vaccine outcome.…”

Section: Environmental Enteric Dysfunctionmentioning

confidence: 99%

“…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%

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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: Conclusion and Future Perspectiveunclassified

Section: Environmental Enteric Dysfunctionmentioning

confidence: 99%

Section: Environmental Enteric Dysfunctionmentioning

confidence: 99%

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Causes of Impaired Oral Vaccine Efficacy in Developing Countries

et al. 2017

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“…15 Some of these biomarkers have also been found to correlate with the outcome of immunisation with oral rotavirus and poliovirus vaccines. 16 We investigated the association between infection with intestinal pathogens, EE and the immune response to oral vaccination in a randomised placebo-controlled trial of the effect of a 3-day course of oral azithromycin on the immunogenicity of a subsequent dose of serotype-3 monovalent OPV given to Indian infants who lacked immunity to this serotype. Azithromycin is a broad spectrum, bacteriostatic macrolide antibiotic with a long half-life that has been shown to be effective against a range of intestinal pathogens and has been safely used in many countries in mass treatment campaigns to prevent trachoma.…”

Section: Introductionmentioning

confidence: 99%

The effect of azithromycin on the immunogenicity of oral poliovirus vaccine: a double-blind randomised placebo-controlled trial in seronegative Indian infants

Grassly

Praharaj

Babji

et al. 2016

The Lancet Infectious Diseases

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“…A number of hypotheses have been put forward to explain the differences in efficacy and vaccineelicited immunity between HIC and LMIC. The hypotheses include (i) maternal factors (such as interference from transplacental antibodies and antibody and nonantibody breast milk components [13,[19][20][21][22][23]), (ii) coadministration with the oral polio vaccine (24-27), (iii) concurrent infection with other enteric pathogens (28), (iv) micronutrient or protein-energy malnutrition (29-31), (v) effects of environmental enteropathy or dysbiosis of the gut microbiome (32)(33)(34)(35)(36)(37), and (vi) host genetic factors (histo-blood group antigens [38,39]). A better understanding of these factors which decrease the efficacy of RV in LMIC may help to inform interventions to improve efficacy and to further reduce the number of child deaths due to rotavirus disease.…”

mentioning

confidence: 99%

Contribution of Maternal Immunity to Decreased Rotavirus Vaccine Performance in Low- and Middle-Income Countries

Mwila

Chilengi

Simuyandi

et al. 2017

Clin Vaccine Immunol

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The role of maternal immunity, received by infants either transplacentally or orally from breast milk, in rotavirus vaccine (RV) performance is evaluated here. Breastfeeding withholding has no effect on vaccine responses, but higher levels of transplacental rotavirus-specific IgG antibody contribute to reduced vaccine seroconversion. The gaps in knowledge on the factors associated with low RV efficacy in low-and middle-income countries (LMIC) remain, and further research is needed to shed more light on these issues. KEYWORDS immunization, low-and middle-income countries, maternal, rotavirus D espite the progress seen with the global introduction of rotavirus vaccines (RV), diarrhea is still a leading cause of death in children under the age of 5 years, and a substantial proportion of disease cases are still attributable to rotavirus infection. The latest estimates show that approximately 215,000 children die each year from rotavirusassociated diarrhea, and approximately 56% of these deaths are in sub-Saharan Africa (1). The World Health Organization (WHO) recommended the introduction of oral RV into national immunization programs (2), and many countries have heeded this call. As of September 2016, the WHO lists 86 countries as having included RV in their national immunization programs, and 6 more are in the course of doing so in 2016 (www.who.int/immunization/monitoring_surveillance/VaccineIntroStatus.pptx). Approximately 50% of the countries in Africa and Asia, over 80% of those in North America, South America, and Australia, and approximately 40% of those in Europe have introduced RV. Following RV introduction, there was a notable reduction in the number of deaths due to diarrhea (1). However, there is consistent evidence from clinical trials that RV have lower efficacies in low-and middle-income countries (LMIC): vaccine efficacies are 80 to 90% in high-income countries (HIC) and 40 to 60% in LMIC (3-8). Indeed, there is growing evidence from vaccine effectiveness studies emerging from the field that in real-life use, vaccine effectiveness is also consistently lower in LMIC (9-12).In addition to the differences in observed vaccine efficacy and effectiveness, there are also marked differences in vaccine-elicited immunity as reported by various vaccine-elicited antibody titers following rotavirus immunization (13)(14)(15)(16)(17)(18). A number of hypotheses have been put forward to explain the differences in efficacy and vaccineelicited immunity between HIC and LMIC. The hypotheses include (i) maternal factors (such as interference from transplacental antibodies and antibody and nonantibody breast milk components [13,[19][20][21][22][23] [38,39]). A better understanding of these factors which decrease the efficacy of RV in LMIC may help to inform interventions to improve efficacy and to further reduce the number of child deaths due to rotavirus disease. This review examines the correlations between maternal immune factors and RV responses and their potential effect on vaccine efficacy. NATURAL ROTAVIRUS...

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Environmental Enteropathy, Oral Vaccine Failure and Growth Faltering in Infants in Bangladesh

Cited by 221 publications

References 31 publications

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

The effect of azithromycin on the immunogenicity of oral poliovirus vaccine: a double-blind randomised placebo-controlled trial in seronegative Indian infants

Contribution of Maternal Immunity to Decreased Rotavirus Vaccine Performance in Low- and Middle-Income Countries

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