Evaluation of vaccines against enteric infections: a clinical and public health research agenda for developing countries

Clemens, John D.

doi:10.1098/rstb.2011.0033

Cited by 14 publications

(8 citation statements)

References 34 publications

(47 reference statements)

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“…A sialidase-sensitive group A porcine RV OSU strain (P9 [7], G5) was obtained from the American Type Culture Collection. The virus was propagated in MA-104 cells as described previously (17) .…”

Section: Rotavirus Preparationmentioning

confidence: 99%

Human milk oligosaccharides inhibit rotavirus infectivityin vitroand in acutely infected piglets

et al. 2013

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Human milk (HM) is rich in oligosaccharides (HMO) that exert prebiotic and anti-infective activities. HM feeding reduces the incidence of rotavirus (RV) infection in infants. Herein, the anti-RV activity of oligosaccharides was tested in an established in vitro system for assessing cellular binding and viral infectivity/replication, and also tested in a newly developed, acute RV infection, in situ piglet model. For the in vitro work, crude HMO isolated from pooled HM, neutral HMO (lacto-N-neotetraose, LNnT; 2 0 -fucosyllactose) and acidic HMO (aHMO, 3 0 -sialyllactose, 3 0 -SL; 6 0 -sialyllactose, 6 0 -SL) were tested against the porcine OSU strain and human RV Wa strain. The RV Wa strain was not inhibited by any oligosaccharides. However, the RV OSU strain infectivity was dose-dependently inhibited by sialic acid (SA)-containing HMO. 3 0 -SL and 6 0 -SL concordantly inhibited 125 I-radiolabelled RV cellular binding and infectivity/replication. For the in situ study, a midline laparotomy was performed on 21-d-old formula-fed piglets and six 10 cm loops of ileum were isolated in situ. Briefly, 2 mg/ml of LNnT, aHMO mixture (40 % 6 0 -SL/10 % 3 0 -SL/50 % SA) or media with or without the RV OSU strain (1 £ 10 7 focus-forming units)were injected into the loops and maintained for 6 h. The loops treated with HMO treatments þ RV had lower RV replication, as assessed by non-structural protein-4 (NSP4) mRNA expression, than RV-treated loops alone. In conclusion, SA-containing HMO inhibited RV infectivity in vitro; however, both neutral HMO and SA with aHMO decreased NSP4 replication during acute RV infection in situ.Key words: Human milk oligosaccharides: Rotavirus: Piglets: Infection Rotaviruses (RV) are double-stranded RNA viruses of the family Reoviridae, which are the most common viral agents causing viral gastroenteritis and diarrhoea in infants and young children worldwide. Each year, approximately 1·4 billion episodes of RV gastroenteritis (RVGE) occur in children under 5 years of age in developing countries, and half a million children die (1,2) .Vaccination is the main public health intervention to prevent RV infection. Systematic reviews of vaccine effectiveness and vaccination-impact studies in industrialised countries (USA, Europe and Australia) have demonstrated an effectiveness of 85 -100 % associated with decreased hospitalisations for RVGE (3) . Vaccination-impact studies have demonstrated that the burden of RVGE has been reduced significantly since the introduction of RV vaccination (3) . However, efficacy trials in developing countries in Africa and Asia showed that vaccine efficacy was lower than that observed in other countries, typically 40 -70 % (4) . Although the efficacy of RV vaccines correlates closely with the national per capita income (5) , it is unclear why vaccination is less efficacious in developing countries (6) . This reduced vaccine efficacy coupled with the high cost and barriers to a widespread distribution of RV vaccines (7) suggest that other means for preventing RV should...

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Section: Rotavirus Preparationmentioning

confidence: 99%

Human milk oligosaccharides inhibit rotavirus infectivityin vitroand in acutely infected piglets

et al. 2013

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“…The high infection rates and rapid transmission between humans contribute to the significant morbidity associated with enteric viruses [ 4 ]. The absence of specific vaccines for human enteric viruses (except HRVs) further enhances the risk of infection [ 5 ]. More importantly, exposure to enteric virus-contaminated environments and/or drinking water, are generally thought to be responsible for a large proportion of outbreaks of waterborne diseases [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Total coliforms as an indicator of human enterovirus presence in surface water across Tianjin city, China

Miao¹,

Guo²,

Liu³

et al. 2018

BMC Infect Dis

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BackgroundEnteric viruses in surface water pose considerable risk to morbidity in populations living around water catchments and promote outbreaks of waterborne diseases. However, due to poor understanding of the correlation between water quality and the presence of human enteric viruses, the failure to assess viral contamination through alternative viral indicators makes it difficult to control disease transmission.MethodsWe investigated the occurrence of Enteroviruses (EnVs), Rotaviruses (HRVs), Astroviruses (AstVs), Noroviruses GII (HuNoVs GII) and Adenoviruses (HAdVs) from Jinhe River over 4 years and analyzed their correlation with physicochemical and bacterial parameters in water samples.ResultsThe findings showed that all target viruses were detected in water at frequencies of 91.7% for HAdVs, 81.3% for HuNoVs GII, 79.2% for EnVs and AstVs, and 70.8% for HRVs. These viruses had a seasonal pattern, which showed that EnVs were abundant in summer but rare in winter, while HAdVs, HRVs, AstVs, and HuNoVs GII exhibited opposite seasonal trends. Pearson correlation analysis showed that total coliforms (TC) was significantly positively correlated with EnVs concentrations while no consistent significant correlations were observed between bacterial indices and viruses that precipitate acute gastroenteritis.ConclusionsTaken together, the findings provide insights into alternative viral indicators, suggesting that TC is a potentially promising candidate for assessment of EnVs contamination. However, it failed to predict the presence of HAdVs, HRVs, AstVs, and HuNoVs GΙΙ in surface water across the city of Tianjin.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3438-5) contains supplementary material, which is available to authorized users.

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“…An expert panel convened by the Child Health and Nutrition Research Initiative (CHNRI) of the World Bank identified Shigella one of the highest priorities for long-term vaccine development [ 64 ]. In practice, the greatest impact on mortality of enteric vaccines, like Shigella, will be seen in medically underserved populations [ 65 ] and a safe, effective, and practical Shigella vaccine would likely save tens of thousands of lives and prevent hundreds of thousands of diarrheal illnesses in the developing world and in international travelers. Limited field trials of early live attenuated vaccine candidates or more recently, trials of polysaccharide based conjugate vaccines have shown vaccination to be a potentially effective public health tool in disease prevention and control [ 39 , 40 ] but currently there are no commercial products in the market.…”

Section: Discussionmentioning

confidence: 99%

Vaccines for the prevention of diarrhea due to cholera, shigella, ETEC and rotavirus

et al. 2013

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BackgroundDiarrhea is a leading cause of mortality in children under 5 years along with its long-term impact on growth and cognitive development. Despite advances in the understanding of diarrheal disorders and management strategies, globally nearly 750,000 children die annually as a consequence of diarrhea.MethodsWe conducted a systematic review of the efficacy and effectiveness studies. We used a standardized abstraction and grading format and performed meta-analyses for all outcomes. The estimated effect of cholera, shigella, Enterotoxigenic Escherichia coli (ETEC) and rotavirus vaccines was determined by applying the standard Child Health Epidemiology Reference Group (CHERG) rules.ResultsA total of 24 papers were selected and analyzed for all the four vaccines. Based on the evidence, we propose a 74% mortality reduction in rotavirus specific mortality, 52% reduction in cholera incidence due to their respective vaccines. We did not find sufficient evidence and a suitable outcome to project mortality reductions for cholera, ETEC and shigella in children under 5 years.ConclusionVaccines for rotavirus and cholera have the potential to reduce diarrhea morbidity and mortality burden. But there is no substantial evidence of efficacy for ETEC and shigella vaccines, although several promising vaccine concepts are moving from the development and testing pipeline towards efficacy and Phase 3 trials.

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Evaluation of vaccines against enteric infections: a clinical and public health research agenda for developing countries

Cited by 14 publications

References 34 publications

Human milk oligosaccharides inhibit rotavirus infectivityin vitroand in acutely infected piglets

Human milk oligosaccharides inhibit rotavirus infectivityin vitroand in acutely infected piglets

Total coliforms as an indicator of human enterovirus presence in surface water across Tianjin city, China

Vaccines for the prevention of diarrhea due to cholera, shigella, ETEC and rotavirus

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