Rotavirus Vaccine in Nicaragua

Abstract Rotavirus (RV) and norovirus (NoV) are major causes of pediatric diarrhea and are altogether associated with approximately 800,000 deaths in young children every year. In Nicaragua, national RV vaccination program using the pentavalent RV5 vaccine from Merck was implemented in October 2006. To determine whether RV vaccination decreased the overall number of RV infections, we investigated the occurrence of RV and NoV in wastewater in the city o

The fecal virome of South and Central American children with diarrhea includes small circular DNA viral genomes of unknown origin.

Viral metagenomics of feces collected from 58 Peruvian children with unexplained diarrhea revealed several small circular ssDNA genomes. Two genomes related to sequences previously reported in feces from chimpanzees and other mammals and recently named smacoviruses were characterized and then detected by PCR in 1.7 % (1/58) and 19 % (11/58) of diarrheal samples, respectively. Another three genomes from a distinct small circular ssDNA viral group provisionally called pecoviruses encoded Cap and Rep proteins with <35 % identity to those in related genomes reported in human, seal, porcine and dromedary feces. Pecovirus DNA was detected in 15.5 % (9/58), 5.9 % (3/51) and 3 % (3/100) of fecal samples from unexplained diarrhea in Peru, Nicaragua and Chile, respectively. Feces containing these ssDNA genomes also contained known human enteric viral pathogens. The cellular origins of these circular ssDNA viruses, whether human cells, ingested plants, animals or fungal foods, or residents of the gut microbiome, are currently unknown.This study was funded by NHLBI Grant R01 HL105770 to E.L.D and by Sao Paulo Research Foundation (FAPESP) Grant numbers 2014/05211-2 and 2012/03417-7 to A.C.C.Revisión por pare

Both Lewis and Secretor Status Mediate Susceptibility to Rotavirus Infections in a Rotavirus Genotype–Dependent Manner

Background. The live oral rotavirus (RV) vaccines have shown a reduced efficacy in Africa. Recent in vitro studies have shown binding of the RV surface protein (VP4) to histo–blood group antigens (HBGAs) in an RV genotype–dependent manner, suggesting them to be putative receptors for RV. The diversity of HBGA phenotypes in different ethnic populations, combined with prevalence/absence of specific RV genotypes, led us to hypothesize whether the genetic variations in HBGAs in a population limit susceptibility to certain RV genotypes, plausibly leading to reduced vaccine efficacy

Etiology of Childhood Diarrhea After Rotavirus Vaccine Introduction: A Prospective, Population-based Study in Nicaragua

Nicaragua was the first developing nation to implement routine immunization with the pentavalent rotavirus vaccine (RV5). In this RV5-immunized population, understanding infectious etiologies of childhood diarrhea is necessary to direct diarrhea treatment and prevention efforts

Infant antibody and B-cell responses following confirmed pediatric GII.17 norovirus infections functionally distinguish GII.17 genetic clusters

Genogroup II (GII) noroviruses are a major cause of diarrheal disease burden in children in both high- and low-income countries. GII.17 noroviruses are composed of distinct genetic clusters (I, II, IIIa, and IIIb) and have shown potential for replacing historically more prevalent GII.4 strains, but the serological basis for GII.17 antigenic diversity has not been studied in children. Utilizing samples from a birth cohort, we investigated antibody and B-cell responses to GII.17 cluster variants in confirmed GII.17 infections in young children as well as demonstrated that the distinct genetic clusters co-circulate. Polyclonal serum antibodies bound multiple clusters but showed cluster-specific blockade activity in a surrogate virus neutralization assay. Antibodies secreted by immortalized memory B cells (MBCs) from an infant GII.17 case were highly specific to GII.17 and exhibited blockade activity against this genotype. We isolated an MBC-derived GII.17-specific Immunoglobulin A (IgA) monoclonal antibody called NVA.1 that potently and selectively blocked GII.17 cluster IIIb and recognized an epitope targeted in serum from cluster IIIb–infected children. These data indicate that multiple antigenically distinct GII.17 variants co-circulate in young children, suggesting retention of cluster diversity alongside potential for immune escape given the existence of antibody-defined cluster-specific epitopes elicited during infection

Infant antibody and B-cell responses following confirmed pediatric GII.17 norovirus infections functionally distinguish GII.17 genetic clusters

Genogroup II (GII) noroviruses are a major cause of diarrheal disease burden in children in both high- and low-income countries. GII.17 noroviruses are composed of distinct genetic clusters (I, II, IIIa, and IIIb) and have shown potential for replacing historically more prevalent GII.4 strains, but the serological basis for GII.17 antigenic diversity has not been studied in children. Utilizing samples from a birth cohort, we investigated antibody and B-cell responses to GII.17 cluster variants in confirmed GII.17 infections in young children as well as demonstrated that the distinct genetic clusters co-circulate. Polyclonal serum antibodies bound multiple clusters but showed cluster-specific blockade activity in a surrogate virus neutralization assay. Antibodies secreted by immortalized memory B cells (MBCs) from an infant GII.17 case were highly specific to GII.17 and exhibited blockade activity against this genotype. We isolated an MBC-derived GII.17-specific Immunoglobulin A (IgA) monoclonal antibody called NVA.1 that potently and selectively blocked GII.17 cluster IIIb and recognized an epitope targeted in serum from cluster IIIb–infected children. These data indicate that multiple antigenically distinct GII.17 variants co-circulate in young children, suggesting retention of cluster diversity alongside potential for immune escape given the existence of antibody-defined cluster-specific epitopes elicited during infection

Predominance of Norovirus and Sapovirus in Nicaragua after Implementation of Universal Rotavirus Vaccination

Background: Despite significant reduction of rotavirus (RV) infections following implementation of RotaTeq vaccination in Nicaragua, a large burden of patients with diarrhea persists. Methods: We conducted a community-and hospital-based study of the burden of RV, norovirus (NV) and sapovirus (SV) infections as cause of sporadic acute gastroenteritis (GE) among 330 children less than= 5 years of age between September 2009 and October 2010 in two major cities of Nicaragua with a RotaTeq coverage rate of 95%. Results: We found that NV, SV and RV infections altogether accounted for 45% of cases of GE. Notably, NV was found in 24% (79/330) of the children, followed by SV (17%, 57/330) and RV (8%, 25/330). The detection rate in the hospital setting was 27%, 15% and 14% for NV, SV and RV respectively, whereas in the community setting the detection rate of RV was less than 1%. Among each of the investigated viruses one particular genogroup or genotype was dominant; GII.4 (82%) for NV, GI (46%) for SV and G1P[8] (64%) in RV. These variants were also found in higher proportions in the hospital setting compared to the community setting. The GII.4.2006 Minerva strain circulating globally since 2006 was the most common among genotyped NV in this study, with the GII.4-2010 New Orleans emerging in 2010. Conclusions: This study shows that NV has become the leading viral cause of gastroenteritis at hospital and community settings in Nicaragua after implementation of RV vaccination

Low Prevalence of Rotavirus and High Prevalence of Norovirus in Hospital and Community Wastewater after Introduction of Rotavirus Vaccine in Nicaragua

Rotavirus (RV) and norovirus (NoV) are major causes of pediatric diarrhea and are altogether associated with approximately 800,000 deaths in young children every year. In Nicaragua, national RV vaccination program using the pentavalent RV5 vaccine from Merck was implemented in October 2006. To determine whether RV vaccination decreased the overall number of RV infections, we investigated the occurrence of RV and NoV in wastewater in the city of Leon from July 2007 to July 2008 and compared these data with pre-vaccination data. The major finding was the low prevalence of RV compared to NoV in all sampling points (11% vs 44%, pandlt;0.05), and that RV concentration was lower as compared to NoV. RV was observed mainly during the rainy season (July-September), and the majority of all RV detected (6/9) belonged to subgroup (SG) I. The partial VP7-gene obtained from one RV positive sample was similar (99% nt identity) to a G6 VP7-gene of bovine origin and similar to the corresponding gene of the vaccine strain (98%). Furthermore RV G-types 2 and 4 were found in the incoming wastewater. NoV strains were detected throughout the year, of which a majority (20/21) were of genotype GII.4. We conclude that the introduction of RV vaccination reduced the transmission of RV in the community in Nicaragua. However, the burden of diarrhea in the country remains high, and the high prevalence of NoVs in hospital and municipal wastewater is noteworthy. This study highlights the need for further assessment of NoV following RV vaccine introduction.Funding Agencies|Swedish International Development Cooperation Agency|0.75007109|Swedish Research Council|10392|NETROPICA|

Genetic susceptibility to symptomatic norovirus infection in Nicaragua

Host genetic resistance to Norovirus (NoV) has been observed in challenge and outbreak studies in populations from Europe, Asia, and USA. In this study, we have investigated if histo-blood group antigens can predict susceptibility to diarrhea caused by NoV in Nicaragua, Central America, and if this can be reflected in antibody-prevalence and titer to NoV among individuals with different histo-blood group antigen phenotypes. Investigation of 28 individuals infected with NoV and 131 population controls revealed 6% of non-secretors in the population and nil non-secretors among patients infected with NoV, suggesting that non-secretors may be protected against NoV disease in Nicaragua. Surprisingly, 25% of the population was Lewis negative (Le(a-b-)). NoV infections with genogroup I (GI) and GII occurred irrespective of Lewis genotype, but none of the Lewis a positive (Le(a + b-)) were infected. The globally dominating GII.4 virus infected individuals of all blood groups except AB (n = 5), while the GI viruses (n = 4) infected only blood type O individuals. Furthermore, O blood types were susceptible to infections with GI.4, GII.4, GII.7, GII.17, and GII.18-Nica viruses, suggesting that secretors with blood type O are susceptible (OR = 1.52) and non-secretors resistant. The overall antibody-prevalence to NoV GII.3 VLP was 62% with the highest prevalence among blood type B carriers (70%) followed by A (68%) and O (62%). All four investigated individuals carrying blood type AB were antibody-negative. Among secretors, 63% were antibody-positive compared to 33% among non-secretors (P = 0.151). This study extends previous knowledge about the histo-blood group antigens role in NoV disease in a population with different genetic background than North American and European.</p