Comparative analysis of the Rotarix™ vaccine strain and G1P[8] rotaviruses detected before and after vaccine introduction in Belgium

G1P[8] rotaviruses are responsible for the majority of human rotavirus infections worldwide. The effect of universal mass vaccination with rotavirus vaccines on circulating G1P[8] rotaviruses is still poorly understood. Therefore we analyzed the complete genomes of the Rotarix™ vaccine strain, and 70 G1P[8] rotaviruses, detected between 1999 and 2010 in Belgium (36 before and 34 after vaccine introduction) to investigate the impact of rotavirus vaccine introduction on circulating G1P[8] strains. All rotaviruses possessed a complete Wa-like genotype constellation, but frequent intra-genogroup reassortments were observed as well as multiple different cluster constellations circulating in a single season. In addition, identical cluster constellations were found to circulate persistently over multiple seasons. The Rotarix™ vaccine strain possessed a unique cluster constellation that was not present in currently circulating G1P[8] strains. At the nucleotide level, the VP6, VP2 and NSP2 gene segments of Rotarix™ were relatively distantly related to any Belgian G1P[8] strain, but other gene segments of Rotarix™ were found in clusters also containing circulating Belgian strains. At the amino acid level, the genetic distance between Rotarix™ and circulating Belgian strains was considerably lower, except for NSP1. When we compared the Belgian G1P[8] strains collected before and after vaccine introduction a reduction in the proportion of strains that were found in the same cluster as the Rotarix™ vaccine strain was observed for most gene segments. The reduction in the proportion of strains belonging to the same cluster may be the result of the vaccine introduction, although natural fluctuations cannot be ruled out.

Download Full-text

Detection of diarrhoea associated rotavirus and co-infection with diarrhoeagenic pathogens in the Littoral region of Cameroon using ELISA, RT-PCR and Luminex xTAG GPP assays

BMC Infectious Diseases ◽

10.1186/s12879-021-06318-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Rahinatou N. Ghapoutsa ◽

Maurice Boda ◽

Rashi Gautam ◽

Valantine Ngum Ndze ◽

Akongnwi E. Mugyia ◽

...

Keyword(s):

Demographic Data ◽

Laboratory Diagnosis ◽

Epidemiological Studies ◽

Sub Saharan Africa ◽

Rt Pcr ◽

Mortality And Morbidity ◽

Vaccine Introduction ◽

Littoral Region ◽

Rotavirus Vaccines ◽

The Impact

Abstract Background Despite the global roll-out of rotavirus vaccines (RotaTeq/Rotarix / ROTAVAC/Rotasiil), mortality and morbidity due to group A rotavirus (RVA) remains high in sub-Saharan Africa, causing 104,000 deaths and 600,000 hospitalizations yearly. In Cameroon, Rotarix™ was introduced in March 2014, but, routine laboratory diagnosis of rotavirus infection is not yet a common practice, and vaccine effectiveness studies to determine the impact of vaccine introduction have not been done. Thus, studies examining RVA prevalence post vaccine introduction are needed. The study aim was to determine RVA prevalence in severe diarrhoea cases in Littoral region, Cameroon and investigate the role of other diarrheagenic pathogens in RVA-positive cases. Methods We carried out a study among hospitalized children < 5 years of age, presenting with acute gastroenteritis in selected hospitals of the Littoral region of Cameroon, from May 2015 to April 2016. Diarrheic stool samples and socio-demographic data including immunization and breastfeeding status were collected from these participating children. Samples were screened by ELISA (ProSpecT™ Rotavirus) for detection of RVA antigen and by gel-based RT-PCR for detection of the VP6 gene. Co-infection was assessed by multiplexed molecular detection of diarrheal pathogens using the Luminex xTAG GPP assay. Results The ELISA assay detected RVA antigen in 54.6% (71/130) of specimens, with 45, positive by VP6 RT-PCR and 54, positive using Luminex xTAG GPP. Luminex GPP was able to detect all 45 VP6 RT-PCR positive samples. Co-infections were found in 63.0% (34/54) of Luminex positive RVA infections, with Shigella (35.3%; 12/34) and ETEC (29.4%; 10/34) detected frequently. Of the 71 ELISA positive RVA cases, 57.8% (41/71) were fully vaccinated, receiving two doses of Rotarix. Conclusion This study provides insight on RVA prevalence in Cameroon, which could be useful for post-vaccine epidemiological studies, highlights higher than expected RVA prevalence in vaccinated children hospitalized for diarrhoea and provides the trend of RVA co-infection with other enteric pathogens. RVA genotyping is needed to determine circulating rotavirus genotypes in Cameroon, including those causing disease in vaccinated children.

Download Full-text

Impact of Monovalent Rotavirus Vaccine on Rotavirus Hospitalizations among Children Younger Than 5 Years of Age in the Ouest and Artibonite Departments, Haiti, 2013 to 2019

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.21-0414 ◽

2021 ◽

Author(s):

Anne-Marie Desormeaux ◽

Eleanor Burnett ◽

Gérard Joseph ◽

Mentor Ali Ber Lucien ◽

Negar Aliabadi ◽

...

Keyword(s):

Negative Binomial ◽

Hospital Admissions ◽

Absolute Number ◽

Sensitivity Analyses ◽

Rotavirus Vaccine ◽

Vaccine Introduction ◽

Rotavirus Vaccination ◽

Before And After ◽

Rotavirus Diarrhea ◽

The Impact

Rotavirus is responsible for 26% of diarrheal deaths in Latin America and the Caribbean. Haiti introduced the monovalent rotavirus vaccine in April 2014. The objective of this analysis is to describe the impact of the rotavirus vaccine on hospitalizations among Haitian children younger than 5 years old during the first 5 years after introduction. This analysis includes all children with diarrhea who were enrolled as part of a sentinel surveillance system at two hospitals from May 2013 to April 2019. We compare the proportion of rotavirus-positive specimens in each post-vaccine introduction year to the pre-vaccine period. To account for the potential dilution of the proportion of rotavirus-positive specimens from a waning cholera outbreak, we also analyzed annual trends in the absolute number of positive stools, fit a two-component finite-mixture model to the negative specimens, and fit a negative binomial time series model to the pre-vaccine rotavirus-positive specimens to predict the number of rotavirus diarrhea hospital admissions in the absence of rotavirus vaccination. The overall percentage of rotavirus-positive specimens declined by 22% the first year after introduction, increased by 17% the second year, and declined by 33% to 50% the subsequent 3 years. All sensitivity analyses confirmed an overall decline. We observed a clear annual rotavirus seasonality before and after vaccine introduction, with the greatest activity in December through April, and a biennial pattern, with high sharp peaks and flatter longer periods of increased rotavirus activity in alternating years, consistent with suboptimal vaccination coverage. Overall, our study shows evidence that the introduction of the rotavirus vaccine reduced the burden of severe rotavirus diarrhea.

Download Full-text

Diarrheal Diseases Hospitalization in Yemen before and after Rotavirus Vaccination

Scientifica ◽

10.1155/2016/8485417 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Mohammed Amood AL-Kamarany ◽

Lina Al-Areqi ◽

Abulatif Mujally ◽

Fawzya Alkarshy ◽

Arwa Nasser ◽

...

Keyword(s):

Vaccine Coverage ◽

Rotavirus Vaccine ◽

Diarrheal Diseases ◽

Predominant Genotype ◽

Fecal Samples ◽

Vaccine Introduction ◽

Rotavirus Vaccination ◽

Before And After ◽

Rotavirus Diarrhea ◽

The Impact

The study aims to assess the impact of rotavirus vaccine introduction on diarrheal diseases hospitalization and to identify the rotavirus genotypes most prevalent before and after vaccine introduction among children ≤ 5 years of age. Rotarix™® rotavirus vaccine is currently licensed for infants in Yemen and was introduced in 2012. The vaccination course consists of two doses. The first dose is administrated at 6 weeks of age and the second dose is completed by 10 weeks. Based on a longitudinal observational study, we assessed the impact of vaccination on rotavirus hospitalization before and after vaccination among children ≤ 5 years of age at the Yemeni-Swedish Hospital (YSH) in Taiz, Yemen. Prevaccination covered January 2009–July 2012 during which 2335 fecal samples were collected from children ≤ 5 years old. Postvaccination covered January 2013–December 2014 during which 1114 fecal samples were collected. Rotavirus was detected by Enzyme Linkage Immunosorbent Assay (ELISA). The incidence ofrotavirushospitalization decreased from 43.79% in 2009 to 10.54% in 2014. Hospitalization due to rotavirus diarrhea was reduced by 75.93%. Vaccine coverage increased from 23% in 2012 to 72% in 2014. Also, the results showed that the most predominant genotypes in prevaccination period were G2P[4] (55.0%), followed by G1P[8] (15.0%), while in postvaccination period G1P[8] (31%) was the predominant genotype, followed by G9P[8] (27.5%). In conclusion, rotavirus vaccination in Yemen resulted in sharp reduction in diarrheal hospitalization. A successful rotavirus vaccination program in Yemen will rely upon efficient vaccine delivery systems and sustained vaccine efficacy against diverse and evolving rotavirus strains.

Download Full-text

TRENDS IN HOSPITALIZATIONS FROM ALL-CAUSE GASTROENTERITIS IN CHILDREN YOUNGER THAN 5 YEARS OF AGE IN BRAZIL BEFORE AND AFTER HUMAN ROTAVIRUS VACCINE INTRODUCTION, 1998–2007

The Pediatric Infectious Disease Journal ◽

10.1097/inf.0b013e3181da8f23 ◽

2010 ◽

Vol 29 (7) ◽

pp. 673-675 ◽

Cited By ~ 43

Author(s):

Tatiana Miranda Lanzieri ◽

Iolanda Costa ◽

Fakrudeen A. Shafi ◽

Maria Helena Cunha ◽

Eduardo Ortega-Barria ◽

...

Keyword(s):

Rotavirus Vaccine ◽

Vaccine Introduction ◽

Human Rotavirus ◽

Before And After

Download Full-text

Rotavirus disease burden pre-vaccine introduction in young children in Rural Southern Mozambique, an area of high HIV prevalence

PLoS ONE ◽

10.1371/journal.pone.0249714 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0249714

Author(s):

Sozinho Acácio ◽

Tacilta Nhampossa ◽

Llorenç Quintò ◽

Delfino Vubil ◽

Marcelino Garrine ◽

...

Keyword(s):

Risk Factors ◽

Disease Burden ◽

Conditional Logistic Regression ◽

Epidemiological Data ◽

Daily Basis ◽

African Countries ◽

Severe Diarrhea ◽

Vaccine Introduction ◽

Rotavirus Vaccines ◽

The Impact

Background Rotavirus vaccines have been adopted in African countries since 2009, including Mozambique (2015). Disease burden data are needed to evaluate the impact of rotavirus vaccine. We report the burden of rotavirus-associated diarrhea in Mozambique from the Global Enteric Multicenter Study (GEMS) before vaccine introduction. Methods A case-control study (GEMS), was conducted in Manhiça district, recruiting children aged 0–59 months with moderate-to-severe diarrhea (MSD) and less-severe-diarrhea (LSD) between December 2007 and November 2012; including 1–3 matched (age, sex and neighborhood) healthy community controls. Clinical and epidemiological data and stool samples (for laboratory investigation) were collected. Association of rotavirus with MSD or LSD was determined by conditional logistic regression and adjusted attributable fractions (AF) calculated, and risk factors for rotavirus diarrhea assessed. Results Overall 915 cases and 1,977 controls for MSD, and 431 cases and 430 controls for LSD were enrolled. Rotavirus positivity was 44% (217/495) for cases and 15% (160/1046) of controls, with AF = 34.9% (95% CI: 32.85–37.06) and adjusted Odds Ratio (aOR) of 6.4 p< 0.0001 in infants with MSD compared to 30% (46/155) in cases and 14% (22/154) in controls yielding AF = 18.7%, (95% CI: 12.02–25.39) and aOR = 2.8, p = 0.0011 in infants with LSD. The proportion of children with rotavirus was 32% (21/66) among HIV-positive children and 23% (128/566) among HIV-negative ones for MSD. Presence of animals in the compound (OR = 1.9; p = 0.0151) and giving stored water to the child (OR = 2.0, p = 0.0483) were risk factors for MSD; while animals in the compound (OR = 2.37, p = 0.007); not having routine access to water on a daily basis (OR = 1.53, p = 0.015) and washing hands before cooking (OR = 1.76, p = 0.0197) were risk factors for LSD. Conclusion The implementation of vaccination against rotavirus may likely result in a significant reduction of rotavirus-associated diarrhea, suggesting the need for monitoring of vaccine impact.

Download Full-text

Genetic characterization of G12P[6] and G12P[8] rotavirus strains in six African countries

10.21203/rs.3.rs-47541/v1 ◽

2020 ◽

Author(s):

Kebareng G. Rakau ◽

Martin M. Nyaga ◽

Maemu P. Gededzha ◽

Jason M. Mwenda ◽

M. Jeffrey Mphahlele ◽

...

Keyword(s):

Amino Acid Level ◽

Sub Saharan Africa ◽

African Countries ◽

Vaccine Introduction ◽

Rotavirus Vaccination ◽

Human Rotavirus ◽

Sub Saharan ◽

The Stability ◽

Long Term Impact

Abstract Background: G12 rotaviruses were first observed in sub-Saharan Africa in 2004 and since then have continued to emerge and spread across the continent and are reported as a significant human rotavirus genotype in several African countries, both prior to and after rotavirus vaccine introduction. This study investigated the genetic variability of 15 G12 rotavirus strains with either P[6] or P[8] identified between 2010 and 2014 from Ethiopia, Kenya, Rwanda, Tanzania, Togo and Zambia.Methods: The investigation was carried out by comparing VP7 and partial VP4 sequences of the African G12P[6] and G12P[8] strains with the available GenBank sequences and mapping the recognized neutralization epitopes of these strains.Results: The findings suggested that the VP7 and VP4 genes of the G12 strains circulating in African countries are homologous at the nucleotide and amino acid level, irrespective of country of origin and year of detection, although there was a unique clustering of the Ethiopian strains. The study strains shared a common ancestry with G12 strains circulating globally. Neutralization epitope mapping revealed that rotavirus VP4 P[8] genes associated with G12 had amino acids similar to those reported globally including the vaccines RotaTeq® P[8] and Rotarix®.Conclusions: It is unlikely that widespread vaccine use has driven the molecular evolution and sustainability of G12 strains in Africa. Furthermore, it is too early post vaccine introduction to indicate any effect of vaccine-induced pressure on maintaining the stability of these strains in circulation. Continuous monitoring of rotavirus genotypes is recommended to assess the long-term impact of rotavirus vaccination on the dynamic nature of rotavirus evolution on the continent.

Download Full-text

Rotavirus Genotypes in Hospitalized Children With Acute Gastroenteritis Before and After Rotavirus Vaccine Introduction in Blantyre, Malawi, 1997–2019

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa616 ◽

2020 ◽

Cited By ~ 1

Author(s):

Chimwemwe Mhango ◽

Jonathan J Mandolo ◽

End Chinyama ◽

Richard Wachepa ◽

Oscar Kanjerwa ◽

...

Keyword(s):

Rotavirus Vaccine ◽

Predominant Genotype ◽

Vaccine Introduction ◽

Strain Diversity ◽

Positive Stool ◽

Genotype Variation ◽

Before And After ◽

Polymerase Chain ◽

The Impact ◽

Genotype G3

Abstract Background Rotavirus vaccine (Rotarix [RV1]) has reduced diarrhea-associated hospitalizations and deaths in Malawi. We examined the trends in circulating rotavirus genotypes in Malawi over a 22-year period to assess the impact of RV1 introduction on strain distribution. Methods Data on rotavirus-positive stool specimens among children aged <5 years hospitalized with diarrhea in Blantyre, Malawi before (July 1997–October 2012, n = 1765) and after (November 2012–October 2019, n = 934) RV1 introduction were analyzed. Rotavirus G and P genotypes were assigned using reverse-transcription polymerase chain reaction. Results A rich rotavirus strain diversity circulated throughout the 22-year period; Shannon (H′) and Simpson diversity (D′) indices did not differ between the pre- and postvaccine periods (H′ P < .149; D′ P < .287). Overall, G1 (n = 268/924 [28.7%]), G2 (n = 308/924 [33.0%]), G3 (n = 72/924 [7.7%]), and G12 (n = 109/924 [11.8%]) were the most prevalent genotypes identified following RV1 introduction. The prevalence of G1P[8] and G2P[4] genotypes declined each successive year following RV1 introduction, and were not detected after 2018. Genotype G3 reemerged and became the predominant genotype from 2017 onward. No evidence of genotype selection was observed 7 years post–RV1 introduction. Conclusions Rotavirus strain diversity and genotype variation in Malawi are likely driven by natural mechanisms rather than vaccine pressure.

Download Full-text

Trends of Rotavirus in Nepal

Kathmandu University Medical Journal ◽

10.3126/kumj.v9i1.6259 ◽

2012 ◽

Vol 9 (1) ◽

pp. 32-35 ◽

Cited By ~ 2

Author(s):

B D Pandey ◽

S B Pun

Keyword(s):

Meteorological Data ◽

First Year ◽

Rotavirus Vaccine ◽

Policy Makers ◽

Rotavirus Infection ◽

Rotavirus Gastroenteritis ◽

Rotavirus Vaccines ◽

Human Rotavirus ◽

The Impact ◽

Infants And Young Children

Background Rotavirus gastroenteritis is the major cause of morbidity and mortality in infants and young children worldwide. Safe and effective rotavirus vaccine is needed to have significant impact on severe rotavirus gastroenteritis. Currently, two live oral rotavirus vaccines have been licensed in many countries. Knowledge on distribution of human rotavirus of G and P types are essential before rotavirus vaccines are introduced in the target populations. Objective To observe the trends of rotavirus strains in children below five years of age, during the years, 2003-2005 in Nepal. Methods Stool specimen collected from children with acute diarrhea who were referred to observation unit or hospitalized in Kanti Children’s Hospital between 2003 and 2005 were examined. Meteorological data was obtained from Ministry of Environment, Nepal to examine the possibility on the impact of weather on rotavirus infection. Results Of 1250 stool specimens, 271(22%) were positive for rotavirus by Rotaclone ELISA. G1 was the most common serotype in the first year of study, and G2 in the following year. G12 serotype emerged and remained predominant in two consecutive years. In addition, G9 and G3 emerged in the second year of the study. Children less than three years of age were commonly affected. The records reveal that rotavirus infection is related to the climate, and is commonly seen in the dry season, peaking in January. Conclusions Continued surveillance of different regions is needed to monitor the trend of rotavirus strains and to establish rotavirus disease burden, which will help policy makers to make a decision in introducing rotavirus vaccine in Nepal. http://dx.doi.org/10.3126/kumj.v9i1.6259 Kathmandu Univ Med J 2011;9(1):32-35

Download Full-text

Whole-Genome Analyses Identifies Multiple Reassortant Rotavirus Strains in Rwanda Post-Vaccine Introduction

Viruses ◽

10.3390/v13010095 ◽

2021 ◽

Vol 13 (1) ◽

pp. 95

Author(s):

Sebotsana Rasebotsa ◽

Jeannine Uwimana ◽

Milton T. Mogotsi ◽

Kebareng Rakau ◽

Nonkululeko B. Magagula ◽

...

Keyword(s):

Amino Acid ◽

Genome Analysis ◽

Evolutionary Dynamics ◽

Developed Countries ◽

Whole Genome ◽

Whole Genome Analysis ◽

Evolutionary Mechanisms ◽

Vaccine Introduction ◽

Rotavirus Vaccines ◽

The Impact

Children in low-and middle-income countries, including Rwanda, experience a greater burden of rotavirus disease relative to developed countries. Evolutionary mechanisms leading to multiple reassortant rotavirus strains have been documented over time which influence the diversity and evolutionary dynamics of novel rotaviruses. Comprehensive rotavirus whole-genome analysis was conducted on 158 rotavirus group A (RVA) samples collected pre- and post-vaccine introduction in children less than five years in Rwanda. Of these RVA positive samples, five strains with the genotype constellations G4P[4]-I1-R2-C2-M2-A2-N2-T1-E1-H2 (n = 1), G9P[4]-I1-R2-C2-M2-A1-N1-T1-E1-H1 (n = 1), G12P[8]-I1-R2-C2-M1-A1-N2-T1-E2-H3 (n = 2) and G12P[8]-I1-R1-C1-M1-A2-N2-T2-E1-H1 (n = 1), with double and triple gene reassortant rotavirus strains were identified. Phylogenetic analysis revealed a close relationship between the Rwandan strains and cognate human RVA strains as well as the RotaTeq® vaccine strains in the VP1, VP2, NSP2, NSP4 and NSP5 gene segments. Pairwise analyses revealed multiple differences in amino acid residues of the VP7 and VP4 antigenic regions of the RotaTeq® vaccine strain and representative Rwandan study strains. Although the impact of such amino acid changes on the effectiveness of rotavirus vaccines has not been fully explored, this analysis underlines the potential of rotavirus whole-genome analysis by enhancing knowledge and understanding of intergenogroup reassortant strains circulating in Rwanda post vaccine introduction.

Download Full-text

Genetic characterization of G12P[6] and G12P[8] rotavirus strains collected in six African countries between 2010 and 2014

10.21203/rs.3.rs-47541/v2 ◽

2020 ◽

Author(s):

Kebareng G. Rakau ◽

Martin M. Nyaga ◽

Maemu P. Gededzha ◽

Jason M. Mwenda ◽

M. Jeffrey Mphahlele ◽

...

Keyword(s):

Amino Acid Level ◽

Sub Saharan Africa ◽

African Countries ◽

Vaccine Introduction ◽

Rotavirus Vaccination ◽

Human Rotavirus ◽

Sub Saharan ◽

Long Term Impact

Abstract Background: G12 rotaviruses were first observed in sub-Saharan Africa in 2004 and since then have continued to emerge and spread across the continent and are reported as a significant human rotavirus genotype in several African countries, both prior to and after rotavirus vaccine introduction. This study investigated the genetic variability of 15 G12 rotavirus strains associated with either P[6] or P[8] identified between 2010 and 2014 from Ethiopia, Kenya, Rwanda, Tanzania, Togo and Zambia. Methods: The investigation was carried out by comparing partial VP7 and partial VP4 sequences of the African G12P[6] and G12P[8] strains with the available GenBank sequences and exploring the recognized neutralization epitopes of these strains. Results: The findings suggested that the VP7 and VP4 genes of the G12 strains circulating in African countries are closely related at the nucleotide and amino acid level, irrespective of country of origin and year of detection, although there was a unique clustering of the Ethiopian strains. Neutralization epitope screening revealed that rotavirus VP4 P[8] genes associated with G12 had amino acids similar to those reported globally including the vaccines RotaTeq and Rotarix. Conclusions: At present it appears to be unlikely that widespread vaccine use has driven the molecular evolution and sustainability of G12 strains in Africa. Continuous monitoring of rotavirus genotypes is recommended to assess the long-term impact of rotavirus vaccination on the dynamic nature of rotavirus evolution on the continent.

Download Full-text