scholarly journals Rotavirus breakthrough infections responsible for gastroenteritis in vaccinated infants who presented with acute diarrhoea at University Teaching Hospitals, Children’s Hospital in 2016, in Lusaka Zambia

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246025
Author(s):  
Julia Simwaka ◽  
Mapaseka Seheri ◽  
Gina Mulundu ◽  
Patrick Kaonga ◽  
Jason M. Mwenda ◽  
...  

Background In Zambia, before rotavirus vaccine introduction, the virus accounted for about 10 million episodes of diarrhoea, 63 000 hospitalisations and 15 000 deaths in 2015, making diarrhoea the third leading cause of death after pneumonia and malaria. In Zambia, despite the introduction of the vaccine acute diarrhoea due to rotaviruses has continued to affect children aged five years and below. This study aimed to characterise the rotavirus genotypes which were responsible for diarrhoeal infections in vaccinated infants aged 2 to 12 months and to determine the relationship between rotavirus strains and the severity of diarrhoea in 2016. Methods Stool samples from infants aged 2 to 12 months who presented to the hospital with acute diarrhoea of three or more episodes in 24 hours were tested for group A rotavirus. All positive specimens that had enough sample were genotyped using reverse transcriptase Polymerase Chain Reaction (RT-PCR). A 20-point Vesikari clinical score between 1–5 was considered as mild, 6–10 as moderate and greater or equal to 11 as severe. Results A total of 424 stool specimens were tested of which 153 (36%, 95% CI 31.5% to 40.9%) were positive for VP6 rotavirus antigen. The age-specific rotavirus infections decreased significantly (p = 0.041) from 2–4 months, 32.0% (49/118) followed by a 38.8% (70/181) infection rate in the 5–8 months’ category and subsequently dropped in the infants aged 9–12 months with a positivity rate of 27.2%. 38.5% of infants who received a single dose, 34.5% of those who received a complete dose and 45.2% (19/42) of the unvaccinated tested positive for rotavirus. The predominant rotavirus genotypes included G2P[6] 36%, G1P[8] 32%, mixed infections 19%, G2P[4] 6%, G1P[6] 4% and G9P[6] 3%. Discussion and conclusion Results suggest breakthrough infection of heterotypic strains (G2P[6] (36%), homotypic, G1P[8] (32%) and mixed infections (19%) raises concerns about the effects of the vaccination on the rotavirus diversity, considering the selective pressure that rotavirus vaccines could exert on viral populations. This data indicates that the rotavirus vaccine has generally reduced the severity of diarrhoea despite the detection of the virus strains.

2019 ◽  
Author(s):  
Julia Simwaka ◽  
Gina Mulundu ◽  
Jason Mwenda ◽  
Roma Chilengi ◽  
Evans Mpabalwani ◽  
...  

Abstract Background Rotavirus has continued to affect under five children despite the introduction of the vaccine. This study aimed at characterizing the rotavirus genotypes responsible for diarrhoea infections in vaccinated infants aged 2 to 12 months and determined the relationship between rotavirus strains and the severity of diarrhoea in 2016. Materials and Methods We tested stool for group A rotavirus P6 antigen using an ELISA kit (ProSpecT TM , Oxford, UK). All positive specimens with enough sample were genotyped using reverse transcriptase polymerase chain reaction (RT-PCR). A 20-point Vesikari clinical score was used to determine the severity of acute diarrhoea. Diarrhoea scores between 1-5 were considered as mild, 6-10 scores were considered as moderate and scores greater or equal to 11 considered as severe. Results 153/424 (36%, 95% CI 31.5% to 40.9%) were positive for VP6 rotavirus antigen. The age specific rotavirus infections decreased significantly (p = 0.041) from 2 - 4 months 32.0%,followed by a 38.8% infection rate in the 5-8 months category and subsequently dropped in the infants aged 9-12 months with a positivity rate of 27.2%. 12.3% received a single dose of rotarix vaccine, 77.8% received 2 doses, and 9.9% were not vaccinated. 38.5% of those who received a single dose, 34.5% of those who received a complete dose and 45.2% of the unvaccinated tested positive for rotavirus. Infants who tested positive differed significantly from those who tested negative in terms of fever (p = 0.010).The predominant rotavirus genotypes were, G2P[6] 36%, G1P[8] 32%, mixed infections 19%, G2P[4] 6%, G1P[6] 4% and G9P[6] 3%. Infants who were infected with G1P8 and G2P[6] had a median Vesikari score of 6, while those who were infected with G1P[6] and mixed infections had a median score of 7 and those with infections due to G2P[4] and G9P[6] had median scores of 4 and 8 respectively. Discussion and Conclusion The breakthrough infection of heterotypic strains (G2P[6] (36%), homotypic, G1P[8] (32%) and mixed infections (19%) raises concerns about the effects of the vaccination on the rotavirus diversity, considering the selective pressure that rotavirus vaccines could exert on viral populations.


Open Medicine ◽  
2010 ◽  
Vol 5 (5) ◽  
pp. 640-645
Author(s):  
Mustafa Altindis ◽  
Krisztián Bányai ◽  
Raike Kalayci ◽  
Cihangir Gulamber ◽  
Resit Koken ◽  
...  

AbstractVaccines against rotaviruses are now available in numerous countries, including Turkey. As the vaccines may show various efficiencies against different type specificities and routine vaccination in infants might result in selection and immune escape of wild-type rotavirus strains, strain surveillance has been initiated before and during the vaccine introduction. We aimed to provide corresponding information on local strain prevalence in Anatolia, mid-western Turkey during the introduction of rotavirus vaccines. Stool samples positive for group A rotavirus by commercial enzyme immunoassay were subjected to reverse transcription-polymerase chain reaction based genotyping of the outer capsid antigens, VP7 and VP4, determining G and P type specificities respectively. Among 36 fully and 5 partially typeable strains we detected genotype G1, G2, and G9 VP7 specificities and genotype P[4], P[6] and P[8] VP4 specificities in 5 individual and 4 mixed combinations. The most common strain was G2P[4] (n=17), followed by G9P[8] (n=9). Other strains were G1P[8] (n=2), G2P[8] (n=2), G1+2P[8] (n=2), G9P[4] (n=1), G2+9P[8] (n=1), G4+9P[6] (n=1), and G2P[4+8] (n=1). Partially typed strains included 2 G1P[NT] and 3 G2P[NT] strains. Our data may help determine a baseline of the rotavirus genotype prevalence in Turkey and see if changes in the incidence of individual strains will be observed after routine use of vaccine.


Pathogens ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 660
Author(s):  
Arnold W. Lambisia ◽  
Sylvia Onchaga ◽  
Nickson Murunga ◽  
Clement S. Lewa ◽  
Steven Ger Nyanjom ◽  
...  

Using real-time RT-PCR, we screened stool samples from children aged <5 years presenting with diarrhea and admitted to Kilifi County Hospital, coastal Kenya, pre- (2003 and 2013) and post-rotavirus vaccine introduction (2016 and 2019) for five viruses, namely rotavirus group A (RVA), norovirus GII, adenovirus, astrovirus and sapovirus. Of the 984 samples analyzed, at least one virus was detected in 401 (40.8%) patients. Post rotavirus vaccine introduction, the prevalence of RVA decreased (23.3% vs. 13.8%, p < 0.001) while that of norovirus GII increased (6.6% vs. 10.9%, p = 0.023). The prevalence of adenovirus, astrovirus and sapovirus remained statistically unchanged between the two periods: 9.9% vs. 14.2%, 2.4% vs. 3.2 %, 4.6% vs. 2.6%, (p = 0.053, 0.585 and 0.133), respectively. The median age of diarrhea cases was higher post vaccine introduction (12.5 months, interquartile range (IQR): 7.9–21 vs. 11.2 months pre-introduction, IQR: 6.8–16.5, p < 0.001). In this setting, RVA and adenovirus cases peaked in the dry months while norovirus GII and sapovirus peaked in the rainy season. Astrovirus did not display clear seasonality. In conclusion, following rotavirus vaccine introduction, we found a significant reduction in the prevalence of RVA in coastal Kenya but an increase in norovirus GII prevalence in hospitalized children.


2019 ◽  
Vol 31 (1) ◽  
pp. 87-92

Rotaviruses are regarded as the most common cause of viral gastroenteritis and are responsible for considerable morbidity and mortality among children especially under five years of age worldwide. In developing countries like Myanmar, where diarrhoea is in the priority childhood disease, rotavirus surveillance and detection of rotavirus genotypes are utmost important. A hospital-based, cross-sectional descriptive study was conducted at Yangon Children‟s Hospital among under five children admitted for acute diarrhoea from January to October 2016. This study includes detection of Group A rotavirus antigen by commercial enzyme-linked immunosorbent assay (ELISA) and genotyping by multiplex RT-PCR. From a total of 488 collected samples, rotavirus antigen was detected in 219 samples (45%). Rotavirus diarrhoea was most common among the age of 6-11 months (38.8%) followed by 12-23 months (37.9%). The results showed that boys were more commonly affected than girls. Detection of rotavirus positivity was peak in February (57.6 %). Out of 219 stool samples with positive ELISA result, 40 stool samples with high optical density value were proceeded for further determination of G and P genotypes. Regarding distribution of G genotypes, the most common G genotype was G9 which comprised 45%, and that of P genotype was P[8] which comprised 92.5%. Regarding combination of G and P genotypes, the most frequent combination is G9P[8], and it constituted 42.5%. Untypable genotypes were seen in 30% of G and 2.5% of P typing. As rotavirus infection can be prevented by vaccine, WHO recommended that rotavirus vaccination should be included in national immunization program especially in countries where prevalence of rotavirus is high. The distribution of G and P genotypes is important in consideration of appropriate vaccine in pre-vaccination and evaluation of effectiveness of vaccine in post-vaccination period. Therefore, the information on currently circulating genotypes of rotavirus in this study will serve as valuable data for vaccination programme.


Author(s):  
Mike J. Mwanga ◽  
Jennifer R. Verani ◽  
Richard Omore ◽  
Jacqueline E. Tate ◽  
Umesh D. Parashar ◽  
...  

Globally, rotavirus group A (RVA) remains a major cause of severe childhood diarrhea, despite the use of vaccines in &amp;gt; 100 countries. RVA sequencing for local outbreaks facilitates investigation into strain composition, origins, spread, and vaccine failure. In 2018, we collected 248 stool samples from children aged &amp;lt;13 years admitted with diarrheal illness to Kilifi County Hospital, coastal Kenya. Antigen screening detected RVA in 55 samples (22.2%). Of these, VP7 (G) and VP4 (P) segments were successfully sequenced in 48 (87.3%) and phylogenetic analysis based on the VP7 sequences identified seven genetic clusters with six different GP combinations; G3P[8], G1P[8], G2P[4], G2P[8], G9P[8] and G12P[8]. The G3P[8] strains predominated the season (n=37, 67.2%) and comprised three G3 genetic clusters that fell within Lineage I and IX (the latter also known as equine-like G3 lineage). Both two G3 lineages have been recently detected in several countries. Our study is the first to document African children infection with G3 lineage IX. These data highlight the global nature of RVA transmission and the importance of increasing global rotavirus vaccine coverage.


2019 ◽  
Vol 24 (15) ◽  
Author(s):  
Giovanni Ianiro ◽  
Roberto Micolano ◽  
Ilaria Di Bartolo ◽  
Gaia Scavia ◽  
Marina Monini ◽  
...  

Introduction Group A rotaviruses (RVA) are the leading cause of acute gastroenteritis (AGE) in young children, causing ca 250,000 deaths worldwide, mainly in low-income countries. Two proteins, VP7 (glycoprotein, G genotype) and VP4 (protease-sensitive protein, P genotype), are the basis for the binary RVA nomenclature. Although 36 G types and 51 P types are presently known, most RVA infections in humans worldwide are related to five G/P combinations: G1P[8], G2P[4], G3P[8], G4P[8], G9P[8]. Aim This study aimed to characterise the RVA strains circulating in Italy in the pre-vaccination era, to define the trends of circulation of genotypes in the Italian paediatric population. Methods Between September 2014 and August 2017, after routine screening in hospital by commercial antigen detection kit, 2,202 rotavirus-positive samples were collected in Italy from children hospitalised with AGE; the viruses were genotyped following standard European protocols. Results This 3-year study revealed an overall predominance of the G12P[8] genotype (544 of 2,202 cases; 24.70%), followed by G9P[8] (535/2,202; 24.30%), G1P[8] (459/2,202; 20.84%) and G4P[8] (371/2,202; 16.85%). G2P[4] and G3P[8] genotypes were detected at low rates (3.32% and 3.09%, respectively). Mixed infections accounted for 6.49% of cases (143/2,202), uncommon RVA strains for 0.41% of cases (9/2,202). Conclusions The emergence of G12P[8] rotavirus in Italy, as in other countries, marks this genotype as the sixth most common human genotype. Continuous surveillance of RVA strains and monitoring of circulating genotypes are important for a better understanding of rotavirus evolution and genotype distribution, particularly regarding strains that may emerge from reassortment events.


2017 ◽  
Vol 92 (3) ◽  
Author(s):  
Khuzwayo C. Jere ◽  
Chrispin Chaguza ◽  
Naor Bar-Zeev ◽  
Jenna Lowe ◽  
Chikondi Peno ◽  
...  

ABSTRACT To combat the high burden of rotavirus gastroenteritis, multiple African countries have introduced rotavirus vaccines into their childhood immunization programs. Malawi incorporated a G1P[8] rotavirus vaccine (Rotarix) into its immunization schedule in 2012. Utilizing a surveillance platform of hospitalized rotavirus gastroenteritis cases, we examined the phylodynamics of G1P[8] rotavirus strains that circulated in Malawi before (1998 to 2012) and after (2013 to 2014) vaccine introduction. Analysis of whole genomes obtained through next-generation sequencing revealed that all randomly selected prevaccine G1P[8] strains sequenced ( n = 32) possessed a Wa-like genetic constellation, whereas postvaccine G1P[8] strains ( n = 18) had a DS-1-like constellation. Phylodynamic analyses indicated that postvaccine G1P[8] strains emerged through reassortment events between human Wa- and DS-1-like rotaviruses that circulated in Malawi from the 1990s and hence were classified as atypical DS-1-like reassortants. The time to the most recent common ancestor for G1P[8] strains was from 1981 to 1994; their evolutionary rates ranged from 9.7 × 10 −4 to 4.1 × 10 −3 nucleotide substitutions/site/year. Three distinct G1P[8] lineages chronologically replaced each other between 1998 and 2014. Genetic drift was the likely driver for lineage turnover in 2005, whereas replacement in 2013 was due to reassortment. Amino acid substitution within the outer glycoprotein VP7 of G1P[8] strains had no impact on the structural conformation of the antigenic regions, suggesting that it is unlikely that they would affect recognition by vaccine-induced neutralizing antibodies. While the emergence of DS-1-like G1P[8] rotavirus reassortants in Malawi was therefore likely due to natural genotype variation, vaccine effectiveness against such strains needs careful evaluation. IMPORTANCE The error-prone RNA-dependent RNA polymerase and the segmented RNA genome predispose rotaviruses to genetic mutation and genome reassortment, respectively. These evolutionary mechanisms generate novel strains and have the potential to lead to the emergence of vaccine escape mutants. While multiple African countries have introduced a rotavirus vaccine, there are few data describing the evolution of rotaviruses that circulated before and after vaccine introduction. We report the emergence of atypical DS-1-like G1P[8] strains during the postvaccine era in Malawi. Three distinct G1P[8] lineages circulated chronologically from 1998 to 2014; mutation and reassortment drove lineage turnover in 2005 and 2013, respectively. Amino acid substitutions within the outer capsid VP7 glycoprotein did not affect the structural conformation of mapped antigenic sites, suggesting a limited effect on the recognition of G1-specific vaccine-derived antibodies. The genes that constitute the remaining genetic backbone may play important roles in immune evasion, and vaccine effectiveness against such atypical strains needs careful evaluation.


2020 ◽  
Author(s):  
Mike Mwanga ◽  
Betty Owor ◽  
John Ocheing ◽  
Mwanajuma Ngama ◽  
Billy Ogwel ◽  
...  

Abstract Background: Kenya introduced the monovalent G1P[8] Rotarix® vaccine into the infant immunization schedule in July 2014. We examined trends in rotavirus group A (RVA) genotype distribution pre- (January 2010 - June 2014) and post- (July 2014-December 2018) RVA vaccine introduction.Methods: Stool samples were collected from children aged <13 years from four surveillance sites across Kenya: Kilifi County Hospital, Tabitha Clinic, Lwak Mission Hospital, and Siaya County Referral Hospital (children aged <5 years only). Samples were screened for RVA using enzyme linked immunosorbent assay (ELISA) and G and P genes sequenced to infer genotypes.Results: We genotyped 614 samples in pre-vaccine and 261 in post-vaccine introduction periods. During the pre-vaccine introduction period, the most frequent RVA genotypes were G1P[8] (45.8%), G8P[4] (15.8%), G9P[8] (13.2%), G2P[4] (7.0%) and G3P[6] (3.1%). In the post-vaccine introduction period, the most frequent genotypes were G1P[8] (52.1%), G2P[4] (20.7%) and G3P[8] (16.1%). Predominant genotypes varied by year and site in both pre and post-vaccine periods. Temporal genotype patterns showed an increase in prevalence of heterotypic commonly DS-1-like G2P[4] (7.0 to 20.7%, P <.001) and G3P[8] (1.3 to 16.1%, P< .001) genotypes in the post-vaccine introduction period. Additionally, we observed a decline in prevalence of genotypes G8P[4] (15.8 to 0.4%, P <.001) and G9P[8] (13.2 to 5.4%, P <.001) in the post-vaccine introduction period.Conclusion: Genotype prevalence varied from before to after vaccine introduction. Such observations emphasize the need for long-term surveillance to monitor vaccine impact. These changes may represent natural secular variation or possible immuno-epidemiological changes arising from the introduction of the vaccine. Full length sequencing could provide insights into post-vaccine evolutionary pressures and antigenic diversity.


Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 358
Author(s):  
Sarah Thomas ◽  
Celeste M. Donato ◽  
Sokoveti Covea ◽  
Felisita T. Ratu ◽  
Adam W. J. Jenney ◽  
...  

The introduction of the rotavirus vaccine, Rotarix, into the Fiji National Immunisation Program in 2012 has reduced the burden of rotavirus disease and hospitalisations in children less than 5 years of age. The aim of this study was to describe the pattern of rotavirus genotype diversity from 2005 to 2018; to investigate changes following the introduction of the rotavirus vaccine in Fiji. Faecal samples from children less than 5 years with acute diarrhoea between 2005 to 2018 were analysed at the WHO Rotavirus Regional Reference Laboratory at the Murdoch Children’s Research Institute, Melbourne, Australia, and positive samples were serotyped by EIA (2005–2006) or genotyped by heminested RT-PCR (2007 onwards). We observed a transient increase in the zoonotic strain equine-like G3P[8] in the initial period following vaccine introduction. G1P[8] and G2P[4], dominant genotypes prior to vaccine introduction, have not been detected since 2015 and 2014, respectively. A decrease in rotavirus genotypes G2P[8], G3P[6], G8P[8] and G9P[8] was also observed following vaccine introduction. Monitoring the rotavirus genotypes that cause diarrhoeal disease in children in Fiji is important to ensure that the rotavirus vaccine will continue to be protective and to enable early detection of new vaccine escape strains if this occurs.


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