Impact of rotavirus vaccine on all-cause diarrhea and rotavirus hospitalizations in Madagascar

BackgroundRotavirus vaccine was introduced into the Extended Program on Immunization in Madagascar in May 2014. We analyzed trends in prevalence of all cause diarrhea and rotavirus hospitalization in children <5 years of age before and after vaccine introduction and assessed trend of circulating rotavirus genotypes at Centre Hospitalier Universitaire Mère Enfant Tsaralalàna (CHU MET).MethodsFrom January 2010 to December 2016, we reviewed the admission logbook to observe the rate of hospitalization caused by gastroenteritis among 19619 children <5 years of age admitted at the hospital. In June 2013–December 2016, active rotavirus surveillance was also conducted at CHUMET with support from WHO. Rotavirus antigen was detected by EIA from stool specimen of children who are eligible for rotavirus gastroenteritis surveillance at sentinel site laboratory and rotavirus positive specimens were further genotyped at Regional Reference Laboratory by RT-PCR.ResultsDiarrhea hospitalizations decreased after rotavirus vaccine introduction. The median proportion of annual hospitalizations due to diarrhea was 26% (range: 31–22%) before vaccine introduction; the proportion was 25% the year of vaccine introduction, 17% in 2015 and 16% in 2016. Rotavirus positivity paralleled patterns observed in diarrhea. Before vaccine introduction, 56% of stool specimens tested positive for rotavirus; the percent positive was 13% in 2015, 12% in 2016. Diverse genotypes were detected in the pre-vaccine period; the most common were G3P[8] (n = 53; 66%), G2P[4] (n = 12; 15%), and G1P[8] (n = 11; 14%). 6 distinct genotypes were found in 2015; the most common genotype was G2P[4] (n = 10; 67%), the remaining, 5, G12[P8], G3[P8], G1G3[P4], G3G12[P4][P8] and G1G3[NT] had one positive specimen each.ConclusionsFollowing rotavirus vaccine introduction all-cause diarrhea and rotavirus-specific hospitalizations declined dramatically. The most common genotypes detected in the pre-vaccine period were G3P[8] and G2P[4] in 2015, the post vaccine period.     

Pediatric hospitalizations attributable to rotavirus gastroenteritis among Cambodian children: Seven years of active surveillance, 2010–2016

BackgroundEach year, approximately 1,066 Cambodian children under five years old die of diarrhea, and 51% of these deaths are due to rotavirus gastroenteritis. Quantifying childhood hospitalizations caused by severe rotavirus infections is also important in demonstrating disease burden caused by this virus. The objective of this study is to update and confirm the current burden of pediatric hospitalizations attributable to rotavirus gastroenteritis among Cambodian children using seven years of continuous active, prospective surveillance from 2010 to 2016. We also characterize the circulating rotavirus genotypic strains during this period.MethodsActive surveillance for rotavirus gastroenteritis was conducted from January 2010 through December 2016 at a national hospital in Phnom Penh, Cambodia. Children <60 months of age who were hospitalized for acute gastroenteritis (AGE) were consented and enrolled. Information on gender, age, clinical characteristics, and month of onset were collected. Stool specimens were collected and tested by enzyme immunoassay for the presence of rotavirus antigen, and genotyping was performed on rotavirus test-positive specimens to characterize predominant rotavirus strains during the surveillance period.ResultsOf 7007 children enrolled with AGE and having specimens collected, 3473 (50%) were attributed to rotavirus gastroenteritis. The majority of rotavirus hospitalizations occurred in children younger than two years old (92%). Year-round rotavirus transmission was observed, with seasonal peaks during the cooler, dry months between November and May. Genotypic trends in rotavirus were observed over the surveillance period; the predominant rotavirus strains changed from G1P[8] (2010–2012), to G2P[4] (2013–2014), the emergence of genotype G8P[8] in 2015, and G3P[8] in 2016.ConclusionsRotavirus is the leading cause of severe acute gastroenteritis hospitalizations in Cambodian children under five years old, with 50% of such hospitalizations attributable to rotavirus. Over 90% of rotavirus hospitalizations occurred in children under 2 years of age. Changes in the predominant rotavirus strains occurred over time among these unvaccinated children. This information is important to understand and prioritize the current potential impacts upon child health that could be achieved through the introduction of rotavirus vaccines in Cambodia.     

Epidemiology and pre-vaccine burden of rotavirus diarrhea in Democratic Republic of Congo (DRC): Results of sentinel surveillance, 2009–2019

IntroductionSince August 2009, the Democratic Republic of Congo (DRC) has implemented sentinel site surveillance for rotavirus gastroenteritis. Limited hospital studies have been carried out, in DRC, describing the epidemiology of rotavirus diarrhea before rotavirus vaccine introduction in October 2019. This analysis describes the epidemiology of rotavirus gastroenteritis and characteristics of circulating viral strains from 2009 to 2019.Materials and methodsWe analyzed demographic and clinic data collected from children < 5 years old enrolled at three rotavirus sentinel surveillance sites in DRC during 2009–2019, prior to rotavirus vaccine introduction in 2019. Data have been described and presented as mean ± standard deviation for quantitative variables with normal distribution, or as median with an interquartile range [Q1-Q3] for quantitative variables with non-normal distribution, or as absolute value with percentage for qualitative variables.ResultsBetween August 2009 and December 2019, 4,928 children < 5 years old were admitted to sentinel surveillance sites for gastroenteritis in the DRC; the rotavirus positivity rate was 60 %. There was a slight male gender predominance (56 %), and the majority of children (79 %) were 0–11 months of age. Every year, the incidence was highest between May and September corresponding to the dry and cool season. Genotyping was performed for 50 % of confirmed rotavirus cases. The most common G genotypes were G1 (39 %) and G2 (24 %) and most common P genotypes were P[6] (49 %) and P[8] (37 %). The most common G-P genotype combinations were G1P[8] (22 %), G2P[6] (16 %) and G1P[6] (14 %). Genotype distribution varied by site, age group, and year.ConclusionFrom 2009 to 2019, rotavirus-associated gastroenteritis represented a significant burden among DRC children under 5 who were admitted to sentinel sites. G1P[8] was the most commonly identified genotype. Continued monitoring after the introduction of rotavirus vaccine will be essential to monitor any changes in epidemiology.     

Rotavirus hospitalizations among children <5 years of age—Tajikistan, 2013–2014

BackgroundIn January 2015, Tajikistan introduced the monovalent rotavirus vaccine into the national immunization program. Our objective was to estimate pre-vaccine burden of rotavirus-associated hospitalizations in children <5 years of age in Tajikistan.MethodsDuring January 2013–December 2014, active surveillance for acute gastroenteritis (AGE)-associated hospitalizations in children <5 years of age was conducted by sentinel surveillance site staff. Patients’ demographic and clinical data were summarized and a stool sample was collected. An Enzyme Linked Immunosorbent Assay was used for diagnosis of rotavirus infection and subset of the specimens was sent for polymerase chain reaction (PCR) genotyping.ResultsOf 2860 eligible children enrolled and tested, 1207 (42%) were positive for rotavirus. An increase in the number and proportion of rotavirus cases attributed to rotavirus season, with positivity rates >40%, was annually observed during June–September.The median age of rotavirus patients was 9 months and 939/1207 (78%) rotavirus patients were aged 6–23 months. Most (1097/1203; 91%) rotavirus patients were treated with intravenous fluids. G1P[8] was the predominant genotype during both years of surveillance, accounting for 133/222 (60%) of genotyped cases.ConclusionRotavirus is a major cause of hospitalization due to severe AGE in children <5 years of age in Tajikistan, accounting for >40% of cases. Continued, enhanced rotavirus surveillance may allow documentation of changes in rotavirus disease burden following vaccine introduction and assessment of vaccine effectiveness.     

Distribution of rotavirus genotypes in Dhaka,Bangladesh, 2012–2016: Re-emergence of G3P[8] after over a decade of interval

Group A rotavirus causes a substantial proportion of diarrhoea related deaths worldwide among children under five years. We analyzed rotavirus prevalence and genotypes distribution among patients admitted with diarrhoea at icddr,b hospital in Dhaka during 2012–16. Stool specimens (n = 1110) were collected from diarrhoea patients and tested for RVA antigen using enzyme immunoassay. Rotavirus positive samples were G (VP7) and P (VP4) genotyped by RT-PCR and sanger sequencing. Data on clinical manifestations were collected from icddr,b hospital surveillance system. A total of 351 (32%) patients were positive for rotavirus antigen, about half of those were children under two years old. During the study period, G1P[8] (27%) was the most prevalent strain, followed by G12P[8] (15%) and G9[P4] (9%). Mixed G or P genotypes were identified in a substantial proportion (23%) with few strains of rare combinations such as G1P[4], G1P[6], G2P[6], G2P[8], G9P[6]. The genotypic fluctuation was noteworthy; G12P[8] was the major strain in 2012–14 but sharply decreased in 2015–16 when G1P[8] became the most common strain. G3P[8] re-emerged (17%) in 2016 after 11 years. Since the Government of Bangladesh has planned to include rotavirus vaccine in national immunization programme from 2018, our data will provide baseline information on rotavirus genotypes in the pre-vaccination era to observe the selection pressure on genotypes in the post vaccination epoch.     

Rotavirus strain diversity in Eastern and Southern African countries before and after vaccine introduction

BackgroundThe African Rotavirus Surveillance Network has been detecting and documenting rotavirus genotypes in the African sub-continent since 1998 in anticipation of the rollout of rotavirus vaccination in routine Expanded Programme on Immunisation. This paper reports distribution of the rotavirus strains circulating in 15 Eastern and Southern African (ESA) countries from 2010-2015 as part of active World Health Organization (WHO) rotavirus surveillance, and investigates possibility of emergence of non-vaccine or unusual strains in six selected countries post-vaccine introduction.Material and methodsStool samples were collected from children <5 years of age presenting with acute gastroenteritis at sentinel hospitals pre- and post-rotavirus vaccine introduction. Samples were tested for group A rotavirus using an enzyme immunoassay by the national and sentinel laboratories. At the WHO Rotavirus Regional Reference Laboratory in South Africa, molecular characterisation was determined by PAGE (n = 4186), G and P genotyping (n = 6447) and DNA sequencing for both G and P types (n = 400).ResultsThe six-year surveillance period demonstrated that 23.8% of the strains were G1P[8], followed by G2P[4] (11.8%), G9P[8] (10.4%), G12P[8] (4.9%), G2P[6] (4.2%) and G3P[6] (3.7%) in 15 ESA countries. There was no difference in circulating strains pre- and post-rotavirus vaccine introduction with yearly fluctuation of strains observed over time. Atypical rotavirus G and P combinations (such as G1P[4], G2P[8], G9P[4] and G12P[4]) that might have arisen through inter-genogroup or inter-genotypes reassortment were detected at low frequency (2%). Close genetic relationship of African strains were reflected on the phylogenetic analysis, strains segregated together to form an African cluster in the same lineages/sub-lineage or monophyletic branch.ConclusionThere has been considerable concern about strain replacement post-vaccine introduction, it was not clear at this early stage whether observed cyclical changes of rotavirus strains were due to vaccine pressure or this was just part of natural annual fluctuations in the six ESA countries, long-term surveillance is required.     

Hospital based surveillance and molecular characterization of rotavirus in children less than 5 years of age with acute gastroenteritis in Nepal

BackgroundRotavirus remains a significant causative agent of childhood acute gastroenteritis, particularly among children less than 5 years of age. Although precise data on childhood mortality associated with diarrheal disease in Nepal is not available, it is estimated that 22% of all rotavirus deaths globally occurs in neighboring country of India. In spite of the substantial burden of rotavirus gastroenteritis in the Indian subcontinent, rotavirus vaccine has not been introduced in Nepal. Continuous surveillance for monitoring rotavirus disease burden and molecular characterization is needed prior to rotavirus vaccine introduction in Nepal.MethodsA total of 3310 stool samples (2849 hospitalized cases and 461 non-hospitalized cases), were collected from patients <5 years of age from January 2013 to December 2016 and tested for rotavirus antigen by ELISA (ProSpecT, USA). A subset of ELISA positive stool samples was genotyped. Demographic data were collected.ResultsDuring the four-year surveillance period, the overall burden of rotavirus infection was 24% among hospitalized children which was much higher than among non-hospitalized children (12%). The majority of children hospitalized with rotavirus gastroenteritis were less than 2 years of age (86%). Rotavirus-associated gastroenteritis hospitalizations occur year-round in Nepal, but a distinct peak in winter (up to 40% among hospitalized) was observed. Of 735 ELISA positive samples, 492 were genotyped by RT-PCR. The most prevalent genotype was G12P[6] (45.3%), followed byG2P[4](12.2%), G1P[8] (9.6%), G9P[4](7.3%), and G9P[8](4.5%). Mixed infection accounted for 4.4% of cases, 6.2% were partially typed and 10.5% of the samples were G and P untypable.ConclusionsA high burden of rotavirus gastroenteritis and a diversity of circulating rotavirus strains in Nepal were observed. Recommendation to introduce a rotavirus vaccine with known vaccine effectiveness would help in reducing the severity of Rotavirus diarrheal disease in children less than 5 years of age.     

Rotavirus strain distribution in Ghana pre- and post- rotavirus vaccine introduction

BackgroundGhana introduced the monovalent rotavirus vaccine (Rotarix) into its national paediatric vaccination programme in May2012. Vaccine introduction was initiated nationwide and achieved >85% coverage within a few months. Rotavirus strain distribution pre- and post-RV vaccine introduction is reported.MethodsStool samples were collected from diarrhoeic children <5 years of age hospitalized between 2009 and 2016 at sentinel sites across Ghana and analyzed for the presence of group A rotavirus by enzyme immunoassay. Rotavirus strains were characterized by RT-PCR and sequencing.ResultsA total of 1363 rotavirus EIA-positive samples were subjected to molecular characterization. These were made up of 823 (60.4%) and 540 (39.6%) samples from the pre- and post-vaccine periods respectively. Rotavirus VP7 genotypes G1, G2 and G3, and VP4 genotypes P[6] and P[8] constituted more than 65% of circulating G and P types in the pre–vaccine period. The common strains detected were G1P[8] (20%), G3P[6] (9.2%) and G2P[6] (4.9%).During the post-vaccine period, G12, G1 and G10 genotypes, constituted more than 65% of the VP7 genotypes whilst P[6] and P[8] made up more than 75% of the VP4 genotypes. The predominant circulating strains were G12P[8] (26%), G10P[6] (10%) G3P[6] (8.1%) and G1P[8] (8.0%). We also observed the emergence of the unusual rotavirus strain G9P[4] during this period.ConclusionRotavirus G1P[8], the major strain in circulation during the pre-vaccination era, was replaced by G12P[8] as the most predominant strain after vaccine introduction. This strain replacement could be temporary and unrelated to vaccine introduction since an increase in G12 was observed in countries yet to introduce the rotavirus vaccine in West Africa. A continuous surveillance programme in the post-vaccine era is necessary for the monitoring of circulating rotavirus strains and the detection of unusual/emerging genotypes.     

Temporal association of rotavirus vaccination and genotype circulation in South Africa: Observations from 2002 to 2014

BackgroundRotavirus vaccination has reduced diarrhoeal morbidity and mortality globally. The monovalent rotavirus vaccine was introduced into the public immunization program in South Africa (SA) in 2009 and led to approximately 50% reduction in rotavirus hospitalization in young children. The aim of this study was to investigate the rotavirus genotype distribution in SA before and after vaccine introduction.Materials and methodsIn addition to pre-vaccine era surveillance conducted from 2002 to 2008 at Dr George Mukhari Hospital (DGM), rotavirus surveillance among children <5 years hospitalized for acute diarrhoea was established at seven sentinel sites in SA from April 2009 to December 2014. Stool specimens were screened by enzyme immunoassay and rotavirus positive specimens genotyped using standardised methods.ResultsAt DGM, there was a significant decrease in G1 strains from pre-vaccine introduction (34%; 479/1418; 2002–2009) compared to post-vaccine introduction (22%; 37/170; 2010–2014; p for trend <.001). Similarly, there was a significant increase in non-G1P[8] strains at this site (p for trend <.001). In expanded sentinel surveillance, when adjusted for age and site, the odds of rotavirus detection in hospitalized children with diarrhoea declined significantly from 2009 (46%; 423/917) to 2014 (22%; 205/939; p < .001). The odds of G1 detection declined significantly from 2009 (53%; 224/421) to 2010–2011 (26%; 183/703; aOR = 0.5; p < .001) and 2012–2014 (9%; 80/905; aOR = 0.1; p < .001). Non-G1P[8] strains showed a significant increase from 2009 (33%; 139/421) to 2012–2014 (52%; 473/905; aOR = 2.5; p < .001).ConclusionsRotavirus vaccination of children was associated with temporal changes in circulating genotypes. Despite these temporal changes in circulating genotypes, the overall reduction in rotavirus disease in South Africa remains significant.     

Impact and effectiveness of pentavalent rotavirus vaccine in children <5 years of age in Burkina Faso

BackgroundBurkina Faso was one of the first African nations to introduce pentavalent rotavirus vaccine (RV5, RotaTeq) into its national immunization program in October 2013. We describe the impact and effectiveness of rotavirus vaccine on acute gastroenteritis (AGE) hospitalizations among Burkinabe children.MethodsSentinel hospital-based surveillance for AGE was conducted at four hospitals during December 2013 – February 2017. Demographic, clinical, and vaccination information was collected and stool specimens were tested by EIA. Trends in rotavirus AGE hospitalizations and changes in the proportion of AGE hospitalizations due to rotavirus were examined at two sentinel sites from January 2014 – December 2016. Unconditional logistic regression models using data from all 4 surveillance sites were used to calculate vaccine effectiveness (VE, defined as 1-odds ratio) by comparing the odds of vaccination among rotavirus AGE (cases) and non-rotavirus AGE (controls) patients, controlling for age, season, hospital site and socioeconomic factors.ResultsThe proportion of AGE hospitalizations that tested positive for rotavirus declined significantly among children <5 years of age, from 36% (154/422) in 2014 to 22% (71/323, 40% reduction, p < .01) in 2015 and 20% (61/298, 44% reduction, p < .01) in 2016. Among infants, the percentage of AGE admissions due to rotavirus fell significantly from 38% (94/250) in 2014 to 21% (32/153, 44% reduction, p < .01) in 2015 and 17% (26/149, 54% reduction, p < .01) in 2016. The adjusted VE for full 3-dose series of RV5 against rotavirus hospitalization was 58% (95% [CI], 10%, 81%) in children 6–11 months of age and 19% (−78%, 63%) in children ≥12 months.ConclusionRotavirus hospitalizations declined after introduction of pentavalent rotavirus vaccine in children, particularly among infants. RV5 significantly protected against severe rotavirus gastroenteritis in infants, but effectiveness decreased in older children.     

Genotype distribution of Group A rotavirus in children before and after massive vaccination in Latin America and the Caribbean: Systematic review

BackgroundDuring the last decade, most of Latin American and the Caribbean (LAC) countries have implemented oral live rotavirus vaccines in their national vaccination programs with remarkable results. However, it has been suggested that massive vaccination could lead to the replacement of circulating genotypes or the emergence of new variants or neutralizing antibodies escape mutants, which may reduce the effectiveness of the vaccine. The objective was to analyze the genetic diversity of Group A rotavirus before and after the introduction of universal vaccination in LAC.MethodsWe conducted a systematic review of studies published in PubMed, Scielo and LILACS. There were considered only LAC countries with rotavirus massive vaccination strategy which had described circulating genotypes data in children under 5 years of age, either for surveillance or vaccine effectiveness purposes, from 2001 to 2017. Systematic review stages were carried out following the recommendations of PRISMA.ResultsOf the 18 countries that included any of the two licensed rotavirus vaccines in their national schedules since 2006, only 7 (~39%) presented studies of RVA genetic diversity before and after implementation, and met the inclusion criteria. Four of them (Argentina, Brazil, Colombia and Nicaragua) experienced a rapid switch from Wa-like to DS-1-like strains. Also, G1P[8] association, considered the most predominant worldwide in the pre-vaccination era, decreased significantly and was only frequently detected in Venezuela and Nicaragua. No defined pattern of emergence at high frequencies of unusual associations was observed in the post vaccination period, except for some evidence of G9P[4] in Colombia, G3P[6] and G1P[4] in Nicaragua.ConclusionsEven though the evidence shows a DS-1-like change trend, data from studies conducted in Latin America and the Caribbean are diverse and still not sufficient to assess the impact of vaccines on viral ecology or if genetic diversity is influenced by natural mechanisms of fluctuation.     

Role of rotavirus vaccination on an emerging G8P[8] rotavirus strain causing an outbreak in central Japan

BackgroundIn this study, we examined the effectiveness of RV1 and RV5 vaccines during an outbreak of G8P[8] rotavirus group A strain (G8P[8]-RVA). These vaccines were originally designed to provide protection against severe diseases caused by common circulating strains, whereas G8P[8]-RVA remains emerging strain and partially heterotypic to the vaccines. It is imperative to investigate vaccine effectiveness (VE) against G8P[8]-RVA because this strain appears to be predominant in recent years, particularly, in post-vaccine era.MethodsRVA infection and genotypes were confirmed by polymerase chain reaction (PCR) followed by sequence-based genotyping. VE was determined during an outbreak of G8P[8]-RVA in Shizuoka Prefecture, Japan, in February-July 2017, retrospectively, by comparing vaccination status of children suffering from acute gastroenteritis (AGE) between ‘PCR-positive’ and ‘PCR-negative’ cases using conditional logistic regression adjusted for age.ResultsAmong 80 AGE children, RVA was detected in 58 (73%), of which 53 (66%) was G8P[8]-RVA. The clinical characteristics of G8P[8]-RVA and other RVA strains were identically severe. Notably, the attack rates of G8P[8]-RVA in vaccinated (61.1%) and unvaccinated (65.5%) children were almost similar. Indeed, no substantial effectiveness were found against G8P[8]-RVA (VE, 14% [95% CI: −140% to 70%]) or other RVA strains (VE, 58% [95% CI: −20% to 90%]) for mild infections. However, these vaccines remained strongly effective against moderate (VE, 75% [95% CI: 1% to 40%]) and severe (VE, 92% [95% CI: 60% to 98%]) RVA infections. The disease severity including Vesikari score, duration and frequency of diarrhea, and body temperature were significantly lower in vaccinated children.ConclusionsThis study demonstrates the effectiveness of current RV vaccines against moderate and severe, but not against the mild infections during an outbreak caused by unusual G8P[8]-RVA, which was virtually not targeted in the vaccines.     

Incidence of rotavirus gastroenteritis hospitalizations and genotypes,before and five years after introducing universal immunization in Israel

BackgroundUncertainty exists about the sustainability of the reduction in rotavirus gastroenteritis (RVGE) following the introduction of rotavirus vaccines into national immunization programs, and on its potential impact on circulating genotypes. RotaTeq was introduced into the Israeli national immunization program in December 2010, and vaccination coverage is around 80%.AimsTo examine the change in incidence of RVGE hospitalization and rotavirus genotypes, during the five years after introduction of RotaTeq into the Israeli national immunization program.MethodsData were obtained prospectively on hospitalization of children aged 0–59 months due to acute gastroenteritis (N = 7346) from three hospitals in northern Israel. Stool samples were tested for rotavirus by immunochromatography. Rotavirus was genotyped (N = 506) by RT-PCR and/or sequencing.ResultsThe average incidence of RVGE hospitalization declined by 61.0% (95% CI 49.0–73.4%), from 5.6 per 1000 (95% CI 5.0–6.2) in the pre-universal immunization period (2008–2010) to 2.2 per 1000 (95% CI 1.8–2.5) during the universal immunization period (2012–2015), but yearly fluctuations were still observed.The most common genotypes in the pre-universal immunization period were G1P[8] (35.3%) followed by G2P[4] (15.5%), G3P[8] (8.8%), G4P[8] (4.3%) and G9P[8] (4.3%), and 19.5% were mixed infections. The dominance of G1P[8] continued into the universal immunization period (48.6%), followed by G3P[8] (21.5%), G9P[8] (15.9%) and G12P[8] (4.7%), while mixed rotavirus infections were no longer detected.ConclusionsUniversal immunization with RotaTeq in Israel was associated a sustained reduction in RVGE hospitalization. It is unclear whether changes in the circulating rotavirus genotypes are due to vaccine-induced selective pressure. Assessment of the long-term impact of rotavirus vaccination on the incidence of rotavirus gastroenteritis and continued strain surveillance is warranted.