Rotavirus trends and distribution of genotypes before and during COVID-19 pandemic era: Bangladesh, 2017-2021.

Rotavirus gastroenteritis is accountable for an estimated 128 500 deaths among children younger than 5 years worldwide, and the majority occur in low-income countries. Although the clinical trials of rotavirus vaccines in Bangladesh revealed a significant reduction of severe rotavirus disease by around 50%, the vaccines are not yet included in the routine immunization program. The present study was designed to provide data on rotavirus diarrhea with clinical profiles and genotypes before (2017-2019) and during the COVID-19 pandemic period (2020-2021). Fecal samples were collected from 2% of the diarrheal patients at icddr,b Dhaka hospital of all ages between January 2017 and December 2021 and were tested for VP6 rotavirus antigen using ELISA. The clinical manifestations such as fever, duration of diarrhea and hospitalization, number of stools, and dehydration and so on were collected from the surveillance database (n = 3127). Of the positive samples, 10% were randomly selected for genotyping using Sanger sequencing method. A total of 12 705 fecal samples were screened for rotavirus A antigen by enzyme immunoassay. Overall, 3369 (27%) were rotavirus antigen-positive, of whom children <2 years had the highest prevalence (88.6%). The risk of rotavirus A infection was 4.2 times higher in winter than in summer. Overall, G3P[8] was the most prominent genotype (45.3%), followed by G1P[8] (32.1%), G9P[8] (6.8%), and G2P[4] (6.1%). The other unusual combinations, such as G1P[4], G1P[6], G2P[6], G3P[4], G3P[6], and G9P[6], were also present. Genetic analysis on Bangladeshi strains revealed that the selection pressure (dN/dS) was estimated as <1. The number of hospital visits showed a 37% drop during the COVID-19 pandemic relative to the years before the pandemic. Conversely, there was a notable increase in the rate of rotavirus positivity during the pandemic (34%, p < 0.00) compared to the period before COVID-19 (23%). Among the various clinical symptoms, only the occurrence of watery stool significantly increased during the pandemic. The G2P[4] strain showed a sudden rise (19%) in 2020, which then declined in 2021. In the same year, G1P[8] was more prevalent than G3P[8] (40% vs. 38%, respectively). The remaining genotypes were negligible and did not exhibit much fluctuation. This study reveals that the rotavirus burden remained high during the COVID-19 prepandemic and pandemic in Bangladesh. Considering the lack of antigenic variations between the circulating and vaccine-targeted strains, integrating the vaccine into the national immunization program could reduce the prevalence of the disease, the number of hospitalizations, and the severity of cases.

The evolutionary footprint of influenza A subtype H3N2 strains in Bangladesh: implication of vaccine strain selection.

In February each year, World Health Organization (WHO) recommends candidate vaccine viruses for the forthcoming northern hemisphere (NH) season; however, the influenza season in the temperate zone of NH begins in October. During egg- or cell culture-propagation, the vaccine viruses become too old to confer the highest match with the latest strains, impacting vaccine effectiveness. Therefore, an alternative strategy like mRNA-based vaccine using the most recent strains should be considered. We analyzed influenza A subtype H3N2 strains circulating in NH during the last 10 years (2009-2020). Phylogenetic analysis revealed multiple clades of influenza strains circulating every season, which had substantial mismatches with WHO-recommended vaccine strains. The clustering pattern suggests that influenza A subtype H3N2 strains are not fixed to the specific geographical region but circulate globally in the same season. By analyzing 39 seasons from eight NH countries with the highest vaccine coverage, we also provide evidence that the influenza A, subtype H3N2 strains from South and Southeast Asia, including Bangladesh, had the highest genetic proximity to the NH strains. Furthermore, insilico analysis showed minimal effect on the Bangladeshi HA protein structure, indicating the stability of Bangladeshi strains. Therefore, we propose that Bangladeshi influenza strains represent genetic makeup that may better fit and serve as the most suitable candidate vaccine viruses for the forthcoming NH season.

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.

Changing profile of rotavirus genotypes in Bangladesh, 2006-2012.

BACKGROUND: Rotavirus is the leading cause of severe diarrhea in infants and young children worldwide including Bangladesh. Unlike what was seen in high-income countries, the licensed rotavirus vaccines did not show high efficacy in Bangladeshi trials. We assessed rotavirus prevalence and genotypes in Bangladesh over six-year period to provide baseline information on the rotavirus burden and changing profile in the country. METHODS: This study was conducted from June 2006 to May 2012 in Matlab, Bangladesh. Group A rotaviruses were detected in stools collected from diarrhea patients by ELISA and genotyped using multiplex reverse transcription PCR followed by nucleotide sequencing. RESULTS: Of the 9678 stool samples, 20.3% were positive for rotavirus. The most predominant genotype was G1P[8] (22.4%), followed by G9P[8] (20.8%), G2P[4] (16.9%) and G12P[8] (10.4%). Mixed infections were detected in 14.2% of the samples. Emergence of an unusual strain, G9P[4] was documented during 2011-12. Several amino acid mismatches in the antigenic epitopes of VP7 and VP4 between Bangladeshi and the vaccine strains were identified. CONCLUSIONS: Our study provides important information on rotavirus genotypes that should be considered for the selection and introduction of rotavirus vaccines in Bangladesh.

Genetic characterization of a rare bovine-like human VP4 mono-reassortant G6P[8] rotavirus strain detected from an infant in Bangladesh.

During an ongoing diarrhea etiology surveillance in Mirzapur, Bangladesh, a rare human G6P[8] RVA strain (RVA/Human-wt/BGD/KH2288/2011/G6P[8]) was detected in a stool sample of a 7-month-old infant with acute diarrhea. Complete genotype analyses revealed that KH2288 possessed the G6-P[8]-I2-R2-C2-M2-A11-N2-T6-E2-H3 genotype constellation. Sequence analysis of the VP7 gene revealed a close phylogenetic relationship with bovine G6 strains from India, whereas, the VP4 gene segment was nearly identical to typical human P[8] strain circulating in Bangladesh and the rest of the world. Phylogenetic analysis of the remaining nine gene segments revealed a close relatedness to either animal or animal derived human RVA strain. We speculated that, strain KH2288 was a monoreassortant between a human RVA strain and a RVA strain typically infecting member of the Artiodactyla, such as cattle, goat or sheep. To our knowledge, this is the first complete genotyping report of a naturally occurring G6P[8] RVA strain, worldwide.

A novel norovirus recombinant strain GII.4/GII.21 in Bangladesh, 2011.

We identified a novel inter-genotype recombinant norovirus strain, Dhaka85/2011/BGD, collected from a stool specimen of a nine-month-old infant who was hospitalized with diarrhea. Molecular investigation and phylogenetic analysis classified its RNA polymerase gene as GII.4-like, which commonly circulates in humans. The capsid gene was classified as GII.21-like, most likely originated from water. The discovery of this novel strain is an illustration of the enormous diversity among the norovirus strains, especially in developing countries and has important implications for future vaccine strategies.

Clinical presentation and molecular characterization of group B rotaviruses in diarrhoea patients in Bangladesh.

A total of 1106 stool samples collected from diarrhoea patients admitted to Dhaka hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh, during January-December 2008 were analysed for the presence of rotavirus-specific RNA by PAGE. The group B-specific RNA migration pattern was detected in 26 patients (2.4%) and group A-specific pattern in 259 patients (23.4%). Clinical data from group A and group B rotavirus-infected patients indicated that episodes did not differ much in the prevalence of diarrhoea, number of stools, outcome or differences in gender. However, abdominal pain was more common in group B rotavirus infections (36 vs 15%, P=0.02) and the virus was responsible for more severe dehydration compared with group A-infected patients (12 vs 3%, P=0.04). Sequence analyses of VP4, VP7 and NSP2 indicated that an Indian-Bangladeshi lineage of the virus, which is different from both the prototype (Chinese) lineage and from the animal group B rotaviruses, has been circulating in Bangladesh. Continuous monitoring of group B rotaviruses both in hospitals and in the community will be helpful to determine the true burden of group B rotaviruses.