Circulating rotavirus strains in children with acute gastroenteritis in Iran, 1986 to 2023 and their genetic/antigenic divergence compared to approved vaccines strains (Rotarix, RotaTeq, ROTAVAC, ROTASIIL) before mass vaccination: Clues for vaccination policy makers.

In the present study, first, rotaviruses that caused acute gastroenteritis in children under five years of age during the time before the vaccine was introduced in Iran (1986 to 2023) are reviewed. Subsequently, the antigenic epitopes of the VP7 and VP4/VP8 proteins in circulating rotavirus strains in Iran and that of the vaccine strains were compared and their genetic differences in histo-blood group antigens (HBGAs) and the potential impact on rotavirus infection susceptibility and vaccine efficacy were discussed. Overall data indicate that rotavirus was estimated in about 38.1 % of samples tested. The most common genotypes or combinations were G1 and P[8], or G1P[8]. From 2015 to 2023, there was a decline in the prevalence of G1P[8], with intermittent peaks of genotypes G3P[8] and G9P[8]. The analyses suggested that the monovalent Rotarix vaccine or monovalent vaccines containing the G1P[8] component might be proper in areas with a similar rotavirus genotype pattern and genetic background as the Iranian population where the G1P[8] strain is the most predominant and has the ability to bind to HBGA secretors. While the same concept can be applied to RotaTeq and RotasIIL vaccines, their complex vaccine technology, which involves reassortment, makes them less of a priority. The ROTASIIL vaccine, despite not having the VP4 arm (P[5]) as a suitable protection option, has previously shown the ability to neutralize not only G9-lineage I strains but also other G9-lineages at high titers. Thus, vaccination with the ROTASIIL vaccine may be more effective in Iran compared to RotaTeq. However, considering the rotavirus genotypic pattern, ROTAVAC might not be a good choice for Iran. Overall, the findings of this study provide valuable insights into the prevalence of rotavirus strains and the potential effectiveness of different vaccines in the Iranian and similar populations.

Molecular characterization of human astrovirus infection in children under 5 years of age with acute gastroenteritis in Tehran, Iran, 2021-2022: co-infection with rotavirus.

Human astroviruses (HAstVs) are considered important causative pathogens of acute gastroenteritis (AGE) in children under 5 years of age worldwide, along with group A rotavirus (RVA), norovirus (NoV), and enteric adenovirus (EAdV). The present study was aimed to both detect HAstV and its co-infections and investigate genetic analysis of circulating HAstV and co-infected virus in hospitalized children under 5 years of age with AGE in Iran. Accordingly, a sum of 200 stool specimens were screened by PCR for HAstV during 2021-2022. The HAstV was found in 0.5% of 200 specimens (n = 1) while was co-infected with RVA. The genetic and phylogenetic analysis indicated HAstV1 genotype, which clustered with viruses from lineage 1b, which has not been previously reported in Iran. The detected RVA strain belonged to G1 lineage II/P[8]-lineage III, which has been reported previously in Iran as the most common strain. The further genetic analysis of RVA VP6 and NSP4 demonstrated an atypical genotype pattern G1P[8]-I1-E2, as a mono-reassortant of a Wa-like genogroup, which appeared to be reassorted with the NSP4 gene of E2 genotype of the G2P[4] DS-1 genogroup. Although the clinical outcomes of the AGE-causing viruses co-infection is not yet entirely clear, it seems that future studies will be helpful to merge clinical and epidemiological data of co-infecting viruses for a more accurate medical and clinical relevance in symptomatic children.

Correlates of immune protection against human rotaviruses: natural infection and vaccination.

Species A rotaviruses are the leading viral cause of acute gastroenteritis in children under 5 years of age worldwide. Despite progress in the characterization of the pathogenesis and immunology of rotavirus-induced gastroenteritis, correlates of protection (CoPs) in the course of either natural infection or vaccine-induced immunity are not fully understood. There are numerous factors such as serological responses (IgA and IgG), the presence of maternal antibodies (Abs) in breast milk, changes in the intestinal microbiome, and rotavirus structural and non-structural proteins that contribute to the outcome of the CoP. Indeed, while an intestinal IgA response and its surrogate, the serum IgA level, are suggested as the principal CoPs for oral rotavirus vaccines, the IgG level is more likely to be a CoP for parenteral non-replicating rotavirus vaccines. Integrating clinical and immunological data will be instrumental in improving rotavirus vaccine efficacy, especially in low- and middle-income countries, where vaccine efficacy is significantly lower than in high-income countries. Further knowledge on CoPs against rotavirus disease will be helpful for next-generation vaccine development. Herein, available data and literature on interacting components and proposed CoPs against human rotavirus disease are reviewed, and limitations and gaps in our knowledge in this area are discussed.

Prevalence, molecular characterization, and clinical features of human bocavirus in children under 5 years of age with acute gastroenteritis admitted to a specialized children's hospital in Iran: A cross-sectional study.

Background and Aims: Although some reports have confirmed the role of human bocavirus (HBoV) in respiratory infections, the importance of this virus in causing acute gastroenteritis has not yet been proven. This study aimed to determine the molecular prevalence of HBoV in children under 5 years old with gastroenteritis and to compare the clinical symptoms of HBoV-positive and -negative gastroenteritis cases. Methods: A total of 100 stool samples were collected from children with gastroenteritis hospitalized in a pediatric hospital in Tehran, Iran. Demographic and clinical data were collected from patients' medical records. Viral genomic DNA was extracted from stool samples and amplified using the PCR assay. Finally, sequencing was used to determine the genotype of HBoV. Results: The HBoV genome was detected in 14 samples (14%). The highest prevalence of HBoV was observed in the age range of 24-60 months (n = 5; 35.7%); However, no statistically significant relationship was observed between the prevalence of HBoV and age groups (p = 0.09). Nine (64.3%) and 5 (35.7%) HBoV-positive cases were boys and girls, respectively (p = 0.45). Fever, vomiting, and heartache were seen in 5 (35.7%), 3 (21.4%), and 1 (7.1%) HBoV-positive patients, respectively. Overall, no significant difference was observed in any of the investigated clinical manifestations between patients positive or negative for HBoV. Five HBoV-positive samples were subjected to sequencing and all five sequenced samples were genotype 3. Conclusion: HBoV infections can be considered a risk factor for causing at least a portion of acute gastroenteritis cases in children under 5 years of age.

Characterization and immunogenicity of a novel chimeric hepatitis B core-virus like particles (cVLPs) carrying rotavirus VP8*protein in mice model.

Given the efficacy and safety issues of the WHO for approved/prequalified live attenuated rotavirus (RV) vaccines, studies on alternative non-replicating modals and proper RV antigens are actively undertaken. Herein, we report the novel chimeric hepatitis B core-virus like particles (VLPs) carrying RV VP8*26-231 protein of a P [8] strain (cVLPVP8*), as a parenteral VLP RV vaccine candidate. SDS-PAGE and Western blotting analyses indicated the expected size of the E. coli-derived HBc-VP8* protein that self-assembled to cVLPVP8* particles. Immunization in mice indicated development of higher levels of IgG and IgA as well as higher IgG1/IgG2a ratios by cVLPVP8* vaccination compared to the VP8* alone. Assessment of neutralizing antibodies (nAbs) indicated development of heterotypic nAbs with cross-reactivity to a heterotypic RV strain by cVLPVP8* immunization compared to VP8* alone. The observed anti-VP8* cross-reactivity might indicate the possibility of developing a Pan-genomic RVA vaccine based on the cVLPVP8* formulation that deserves further challenge studies.

Molecular Prevalence and Genotype Distribution of Human Adenovirus in Iranian Children with Gastroenteritis.

OBJECTIVE: We determined the molecular prevalence and genotype distribution of human adenovirus (HAdV) among children under five years of age with gastroenteritis in Iran. METHODS: One hundred stool samples from children hospitalized were tested by PCR for adenovirus, and some of the positive samples were sequenced to determine the specific genotype. RESULTS: HAdV DNA was found in 15 samples (15%). The highest and the lowest prevalence of HAdV was observed in the age groups 24-60 months (n = 6; 40%) and 7-12 months (n = 2; 13.3%), respectively (p = 0.01). Nine HAdV-positive samples were sequenced, of which four isolates were HAdV type 2 and five isolates were HAdV type 41. CONCLUSION: HAdV was most common in the 24-60-month-old children. Of the samples sequenced, we found only types 2 and 41. Our results show that in addition to HAdV types 40 and 41, HAdV type 2 may also play a role in causing gastroenteritis in children.

The predominance of recombinant Norovirus GII.4Sydney[P16] strains in children less than 5 years of age with acute gastroenteritis in Tehran, Iran, 2021-2022.

The present study was aimed to both detect emerging noroviruses and investigate RdRp and VP1-based dual typing of circulating noroviruses in hospitalized children less than 5 years of age with acute gastroenteritis (AGE) in Iran. For this purpose, a total of 200 stool specimens were screened during 2021-2022 by real-time RT-PCR for genogroup I and II (GI and GII) and dual-typed by sequence analysis of PCR products, using a web-based norovirus Typing Tool and phylogenetic analysis. The GI and GII noroviruses were detected in 20% of 200 specimens. The GII.4 norovirus was found to be the most common VP1 genotype (53%) followed by GII.8 (32%), GII.7 (6%), GII.17 (6%), and GII.3 (3%). The GII.P16 norovirus was also found as the predominant RdRp type (53%) followed by GII.P8 (32%), GII.P7 (6%), GII.P17 (6%), and GII.P31 (3%). To our knowledge, this is the first report that highlights the dominancy of recombinant norovirus GII.4Sydney[P16] and newly emerging of norovirus GII.8 [P8], GII.17 [P17] and GII.3 [P16] in Iran. These findings further indicate inter-genotype recombinant strains of noroviruses.

Is SARS-CoV-2 a concern in the largest wastewater treatment plant in middle east?

The surveillance of wastewater treatment plant (WWTP) as the end point of SARS-CoV-2 shed from infected people arise a speculation on transmission of this virus of concern from WWTP in epidemic period. To this end, the present study was developed to comprehensively investigate the presence of SARS-CoV-2 in raw wastewater, effluent and air inhaled by workers and employee in the largest WWTP in Tehran for one-year study period. The monthly raw wastewater, effluent and air samples of WWTP were taken and the SARS-CoV-2 RNA were detected using QIAamp Viral RNA Mini Kit and real-time RT-PCR assay. According to results, the speculation on the presence of SARS-CoV-2 was proved in WWTP by detection this virus in raw wastewater. However, no SARS-CoV-2 was found in both effluent and air of WWTP; this presents the low or no infection for workers and employee in WWTP. Furthermore, further research are needed for detection the SARS-CoV-2 in solid and biomass produced from WWTP processes due to flaks formation, followed by sedimentation in order to better understand the wastewater-based epidemiology and preventive measurement for other epidemics probably encountered in the future.

Global epidemiology of HBV infection among hemodialysis patients: A systematic review and meta-analysis.

BACKGROUND & AIMS: Hemodialysis (HD) is a life-saving procedure that purifies the blood in patients with end-stage renal disease (ESRD). Among all major complications, blood-borne diseases like hepatitis B virus (HBV) may be exposed as serious side effects of hemodialysis. A comprehensive review of the global burden of HBV among HD patients has not been written so far. The aim of the current systematic review and meta-analysis was to determine the globally epidemiology of HBV infection among HD patients. METHODS: Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, articles that investigated the prevalence of HBV among HD patients were searched from the major databases such as EMBASE, PubMed, Web of Science collection, and Scopus. Pooled prevalence with 95% CI and identification of heterogeneity were obtained using the random effects model and Cochran's Q-test, respectively, and quantification was evaluated using the I2 statistics. All statistical analyses were performed by STATA 14.1 statistical software. RESULTS: among 322 datasets (795,623 cases) that included in this study, the pooled prevalence of HBV infection among HD patients was 7.32% (95% CI: 6.53-8.15%; I2 = 97.91%), including 7.57% (95% CI: 6.69-8.48%) for HBsAg and 6.09% (95% CI: 4.05-8.49%) for DNA, respectively. In addition, based on geographic area, the prevalence was 7.44% (95% CI: 6.35-8.61%) in Asia, 4.32% (95% CI: 2.21-7.04%) in North America, 7.07% (95% CI: 6.35-8.61%) in Europe, 5.52% (95% CI: 3.60-7.78%) in Africa, 8.45% (95% CI: 5.81-11.78%) in Oceania, and 9.73% (95% CI: 7.11-12.70%) in South America. CONCLUSIONS: Our analysis indicates a relatively high prevalence of HBV infection in HD patients, even in some developed countries. Considering that ESRD patients are not able to properly respond to the vaccination strategies in order to develop an acceptable immunity, vaccination of healthy individuals is highly recommended to arm their bodies for possible immunocompromise conditions in the future. Moreover, donated blood in blood transfusion centers should be checked for possible hepatitis B virus infection using sensitive molecular tests.

Molecular characterization of rotavirus infections in children less than 5 years of age with acute gastroenteritis in Tehran, Iran, 2021-2022: Emergence of uncommon G9P[4] and G9P[8] rotavirus strains.

The present study was conducted to monitor the genotypes of circulating species A rotavirus (RVA) in Iran and investigate genetic linkages between specific RVA VP7, VP4, VP6, and NSP4 segments. For this purpose, 48 RVA strains were detected during the 2021-2022 seasons. The two combinations of G9P[4] and G9P[8] RVA strains were predominant. However, several other combinations of RVA also were detected. Based on the distribution of I and E genotypes (46 strains) with respect to G and P, the most common strains were G9P[4]-I2-E2 (19.5%), G9P[4]-I2-E1 (6.5%), G9P[4]-I1-E1 (4.3%), G9P[8]-I1-E1 (19.5%), and G9P[8]-I2-E2 (10.9%), which were followed by several other combinations of G and P RVA strains with different pattern of I-E genotypes and also emerging, rare and uncommon strains. The present study described the continued circulation of G9 strains with the emergence of uncommon G9P[4] and G9P[8] reassortants with three and two different I-E genotypes, respectively, which have not been reported previously in Iran. Our findings indicated that these uncommon strains exhibited a unique genotype pattern comprising a mixture of genogroup 1 and 2 genes and suggest the need for further analysis of rare, uncommon, and emerging strains of RVA at all 11 gene segments to determine intergenogroup and intragenotype reassortments.

Circulating rotavirus P[8]-lineage IV, unlike P[8]-lineage III, significantly related to nonsecretors status in Iranian children.

Rotavirus (RV) P[8] strains are responsible for the most of the RV infections globally and are significantly associated with the secretor and Lewis positive status. Among the distinct P[8] lineages, different ligand affinities have been detected which can be linked to differences in secretor status associated histo-blood group antigens (HBGAs). Herein, we report the lineages of P[8] strains and their associated secretor and Lewis antigen phenotypes in Iranian children. The phylogenetic tree and sequence analyses showed that the most common detected RV P[8] strain belonged to P[8]-lineage III (92%) and were significantly associated with secretor and Lewis positive status. In contrast, 8% of P[8] strains clustered into the P[8]-lineage IV and were significantly associated with nonsecretor status, implying that lineage IV tends to infect nonsecretor individuals. Furthermore, protein modeling and amino acid analyses of the VP8* glycan binding site of Iranian P[8]-lineage IV strains indicated two residual substitutions (T184V and N216V/I) compared to the P[8]-lineage III strains that might have affected the glycan affinity among P[8]-lineages IV strains. The corresponding residual changes might permit their continued transmission in nonsecretor children in competition with other P[8]-lineages. Although nonsecretors show natural resistant to P[8] strains, but such residual changes might overcome this natural resistance which in turn might indirectly contribute to the decline in the vaccine efficacy in populations where HBGA polymorphism allows their circulation at high frequency.

An annoying enteric virus: A systematic review and meta-analysis of human astroviruses and gastrointestinal complications in children.

Human astroviruses (HAstVs) have frequently been detected in individuals with acute gastroenteritis (AGE). However, a precise estimate of the overall prevalence of the virus in children with AGE as well as the possible association of the virus with gastrointestinal complications is not available up to now. The present study estimated the overall prevalence of HAstVs in children with gastrointestinal complications as well as the association between the virus and symptoms. We systematically searched four international databases (PubMed, Scopus, Web of Science, and Google scholar) to find studies on the prevalence of HAstVs in people with AGE published between Jan 2000 and Sep 2021. Analysis of the 223 included studies presented a 4.2% (95% CI 3.8%-4.8%) prevalence of the virus in AGE individuals. Based on case-control studies, a significant association between these viruses and AGE was detected (OR: 2.059, 95% CI; 1.438-2.949). HAstV-1 and HAstV-VA-2 is the most and least common genotypes in the AGE patients, respectively (59.0%, 95% CI: 52.1%-65.6% vs. 4.9%, 95% CI: 2.6%-9.1%). Due to the statistically significant association between HAstV and gastrointestinal complications, more attention should be paid to these viruses in people with AGE and more studies should employ case-control design.