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Acta Tropica Jun 2024Rotavirus A (RVA) is a leading cause of severe gastroenteritis in children worldwide, and vaccination has become a pivotal strategy to reduce the associated morbidity...
Rotavirus A (RVA) is a leading cause of severe gastroenteritis in children worldwide, and vaccination has become a pivotal strategy to reduce the associated morbidity and mortality. This study presents a molecular characterization of RVA genotypes circulating among vaccinated children in Pakistan during the year 2019. A total of 510 stool samples were collected from children of up to five years of age presenting with acute gastroenteritis symptoms in Rawalpindi, Islamabad regions of Pakistan. The RVA antigen was detected using ELISA on these samples. RVA G/P genotyping was performed on ELISA positive samples using Multiplex semi-nested reverse transcriptase PCR. RVA was found in 130 fecal samples, with an overall prevalence of 25.4 %. G9P[8] (20 %) is the most prevalent genotype, followed by G12P[6] (17 %), G3P[8] (14 %), G1P[8] (12 %), G2P[4] (10 %), G12P[8] (7 %), G9P[6] (7 %), G3P[6] (6 %), G3P[4] (4 %) and G1P[6] (3 %) respectively. There is a statistically significant difference (p < 0.05) found in the group age (in months) of RVA gastroenteritis cases as detected by RT-PCR. The highest number of positive cases was found in the age range from 0 to 6 months, followed by 7-12 months, 13-24 months, and 25-60 months, respectively. Dehydration is statistically significantly associated (p˂ 0.05) in RVA gastroenteritis cases compared to those who tested negative. This study emphasizes the significance of maintaining a continuous surveillance system and conducting genomic analysis of RVA genotypes in children upto the age of 5 years. This is essential for tracking the circulation of RVA genotypes. The results from this research enhance our comprehension of how RVA genotypes are changing over time in Pakistan, underscoring the ongoing necessity for improving vaccine coverage and effectiveness. This, in turn, can help reduce the impact of RVA-related illnesses in children.
PubMed: 38909724
DOI: 10.1016/j.actatropica.2024.107300 -
The International Journal of Risk &... Jun 2024The self-controlled case series (SCCS) is often used to monitor vaccine safety. The evaluation of intussusception after the rotavirus vaccine is complicated because the...
BACKGROUND
The self-controlled case series (SCCS) is often used to monitor vaccine safety. The evaluation of intussusception after the rotavirus vaccine is complicated because the baseline rate varies with age. Time-varying baseline risk adjustments with data from unexposed cohorts are utilised. Self-controlled risk interval (SCRI), with a shorter observation period, can also mitigate the problem by studying a control period close to the risk period.
OBJECTIVE
An Indian rotavirus vaccine has previously been studied using SCCS. The risk of intussusception in the high-risk windows (21 days after vaccination) was comparable to the background risk. The aim was to re-analyse data of an existing SCCS study using alternate statistical methods to examine vaccine safety.
METHODS
We examined the mean age of intussusception in the vaccinated and the unvaccinated. We performed an SCRI analysis of the surveillance data from the SCCS study, limiting the observation period to 180 days. We analysed the time-to-intussusception from the last vaccination. Finally, we performed an SCCS analysis, excluding unvaccinated cases from the analysis.
RESULTS
We found that the mean age of intussusception was significantly lower in the vaccinated (205 days) compared to the unvaccinated (223 days) (p-value 0.0026). The Incident Risk Ratio (IRR) on SCRI analysis was 1.62 (95% CI 1.07-2.44). There were significantly more intussusceptions in the first 30 days after vaccination compared to the next 30-day window. (92 vs 63 p-value = 0.009). We found that excluding unvaccinated infants from the SCCS analysis demonstrated significantly increased risk for the risk period 1-21 days after the 3rd dose (IRR 2.47, 95% CI 1.70-3.59). The risks of intussusception were missed in traditional SCCS analysis using unvaccinated infants as controls.
CONCLUSION
Traditional risk adjustments using data from unexposed cohorts in SCCS may not be appropriate for investigating the risk of intussusception where vaccination lowers the mean age of intussusception.
PubMed: 38875047
DOI: 10.3233/JRS-230049 -
European Journal of Haematology Jun 2024The scarcity of studies on vaccine-induced thrombosis and thrombocytopenia syndrome (TTS) limits the comprehensive understanding of vaccine safety on a global scale....
Global and regional burden of vaccine-induced thrombotic thrombocytopenia, 1969-2023: Comprehensive findings with critical analysis of the international pharmacovigilance database.
OBJECTIVE
The scarcity of studies on vaccine-induced thrombosis and thrombocytopenia syndrome (TTS) limits the comprehensive understanding of vaccine safety on a global scale. Therefore, the objective of this study is to assess the global burden of vaccine-induced TTS, identify the vaccines most associated with it, and suggest clinical implications regarding vaccination.
METHODS
This study employed the World Health Organization international pharmacovigilance database, extracting records of vaccine-induced immune thrombotic thrombocytopenia from 1969 to 2023 (total reports, n > 130 million). Global reporting counts, reported odds ratios (ROR), and information components (IC) were calculated to identify the association between 19 vaccines and the occurrence of vaccine-induced TTS across 156 countries.
RESULTS
We identified 24 233 cases (male, n = 11 559 [47.7%]) of vaccine-induced TTS among 404 388 reports of all-cause TTS. There has been a significant increase in reports of vaccine-induced TTS events over time, with a noteworthy surge observed after 2020, attributed to cases of TTS associated with COVID-19 vaccines. Measles, mumps, and rubella (MMR) vaccines were associated with most TTS reports (ROR [95% confidence interval], 2.87 [2.75-3.00]; IC [IC], 1.51 [1.43]), followed by hepatitis B (HBV, 2.23 [2.07-2.39]; 1.15 [1.03]), rotavirus diarrhea (1.95 [1.78-2.13]; 0.81 [0.53]), encephalitis (1.80 [1.50-2.16]; 0.84 [0.53]), hepatitis A (1.67 [1.50-1.86]; 0.73 [0.55]), adenovirus Type 5 vector-based (Ad5-vectored) COVID-19 (1.64 [1.59-1.68]; 0.69 [0.64]), pneumococcal (1.57 [1.49-1.66]; 0.65 [0.56]), and typhoid vaccines (1.41 [1.12-1.78]; 0.49 [0.11]). Concerning age and sex-specific risks, reports of vaccine-induced TTS were more associated with females and younger age groups. The age group between 12 and 17 years exhibited significant sex disproportion. Most of these adverse events had a short time to onset (days; mean [SD], 4.99 [40.30]) and the fatality rate was 2.20%, the highest rate observed in the age group over 65 years (3.79%) and lowest in the age group between 0 and 11 years (0.31%).
CONCLUSION
A rise in vaccine-induced TTS reports, notably MMR, HBV, and rotavirus diarrhea vaccines, was particularly related to young females. Ad5-vectored COVID-19 vaccines showed comparable or lower association with TTS compared to other vaccines. Despite the rarity of these adverse events, vigilance is essential as rare complications can be fatal, especially in older groups. Further studies with validated reporting are imperative to improve the accuracy of assessing the vaccine-induced TTS for preventive interventions and early diagnosis.
PubMed: 38863260
DOI: 10.1111/ejh.14250 -
Revista Panamericana de Salud Publica =... 2024To assess changes in reproductive, maternal, newborn, child, and adolescent health (RMNCAH) in Haiti from August 2018 to September 2021, before and during the COVID-19...
OBJECTIVE
To assess changes in reproductive, maternal, newborn, child, and adolescent health (RMNCAH) in Haiti from August 2018 to September 2021, before and during the COVID-19 pandemic.
METHODS
A retrospective study using surveillance data from the Haitian Unique Health Information System, examining two periods: pre- and peri-COVID-19 pandemic. Health indicators at the national level in the two periods were compared using two-sample -tests for proportions, and average absolute monthly changes were calculated using variance-weighted regression.
RESULTS
There was a statistically significant decline in the proportion of most of the indicators assessed from the pre- to the peri-COVID-19 pandemic period. However, the most affected indicators were the proportions of pregnant women with four antenatal care visits, with five antenatal care visits or more, and those who received a second dose of tetanus vaccine, which decreased by over 4 percentage points during the two periods. Likewise, the proportions of children who received diphtheria, tetanus, and pertussis (DTaP), BCG, polio, pentavalent, and rotavirus vaccines also all declined by over 8 percentage points. In contrast, pneumococcal conjugate vaccine increased by over 4 percentage points. A statistically significant decrease was also observed in the average absolute monthly changes of several reproductive and child health indicators assessed.
CONCLUSIONS
The COVID-19 pandemic may have contributed to the decline observed in several RMNCAH indicators in Haiti. However, the role played by the sociopolitical crisis and control exercised by armed groups over the population in the last three years cannot be ruled out.
PubMed: 38859812
DOI: 10.26633/RPSP.2024.57 -
MedRxiv : the Preprint Server For... May 2024Rotarix rotavirus vaccine was introduced into the Malawi national immunization program in October 2012. We used a previously developed mathematical models to estimate...
BACKGROUND
Rotarix rotavirus vaccine was introduced into the Malawi national immunization program in October 2012. We used a previously developed mathematical models to estimate overall vaccine effectiveness over a 10-year period following rotavirus vaccine introduction.
METHODS
We analyzed data on children <5 years old hospitalized with acute gastroenteritis in Blantyre, Malawi from January 2012 to June 2022, compared to pre-vaccination data. We estimated vaccine coverage before, during, and after the COVID-19 pandemic using data from rotavirus-negative children. We compared model predictions for the weekly number of rotavirus-associated gastroenteritis (RVGE) cases to the observed number by age to validate model predictions and estimate overall vaccine effectiveness.
RESULTS
The number of RVGE and rotavirus-negative acute gastroenteritis cases declined substantially following vaccine introduction. Vaccine coverage among rotavirus-negative controls was >90% with two doses by July 2014, and declined to a low of ~80% in October 2020, before returning to pre-pandemic levels by July 2021. Our models captured the post-vaccination trends in RVGE incidence, with 5.4% to 19.4% of observed weekly RVGE cases falling outside of the 95% prediction intervals. Comparing observed RVGE cases to the model-predicted incidence without vaccination, overall vaccine effectiveness was estimated to be 36.0% (95% prediction interval: 33.6%, 39.9%) peaking in 2014 and was highest in infants (52.5%; 95% prediction interval: 50.1%, 54.9%).
CONCLUSIONS
Overall effectiveness of rotavirus vaccination in Malawi is modest despite high vaccine coverage and has plateaued since 2016. Our mathematical models provide a validated platform for assessing strategies to improve rotavirus vaccine impact.
PubMed: 38853885
DOI: 10.1101/2024.05.29.24308124 -
Virology Jun 2024Porcine rotavirus (PoRV) is one of the main pathogens causing diarrhea in piglets, and multiple genotypes coexist. However, an effective vaccine is currently lacking....
Porcine rotavirus (PoRV) is one of the main pathogens causing diarrhea in piglets, and multiple genotypes coexist. However, an effective vaccine is currently lacking. Here, the potential adjuvant of nonstructural protein 4 (NSP4) and highly immunogenic structural protein VP4 prompted us to construct recombinant NSP4 (NSP4*) and VP4 (VP4*) proteins, combine them as immunogens to evaluate their efficacy. Results indicated that NSP4* enhanced systemic and local mucosal responses induced by VP4*. The VP4*-IgG, VP4*-IgA in feces and IgA-secreting cells in intestines induced by the co-immunization were significantly higher than those induced by VP4* alone. Co-immunization of NSP4* and VP4* also induced strong cellular immunity with significantly increased IFN-λ than the single VP4*. Summarily, the NSP4* as a synergistical antigen exerted limited effects on the PoRV NAbs elevation, but conferred strong VP4*-specific mucosal and cellular efficacy, which lays the foundation for the development of a more effective porcine rotavirus subunit vaccine.
PubMed: 38850894
DOI: 10.1016/j.virol.2024.110130 -
Medecine Tropicale Et Sante... Mar 2024Vaccination is a protective measure against infectious diseases and remains one of the best investments in public health. Some African countries are still struggling to...
BACKGROUND
Vaccination is a protective measure against infectious diseases and remains one of the best investments in public health. Some African countries are still struggling to reach the required child immunization coverage. Several factors are responsible for limiting immunization coverage. Most of the factors considered to limit immunization coverage are related to the health system. In addition, inaccessibility to care, especially during the critical period of the Covid-19 pandemic, greatly reduced vaccination coverage rates. In Benin, several vaccines are included in the Expanded Programme on Immunization or are administered as part of routine immunization. However, cases of non-compliance with the vaccine and persistent flaccid paralysis are still recorded in the commune of Ouidah in southern Benin. The aim of this study was to investigate the coverage and factors associated with full immunization for age in children aged 0-5 years.
METHODS
A cross-sectional survey was conducted from August to October 2021 in two villages (Adjara-Hounvè and Ahouicodji) in southern Benin. All the households were included. The survey regarded children under 5 for whom a vaccination record was presented. A couple child/mother was recruited after informed consent of the mother and her child. An univariate analysis followed by a multivariate analysis was performed by using a logistic regression model to identify the variables that influence vaccine completeness. Spatial description of vaccine completeness was performed using the kriging method using ArcGIS 10.8 mapping software. Results. Of the 414 mothers surveyed, 57.49% had an immunization card, from which information was collected. Of the 238 children recruited, 141 were in Adjara-Hounvè and 97 in Ahouicodji. Of the 238 children with an immunization card, 20.6% were fully immunized for their age. All children received Baccille Calmette Guérin vaccine at birth. Since poliomyelitis, pentavalent, pneumococcal conjugate, and rotavirus are three-dose vaccines, the percentage of children who received these vaccines decreased as the number of doses increased: 96.6%, 88.2%, 78.1% and 72.3% for the four doses of polio respectively. According to 53.4% of the respondents the reception at the vaccination site was poor, and according to 70.3% of them waiting time for vaccination sessions was long. Several reasons justified the absence of complete vaccination for the age of the children: vaccination site too far from the place of residence (59.54%), lack of financial means (29.78%) and the mother's ignorance (12.76%). Education level "primary" "none" (ORa = 3.32; CI95% 1.07-10.25), occupation "health staff" "housewife" (ORa = 21.18; CI95% 3.07-145.94), mothers' knowledge of Expanded Programme on Immunization diseases (ORa = 2, 20; CI95% 1.03-4.68) and children's age 0-2 months vs ≥ 16 months (ORa = 8.53; CI95% 2.52-28.85) and 9-15 months vs ≥ 16 months (ORa = 2.99; CI95% 1.24-7.23) increased complete immunization status for age. The homogeneity of behaviour related to age-complete immunization coverage in children under 5 years was evident at mapping.
CONCLUSION
Age-complete immunization coverage in children under 5 years of age is very low, with a spatial homogeneity in community immunization uptake behaviour. Age-complete immunization coverage is an innovative indicator that can contribute to achieving age-specific immunization targets.
Topics: Humans; Benin; Infant; Vaccination Coverage; Child, Preschool; Female; Male; Cross-Sectional Studies; Vaccination; Infant, Newborn; COVID-19; Health Services Accessibility; Immunization Programs
PubMed: 38846123
DOI: 10.48327/mtsi.v4i1.2024.352 -
Journal of Virology Jun 2024Rotavirus causes severe diarrhea in infants. Although live attenuated rotavirus vaccines are available, vaccine-derived infections have been reported, which warrants...
Rotavirus causes severe diarrhea in infants. Although live attenuated rotavirus vaccines are available, vaccine-derived infections have been reported, which warrants development of next-generation rotavirus vaccines. A single-round infectious virus is a promising vaccine platform; however, this platform has not been studied extensively in the context of rotavirus. Here, we aimed to develop a single-round infectious rotavirus by impairing the function of the viral intermediate capsid protein VP6. Recombinant rotaviruses harboring mutations in VP6 were rescued using a reverse genetics system. Mutations were targeted at VP6 residues involved in virion assembly. Although the VP6-mutated rotavirus expressed viral proteins, it did not produce progeny virions in wild-type cells; however, the virus did produce progeny virions in VP6-expressing cells. This indicates that the VP6-mutated rotavirus is a single-round infectious rotavirus. Insertion of a foreign gene, and replacement of the VP7 gene segment with that of human rotavirus clinical isolates, was successful. No infectious virions were detected in mice infected with the single-round infectious rotavirus. Immunizing mice with the single-round infectious rotavirus induced neutralizing antibody titers as high as those induced by wild-type rotavirus. Taken together, the data suggest that this single-round infectious rotavirus has potential as a safe and effective rotavirus vaccine. This system is also applicable for generation of safe and orally administrable viral vectors.IMPORTANCERotavirus, a leading cause of acute gastroenteritis in infants, causes an annual estimated 128,500 infant deaths worldwide. Although live attenuated rotavirus vaccines are available, they are replicable and may cause vaccine-derived infections. Thus, development of safe and effective rotavirus vaccine is important. In this study, we report the development of a single-round infectious rotavirus that can replicate only in cells expressing viral VP6 protein. We demonstrated that (1) the single-round infectious rotavirus did not replicate in wild-type cells or in mice; (2) insertion of foreign genes and replacement of the outer capsid gene were possible; and (3) it was as immunogenic as the wild-type virus. Thus, the mutated virus shows promise as a next-generation rotavirus vaccine. The system is also applicable to orally administrable viral vectors, facilitating development of vaccines against other enteric pathogens.
PubMed: 38837379
DOI: 10.1128/jvi.00762-24 -
The Journal of General Virology Jun 2024Historically, the Wa-like strains of human group A rotavirus (RVA) have been major causes of gastroenteritis. However, since the 2010s, the circulation of non-Wa-like...
Historically, the Wa-like strains of human group A rotavirus (RVA) have been major causes of gastroenteritis. However, since the 2010s, the circulation of non-Wa-like strains has been increasingly reported, indicating a shift in the molecular epidemiology of RVA. Although understanding RVA evolution requires the analysis of both current and historical strains, comprehensive pre-1980's sequencing data are scarce globally. We determined the whole-genome sequences of representative strains from six RVA gastroenteritis outbreaks observed at an infant home in Sapporo, Japan, between 1981 and 1989. These outbreaks were mainly caused by G1 or G3 Wa-like strains, resembling strains from the United States in the 1970s-1980s and from Malawi in the 1990s. Phylogenetic analysis of these infant home strains, together with Wa-like strains collected worldwide from the 1970s to 2020, revealed a notable trend: pre-2010 strains diverged into multiple lineages in many genomic segments, whereas post-2010 strains tended to converge into a single lineage. However, Bayesian skyline plot indicated near-constant effective population sizes from the 1970s to 2020, and selection pressure analysis identified positive selection only at amino acid 75 of NSP2. These results suggest that evidence supporting the influence of rotavirus vaccines, introduced globally since 2006, on Wa-like RVA molecular evolution is lacking at present, and phylogenetic analysis may simply reflect natural fluctuations in RVA molecular evolution. Evaluating the long-term impact of RV vaccines on the molecular evolution of RVA requires sustained surveillance.
Topics: Rotavirus; Humans; Rotavirus Infections; Phylogeny; Japan; Genome, Viral; Evolution, Molecular; Gastroenteritis; Whole Genome Sequencing; Disease Outbreaks; Infant; Genotype; Molecular Epidemiology; History, 20th Century
PubMed: 38836747
DOI: 10.1099/jgv.0.001998