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Two widely used rotavirus vaccines performed comparably in a meta-analysis, reducing risk of rotavirus gastroenteritis (RVGE) by more than 60% in young children. While the findings evidence a high protection level and low-risk safety profile, bupropion effects side wellbutrin zyban investigators of the study called for additional head-to-head comparisons to assess risks and benefits.
RVGE, which accounts for 28.8% of all deaths from diarrhea worldwide, is the leading cause of diarrhea in children under age 5. More than 100 countries include rotavirus vaccines in their immunization programs. Among six types of vaccines currently in use, two live-attenuated oral vaccines: the two-dose monovalent Rotarix (RV1) and three-dose pentavalent RotaTeq (RV5]) are in use worldwide.
Not much is known about their interchangeability, although a previous meta-analysis reported similarities in effectiveness of Rotarix (83%), RotaTeq (85%), and Rotarix and RotaTeq mixed series (86%) in low-mortality countries. RVGE morbidity and mortality have declined since the introduction of these vaccines, but concerns persist about their safety, Zi-Wei Sun, MSc, of Nanjing (China) Medical University and colleagues wrote in JAMA Pediatrics.
Their systematic review and meta-analysis of randomized clinical trials, case-control, and cohort studies compared benefit, risk, and immunogenicity of these vaccines and their effectiveness in reducing RVGE. Combing through databases Embase, PubMed, the Cochrane Library, and Web of Science using search terms “rotavirus” and “vaccine,” they chose 121 randomized clinical trials and cohort and case-control studies that included more than 100 children younger than 5 years. Twenty of the randomized clinical trials had related data that examined the vaccines’ protection against RVGE hospitalization, study coauthor Hemant Goyal, MD, FACP, explained in an interview.
All of the studies reported on the safety and effectiveness or immunogenicity of rotavirus vaccines. The investigators used a random-effects model to calculate relative risks, odds ratios, risk differences, and 95% confidence intervals. They also stratified studies by economic development of countries, given that vaccine efficacy is often higher in middle- and high-income countries, compared with low-income countries. An adjusted indirect treatment comparison evaluated differences in vaccine protection among different subgroups, adopting P < .05 as the level of statistical significance.
Primary outcomes included RVGE, severe RVGE, and RVGE hospitalization and safety-associated outcomes such as serious adverse events, intussusception, and mortality.
Rotarix and RotaTeq reduced RVGE in children younger than 5 years by 68.4% and 63.6%, respectively. Goyal and colleagues confirmed these results in case-control studies (65.3% and 72.8%, respectively). Both vaccines significantly reduced RVGE and RVGE hospitalization risk and demonstrated higher protection against severe RVGE. In adjusted indirect comparisons, the two vaccines showed no significant differences in protection. They also found a positive correlation between immunogenicity and vaccine protection.
“RotaTeq seems to show lower protection in low-income countries, compared with Rotarix, but these estimates should be interpreted with caution as there was only one study for low-income countries and indirect comparison, said Goyal, a second-year gastroenterology fellow at the Wright Center for Graduate Medical Education, Scranton, Penn.
None of the vaccines demonstrated risk of serious adverse events. However, an Australian study in 2013 did report a small increased risk of intussusception after RV1 and RV5 vaccination. “Therefore, continuous surveillance of the benefits and adverse effects of rotavirus vaccines is required after vaccination,” the investigators noted.
Analyzing newer, less widely distributed vaccines, Rotavac, Rotasiil, and Lanzhou lamb rotavirus vaccine also showed moderate effectiveness in reducing RVGE risk.
Immunity Wanes Over Time
Protection against rotavirus diseases seems to wane over time after vaccination. “Although our results indicated that rotavirus vaccines can provide substantial protection against RVGE during the first 2 years of life, more studies following up the vaccine efficacy for more than 2 years are required,” the investigators recommended.
Declining vaccine-induced antibodies, RVGE-acquired protection from the vaccine’s indirect effects, or exposure to unvaccinated populations may explain gradual loss of immunity.
Monitoring of rotavirus strains following vaccination should take place “to avoid population-based selection of so-called escape strains, especially fully heterotypic strains and new strains, because of the long-term pressure of vaccine immunity,” they recommended.
The findings emphasize the importance of introducing vaccines worldwide to reduce infection, summarized Goyal and colleagues. Given how challenging it is to treat the wide varieties of rotavirus, “It encouraging that RV1 and RV5 work well against heterotypic strains,” they added. Similar performance between Rotarix and RotaTeq also makes it easier for clinicians to choose a vaccine.
Increasing the availability and efficacy of these vaccines in low-income countries with high mortality rates is a high priority,
David I. Bernstein, MD, MA, wrote in a related editorial: “A clear gradient in vaccine protections was noted by country income level in the analysis presented, and much effort has been spent to understand this discrepancy.”
Overall, the study confirmed the efficacy of these two vaccines and their equivalence, noted Bernstein.
The study’s literature search process had some limitations. “Especially in stratified analyses, sparse data in some subgroups limit generalizability. … The most accurate method, head-to-head comparisons, to evaluate the comparative efficacy of different vaccines is required in further studies,” the study investigators wrote.
Such studies would directly compare Rotarix and RotaTeq from multiple perspectives: efficacy, cost-effectiveness, strain-specific protection, the duration of protection, safety, and immunogenicity, said Goyal.
This article originally appeared on MDedge.com, part of the Medscape Professional Network.
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