Rotavirus vaccines reduced severe diarrhea by 82-92% in low-mortality countries and 35-63% in high-mortality countries in children up to 2 years.
Photos by: Curt Carnemark (L); GAVI/Amira Al-Sharif (R)
Why are rotavirus vaccines important?
- Rotavirus is the number one cause of severe diarrhea in children and infants worldwide. Diarrhea from rotavirus causes almost half a million deaths each year, mostly in developing countries because of the lack of availability of oral rehydration therapy and medical facilities, and because of underlying conditions, such as malnutrition. Rotavirus also affects children and infants in developed countries and is a major cause of diarrhea-related hospitalization. Most children become infected with rotavirus at least once before they are three years old. Hand hygiene and sanitation measures have only limited impact on preventing transmission. The World Health Organization has recommended the inclusion of rotavirus vaccine in national immunization schedules.
Do rotavirus vaccines work?
Rotavirus vaccines reduces severe diarrhea by 82-92% in low-mortality countries and 35-63% in high-mortality countries in children up to 2 years depending on the vaccine given.
Equity: Do they work in the disadvantaged?
Rotavirus vaccines are effective in disadvantaged populations but have higher success rates in countries with lower rotavirus mortality. This may be because of other factors such as comorbidities and malnutrition.
Intervention Delivery
3 oral rotavirus vaccines were evaluated, RV1 and RV5 (both approved in many countries).
The WHO recommends delivering the first dose of vaccine as soon as possible after an infant is 6 weeks old. Two doses of the vaccine are required.
Most RV1 trials included administered rotavirus or placebo vaccines at the time of routine vaccination however some trials kept a two week waiting period between rotavirus and other vaccinations. The included RV1 trials used 2-3 doses of the vaccine with 4-10 weeks between doses. The RV5 trials administered 3 doses of vaccine with intervals of 4-10 weeks between doses.
Population and Setting
Included studies were conducted in 48 countries around the world including a mix of high, middle, and low income countries: Argentina, Austria, Bangladesh, Belgium, Botswana, Brazil, Canada, Chile, China, Colombia, Costa Rica, Czech Republic, Dominican Republic, Finland, France, Germany, Ghana, Guatemala, Honduras, Hong Kong, India, Italy, Jamaica, Japan, Kenya, Malawi, Mali, Mexico, Nicaragua, Panama, Peru, Philippines, Poland, Portugal, Puerto Rico, Russia, Singapore, South Africa, South Korea, Spain, Sweden, Taiwan, Tanzania, Thailand , USA, Venezuela, Vietnam, Zimbabwe
Included infants were between 5 and 10 weeks at the time of enrollment.
Summary of Findings [SOF] Table: Vaccines for preventing rotavirus in children
Patient or population: children
Settings: Low mortality countries (WHO strata A&B) and high mortality countries (WHO strata D&E)
Intervention: RV1
Comparison: Placebo
| Outcomes | Anticipated absolute effects | Relative effect | No of Participants | Quality of the evidence | ||
| Without rotavirus vaccine | With rotavirus vaccine (95% CI) | |||||
| Low mortality countries* |
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| Severe rotavirus diarrhea (Follow up: up to 1 yr) | 13 per 1000 | 11 fewer per 1000 (from 8-12 fewer) | RR 0.16 (0.09-0.26) | 43,779 (7) | High | |
| Severe rotavirus diarrhea (Follow up: up to 2 yrs) | 24 per 1000 | 20 fewer per 1000 (from 19-21 fewer) | RR 0.18 (0.14-0.23) | 36,002 (9) | High | |
| All serious adverse events (follow up: 2 mos to 2 yrs) | 45 per 1000 | 5 fewer per 1000 (from 3-8 fewer) | RR 0.88 (0.83-0.93) | 96,233 (24) | High | |
| Serious adverse events: intussusception (follow up: 2 mos to 2 yrs) | 100 per 100,000 | 0 fewer per 100,000 (from 0 fewer to 1 more) | RR 0.69 (0.45-1.04) | 96,513 (17) | Low1 | |
| High mortality Countries* |
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| Severe rotavirus diarrhea (Follow up: up to 1 yr) | 60 per 1000 | 38 fewer per 1000 (from 24-46 fewer) | RR 0.37 (0.23-0.60) | 6114 (3) | High | |
| Severe rotavirus diarrhea (Follow up: up to 2 yrs) | 43 per 1000 | 15 fewer per 1000 (from 8-21 fewer) | RR 0.65 (0.51-0.83) | 13,768 (2) | High | |
| All serious adverse events (follow up: 2 mos to 2 yrs) | 95 per 1000 | 11 fewer per 1000 (from 23 fewer to 4 more) | RR 0.89 (0.76-1.04) | 7481 (7) | High | |
| Serious adverse events: intussusception (follow up: 2 mos to 2 yrs) | 0 per 100,000 | 0 fewer per 100,000 (0-0) | RR 1.49 (0.06-36.63) | 17,492 (4) | Low1 | |
| Adverse Events: Children receiving the rotavirus vaccine had 10% fewer serious adverse events than those recieivng placebo. | ||||||
| * Countries were classified as low mortality or high mortality according to the WHO Mortality Stratum. All developed countries are classified as low mortality. Developing countries may be classified as low or high according to the under-five mortality rates. | ||||||
| About quality of evidence (GRADE) | ||||||
1. Downgraded by 2 for imprecision. There was a 1 in 10,000 to 1 in 32,000 increased risk of intussusception with a previous rotavirus vaccine, therefore, these trials were not powered to detect an associated between RV1 and intussusception.
Summary of Findings [SOF] Table: Vaccines for preventing rotavirus in children
Patient or population: children
Settings: Low mortality countries (WHO strata A&B) and high mortality countries (WHO strata D&E)
Intervention: RV5
Comparison: Placebo
| Outcomes | Anticipated absolute effects | Relative effect | No of Participants | Quality of the evidence | ||
| Without rotavirus vaccine | With rotavirus vaccine (95% CI) | |||||
| Low mortality countries* |
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|
|
| |
| Severe rotavirus diarrhea (Follow up: up to 1 yr) | 17 per 1000 | 16 fewer per 1000 (from 12-16 fewer) | RR 0.08 (0.03-0.22) | 4132 (5) | Moderate1 | |
| Severe rotavirus diarrhea (Follow up: up to 2 yrs) | 25 per 1000 | 21 fewer per 1000 (from 15-23 fewer) | RR 0.18 (0.08-0.39) | 7318 (4) | Moderate2 | |
| All serious adverse events (follow up: 2 mos to 2 yrs) | 27 per 1000 | 2 fewer per 1000 (from 4 fewer to 1 more) | RR 0.93 (0.86-1.02) | 75,672 (8) | High | |
| Serious adverse events: intussusception (follow up: 2 mos to 2 yrs) | 100 per 100,000 | 100 fewer per 100,000 (from 0-100 fewer) | RR 0.77 (0.41-1.45) | 78,907 (12) | Low3 | |
| High mortality Countries* |
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| Severe rotavirus diarrhea (Follow up: up to 1 yr) | 30 per 1000 | 17 fewer per 1000 (from 11-21 fewer) | RR 0.43 (0.29-0.62) | 5916 (2) | High | |
| Severe rotavirus diarrhea (Follow up: up to 2 yrs) | 63 per 1000 | 26 fewer per 1000 (from 12-36 fewer) | RR 0.59 (0.43-0.82) | 5885 (2) | High | |
| All serious adverse events (follow up: 2 mos to 2 yrs) | 21 per 1000 | 2 fewer per 1000 (7 fewer to 6 more) | RR 0.92 (0.66-1.28) | 6830 (4) | Moderate4 | |
| Serious adverse events: intussusception (follow up: 2 mos to 2 yrs) | No events reported | No events reported | Not estimable | 6588 (2) | Low5 | |
| Adverse Events: there was no significant difference in the number of severe adverse events for the rotavirus vaccine group compared to the placebo group. | ||||||
| * Countries were classified as low mortality or high mortality according to the WHO Mortality Stratum. All developed countries are classified as low mortality. Developing countries may be classified as low or high according to the under-five mortality rates. | ||||||
| About quality of evidence (GRADE) | ||||||
1. Downgraded by 1 for imprecision. The total number of events was low.
2. Downgraded by 1 for inconsistency. Substantial heterogeneity (I2 statistic = 44%) was found. Consistency was restored when removing the one study carried out only in a very low-mortality (stratum A) country, with results then showing a slightly smaller effect (RR 0.22, 95% CI 0.13 to 0.36, 6291 participants, 3 studies)
3. Downgraded by 2 for imprecision. These trials were not powered to detect an effect on mortality
4. Downgraded by 1 for imprecision. The 95% CI includes both no effect and appreciable harm.
5. Downgraded by 2 for imprecision. There was a 1 in 10,000 in 1 in 32,000 increased risk of intussusception with a previous rotavirus vaccine, therefore, these trials were not powered to detect an association beetween RV1 and intussusception
| Relevance of the review for disadvantaged communities | |
| Findings | Interpretation |
| Equity – Which of the PROGRESS groups examined |
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| The studies included children from a variety of low-, middle- and high-income countries and from most regions of the world including Africa, Asia, Europe, Central America, North America, and South America,. | The results of this review can be applied to most countries in the world. |
| Reduced efficacy of the vaccine in high mortality countries could be due to many factors, such as malnutrition, co-infections, and maternal rotavirus antibodies passed through breast milk. However, the burden of rotavirus disease is greater in these countries so the absolute number of events prevented is higher. | Rotavirus vaccine is recommended for use in both low and high mortality countries. Although the effectiveness of the vaccine seems to be lower in the high mortality countries, a large number of events are still prevented. The decrease in effectiveness over time may also be attributed to infection-acquired immunity among those receiving the placebo vaccine. |
| One trial examined a subgroup of malnourished children and found that the RV1 vaccine was more effective than placebo in preventing diarrhea at 1 year after vaccination (RR 0.39, 95% CI 0.19-0.79). | Rotavirus vaccine can help prevent rotavirus caused diarrhea in malnourished children. |
| The review did not report on the differences in effect across other PROGRESS factors. | It is unclear whether there are differences in effect for infants of different sex or socioeconomic status. |
| Equity Applicability |
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| The included studies varied the doses and frequency. Most trials gave 2 doses but some gave 3. The doses were given between 4 and 10 weeks apart. | Policymakers planning to add rotavirus vaccine should review the WHO guidelines and recommend dosing and timing that suits the local settings. The WHO guidelines allow for flexibility to ensure that the most disadvantaged children can receive the vaccine even if the first dose is given later than 32 weeks |
| Most of the studies included only health infants, between 5 and 15 weeks old. Infants who were born premature, under 2 kgs, were in a household with an immunosuppressed or pregnant person, had HIV or other chronic conditions or immunosuppression were excluded from most of the trials. One trial excluded infants whose households did not have a telephone. However, one study included only HIV positive infants found no difference in effect for the group receiving the vaccine versus the group receiving a placebo. | The results of this review are only applicable to healthy infants. More research is needed to determine whether the rotavirus vaccine is safe and effective for preterm infants and those with immunosuppression or other chronic condition. |
| Cost-equity |
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| The review does not report on costs of rotavirus vaccine. | Policymakers planning to add rotavirus to the national vaccination schedule need to consider the costs of the vaccine, the resources to administer it (if provided at separate times than other vaccines in the schedule), and weigh these against the costs of hospitalizations and other health care costs due to rotavirus. |
| Monitoring & Evaluation for PROGRESS Groups |
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| For RV1 vaccine in low-mortality countries the vaccine was not significantly more effective than placebo 3 years after vaccination. | Policymakers planning to implement a rotavirus vaccination program need to ensure that the vaccine is available to infants as soon as possible after 6 weeks of birth to ensure maximum benefits. More research is needed to determine the effectiveness of booster vaccines. |
| All of the included studies were placebo controlled studies. | Future research should compare RV1 to RV5 instead of placebo. A third vaccine is available and approved for use in China, however, no RCTs were identified for inclusion in this review. |
| Including rotavirus vaccine in the national immunization schedule requires monitoring and evaluation. | Policymakers should ensure that there is an evaluation and monitoring plan to ensure the effectiveness of the intervention and its delivery. |
Comments on this summary? Please contact Jennifer Petkovic.
Drafted by Chaeyon Lee