Home > Efficacy, Rotavirus > Rotavirus vaccine shown to be effective in preventing gastroenteritis in 2 new studies in Asian and African populations

Rotavirus vaccine shown to be effective in preventing gastroenteritis in 2 new studies in Asian and African populations


Two new studies, published online in The Lancet (the full text can be accessed here and here; free registration to The Lancet required), have produced similar results to the results of a similar US study on which I reported here at Vaccine Central which showed the RotaTeq pentavalent rotavirus vaccine to be 45% in reducing all cause gastroenteritis hospitalization rates, an excellent track record given that the rotavirus is credited with causing up to 50% of all cause gastroenteritis hospitalizations in children. At that time, I concluded that although the study showed a strong correlation between the introduction of the vaccine and the reduction in AGE hospitalization rates, given that we only had 2 data points, we couldn’t make a direct causation link between the two events, and that further evidence was needed in order to reach that conclusion.

That further evidence has been provided by the above-mentioned 2 studies. I will summarize each study separately.

ASIAN STUDY

Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in Asia: a randomised, double-blind, placebo-controlled trial

K Zaman, Dang Duc Anh, John C Victor, Sunheang Shin, Md Yunus, Michael J Dallas, Goutam Podder, Vu Dinh Thiem, Le Thi Phuong Mai,Stephen P Luby, Le Huu Tho, Michele L Coia, Kristen Lewis, Stephen B Rivers, David A Sack, Florian Schödel, A Duncan Steele, Kathleen M Neuzil,Max Ciarlet

Study Summary-This was a multicentre, double-blind, placebo-controlled trial, undertaken in rural Matlab, Bangladesh (2 year observation period), and urban and periurban Nha Trang, Vietnam (One and a half years observation period). Infants aged 4–12 weeks without symptoms of gastrointestinal disorders were randomly assigned (1:1) to receive three oral doses of pentavalent rotavirus vaccine 2 mL or placebo at around 6 weeks, 10 weeks, and 14 weeks of age. Infants who received vaccine or placebo were visited once a month to remind parents to bring their child to a clinic or hospital if their child developed symptoms of gastroenteritis. Any adverse reactions occurring within 14 days of receipt of each dose (both vaccine and placebo) were recorded.

To assess immune responses to vaccination, a small amount of venous blood was obtained immediately before the first dose of study vaccine or placebo was given and about 14 days after the third dose was given in a subset of around 300 participants (around 150 per site).

The primary outcome was severe rotavirus gastroenteritis, irrespective of serotype, occurring 14 days or more after the third dose of vaccine or placebo until end of study. Secondary outcomes were efficacy of vaccination against rotavirus gastroenteritis of any severity, proportion of participants with a serious adverse event within 14 days of any dose, and the proportion of participants with seroresponse for antirotavirus IgA.

Results – Overall, the vaccine had a success rate of 48.3% in preventing severe rotavirus gastroenteritis (RVGE), 42.5 % reduction in any severity RVGE, and 27% in severe GE of any cause. Seroresponse, rotavirus antibodies present in the blood stream, was significantly  higher in the vaccinated groups (87.8%) than the placebo group (18.2%).  Serious side effects within 14 days of any dose were virtually the same for both the vaccine and the placebo group (Table 5).

Conclusion – The study is methodologically sound. It is randomized, double-blind and placebo-controlled. The results strongly suggest that the pentavalent rotavirus vaccine reduces both RVGE and all cause GE rates, by about 48% and 27% respectively, while being safe and inducing a strong immune system response in the participants. Side effects for the vaccinated children were comparable to those of the children in the control group.

Conflicts of Interest – The study was designed and run by Merck, one of the vaccine makers, with input from World Health Organization staff and site investigators. Here is the complete “Role of funding source” section from the study:

The study was designed by Merck investigators, with substantial input from PATH staff and site investigators. Merck had direct oversight or participation in every stage of the study. Merck also participated in pharmacovigilance, organised and led the data and safety monitoring board meetings, and did the data analysis. Staff from PATH independently monitored study execution at sites and participated in pharmacovigilence, data analysis, and data and safety monitoring board meetings. All authors had full access to the data, and the corresponding author had final responsibility for the decision to submit for publication.


AFRICAN STUDY


Effi cacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in sub-Saharan Africa: a randomised, double-blind,
placebo-controlled trial

George E Armah, Samba O Sow, Robert F Breiman, Michael J Dallas, Milagritos D Tapia, Daniel R Feikin, Fred N Binka, A Duncan Steele, Kayla F Laserson, Nana A Ansah, Myron M Levine, Kristen Lewis, Michele L Coia, Margaret Attah-Poku, Joel Ojwando, Stephen B Rivers, John C Victor, Geoff rey Nyambane, Abraham Hodgson, Florian Schödel, Max Ciarlet, Kathleen M Neuzil

Study Summary – The design of this study is identical to that of the Asian study. The only difference is the number of children; the African study enrolled about twice as many subjects. 5468 infants, in Ghana, Kenya and Mali, were randomly assigned to receive pentavalent rotavirus vaccine (n=2733) or placebo (n=2735) with an observation period of 23 months. Immune responses to vaccination were assessed in a subset of around 450 participants (around 150 per site). Primary and secondary outcomes were identical to the Asian study.

Results – Overall, the vaccine had a success rate of 39.3% in preventing severe rotavirus gastroenteritis (RVGE), 30.5 % reduction in any severity RVGE, and 10.6% in severe GE of any cause. Seroresponse, rotavirus antibodies present in the blood stream, was significantly  higher in the vaccinated groups (78.3%) than the placebo group (20.1%).  Serious side effects within 14 days of any dose were virtually the same for both the vaccine and the placebo group (Table 5).

Conclusion – The study is methodologically sound. It is randomized, double-blind and placebo-controlled. The results strongly suggest that the pentavalent rotavirus vaccine reduces both RVGE and all cause GE rates, by about 30.5% and 10.6% respectively, while being safe and inducing a strong immune system response in the participants. Side effects for the vaccinated children were comparable to those of the children in the control group.

Conflicts of Interest – The study was designed and run by Merck, one of the vaccine makers, with input from World Health Organization staff and site investigators. Here is the complete “Role of funding source” section from the study:

The study was designed by scientists from Merck, with substantial input from PATH staff and site investigators. Merck had direct oversight or participation in every stage
of the study. Merck also participated in pharmacovigilance, organised and led the data and safety monitoring board meetings, and did the data analysis. Staff from PATH
independently monitored study execution at sites and participated in pharmaco vigilance, data analysis, and data and safety monitoring board meetings. All authors had full access to the data, and the corresponding author had final responsibility for the decision to submit for publication.

Where do these 3 studies leave us?

It is important to note, that while all 3 studies (US, Asia and Africa) point to the same direction, and all three show that the pentavalent rotavirus vaccine does have a substantial effect in reducing all cause gastroenteritis cases, the actual effect size of the vaccine seems to vary considerably from region to region. The US study reported a 45% decrease in all cause AGE hospitalization rates; the Asian study reported a 27% decrease while the African study reported a 10.6% decrease. The authors have picked up on this as  well and have included this issue in their discussion. For example, this is what they say in the African study:

Although the efficacy noted in this trial and the accompanying study in Asia were significant, both estimates of efficacy were lower than that reported with pentavalent rotavirus vaccine in developed countries or in developing countries in Latin America. Direct comparisons of results from previous studies of pentavalent rotavirus vaccine are limited by differences in study design, collection procedures, and clinical scoring systems. However, the comparatively low efficacy noted in this study is consistent with the low efficacy with another rotavirus vaccine reported in Africa compared with more developed countries, and with the low efficacy reported in low-income populations with other orally administered vaccines. The immunogenicity of pentavalent rotavirus vaccine in our study population was substantially lower than were results obtained in more developed countries.

So why this variation? It’s hard to say, it does not seem clear to me from these studies at least, why there would be such variation. As far as the US study is concerned, part of the answer may have to do with the fact that it was a retrospective study, comparing rates before vaccination with rates after vaccination, thus lacking a proper control group which the Asian and African studies had. On the other hand geography seems to have an important effect, as even within the Asian group there were some considerable differences between the two countries.

Nevertheless, while these issues may need more time to be sorted out, the take-home message is a very encouraging one: the pentavalent rotavirus vaccine seems to have a considerable positive effect in reducing all cause gastroenteritis rates in infants, while being safe. And given that there are an estimated 527,000 rotavirus deaths worldwide per year, even if the true effect turns out to be the lowest value of the three, the 10.6%, we are still talking about roughly 56,000 lives saved per year, with basically next to zero side effects from the vaccine.

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Categories: Efficacy, Rotavirus
  1. August 10, 2010 at 9:19 AM

    To anyone grounded in reality, the reaction to this should be, “No $h!t, Sherlock!”

  1. October 2, 2010 at 11:09 PM
  2. November 6, 2010 at 9:36 AM

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