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Rotavirus Vaccine: Benefits and a Possible Risk

Three new studies show that rotavirus vaccine is safe and effective, even in developing countries, but it may be risky for severely immunodeficient children.

Rotavirus is the most important cause of severe gastroenteritis in young children worldwide. Although two rotavirus vaccines have shown excellent efficacy in previous trials, conducted mainly in Latin America, Europe, and the U.S., concern remains about their effectiveness in the poorest of countries, where children's immunologic response to antigens presented orally might be inadequate, and about their safety in immunocompromised patients. Three new studies address these issues.

In a partially industry-funded, double-blind, randomized trial conducted in South Africa and Malawi from 2005 to 2007, Madhi and colleagues assessed the efficacy, safety, and immunogenicity of the monovalent attenuated human rotavirus vaccine (Rotarix). At 6, 10, and 14 weeks of age, infants (including some with HIV infection) received three doses of Rotarix, three doses of placebo, or one dose of placebo and then two of Rotarix. They were followed until age 1 year, with assessment for number and severity of gastroenteritis episodes. A total of 4417 infants were included in the per-protocol efficacy analysis. Severe rotavirus gastroenteritis occurred during the first year of life in 1.9% of the pooled vaccine group and in 4.9% of controls, for an overall vaccine efficacy of 61.2% (P<0.001). Efficacy was lower in Malawi than in South Africa (49.4% vs. 76.9%), perhaps because of a difference in prevalent rotavirus subtypes. The incidence of vaccine-related adverse events was similar between vaccine and placebo recipients (0.1% and 0%).

To examine the effect of rotavirus vaccination on death from diarrhea in Mexico, Richardson and colleagues compared diarrhea-related death rates among young children in 2003–2006 with those in 2008. (Monovalent rotavirus vaccine [Rotarix] was introduced in Mexico in 2006, and in May 2007, it was recommended for all children born after February 1, 2007.) In 2003–2006, the median annual diarrhea-related death rate for children aged <5 years was 18.1/100,000. In 2008, the rate was 11.8/100,000 — a relative reduction of 34.8% (P<0.001). The decline was greatest among children aged <1 year (from 61.5/100,000 to 36.0/100,000; relative reduction, 41.5%). Further reductions were seen during the 2008–2009 rotavirus season in children aged <2 years.

Although live rotavirus vaccine is safe for immunologically normal children, concerns have been raised regarding its safety for severely immunocompromised patients. Patel and colleagues described three infants who received live pentavalent rotavirus vaccine (RotaTeq) and then developed prolonged diarrhea caused by the vaccine strain of rotavirus. All three were later determined to have severe combined immunodeficiency associated with adenosine deaminase deficiency. All received immunotherapy, and eventually their stools were negative for rotavirus.

Comment: Good news regarding rotavirus vaccine. Based on these reports, the monovalent vaccine appears to be safe and effective for children in developing countries. Progress toward eliminating severe and fatal rotavirus-related gastroenteritis (particularly in areas with many deaths from such infections) is a major public health accomplishment that should be applauded. Presumably, the pentavalent vaccine would also be effective. Nothing is perfect, however, and the vaccine virus may cause symptomatic infection in infants with undiscovered severe immunodeficiency who are inadvertently immunized.

— Robert S. Baltimore, MD

Published in Journal Watch Infectious Diseases January 27, 2010

Citation(s):

Madhi SA et al. Effect of human rotavirus vaccine on severe diarrhea in African infants. N Engl J Med 2010 Jan 28; 362:289.

• Medline abstract (Free)

Richardson V et al. Effect of rotavirus vaccination on death from childhood diarrhea in Mexico. N Engl J Med 2010 Jan 28; 362:299.

• Medline abstract (Free)

Patel NC et al. Vaccine-acquired rotavirus in infants with severe combined immunodeficiency. N Engl J Med 2010 Jan 28; 362:314.

• Medline abstract (Free)

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