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Success in the fight against childhood diarrhea

Rotavirus is the world’s most common cause of severe childhood diarrhea.  In the U.S. alone, rotavirus disease leads to around 70,000 hospitalizations, 3/4 million ER visits, and nearly half-a-million doctor office visits yearly.  But it rarely causes death.

The same is not true for the developing world.  Rotavirus disease is estimated to kill around a half-million children a year world wide.   Finding a way to mitigate this is an active public health concern, with the World Health Organization specifically recommending rotavirus vaccinations in areas where the virus has a significant public health impact.

Rotavirus causes a severe diarrheal illness. It is passed via a fecal-oral route, meaning that contaminated food, surfaces, and water can all be sources.   In developed countries like the US, rotavirus disease is unpleasant and inconvenient.  Since rotavirus spreads more readily in areas without access to clean water and medical care, it takes a greater toll in these areas, and children afflicted are at risk of death due to dehydration.  The US has seen a decline in rotavirus disease in the last few years, an effect that appears to be due to increased vaccination and a herd immunity effect.

Given the large number of pediatric rotavirus deaths in developing countries, the World Health Organization (WHO) has made vaccination a priority. Two articles in this week’s New England Journal of Medicine report on the progress of the fight against rotavirus.

The first article looked at the affect of the vaccine in  Africa.  It was a randomized, placebo-controlled trial of several thousand infants (the ethics of such trials in developing nations has been discussed at length elsewhere, including here).  It found a very significant reduction in severe diarrhea during the first year of life, with a vaccine-attributable reduction in severe rotavirus gastroenteritis of 5.0 cases per 100 infant-years.  This study did not specifically study mortality.

The next study specifically assessed mortality, but using an “ecologic assessment”.  The authors looked at deaths from diarrhea over a several year period which included a period before and after the regular use of rotavirus vaccine.  They found that:

Among infants who were 11 months of age or younger, diarrhea-related mortality fell from 61.5 deaths per 100,000 children at baseline to 36.0 per 100,000 children in 2008 (rate reduction, 41%; 95% CI, 36 to 47; P<0.001)

This type of study has certain limitations, but the seasonal peak of rotavirus deaths was found to be significantly blunted since the introduction of the vaccine.

The final piece in the Journal was a case series. It looked at three infants who appeared to have developed rotavirus infection from the vaccine itself.  The two available rotavirus vaccines are live attenuated viruses.  They should not cause disease under normal circumstances, and in these three cases, the circumstances were not normal.  All three children had severe combined immunodeficiency (SCID).   Immune diseases are a relative contraindication to vaccination. In the African experience, where HIV is endemic, children were vaccinated independent of HIV status and HIV rates were similar in all groups.  Despite this, there was still a reduction in severe diarrheal disease.

The two currently available rotavirus vaccines are not associated with intussusception as a previous vaccine was, and appear to be safe, effective at preventing severe diarrhea in small children, and effective at reducing deaths in small children.  These vaccines appear to be effective across geographic and economic regions, although the magnitude of the effect was greatest in hardest-hit areas.

This puts a very heavy  burden on those who would choose to fight the introduction of these vaccines.  Rotavirus vaccine appears to be a safe, effective measure for preventing one of the world’s most common causes of childhood mortality.

References

Madhi, S., Cunliffe, N., Steele, D., Witte, D., Kirsten, M., Louw, C., Ngwira, B., Victor, J., Gillard, P., Cheuvart, B., Han, H., & Neuzil, K. (2010). Effect of Human Rotavirus Vaccine on Severe Diarrhea in African Infants New England Journal of Medicine, 362 (4), 289-298 DOI: 10.1056/NEJMoa0904797

Richardson, V., Hernandez-Pichardo, J., Quintanar-Solares, M., Esparza-Aguilar, M., Johnson, B., Gomez-Altamirano, C., Parashar, U., & Patel, M. (2010). Effect of Rotavirus Vaccination on Death from Childhood Diarrhea in Mexico New England Journal of Medicine, 362 (4), 299-305 DOI: 10.1056/NEJMoa0905211

Patel, N., Hertel, P., Estes, M., de la Morena, M., Petru, A., Noroski, L., Revell, P., Hanson, I., Paul, M., Rosenblatt, H., & Abramson, S. (2010). Vaccine-Acquired Rotavirus in Infants with Severe Combined Immunodeficiency New England Journal of Medicine, 362 (4), 314-319 DOI: 10.1056/NEJMoa0904485

Posted in: Science and Medicine, Vaccines

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