Global Health PrimerGlobal Health Primer

Global Burden

Rotavirus is distributed worldwide, and, in the absence of a vaccine, nearly all children in both the developed and developing worlds have been infected by the time they are three years old.¹ While nearly every child is at risk of rotavirus infection,complicating factors, such as poverty, malnutrition, and low birth weight, increase the risk for hospitalization irrespective of geographic location. The WHO estimates that each year rotavirus results in over 453,000 deaths and over 2 million hospitalizations of infants and young children around the world.² Of these deaths, 85 % occur in developing countries in Asia and sub-Saharan Africa where access to treatment is limited or unavailable.³

In the United States alone, rotavirus infection leads to over 200,000 emergency room visits and 55,000 - 70,000 hospitalizations each year, translating into an economic impact of approximately US$1 billion annually.⁴ Globally, rotavirus is estimated to result in 25 million doctors visits and 2 million hospitalizations each year.⁵

Causative Agent

Rotaviruses are non-enveloped, double-stranded RNA viruses belonging to the family Reoviridae. Rotavirus particles are made up of three concentric layers of capsid proteins, giving them a wheel-like (latin, rota) appearance under the electronmicroscope.

Rotaviruses are classified into seven groups (A-G), which infect different species including humans, other mammals, and birds.⁶ Group A rotaviruses cause the majority of human infections. Rotaviruses are further characterized into multiple genotypes based on the antigenic specificity of the outer capsid proteins. Primary infection leads to the generation of antibodies that can protect against the initial serotype, and can give partial protection against other serotypes. Although primary infection does not provide full immunity against the many strains of rotavirus, subsequent infections are generally less severe.

Transmission of rotavirus occurs by ingestion of feces from an infected individual. The high numbers of virus particles shed from an acutely infected patient, combined with the low number of viruses required to cause infection, lead to rapid spread of the virus. Rotavirus can be found in the stool of both symptomatic and asymptomatic children. Rotavirus particles are highly stable and can remain infectious for months at room temperature, further facilitating transmission. Rotavirus is so infectious that good hygiene and hand washing are not enough to prevent its spread.⁵ In temperate climates, rotavirus infections are seasonal, with the highest incidence from December to June; in the tropics, infections occur year-round with peak infections occurring in some countries during the cool dry months.

Pathogenesis

Rotavirus is taken into the body by ingestion, and infects epithelial cells lining the small intestine. Viral replication in the cytoplasm causes cellular damage and fluid secretion, which result in profuse, watery diarrhea. The appearance of symptoms generally occurs suddenly after an incubation period of 1-2 days. Diarrhea, vomiting, and fever can last between 4-7 days, during which time very large numbers of virus particles are shed in the feces.

Current Control Strategy

There is presently no known effective intervention for rotavirus infection except vaccinarion.. Two rotavirus vaccines were recently approved by the World health Organization (WHO) for inclusion in the Expanded Programme on Immunization (EPI), and vaccination campaigns for children worldwide have begun. These vaccines provide protection against severe disease and are beneficial for reducing infection rates in children in both developed and developing countries.

Existing Products

Drugs

There are no specific antiviral drugs available to treat rotavirus infection. Symptoms are managed by oral or intravenous rehydration therapy.

Vaccines

There are currently two vaccines available for the prevention of rotavirus: 

1. RotaTeq, developed by Merck: Contains five strains of rotaviruses, each of which is a reassortant of the bovine rotavirus isolate (G genotype) and a human isolate (P genotype) attenuated through multiple passages in culture.
2. Rotarix, developed by GlaxoSmithKline: Contains a single strain of rotavirus, which is derived from a human isolate and was attenuated by multiple passages in cell culture.

Both vaccines are administered orally and are based on live attenuated viruses. Although vaccination does not completely protect against the many rotavirus strains, it is effective at preventing severe infection. These vaccines have been highly beneficial in the United States, reducing rotavirus infections by 50% in the 2007-2008 season as immunization became widespread.¹ In the developing world (El Salvador, Nicaragua, Mexico, etc.) these vaccines have also shown high efficacy and reduced the number of infections and diarrhea incidence significantly.^9-16

Diagnostics

Commercial Enzyme based Immunosorbent Assays (EIA) are available for rotavirus diagnosis as well as nucleic acid amplification-based diagnostic techniques.. It should be noted that the nucleic acid based methods require access to sophisticated laboratory facilities.

As diarrhea due to rotavirus, like other diarrheal disease, is primarily treated by supportive rehydration therapy rather than medications, specific diagnosis of rotavirus is not considered essential.

References

1. WHO, Initiative for Vaccine Research: Diarrheal Diseases.
2. Tate JE et al. 2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: a systematic review and meta-analysis. Lancet Infectious Diseases, 2011, doi:10.1016/S1473-3099(11)70253-5.)
3. WHO. 2008 rotavirus deaths, under 5 years of age, as of 31 January 2012. Available here.
4. Parashar UD et al. (2006) “Prevention of Rotavirus Gastroenteritis Among Infants and Children.” MMWR 55: 1-13.
5. Parashar UD et al. (2003) “Global illness and deaths caused by rotavirus disease in children.” Emerg Infect Dis 9: 565-72.
6. Desselberger U et al. (2009) “Rotaviruses and rotavirus vaccines.” Br Med Bull 90: 37-51.
7. CDC: About Rotavirus.
8. Patel MM et al (2010) “Real-world Impact of Rotavirus Vaccination.” The Pediatric Infectious Disease Journal 30: S1-S5
9. Linhares AC, et al. Lancet 2008; 371: 1181–9, 2. Ruiz-Palacios GM, et al. N Engl J Med 2006; 354: 11–22
10. Vesikari T, et al. Lancet 2007; 370: 1757–63
11. Tregnaghi M et al. ICID. 2008
12. Phua KB, et al. APCP. 2009,
13. Phua KB, et al. Vaccine 2009; 27: 5936–41
14. Phua KB, et al. ESPID. 2009,
15. Madhi S et al. N Engl J Med 2010; 362: 289–98,;
16. Armah GE et al. Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in sub-Saharan Africa: a randomised, double-blind, placebo-controlled trial. The Lancet. 2010;376(9741):606–614.

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