Winning the Battle Against Rotavirus Diarrhea…One Step at a Time

(See the Major Article by Burnett et al on pages 1731–39.)

Soon after the discovery of rotavirus in 1973 and its identification as the most common cause of severe diarrhea in children, the journey began to develop a rotavirus vaccine that would decrease diarrheal morbidity and mortality in young children, especially in countries with the greatest burden of rotavirus deaths. There were hiccups along the way—for example, the withdrawal of the first licensed rotavirus vaccine due to the rare occurrence of intussusception after the first dose—but the newer vaccines have been safer and are in use globally. Four live-attenuated oral rotavirus vaccines, Rotarix, RotaTeq, Rotavac, and RotaSiil, have been prequalified by the World Health Organization and are available from UNICEF and Gavi for use in low-income countries [1]. Today, rotavirus vaccines have been introduced into the national childhood immunization programs in over 100 countries and, as the article by Burnett et al [2] in this issue of the Journal of Infectious Diseases highlights, are improving the health and survival of children all over the world.

Burnett et al [2] provide an updated and detailed review of the impact of oral rotavirus vaccines on rotavirus-specific and all-cause diarrheal hospitalizations and deaths among children under 5 years of age, stratified by a country’s likelihood that a child will die from the disease. Their analysis includes published data from several African countries where mortality from the disease was relatively high before introduction of Rotarix and Rotateq. Their results document substantial reductions in rotavirus and diarrheal hospitalizations, and diarrheal deaths after introduction of these vaccines, especially in children under 1 year of age. The reductions were sustained for 7 years’ postvaccine introduction, and herd protection was demonstrated in older children. Only one third of the observations were from low-income countries with high diarrhea mortality, highlighting the need for additional data from these critical settings. In addition, the review only evaluated the impact of the first 2 licensed vaccines, Rotarix and Rotateq, so we can expect impact data from India after the introduction of Rotavac and Rotasiil in the near future.

The results confirm the greater efficacy and effectiveness of oral rotavirus vaccination in high-income countries with low under 5 mortality, consistent with previous observations of the lower vaccine efficacy and effectiveness seen in low-middle income countries with higher under 5 mortality [3, 4]. Research to date has failed to fully elucidate the reason for these differences. Interventions such as delaying breastfeeding around the time of vaccination, or supplementing the child with zinc and vitamin A, have not been successful in significantly improving immune responses to oral vaccines [5, 6]. Several new vaccines such as a novel live-attenuated oral rotavirus vaccine candidate in development in Australia that uses a different rotavirus strain, and parenterally administered vaccines—a nonreplicating subunit vaccine, P2-VP8, and an inactivated whole virus vaccine—are currently under clinical development [7]. These approaches may overcome some of the barriers to current orally administered vaccines and lead to improved effectiveness and impact in low-income countries where mortality from rotavirus remains high [8].

Burnett et al [2] also noted that among children under 5 years hospitalized for diarrhea, rotavirus prevalence in fecal specimens decreased from 40% to ~20% after vaccine introduction [2]. However, rotavirus still remains the most common cause of severe diarrhea in hospitalized children in many low-income countries. Rotavirus, detected by quantitative polymerase chain reaction, remained the leading cause of severe acute watery diarrhea requiring hospitalization in children under 2 years of age in the Africa Region of the Global Rotavirus Surveillance Network [9]. Likewise, rotavirus remained the leading pathogen detected in children under 5 years of age hospitalized with diarrhea in Malawi and Tanzania after introduction of the monovalent oral rotavirus vaccine [10, 11]. By contrast, in the United States and other high-income settings, norovirus has become the leading cause of medically attended acute gastroenteritis in children after the introduction of rotavirus vaccines [12]; data emerging from some low-middle countries do not show a similar trend.

The article also highlights the need for continued efforts to increase vaccine coverage in countries that have introduced the vaccine. Impact of vaccination was lower in settings with lower vaccine coverage, so addressing this vaccine coverage issue will be important in the fight against rotavirus diarrhea. Even novel vaccines and schedules have limited potential if vaccine coverage remains low.

Despite tremendous strides in the fight against rotavirus disease, as evidenced by substantial reductions in severe rotavirus disease and death after oral rotavirus vaccination, the battle has not yet been won. Increasing vaccine coverage in countries already using rotavirus vaccines and introducing vaccines in countries that have not, represents one step to increase the impact of the vaccination worldwide. The next step must include the continued search for ways to improve the efficacy of live oral rotavirus vaccines while pursing development of novel vaccine schedules (eg, booster doses or neonatal immunization), adoption of new strains or higher titer vaccines, or the use of parenterally administered vaccines. For now, we must celebrate the many lives saved and hospitalizations and clinic visits prevented with the vaccines in hand, and we must appreciate that continued efforts in rotavirus vaccine research will ensure that many more lives are saved in the future.

Notes

Disclaimer. The content is solely the responsibility of the authors and does not represent official views of the National Institutes of Health.

Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

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