<span class="paragraphSection"><div class="boxTitle">Background</div>Low-income settings challenge the level of protection provided by live attenuated oral rotavirus vaccines. Rotarix (RV1) was introduced in the United Republic of Tanzania in early 2013, with 2 doses given at the World Health Organization–recommended schedule of ages 6 and 10 weeks, along with oral poliovirus vaccine.<div class="boxTitle">Methods</div>We performed active surveillance for rotavirus hospitalizations at the largest hospital in Zanzibar, Tanzania, from 2010 through 2015. Using a case–test-negative control design, we estimated the vaccine effectiveness (VE) of 2 RV1 doses in preventing rotavirus hospitalizations.<div class="boxTitle">Results</div>Based on 204 rotavirus case patients and 601 test-negative controls aged 5–23 months, the VE of 2 RV1 doses against hospitalization for rotavirus diarrhea was 57% (95% confidence interval, 14%–78%). VE tended to increase against hospitalizations with higher severity, reaching 69% (95% confidence interval, 15%–88%) against the severity score for the top quarter of case patients. Compared with the prevaccine period, there were estimated reductions of 40%, 46%, and 69% in the number of rotavirus hospitalizations among infants in 2013, 2014, and 2015, respectively, and reductions of 36%, 26%, and 64%, respectively, among children aged <5 years.<div class="boxTitle">Conclusions</div>With data encompassing 3 years before and 3 years after vaccine introduction, our results indicate that successful delivery of RV1 on the current World Health Organization schedule can provide substantial health benefits in a resource-limited setting.</span>
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