Background

In May, 2012, Rwanda became the first low-income African country to introduce pentavalent rotavirus vaccine into its routine national immunisation programme. Although the potential health benefits of rotavirus vaccination are huge in low-income African countries that account for more than half the global deaths from rotavirus, concerns remain about the performance of oral rotavirus vaccines in these challenging settings.

Methods

We conducted a time-series analysis to examine trends in admissions to hospital for non-bloody diarrhoea in children younger than 5 years in Rwanda between Jan 1, 2009, and Dec 31, 2014, using monthly discharge data from the Health Management Information System. Additionally, we reviewed the registries in the paediatric wards at six hospitals from 2009 to 2014 and abstracted the number of total admissions and admissions for diarrhoea in children younger than 5 years by admission month and age group. We studied trends in admissions specific to rotavirus at one hospital that had undertaken active rotavirus surveillance from 2011 to 2014. We assessed changes in rotavirus epidemiology by use of data from eight active surveillance hospitals.

Findings

Compared with the 2009–11 prevaccine baseline, hospital admissions for non-bloody diarrhoea captured by the Health Management Information System fell by 17–29% from a pre-vaccine median of 4051 to 2881 in 2013 and 3371 in 2014, admissions for acute gastroenteritis captured in paediatric ward registries decreased by 48–49%, and admissions specific to rotavirus captured by active surveillance fell by 61–70%. The greatest effect was recorded in children age-eligible to be vaccinated, but we noted a decrease in the proportion of children with diarrhoea testing positive for rotavirus in almost every age group.

Interpretation

The number of admissions to hospital for diarrhoea and rotavirus in Rwanda fell substantially after rotavirus vaccine implementation, including among older children age-ineligible for vaccination, suggesting indirect protection through reduced transmission of rotavirus. These data highlight the benefits of routine vaccination against rotavirus in low-income settings.

Funding

Gavi, the Vaccine Alliance and the Government of Rwanda.

Rotavirus accounts for more than a third of diarrhoea deaths in children younger than 5 years worldwide, with more than half of these deaths happening in sub-Saharan Africa. ¹ In response to this large disease burden, two live attenuated, orally taken rotavirus vaccines (RotaTeq [RV5], Merck Vaccines, Whitehouse Station, NJ, USA, and Rotarix [RV1], GSK Biologicals, Rixensart, Belgium) ² are recommended by WHO for use in all countries and especially in those with high mortality caused by diarrhoea. ² By September, 2015, 79 countries had introduced one or other of these rotavirus vaccines. ³ Most countries that introduced the vaccine early were high-income and middle-income countries in the Americas and Europe, and these countries have provided much of the early evidence of the substantial effect of rotavirus vaccination. In Mexico, where rotavirus vaccine was introduced nationally in 2007, all-cause diarrhoea deaths in children younger than 5 years of age fell by 35–50% during 2008–11. ^{4 , 5 and 6} Similar decreases of 17–39% in Brazil and 50% in Panama were documented after rotavirus vaccine introduction. ^{7 , 8 and 9} Additionally, many other countries have noted a substantial reduction in the number of hospital admissions for all-cause diarrhoea and rotavirus after the rotavirus vaccine introduction. ^{7 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 and 30}

Live oral vaccines, including those for rotavirus, have had poor performance in developing country settings. ^{31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 and 40} Although the reasons for this lower performance are unknown and probably complex, possible explanations could be interference by maternal antibodies, concurrent oral polio vaccine administration, prevalent viral and bacterial gut infections, and malnutrition. ⁴¹ Clinical trials for both the available rotavirus vaccines done in Africa and Asia showed modest efficacy (50–70%) compared with the high efficacy (85–98%) that was recorded in trials in Latin America, the USA, and Europe. ^{42 , 43 , 44 , 45 and 46} In view of the substantial disease burden in Africa and Asia, the absolute burden of severe diarrhoea disease prevented in these settings is expected to be substantial even with moderately efficacious vaccines, but concerns remain about vaccine performance in these high burden settings. ⁴⁴

Research in context

Evidence before this study

We searched PubMed for articles published since 2000 in any language using the terms “rotavirus” and “vaccine” and “sub-Saharan Africa” and “impact OR effectiveness”. Of the 42 articles identified, two articles examined the effectiveness of rotavirus vaccine in routine use in South Africa and Malawi and one study assessed the effect of rotavirus vaccine on disease burden in South Africa. We found no reports of the effect or effectiveness of rotavirus vaccine in Rwanda or of the effect or effectiveness of pentavalent rotavirus vaccine in sub-Saharan Africa.

Added value of this study

This study provides the first evidence of the effect of pentavalent rotavirus vaccine on the severe all-cause and rotavirus diarrhoea disease burden in sub-Saharan Africa after introduction of the vaccine into the routine childhood immunisation programme. Diarrhoea and rotavirus-specific hospital admissions in Rwanda fell substantially after rotavirus vaccine implementation, including among older children age-ineligible for vaccination, suggesting indirect protection through reduced transmission of rotavirus.

Implications of all the available evidence

Our findings support the continued use of rotavirus vaccine in Rwanda and highlight the benefits of routine vaccination against rotavirus in low-income settings.