Estimating the health and economic impact attributable to the pentavalent rotavirus vaccine introduction in Rwanda

Rotavirus is the most common cause of severe gastroenteritis among children <5 years of age worldwide and is responsible for 453,000 deaths among children in this age group. More than half of these deaths occur in sub-Saharan Africa. Because of the tremendous global burden of rotavirus, vaccine development and introduction has been a high priority for several international agencies, including the World Health Organization (WHO) and GAVI. Two live, attenuated, orally administered rotavirus vaccines, a pentavalent bovine-human reassortant vaccine (RV5; RotaTeq® (Merck and Co, Inc, Pennsylvania)) and a monovalent vaccine (RV1; Rotarix™ (GSK Biologicals, Rixensart, Belgium)) based on a human rotavirus strain, are licensed and available for use in many countries worldwide. Pre-licensure clinical trials of each of these vaccines in high and middle-income countries demonstrated high efficacy (85-98%) against severe rotavirus disease. Further studies conducted in low-income countries of Asia and Africa found modest efficacy (50%-70%) of these vaccines against severe rotavirus disease. However, the public health impact of vaccination (in terms of burden of severe rotavirus disease prevented by vaccinating a given number of children) is greater in developing countries because of the substantially higher baseline rotavirus disease burden in these settings. In 2009, the World Health Organization recommended the inclusion of rotavirus vaccine in the national immunization programs of all countries globally and particularly in those countries with high child mortality due to diarrhea. Of the 16 countries recently approved by GAVI for rotavirus vaccine introduction, 12 countries are located in Africa. As rotavirus vaccines are introduced into national immunization programs, monitoring their impact is a high priority for several reasons. There is a need to assess the effectiveness of these vaccines in routine use to ensure it parallels that of pre-licensure trials, particularly when used in developing countries. Assessing the impact of vaccination on disease burden in countries such as Rwanda will be vital to understanding the full public health benefit of the vaccine. The primary purpose of this program evaluation is to determine the impact of pentavalent rotavirus vaccine on rotavirus and all-cause diarrhea morbidity following introduction into the national immunization program in Rwanda in May 2012. Additionally, this evaluation will document changes in circulating strains over time pre- and post-vaccine introduction. It will also strengthen support for economic evaluation of treating diarrhea versus introduction of new vaccine in routine immunization. Methodology Various studies have been implemented since 2011 in the health sector in Rwanda to reach the goal of this thesis. First, we analyzed data for all-cause, non-bloody diarrheal disease among children <5 years of age from the routine health management information system (HMIS) in Rwanda from January 2008 through December 2011, The objective of this analysis was to determine whether routinely collected health information on national diarrhea hospitalizations, in-hospital deaths, and outpatient visits can be used to monitor the impact of rotavirus vaccine. We used data from the health management information system (HMIS) in Rwanda to describe trends in all-cause, non-bloody diarrhea hospitalizations and outpatient visits among children <5 years of age from 2008 to 2011 prior to vaccine introduction. Second, we evaluated the economic burden attributable to hospitalization for diarrhea among children aged less than 5 years in Rwanda. This was a prospective costing study where medical records and hospital bills for children admitted with diarrhea at 3 hospitals were collected to estimate costs. Interviews with the child’s caregivers provided medical costs incurred before and after hospitalization and the household costs. Third, we analyzed and tried to understand the introduction and delivery cost per dose or per child of the three new vaccines in Rwanda including the rotavirus vaccine for domestic and external financial resource mobilization. Fourth, we determined the rotavirus prevalence rates and circulating genotypes directly pre- and post-introduction of the RotaTeq rotavirus vaccine in May 2012. Stool samples were collected from 1,847 children <5 admitted to 8 surveillance sites for acute gastroenteritis (AGE) and tested for rotavirus antigens by enzyme immunoassay. Fifth, to monitor the effect of rotavirus vaccine in Rwanda, we studied trends in the number of hospital admissions for diarrhea and rotavirus before and after the introduction of the rotavirus vaccine. We conducted a time-series analysis to examine trends in admissions to hospital for non-bloody diarrhea in children younger than 5 years in Rwanda between Jan 1, 2009, and Dec 31, 2014, using monthly discharge data from the HMIS.Result All-cause, non bloody diarrheal hospitalizations and outpatient visits among children <5 years of age in Rwanda from 2008 to 2011 peaked during the June to August dry season, coinciding with the rotavirus season. The bulk of the diarrheal disease burden occurred in children