Timeliness of rotavirus vaccination at sentinel sites in four early-adopter African countries.

BACKGROUND: The majority of countries with the highest rotavirus-associated death rates are in sub-Saharan Africa. In 2009, the World Health Organization (WHO) recommended routine vaccination against rotavirus worldwide, with unique age recommendations to administer the first dose before 15 weeks of age and last dose by 32 weeks of age. These age restrictions were relaxed in January 2013, but they may still lead to lower rotavirus vaccine coverage. METHODS: Children age-eligible to have received rotavirus vaccine that were enrolled in Ghana, Zimbabwe, Rwanda or Burkina Faso's active rotavirus surveillance platforms from 2013 to 2017 and had a stool specimen that tested rotavirus-negative were included in the analysis. Proportion vaccinated and timeliness of rotavirus vaccine versus DTPw-HepB-Hib (pentavalent) first dose and last dose were compared at weeks 15 and 32, respectively, using Chi-square analyses. Odds ratios were calculated using logistic regression. RESULTS: Among children who received rotavirus vaccine dose 1, 96-99% received this dose by 15 weeks of age and among children who received the last dose, 98-99% received it by 32 weeks of age. In all four countries, there was no significant difference in the proportion of children who received first dose rotavirus versus pentavalent vaccine by week 15, or last dose rotavirus versus concordant pentavalent vaccine by week 32. Delayed administration of first dose pentavalent vaccine was significantly associated with missing first dose of rotavirus vaccine in 3 of the 4 countries studied, although delays in administration were rare (1-4%). CONCLUSIONS: Rotavirus vaccination was timely among sentinel sites in these four early rotavirus vaccine-introducing countries in Africa. Late presentation for vaccination may have resulted in some children with access to care missing first dose of rotavirus vaccine; however, vaccination delays were infrequent and therefore the potential impact of the age restrictions on overall proportion vaccinated was minimal.

Impact of routine rotavirus vaccination on all-cause and rotavirus hospitalizations during the first four years following vaccine introduction in Rwanda.

BACKGROUND: Rwanda introduced pentavalent rotavirus vaccine into its national immunization program in 2012. To determine the long-term impact of rotavirus vaccine on disease burden in a high burden setting, we examined trends in rotavirus and all-cause diarrhea hospitalizations in the first four years following rotavirus vaccine introduction. METHODS: We used data from an active surveillance system, from a review of pediatric ward registries, and from the Health Management Information System to describe trends in rotavirus and all-cause diarrhea hospitalizations from January 2009 through December 2016. Percent reductions were calculated to compare the number of all-cause and rotavirus diarrhea hospitalizations pre- and post-rotavirus vaccine introduction. RESULTS: The proportion of diarrhea hospitalizations due to rotavirus declined by 25-44% among all children <5 years of age during 2013-2015 with a shift in rotavirus hospitalizations to older age groups. The proportion of total hospitalizations due to diarrhea among children <5 years of age decreased from 19% pre-vaccine introduction to 12-13% post-vaccine introduction. In the national hospital discharge data, substantial decreases were observed in all-cause diarrhea hospitalizations among children <5 years of age in 2013 and 2014 but these gains lessened in 2015-2016. DISCUSSION: Continued monitoring of long-term trends in all-cause diarrhea and rotavirus hospitalizations is important to ensure that the impact of the vaccination program is sustained over time and to better understand the changing age dynamics of diarrhea and rotavirus hospitalizations in the post-vaccine introduction era.

Effectiveness of Pentavalent Rotavirus Vaccine Under Conditions of Routine Use in Rwanda.

BACKGROUND: Rotavirus vaccine efficacy is lower in low-income countries than in high-income countries. Rwanda was one of the first low-income countries in sub-Saharan Africa to introduce rotavirus vaccine into its national immunization program. We sought to evaluate rotavirus vaccine effectiveness (VE) in this setting. METHODS: VE was assessed using a case-control design. Cases and test-negative controls were children who presented with a diarrheal illness to 1 of 8 sentinel district hospitals and 10 associated health centers and had a stool specimen that tested positive (cases) or negative (controls) for rotavirus by enzyme immunoassay. Due to high vaccine coverage almost immediately after vaccine introduction, the analysis was restricted to children 7-18 weeks of age at time of rotavirus vaccine introduction. VE was calculated as (1 - odds ratio) × 100, where the odds ratio was the adjusted odds ratio for the rotavirus vaccination rate among case-patients compared with controls. RESULTS: Forty-eight rotavirus-positive and 152 rotavirus-negative children were enrolled. Rotavirus-positive children were significantly less likely to have received rotavirus vaccine (33/44 [73%] unvaccinated) compared with rotavirus-negative children (81/136 [59%] unvaccinated) (P= .002). A full 3-dose series was 75% (95% confidence interval [CI], 31%-91%) effective against rotavirus gastroenteritis requiring hospitalization or a health center visit and was 65% (95% CI, -80% to 93%) in children 6-11 months of age and 81% (95% CI, 25%-95%) in children ≥12 months of age. CONCLUSIONS: Rotavirus vaccine is effective in preventing rotavirus disease in Rwandan children who began their rotavirus vaccine series from 7 to 18 weeks of age. Protection from vaccination was sustained after the first year of life.

The Economic Burden Attributable to a Child's Inpatient Admission for Diarrheal Disease in Rwanda.

BACKGROUND: Diarrhea is one of the leading causes of childhood morbidity and mortality. Hospitalization for diarrhea can pose a significant burden to health systems and households. The objective of this study was to estimate the economic burden attributable to hospitalization for diarrhea among children less than five years old in Rwanda. These data can be used by decision-makers to assess the impact of interventions that reduce diarrhea morbidity, including rotavirus vaccine introduction. METHODS: This was a prospective costing study where medical records and hospital bills for children admitted with diarrhea at three hospitals were collected to estimate resource use and costs. Hospital length of stay was calculated from medical records. Costs incurred during the hospitalization were abstracted from the hospital bills. Interviews with the child's caregivers provided data to estimate household costs which included transport costs and lost income. The portion of medical costs borne by insurance and household were reported separately. Annual economic burden before and after rotavirus vaccine introduction was estimated by multiplying the reported number of diarrhea hospitalizations in public health centers and district hospitals by the estimated economic burden per hospitalization. All costs are presented in 2014 US$. RESULTS: Costs for 203 children were analyzed. Approximately 93% of the children had health insurance coverage. Average hospital length of stay was 5.3 ± 3.9 days. Average medical costs for each child for the illness resulting in a hospitalization were $44.22 ± $23.74 and the total economic burden was $101, of which 65% was borne by the household. For households in the lowest income quintile, the household costs were 110% of their monthly income. The annual economic burden to Rwanda attributable to diarrhea hospitalizations ranged from $1.3 million to $1.7 million before rotavirus vaccine introduction. CONCLUSION: Households often bear the largest share of the economic burden attributable to diarrhea hospitalization and the burden can be substantial, especially for households in the lowest income quintile.

Effect of pentavalent rotavirus vaccine introduction on hospital admissions for diarrhoea and rotavirus in children in Rwanda: a time-series analysis.

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.

A cost comparison of introducing and delivering pneumococcal, rotavirus and human papillomavirus vaccines in Rwanda.

BACKGROUND: Detailed cost evaluations of delivery of new vaccines such as pneumococcal conjugate, human papillomavirus (HPV), and rotavirus vaccines in low and middle-income countries are scarce. This paper differs from others by comparing the costs of introducing multiple vaccines in a single country and then assessing the financial and economic impact at the time and implications for the future. The objective of the analysis was to understand the introduction and delivery cost per dose or per child of the three new vaccines in Rwanda to inform domestic and external financial resource mobilization. METHODS: Start-up, recurrent, and capital costs from a government perspective were collected in 2012. Since pneumococcal conjugate and HPV vaccines had already been introduced, cost data for those vaccines were collected retrospectively while prospective (projected) costing was done for rotavirus vaccine. RESULTS: The financial unit cost per fully immunized child (or girl for HPV vaccine) of delivering 3 doses of each vaccine (without costs related to vaccine procurement) was $0.37 for rotavirus (RotaTeq(®)) vaccine, $0.54 for pneumococcal (Prevnar(®)) vaccine in pre-filled syringes, and $10.23 for HPV (Gardasil (®)) vaccine. The financial delivery costs of Prevnar(®) and RotaTeq(®) were similar since both were delivered using existing health system infrastructure to deliver infant vaccines at health centers. The total financial cost of delivering Gardasil(®) was higher than those of the two infant vaccines due to greater resource requirements associated with creating a new vaccine delivery system in for a new target population of 12-year-old girls who have not previously been served by the existing routine infant immunization program. CONCLUSION: The analysis indicates that service delivery strategies have an important influence on costs of introducing new vaccines and costs per girl reached with HPV vaccine are higher than the other two vaccines because of its delivery strategy. Documented information on financial commitments for new vaccines, particularly from government sources, is a useful input into country policy dialogue on sustainable financing and co-financing of new vaccines, as well as for policy decisions by donors such as Gavi, the Vaccine Alliance.

Can routinely collected national data on childhood morbidity and mortality from diarrhea be used to monitor health impact of rotavirus vaccination in Africa? Examination of pre-vaccine baseline data from Rwanda.

BACKGROUND: As rotavirus vaccine is introduced into routine childhood immunization programs in Africa, understanding its impact on diarrheal disease burden is important. The objective of this analysis was to determine whether routinely collected health information on national diarrhea hospitalizations, in-hospital deaths and outpatient visits would be useful to monitor rotavirus vaccine impact. METHODS: We analyzed data for all-cause, nonbloody diarrheal disease among children <5 years of age from the routine health management information system (HMIS) in Rwanda from January 2008 through December 2011. We described trends in absolute numbers of inpatient admissions, in-hospital deaths and outpatient visits by year, age and setting. RESULTS: All-cause, nonbloody 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 <1 year of age. Health centers provided many care to children with diarrhea including 60-72% of hospitalizations and 97-99% of outpatient visits. Many in-hospital diarrheal deaths (84%) occurred in district hospitals. DISCUSSION: Given the stable and consistent trends and the prominent seasonality consistent with that of rotavirus, HMIS data should provide a useful baseline to monitor rotavirus vaccine impact on the overall diarrheal disease burden in Rwanda. Active, sentinel surveillance for rotavirus diarrhea will help interpret changes in diarrheal disease trends following vaccine introduction. Other countries planning rotavirus vaccine introduction should explore the availability and quality of their HMIS data.

Haemophilus influenzae type b conjugate vaccine impact against purulent meningitis in Rwanda.

Rwanda introduced Haemophilus influenzae type b (Hib) conjugate vaccine in January 2002 and simultaneously implemented pediatric bacterial meningitis surveillance at a major referral hospital in the capital Kigali. We reviewed clinical and laboratory information collected during January 2002 to June 2006. Due to a variety of laboratory limitations, only eight confirmed Hib cases were identified, all before 2004. However, the proportion of cerebrospinal fluid with purulence decreased from 26.0% during 2002, to 15.9% during 2003, 9.7% during 2004 and 8.4% in 2005 (p<0.001). Vaccine effectiveness of two or three doses of Hib vaccine against purulent meningitis was 52% (95% confidence interval, 5-75%). In an African setting with few resources and in which few confirmed Hib meningitis cases were identified, Hib vaccine impact nevertheless could be demonstrated against the outcome of purulent meningitis and was found to be high.