Cost and operational context for national human papillomavirus (HPV) vaccine delivery in six low- and middle-income countries.

INTRODUCTION: There are concerns from immunization program planners about high delivery costs for human papillomavirus (HPV) vaccine. Most prior research evaluated costs of HPV vaccine delivery during demonstration projects or at introduction, showing relatively high costs, which may not reflect the costs beyond the pilot or introduction years. This study sought to understand the operational context and estimate delivery costs for HPV vaccine in six national programs, beyond their introduction years. METHODS: Operational research and microcosting methods were used to retrospectively collect primary data on HPV vaccination program activities in Ethiopia, Guyana, Rwanda, Senegal, Sri Lanka, and Uganda. Data were collected from the national level and a sample of subnational administrative offices and health facilities. Operational data collected were tabulated as percentages and frequencies. Financial costs (monetary outlays) and economic costs (financial plus opportunity costs) were estimated, as was the cost per HPV vaccine dose delivered. Costing was done from the health system perspective and reported in 2019 United States dollars (US$). RESULTS: Across the study countries, between 53 % and 99 % of HPV vaccination sessions were conducted in schools. Differences were observed in intensity and frequency with which program activities were conducted and resources used. Mean annual economic costs at health facilities in each country ranged from $1,207 to $3,190, while at the national level these ranged from $7,657 to $304,278. Mean annual HPV vaccine doses delivered per health facility in each country ranged from 162 to 761. Mean financial costs per dose per study country ranged from $0.27 to $3.32, while the economic cost per dose ranged from $3.09 to $17.20. CONCLUSION: HPV vaccine delivery costs were lower than at introduction in some study countries. There were differences in the activities carried out for HPV vaccine delivery and the number of doses delivered, impacting the cost estimates.

Long-term impacts of the Bandebereho programme on violence against women and children, maternal health-seeking, and couple relations in Rwanda: a six-year follow-up of a randomised controlled trial.

Background: Programmes that work with parents to build couple relationship and parenting skills and include critical reflection on gender norms are a promising approach for reducing violence against women and children. However, there is limited evidence of their longer-term impact. In Rwanda, the Bandebereho programme engaged expectant and current parents of children under five years. At 21-months, Bandebereho demonstrated positive impacts on intimate partner violence (IPV), child physical punishment, maternal health-seeking, and couple relations. This study seeks to explore whether those outcomes are sustained six years later. Methods: A six-year follow-up to a two-arm, multi-site randomised controlled trial was conducted in four districts of Rwanda between May and September 2021. At baseline, couples were randomly assigned to either the 15-session intervention (n = 575) or a control group (n = 624). At this follow-up, 1003 men and 1021 women were included in intention to treat analysis. Generalised estimating equations with robust standard errors were used to fit the models. This study was registered with Clinicaltrials.gov (NCT04861870). Findings: Bandebereho has lasting effects on IPV and physical punishment of children, alongside multiple health and relationship outcomes. Compared to the control group: intervention women report less past-year physical (OR = 0.45, 95% CI 0.34-0.60 p < 0.001), sexual (OR = 0.50, 95% CI 0.37-0.67, p < 0.001), economic (OR = 0.47 95% CI 0.34-0.64, p < 0.001), and moderate or severe emotional (OR = 0.40 95% CI 0.29-0.56, p < 0.001) IPV. Intervention couples report less child physical punishment (OR = 0.72, p = 0.009 for men; OR = 0.68, p = 0.017 for women), fewer depressive symptoms (OR = 0.52, p < 0.001 for men; OR = 0.50, p < 0.001 for women), less harmful alcohol use, and improved maternal health-seeking, father engagement, and division of household labour and decision-making. Interpretation: Our study expands the evidence, demonstrating that programmes engaging men and women to promote collaborative and non-violent couple relations can result in sustained reductions in family violence six years later. Funding: The Echidna Giving Fund, Grand Challenges Canada, the Oak Foundation, and Wellspring Philanthropic Fund supported this study.

Human papillomavirus vaccine effect against human papillomavirus infection in Rwanda: evidence from repeated cross-sectional cervical-cell-based surveys.

BACKGROUND: Rwanda was the first African country to implement national human papillomavirus (HPV) vaccination (against types HPV6, 11, 16, and 18). In 2011, a school-based catch-up programme was initiated to vaccinate girls aged younger than 15 years but it also reached older girls in schools. We aimed to estimate the population-level effect of HPV vaccination on HPV prevalence. METHODS: Cross-sectional surveys were done between July, 2013, and April, 2014 (baseline), and between March, 2019, and December, 2020 (repeat), in sexually active women aged 17-29 years at health centres in the Nyarugenge District of Kigali, Rwanda. HPV prevalence was assessed in cervical cell samples collected by a health-care worker in PreservCyt solution (Cytyc, Boxbourough, MA, USA) and tested using a general primer (GP5+ or GP6+)-mediated PCR. Adjusted overall, total, and indirect (herd immunity) vaccine effectiveness was computed as the percentage of HPV detection among all women and among unvaccinated women. FINDINGS: 1501 participants completed the baseline survey and 1639 completed the repeat survey. HPV vaccine-type prevalence in participants aged 17-29 years decreased from 12% (173 of 1501) in the baseline survey to 5% (89 of 1639) in the repeat survey, with an adjusted overall vaccine effectiveness of 47% (95% CI 31 to 60) and an adjusted indirect vaccine effectiveness of 32% (9 to 49). Among participants aged 17-23 years, who were eligible for catch-up vaccination, the adjusted overall vaccine effectiveness was 52% (35 to 65) and the adjusted indirect vaccine effectiveness was 36% (8 to 55), with important heterogeneity according to education (overall vaccine effectiveness was 68% [51 to 79] in participants with ≥6 years of school completed and 16% [-34 to 47] in those with <6 years) and HIV status (overall vaccine effectiveness was 55% [36 to 69] for HIV-negative participants and 24% [-62 to 64] for HIV-positive participants). INTERPRETATION: In Rwanda, the prevalence of vaccine-targeted HPV types has been significantly decreased by the HPV vaccine programme, most notably in women who were attending school during the catch-up programme in 2011. HPV vaccine coverage and population-level impact is expected to increase in future cohorts who are eligible for routine HPV vaccination at age 12 years. FUNDING: Bill & Melinda Gates Foundation.

Human papillomavirus vaccine coverage in Rwanda: A population-level analysis by birth cohort.

BACKGROUND: In 2011, Rwanda became the first African nation to implement a national human papillomavirus (HPV) vaccination program, conceived to protect girls aged <15 years (i.e. born ≥1997). After an initial school-grade-targeted catch-up campaign, there was a transition to routine vaccination of 12 year-olds only. We aimed to produce population-level vaccine coverage estimates. METHODS: The Rwandan Expanded Program on Immunization (EPI) collected data on number of eligible girls and HPV vaccines delivered, stratified by calendar year (2011-2018), girl's age, district and vaccination round. HPV vaccine coverage was estimated by birth cohort (reconstituted using calendar year and age), as a proportion of (1) eligible target, and (2) the 2012 Rwandan census population. RESULTS: 1,156,863 girls received first dose of HPV vaccine between 2011 and 2018, corresponding to 98% of the eligible target. Median vaccination age was 15 years (interquartile range [IQR] 13-16) in 2011-2013 (school grade-targeted catch-up), 13 years (IQR 12-14) in 2014 (transition) and 12 years in 2015-2018 (routine). Population-level coverage versus the census increased from 10 to 40% for girls born in 1993-1995 (median vaccination age = 17 years) to 50-65% for 1996-2000 birth cohorts (14 years), and 80-90% for 2001-2006 birth cohorts (12 years). Coverage trends were similar across provinces and in the capital, Kigali. Second and third round coverage suggested most vaccinated girls completed their recommended dosing regimen (which reduced from 3 to 2 doses in 2015). CONCLUSIONS: Birth cohorts provide a clear picture of population-level HPV vaccine coverage after a pragmatic catch-up campaign, particularly in Rwanda where eligible school grades included wide age ranges. Whilst the catch-up campaign resulted in some coverage gaps in out-of-school teenagers, coverage remains high in cohorts routinely targeted as 12 year-olds.

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.

Seroprevalence of Zika virus and Rubella virus IgG among blood donors in Rwanda and in Sweden.

Seroprevalence studies provide information on the susceptibility to infection of certain populations, including women of childbearing age. Such data from Central Africa are scarce regarding two viruses that cause congenital infections: Zika virus (ZIKV), an emerging mosquito-borne infection, and Rubella virus (RuV), a vaccine-preventable infection. We report on the seroprevalence of both ZIKV and RuV from Rwanda, a country without any known cases of ZIKV, but bordering Uganda where this virus was isolated in 1947. Anti-ZIKV-specific and anti-RuV-specific immunoglobulin G (IgG) antibodies were analyzed by enzyme-linked immunosorbent assay (ELISA) in serum samples from 874 Rwandan and 215 Swedish blood donors. Samples positive for IgG antibodies against ZIKV were examined for viral RNA using real-time reverse transcription polymerase chain reaction (RT-qPCR). The seroprevalence of ZIKV IgG in Rwanda was 1.4% (12/874), of which the predominance of positive findings came from the Southeastern region. All anti-ZIKV IgG-positive samples were PCR-negative. Among 297 female blood donors of childbearing age, 295 (99.3%) were seronegative and thus susceptible to ZIKV. All Swedish blood donors were IgG-negative to ZIKV. In contrast, blood donors from both countries showed high seroprevalence of IgG to RuV: 91.2% for Rwandan and 92.1% for Swedish donors. Only 10.5% (31/294) of female donors of childbearing age from Rwanda were seronegative for RuV. In Rwanda, seroprevalence for ZIKV IgG antibodies was low, but high for RuV. Hence, women of childbearing age were susceptible to ZIKV. These data may be of value for decision-making regarding prophylactic measures.

Delivery of Multiple Child and Maternal Health Interventions during Supplementary Immunization Campaign in Rwanda, 2013: Lessons Learnt.

OBJECTIVE: This paper assesses and describes the estimated coverage of the Measles Rubella (MR) campaign in each district; the national estimate of coverage for Human Papilloma Virus (HPV) vaccination campaign and Vitamin A supplementation simultaneously implemented in 2013. METHODS: We applied descriptive statistics and epidemiological tools to the outcomes of the campaigns to assess the coverage achieved on the different child and maternal health interventions. We also assessed the Adverse Events following Immunization (AEFI) where the evaluation was used at the same time to assess the routine immunization performance coverage for children 12-24 months for all childhood antigens, Tetanus Toxoid coverage among mothers of infants, combined with routine immunization performance evaluation, skilled delivery and bed nets use in Rwanda. RESULTS: Results indicated that among the eligible targets, 97.5% received MR vaccine, 91% received HPV doses, and 83% got Vitamin A. The integrated vaccination of MR with HPV did not result in any serious AEFI. Coverage for antigens and doses given early in life was above 95% with card retention of 80%. BCG to measles dropout by card was 8.5%. Main reasons for non-vaccination indicated need for more specific immunization education. About 96.8% of mothers delivered in health institutions and 95% of the mothers slept under bed nets the night before the survey. CONCLUSION: Rwanda successfully implemented an integrated coverage evaluation survey of the integrated vaccination campaign and routine immunization with statistically valid estimates. We drew lessons that information on routine immunization can be collected during post campaign survey evaluations. The district estimates should guide the programme performance improvement.

Successive introduction of four new vaccines in Rwanda: High coverage and rapid scale up of Rwanda's expanded immunization program from 2009 to 2013.

As the pace of vaccine uptake accelerates globally, there is a need to document low-income country experiences with vaccine introductions. Over the course of five years, the government of Rwanda rolled out vaccines against pneumococcus, human papillomavirus, rotavirus, and measles & rubella, achieving over 90% coverage for each. To carry out these rollouts, Rwanda's Ministry of Health engaged in careful review of disease burden information and extensive, cross-sectoral planning at least one year before introducing each vaccine. Rwanda's local leaders, development partners, civil society organizations and widespread community health worker network were mobilized to support communication efforts. Community health workers were also used to confirm target population size. Support from Gavi, UNICEF and WHO was used in combination with government funds to promote country ownership and collaboration. Vaccination was also combined with additional community-based health interventions. Other countries considering rapid consecutive or simultaneous rollouts of new vaccines may consider lessons from Rwanda's experience while tailoring the strategies used to local context.