Report from the World Health Organization's immunization and vaccines related implementation research advisory committee (IVIR-AC) meeting, Geneva, 11-13 September 2023.

Evaluating vaccine-related research is critical to maximize the potential of vaccination programmes. The WHO Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR-AC) provides an independent review of research that estimates the performance, impact and value of vaccines, with a particular focus on transmission and economic modelling. On 11-13 September 2023, IVIR-AC was convened for a bi-annual meeting where the committee reviewed research and presentations across eight different sessions. This report summarizes the background information, proceedings and recommendations from that meeting. Sessions ranged in topic from timing of measles supplementary immunization activities, analyses of conditions necessary to meet measles elimination in the South-East Asia region, translating modelled evidence into policy, a risk-benefit analysis of dengue vaccine, COVID-19 scenario modelling in the African region, therapeutic vaccination against human papilloma virus, the Vaccine Impact Modelling Consortium, and the Immunization Agenda 2030 vaccine impact estimates.

Rotavirus genotype diversity in Tanzania during Rotavirus vaccine implementation between 2013 and 2018.

The study aims to determine Rotavirus genotypes between 2013 and 2018 during implementation of ROTARIX vaccine in Tanzania. The analysis of surveillance data obtained between 2013 and 2018 was done to determine circulating genotypes after introduction of Rotarix vaccine. From 2013 to 2018, a total of 10,557 samples were collected and screened for Rotavirus using an enzyme immunoassay. A significant decrease in Rotavirus positivity (29.3% to 17.8%) from 2013 to 2018 (OR 0.830, 95% CI 0.803-0.857, P < 0.001) was observed. A total of 766 randomly selected Rotavirus positive samples were genotyped. Between 2013 and 2018, a total of 18 Rotavirus genotypes were detected with G1P [8] being the most prevalent. The G1P [8] strain was found to decrease from 72.3% in 2015 to 13.5% in 2018 while the G9P [4] strain increased from 1 to 67.7% in the same years. G2P [4] was found to decrease from 59.7% in 2013 to 6.8% in 2018 while G3P [6] decreased from 11.2% in 2014 to 4.1% in 2018. The data has clearly demonstrated that ROTARIX vaccine has provided protection to varieties of the wild-type Rotavirus strains. Continuous surveillance is needed to monitor the circulation of Rotavirus strains during this era of vaccine implementation.

National introduction of human papillomavirus (HPV) vaccine in Tanzania: Programmatic decision-making and implementation.

BACKGROUND: Cervical cancer is the leading cause of cancer among women in Tanzania, with approximately 10,000 new cases and 7,000 deaths annually. In April 2018, the Government of Tanzania introduced 2 doses of human papillomavirus (HPV) vaccine nationally to adolescent girls to prevent cervical cancer, following a successful 2-year pilot introduction of the vaccine in the Kilimanjaro Region. METHODS: We interviewed key informants at the national level in Tanzania from February to November 2019, using a semi-structured tool to better understand national decision-making and program implementation. We conducted a comprehensive desk review of HPV vaccine introduction materials and reviewed administrative coverage data. RESULTS: Ten key informants were interviewed from the Ministry of Health, Community Development, Gender, Elderly, and Children, the World Health Organization, and other partners, and HPV vaccine planning documents and administrative coverage data were reviewed during the desk review. Tanzania introduced HPV vaccine to a single-age cohort of 14-year-old girls, with the decision-making process involving the Tanzania Immunization Technical Advisory Group and the national Interagency Coordination Committee. HPV vaccine was integrated into the routine immunization delivery strategy, available at health facilities and through outreach services at community sites, community mobile sites (>10 km from the health facility), and primary and secondary schools. Pre-introduction activities included trainings and microplanning workshops for health workers and school personnel at the national, regional, council, and health facility levels. Over 6,000 health workers and 22,000 school personnel were trained nationwide. Stakeholder and primary health care committee meetings were also conducted at the national level and in each of the regions as part of the advocacy and communication strategy. Administrative coverage of the first dose of HPV vaccine at the end of 2019 was 78%, and second dose coverage was 49%. No adverse events following HPV vaccination were reported to the national level. DISCUSSION: Tanzania successfully introduced HPV vaccine nationally targeting 14-year-old girls, using routine delivery strategies. Continued monitoring of vaccination coverage will be important to ensure full 2-dose vaccination of eligible girls. Tanzania can consider periodic intensified vaccination and targeted social mobilization efforts, as needed.

Tanzania's human papillomavirus (HPV) vaccination program: Community awareness, feasibility, and acceptability of a national HPV vaccination program, 2019.

BACKGROUND: In April 2018, Tanzania introduced the human papillomavirus (HPV) vaccine nationally to 14-year-old girls, utilizing routine delivery strategies (i.e. vaccinating girls at health facilities and community outreach, including schools). We sought to assess awareness, feasibility, and acceptability of the HPV vaccination program among health workers and community-level stakeholders. METHODS: We conducted cross-sectional in-person surveys among health workers, school personnel, community leaders, and council leaders in 18 council areas across six regions of Tanzania in October-November 2019. Regions were purposively selected to provide demographic, geographic, and vaccination coverage variability; sub-regional levels used random or stratified random sampling. Surveys included questions on HPV vaccine training and knowledge, delivery strategy, target population, and vaccine and program acceptability. Descriptive analysis was completed for all variables stratified by respondent groups. RESULTS: Across the 18 councils, there were 461 respondents, including health workers (165), school personnel (135), community leaders (143), and council leaders (18). Over half of each respondent group (50-78%) attended a training or orientation on HPV vaccine. Almost 75% of the health workers and school personnel respondent groups, and less than half (45%) of community leaders correctly identified the target age group for HPV vaccine. Most (80%) of the health workers indicated HPV vaccination was available at health facilities and schools; most (79%) indicated that the majority of girls receive HPV vaccine in school. Approximately half (52%) of all respondents reported hearing misinformation about HPV vaccine, but 97% of all respondents indicated that HPV vaccine was either "very accepted" or "somewhat accepted" in their community. CONCLUSION: The HPV vaccination program in Tanzania was well accepted by community stakeholders in 18 councils; adequate knowledge of HPV vaccine and the HPV vaccination program was demonstrated by health workers and school personnel. However, continued technical support for integration of HPV vaccination as a routine immunization activity and reinforcement of basic knowledge about HPV vaccine in specific community groups is needed. The Tanzania experience provides an example of how this vaccine can be integrated into routine immunization delivery strategies and can be a useful resource for countries planning to introduce HPV vaccine as well as informing global partners on how to best support to countries in operationalizing their HPV vaccine introduction plans.

Reduction in Rubella Virus Active Cases among Children and Adolescents after Rubella Vaccine Implementation in Tanzania: A Call for Sustained High Vaccination Coverage.

Rubella virus (RV) infection in susceptible women during the first trimester of pregnancy is associated with congenital Rubella syndrome (CRS). In countries where a vaccination program is implemented, active case surveillance is emphasized. This report documents the magnitude of active cases before and after vaccine implementation in Tanzania. A total of 8750 children and adolescents with signs and symptoms of RV infection were tested for Rubella IgM antibodies between 2013 and 2019 using enzyme immunoassay followed by descriptive analysis. The median age of participants was 3.8 (IQR: 2−6.4) years. About half (4867; 55.6%) of the participants were aged 1−5 years. The prevalence of RV active cases was 534 (32.6%, 95% CI: 30.2−34.9) and 219 (3.2%, 95% CI: 2.7−3.6) before and after vaccine implementation, respectively. Before vaccination, the highest prevalence was recorded in Pemba (78.6%) and the lowest was reported in Geita (15.6%), whereas, after vaccination, the prevalence ranged between 0.5% in Iringa and 6.5% in Pemba. Overall, >50% of the regions had a >90% reduction in active cases. The significant reduction in active cases after vaccine implementation in Tanzania underscores the need to sustain high vaccination coverage to prevent active infections and eventually eliminate CRS, which is the main goal of Rubella vaccine implementation.

Factors affecting non-coverage of measles-rubella vaccination among children aged 9-59 months in Tanzania.

Globally, measles remains a major cause of child mortality, and rubella is the leading cause of birth defects among all infectious diseases. In 2012, the World Health Assembly endorsed the Global Vaccine Action Plan that set a target to eliminate Measles-Rubella (MR) in five of the six World Health Organization (WHO) regions by 2020. This was cross-sectional study employed both quantitative and qualitative research methods. The sample size was calculated to provide overall, age- and sex-specific coverage estimates for MR vaccine among children aged between 9 and 59 months at the national level. Using desired precision of ±5% with an expected coverage of 95%, a total of 15,235 households were required. The age of children, a child who had received the MR vaccine before the campaign, household wealth quintile, the age of caregivers, and their marital status were associated with non-coverage of MR vaccination among children aged 9-59 months in Tanzania. Nationally, an estimated 88.2% (95% CI: 87.3-89%) of children aged 9-59 months received the MR campaign dose, as assessed by caregivers' recall. These estimates revealed slightly higher coverage in Zanzibar 89.6% (95% CI: 84.7-93%) compared to Mainland Tanzania 88.1% (95% CI 87.2-88.9%). These associated factors revealed causes of unvaccinated children and may be some of the reasons for Tanzania's failure to meet the MR campaign target of 95 percent vaccination coverage. Thus, vaccine development must increase programmatic oversight in order to improve immunization activities and communication strategies in Tanzanian areas with low MR coverage.

Lessons learned in the implementation of supplementary immunization activity (SIA) field guidelines for injectable vaccines - Experiences from Tanzania.

BACKGROUND: To achieve Measles and Rubella elimination and Polio Endgame goals, Tanzania implemented country-wide integrated Supplementary Immunization Activities (SIAs) in October 2019 involving two injectable vaccines of MR and IPV. The SIAs targeted children aged between 9 and 59 months for Measles-Rubella and 18 to 42 months for IPV vaccines. This article aims to share lessons learnt in the implementation of SIAs field guidelines in Tanzania in 2019 to inform future implementation of the SIAs within and outside the country's boundaries. METHODS: Focus groups discussions (FGDs) were conducted among Regional Immunization and Vaccines Officers from all regions and National Supervisors and Partners responsible for implementing the SIAs. Key areas discussed were pre-planning activities, implementation, monitoring and evaluation of the SIAs based on key thematic areas including; planning and coordination, logistics management, trainings, and demand creation. Pre-described templates were used to guide the discussion and keep record of the discussions. RESULTS: The SIAs achieved national target based on administrative coverage. This was due to a high sense of ownership of the SIAs and strong staff commitment to attain high coverage rates manifested through effective planning and coordination within and between levels; effective execution of SIAs activities; involvement of key stakeholders at all levels; and strong advocacy, communication and social mobilization activities. Despite the success observed through administrative coverage, the WHO target of attaining 95% coverage using the gold standard - national coverage survey, was not reached. The main barrier to success was inadequate and delayed disbursement of funding. CONCLUSION: The 2019 SIA achieved high administrative coverage as a result of effective coordination; adequate micro-planning; timely logistical preparations; and effective demand creation activities. Future campaigns need to give high priority to hard-to-reach and densely populated areas during planning and ensure timely disbursement of funds to the operational level during implementation.

Immunization costs, from evidence to policy: Findings from a nationally representative costing study and policy translation effort in Tanzania.

INTRODUCTION: Information on the costs of routine immunization programs is needed for budgeting, planning, and domestic resource mobilization. This information is particularly important for countries such as Tanzania that are preparing to transition out of support from Gavi, the Vaccine Alliance. This study aimed to estimate the total and unit costs for of child immunization in Tanzania from July 2016 to June 2017 and make this evidence available to key stakeholders. METHODS: We used an ingredients-based approach to collect routine immunization cost data from the facility, district, regional, and national levels. We collected data on the cost of vaccines as well as non-vaccine delivery costs. We estimated total and unit costs from a provider perspective for each level and overall, and examined how costs varied by delivery strategy, geographic area, and facility-level service delivery volume. An evidence-to-policy plan identified key opportunities and stakeholders to target to facilitate the use of results. RESULTS: The total annual economic cost of the immunization program, inclusive of vaccines, was estimated to be US$138 million (95% CI: 133, 144), or $4.32 ($3.72, $4.98) per dose. The delivery costs made up $45 million (38, 52), or $1.38 (1.06, 1.70) per dose. The costs of facility-based delivery were similar in urban and rural areas, but the costs of outreach delivery were higher in rural areas than in urban areas. The facility-level delivery cost per dose decreased with the facility service delivery volume. DISCUSSION: We estimated the costs of the routine immunization program in Tanzania, where no immunization costing study had been conducted for five years. These estimates can inform the program's budgeting and planning as Tanzania prepares to transition out of Gavi support. Next steps for evidence-to-policy translation have been identified, including technical support requirements for policy advocacy and planning.

Determinants of Facility-Level Use of Electronic Immunization Registries in Tanzania and Zambia: An Observational Analysis.

BACKGROUND: As more countries transition from paper-based to electronic immunization registries (EIRs) to collect and track individual immunization data, guidance is needed for successful adoption and use of these systems. Little research is available on the determinants of EIR use soon after introduction. This observational study assesses the determinants of facility health care workers' use of new EIRs in Tanzania and Zambia, implemented during 2016 to 2018. METHODS: We used EIR data entered between 2016 and 2018 from 3 regions in Tanzania and 1 province in Zambia to measure weekly EIR system use for a total of 50,639 facility-weeks. We joined secondary data on facility characteristics and applied the Performance of Routine Information System Management framework to categorize characteristics as organizational, technical, or behavioral. We used a generalized estimating equations logistic regression model to assess facility characteristics as potential determinants of system use. RESULTS: In both countries, the estimated odds of weekly EIR use declined weekly after EIR introduction. In Tanzania, health centers and hospitals had increased odds of system use compared to dispensaries. For each additional health care worker trained in a facility during the EIR introduction, the estimated odds of weekly EIR use increased. Tanzanian facilities that had transitioned entirely to paperless reporting had higher odds of sustained use compared to those maintaining parallel electronic and paper-based reporting systems. In Zambia, distance from the district health office was significantly associated with decreasing odds of system use. There were significant differences in EIR use by district in both countries. DISCUSSION: The results highlight the importance of organizational and behavioral factors in explaining sustained EIR use. As EIRs are introduced in new settings, we recommend indicators of engagement and use be built directly into the system so they can be routinely monitored, and course corrections can be implemented as needed.

Detection of rotavirus before and after monovalent rotavirus vaccine introduction and vaccine effectiveness among children in mainland Tanzania.

BACKGROUND: Monovalent rotavirus vaccine (RV1) was introduced in Tanzania in January 2013 under the Reach Every Child initiative, to be given at ages 6 and 10 weeks. We used the sentinel hospital rotavirus surveillance system to examine the rotavirus detection rate before and after vaccine introduction and estimate vaccine effectiveness. METHODS: Before vaccine introduction, rotavirus surveillance was established at two mainland hospitals; children admitted for acute diarrhea were eligible for enrollment and stools were tested for rotavirus antigen. We compared the rotavirus positivity rate in the pre-vaccine period (Tanga Hospital, 2009 and 2011; Bugando Medical Centre, 2012) to that from post-introduction years, 2014-2015. In 2013, surveillance was established at 9 additional hospitals. We examined rotavirus positivity among infants at these sites for 2014-2015. We obtained vaccine records and calculated vaccine effectiveness at 3 sites using case-test-negative control design. RESULTS: At Tanga Hospital, the rotavirus positivity rate among infants was 41% (102/251) pre-vaccine and 14% (28/197) in post-vaccine years (rate ratio: 0.35 [95% CI 0.22-0.54]). At Bugando, the positivity rate was 58% (83/143) pre-vaccine, and 18% (49/277) post-introduction (rate ratio 0.30 [95% CI 0.210.44]). Results were similar among children <5 years. At the new sites, the median site rotavirus positivity rate among infants was 26% in 2014 (range 19-44%) and 18% in 2015 (range 16-33%). The effectiveness of ≥1 RV1 dose against rotavirus hospitalization among children 5-23 months was 53% (95% CI: -14, 81), and 66% (95% CI: 9-87) against hospitalization with intravenous rehydration. Following introduction, peak rotavirus activity occurred later in the year and appeared more concentrated in time. CONCLUSION: Rotavirus surveillance data from Tanzania indicate that the rotavirus positivity rate among children hospitalized with diarrhea that were enrolled was substantially reduced after vaccine introduction. Low positivity rates among infants were detected at hospitals across the country. Overall, the data support that rotavirus vaccine has been successfully introduced and is effective in Tanzanian children.

Improving the efficiency and standards of a National Immunization Program Review: lessons learnt from United Republic of Tanzania.

A National Immunization Program Review (NIP Review) is a comprehensive external assessment of the performance of a country's immunization programme. The number of recommended special-topic NIP assessments, such as those for vaccine introduction or vaccine management, has increased. These assessments often have substantial overlap with NIP reviews, raising concern about duplication. Innovative technical and management approaches, including integrating several assessments into one, were applied in the United Republic of Tanzania's 2015 NIP Review. These approaches and processes were documented and a post-Review survey and group discussion. The Tanzania Review found that integrating assessments so they can be conducted at one time was feasible and efficient. There are concrete approaches for successfully managing a Review that can be shared and practiced including having a well-planned desk review and nominating topic-leads. The use of tablets for data entry has the potential to improve Review data quality and timely analysis; however, careful team training is needed. A key area to improve was to better coordinate and link findings from the national-level and field teams.

Integrating Neglected Tropical Disease and Immunization Programs: The Experiences of the Tanzanian Ministry of Health.

Global health practitioners are increasingly advocating for the integration of community-based health-care platforms as a strategy for increasing the coverage of programs, encouraging program efficiency, and promoting universal health-care goals. To leverage the strengths of compatible programs and avoid geographic and temporal duplications in efforts, the Tanzanian Ministry of Health and Social Welfare coordinated immunization and neglected tropical disease programs for the first time in 2014. Specifically, a measles and rubella supplementary vaccine campaign, mass drug administration (MDA) of ivermectin and albendazole, and Vitamin A were provisionally integrated into a shared community-based delivery platform. Over 21 million people were targeted by the integrated campaign, with the immunization program and MDA program reaching 97% and 93% of targeted individuals, respectively. The purpose of this short report is to share the Tanzanian experience of launching and managing this integrated campaign with key stakeholders.

Evaluation of using routine infant immunization visits to identify and follow-up HIV-exposed infants and their mothers in Tanzania.

BACKGROUND: Without treatment, approximately half of HIV-infected infants die by age 2 years, and 80% die before age 5 years. Early identification of HIV-infected and HIV-exposed infants provides opportunities for life-saving interventions. We evaluated integration of HIV-related services with routine infant immunization in Tanzania. METHODS: During April 2009 to March 2010, at 4 urban and 4 rural sites, mothers' HIV status was determined at first-month immunization using antenatal cards. HIV-exposed infants were offered HIV testing and follow-up care. Impact of integrated service delivery was assessed by comparing average monthly vaccine doses administered during the study period and a 2-year baseline period; acceptance was assessed by interviewing mothers and service providers. FINDINGS: During 7569 visits, 308 HIV-exposed infants were identified and registered; of these, 290 (94%) were tested, 15 (5%) were HIV infected. At urban sites, first-month vaccine doses remained stable (+2% for pentavalent vaccine and -4% for polio vaccine), and vaccine doses given later in life (pentavalent, polio, and measles) increased 12%, 8%, and 11%, respectively. At rural sites, first-month vaccine doses decreased 33% and 35% and vaccine doses given later in life decreased 23%, 28%, and 28%. Mothers and service providers generally favored integrated services; however, HIV-related stigma and inadequate confidentiality controls of HIV testing were identified, particularly at rural sites. INTERPRETATION: Integration of HIV-related services at immunization visits identified HIV-exposed infants, HIV-infected infants, and HIV-infected mothers; however, decreases in vaccine doses administered at rural sites were concerning. HIV-related service integration with immunization visits needs careful monitoring to ensure optimum vaccine delivery.