Complete and on-time routine childhood immunisation: determinants and association with severe morbidity in urban informal settlements, Nairobi, Kenya.

Background: Completion of the full series of childhood vaccines on-time is crucial to ensuring greater protection against vaccine-preventable diseases.Aim: To examine determinants of complete and on-time vaccination and evaluate the relationship between vaccination patterns and severe morbidity outcomes.Subjects and methods: Vaccination information from infants in Nairobi Urban Health and Demographic Surveillance System was used to evaluate full and on-time vaccination coverage of routine immunisation. Logistic regression was used to identify determinants of full and on-time vaccination coverage. Cox regression model was used to evaluate the relationship between vaccination status and subsequent severe morbidity. A shared frailty cox model was fitted to account for the heterogeneity in hospitalisation episodes.Results: Maternal age, post-natal care, parity, ethnicity, and residence place were identified as determinants of vaccination completion. Institutional deliveries and residence place were identified as the determinants of on-time vaccination. A significant 58% (confidence interval [CI]: 15-79%) (p = .017) lower mortality was observed among fully immunised children compared with not fully immunised. Lower mortality was observed among on-time immunised children, 64% (CI: 20-84%) compared to those with delays.Conclusions: Improving vaccination timeliness and completion schedule is critical for protection against vaccine preventable diseases and may potentially provide protection beyond these targets.

New Vaccine Introduction and Childhood Vaccination Timeliness in Two Urban, Informal Settlements in Nairobi, Kenya.

New vaccine introduction accompanied by social mobilization activities could contribute to improved routine immunization timeliness. This study assesses the impact of Kenya's introduction of pneumococcal conjugate vaccine (PCV) on the timeliness of routine childhood vaccination in two informal, urban settlements in Nairobi. Data collected from 2007 to 2015 as part of a demographic surveillance system were used to estimate annual vaccination delays of ≥ 4 weeks among children aged 12-23 months in the period before and after the introduction of PCV in Kenya. Binomial segmented regression models using generalized estimating equations examined the association between vaccine introduction and timeliness of routine immunization. Over half of all children vaccinated in the two urban areas received one or more doses ≥ 4 weeks after the recommended age. The timeliness of routine immunization showed slight improvements or nonsignificant changes during the years following PCV introduction compared with the preceding years (adjusted prevalence ratio [aPR]: 0.67, 95% CI: 0.45-0.99 for Bacille Calmette-Guerin receipt; aPR: 0.59, 95% CI: 0.41-0.83 for third dose Pentavalent receipt; aPR: 1.19, 95% CI: 0.99-1.42 for measles). However, as of 2015, delayed vaccination remained prevalent in children, particularly among the poorest residing in the settlements. Many sub-Saharan African countries have introduced new life-saving vaccines into their routine childhood immunization schedule. Additional evidence regarding the positive or neutral influence of new vaccine introduction on the performance of delivery systems provides further justification to sustain the inclusion of these more costly vaccines in the immunization schedule.

Vaccine Delay and Its Association With Undervaccination in Children in Sub-Saharan Africa.

INTRODUCTION: Improving the timeliness and completion of vaccination is the key to reducing under-5 childhood mortality. This study examines the prevalence of delayed vaccination for doses administered at birth and age 6 weeks, 10 weeks, 14 weeks, and 9 months and its association with undervaccination among infants in Sub-Saharan Africa. METHODS: Pooling data across 33 Sub-Saharan Africa countries, vaccination timing and series completion were assessed for children aged 12-35 months who were included in the immunization module of the Demographic and Health Surveys conducted between 2010 and 2019. Survey design-adjusted logistic regression modeled the likelihood of not fully completing the basic immunization schedule associated with dose-specific delays in vaccination. Data were obtained and analyzed in May 2020. RESULTS: Among children with complete date records (n=70,006), the proportion of children vaccinated with delays by ≥1 month was high: 25.9% for Bacille Calmette-Guerin (at birth); 49.1% for the third dose of pentavalent combination vaccine (at 14 weeks); and 63.9% for the first dose of measles vaccines (at 9 months). Late vaccination was more common for children born to mothers with lower levels of educational attainment (p<0.001) and wealth (p<0.001). Controlling for place, time, and sociodemographics, vaccination delays at any dose were significantly associated with not completing the immunization schedule by 12 months (Bacille Calmette-Guerin: AOR=1.93, [95% CI=1.83, 2.02]; pentavalent 3: AOR=1.50 [95% CI=1.35, 1.64]; measles: AOR=3.76 [95% CI=3.37, 4.15]). CONCLUSIONS: Timely initiation of vaccination could contribute to higher rates of immunization schedule completion, improving the reach and impact of vaccination programs on child health outcomes in Sub-Saharan Africa. SUPPLEMENT INFORMATION: This article is part of a supplement entitled Global Vaccination Equity, which is sponsored by the Global Institute for Vaccine Equity at the University of Michigan School of Public Health.

Economic evaluation of the introduction of rotavirus vaccine in Hong Kong.

BACKGROUND: Rotavirus is a common cause of severe gastroenteritis in young children in Hong Kong (HK) with a high economic burden. This study aimed to evaluate the cost-effectiveness of introducing rotavirus vaccination into the HK Government's Childhood Immunisation Programme (CIP) and to include the potential protective effect of the vaccine against seizures. METHODS: A decision-support model was customised to estimate the potential impact, cost-effectiveness and benefit-risk of rotavirus vaccination in children below 5 years over the period 2020-2029 in HK. Two doses of Rotarix® and three doses of RotaTeq® were each compared to no vaccination. Rotavirus treatment costs were calculated from a governmental health sector perspective (i.e., costs of public sector treatment) and an overall health sector perspective (both governmental and patient, i.e., costs of public sector treatment, private sector treatment, transport and diapers). We ran probabilistic and deterministic uncertainty analyses. RESULTS: Introduction of rotavirus vaccination in HK could prevent 49,000 (95% uncertainty interval: ~44,000-54,000) hospitalisations of rotavirus gastroenteritis and seizures and result in ~50 (95% uncertainty interval: ~25-85) intussusception hospitalisations, over the period 2020-2029 (a benefit-risk ratio of ~1000:1), compared to a scenario with no public or private sector vaccine use. The discounted vaccination cost would be US$51-57 million over the period 2020-2029 based on per-course prices of US$72 (Rotarix®) or US$78 (RotaTeq®), but this would be offset by discounted treatment cost savings of US$70 million (government) and US$127 million (governmental and patient health sector). There was a greater than 94% probability that the vaccine could be cost-saving irrespective of the vaccine product or perspective considered. All deterministic 'what-if' scenarios were cost-saving from an overall health sector perspective (governmental and patient). CONCLUSIONS: Rotavirus vaccination is likely to be cost-saving and have a favourable benefit-risk profile in HK. Based on the assumptions made, our analysis supports its introduction into CIP.

Measles vaccination of young infants in China: A cost-effectiveness analysis.

BACKGROUND: Although global progress in measles control has been realized, achieving elimination has proven difficult in many regions of the world. China has adopted a goal of measles elimination but recent outbreaks predominantly affecting children <8 months who are ineligible for vaccination and incompletely protected by maternal antibodies has impeded progress. We assess the cost-effectiveness of adding an initial measles vaccine dose in China to earlier than the currently recommended 8 months of age. METHODS: We conducted a cost-utility analysis comparing the costs and health benefits associated with adding a measles vaccine dose to the routine schedule at 4, 5, 6 or 7 months compared to the current recommendation for the first dose at age 8 months. A decision analytic model was developed in Microsoft Excel, including five non-severe and two fatal health outcomes associated with measles infection. Model parameters were informed by the literature and surveillance data. Future costs and health benefits were discounted at 3%. Primary outcomes included costs, Quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) over a lifetime time horizon. RESULTS: Lowering the recommended age for initiating the measles vaccination series to address susceptibility in children <8 months provided incremental health gains compared to minimal costs at the individual-level. The ICER was most favorable ($232.70 per QALY gain) for administering an initial dose at 4 months of age due to fewer incremental program costs when shifting measles administration to an immunization visit already established under the Chinese vaccination program. CONCLUSION: We found potential beneficial health gains at a minimum cost associated with adding an earlier measles dose <8 months of age in China. Further investigation about disease transmission dynamics is required to more fully assess the tradeoffs of administering measles at a younger age to infants in China.

Cost-effectiveness of HPV vaccination in Belize.

OBJECTIVE: Among women in Belize, cervical cancer is both the leading cancer and the leading cause of cancer deaths. Both the quadrivalent and bivalent human papillomavirus (HPV) vaccines are licensed in Belize. The Ministry of Health of Belize convened a multidisciplinary team to estimate the costs, health benefits, and cost-effectiveness of adding an HPV vaccine to the national immunization schedule. METHODOLOGY: The CERVIVAC cost-effectiveness model (Version 1.123) was used to assess the lifetime health and economic outcomes of vaccinating one cohort of girls aged 10 years against HPV. The comparator was no HPV vaccination. The PAHO Revolving Fund negotiated price of US$ 13.79 per dose was used (for the quadrivalent vaccine) and national data sources were used to define demography, cervical cancer incidence and mortality, cervical cancer treatment costs, and vaccine delivery costs. Estimates from international agencies were used in scenario analysis. RESULTS: In a cohort of ∼4000 Belizean girls tracked over a lifetime, HPV vaccination is estimated to prevent 69 new cases of cervical cancer (undiscounted), and 51 cervical cancer deaths (undiscounted). Considering the potential cervical cancer treatment costs and lost wages avoided by households (societal perspective), the cost per disability-adjusted life year (DALY) averted was estimated to be US$ 429. This increased to US$ 1320 when cervical cancer treatment costs and lost wages were excluded from the analysis. Both estimates are far below the gross domestic product (GDP) per capita of Belize (US$ 4795). The lifetime health care costs saved by the women and their families represent more than 60% of the investment cost needed by the Government for the vaccine. CONCLUSION: Routine HPV vaccination would be highly cost-effective in Belize. If affordable, efforts should be made to expedite the introduction of this vaccine into the Belizean national immunization program.

Tracking financial flows for immunization in Honduras.

INTRODUCTION: In Honduras, until 2008, vaccine and injection supplies were financed with domestic resources. With the introduction of rotavirus vaccine in 2009 and pneumococcal conjugate in 2011, the country's Expanded Program on Immunization required an influx of resources to support not only vaccine procurement but also investments in cold chain infrastructure and programmatic strategies. This paper examines the origin, allocation, and use of resources for immunization in 2011 in Honduras, with the aim of identifying gaps in financing. METHODS: An adaptation of the System of Health Accounts (2011) codes was used to specifically track resources for immunization services in Honduras for 2011. All financial flows were entered into an Excel database, and each transfer of resources was coded with a financing source and a financing agent. These coded financing sources were then distributed by provider, health care function (activity), health care provision (line item or resource input), and beneficiary (geographic, population, and antigen). All costs were calculated in 2011 United States dollars. RESULTS: In 2011, financing for routine immunization in Honduras amounted to US$ 49.1 million, which is equal to 3.3% of the total health spending of US$ 1.49 billion and 0.29% of the GDP. Of the total financing, 64% originate from domestic sources. The other 36% is external financing, most importantly Gavi support for introducing new vaccines. This analysis identified potential financing gaps for many immunization-related activities besides procuring vaccines, such as expanding the cold chain, training, social mobilization, information systems, and research. CONCLUSIONS: The funding for Honduras' immunization program is a small share of total public spending on health. However, new vaccines recently added to the schedule with financial support from Gavi have increased the financing requirements by more than 30% in comparison to 2008. The Honduran government and its partners are developing sustainability plans to cover a financing gap that will occur when the country graduates from Gavi support in 2016. Access to lower vaccine prices will make the existing and future program, including the planned introduction of HPV vaccine to adolescent girls, more affordable.

Cost-effectiveness analysis of pneumococcal conjugate vaccine introduction in Paraguay.

OBJECTIVE: To describe a cost-effectiveness analysis of 10- or 13-valent pneumococcal conjugate vaccine (PCV10 or 13) introduction in Paraguay compared to no vaccination. METHODS: The integrated TRIVAC vaccine cost-effectiveness model (version 2.0) jointly developed by the Pan American Health Organization's ProVac Initiative and the London School of Hygiene & Tropical Medicine was applied from the government and societal perspectives to estimate the cost-effectiveness (CE) of PCV introduction during 2010 and 2011. The cost-effectiveness ratios of PCV10 and PCV13 were separately compared to non-vaccination. The model calculated health and economic benefits of vaccination for 10 birth cohorts of children <5 years of age. A base case scenario with two primary doses at 2 and 4 months and a booster dose at 12 months (2+1 schedule) and alternate scenarios with varying parameters were considered. RESULTS: With PCV10 introduction, the incremental costs of the vaccination program would be approximately US$ 67 million to vaccinate all 10 cohorts of children; with PCV13, US$ 87 million. Health services costs avoided by the government with PCV10 would be US$ 19.5 million; with PCV 13, US$ 17.7 million. From the societal perspective, savings were much greater: with PCV10, US$ 43 million; with PCV13, US$ 35 million. For the higher priced PCV13, the average cost-effectiveness ratio was better than for PCV10 when compared to no vaccination, but regardless both were cost effective for government and society based on a threshold of 3× GDP per capita in Paraguay (2009 US$ 2516). The number of averted meningitis and all-cause pneumonia cases and deaths was greater with PCV13 than with PCV10 when compared to no vaccination. CONCLUSION: The introduction of either PCV10 or PCV13 would be cost effective when compared to no vaccination, and in some scenarios, highly cost effective in Paraguay. The outcomes of these analyses demonstrate that a pneumococcal vaccine could substantially reduce morbidity and mortality in children <5 years in Paraguay.

Cost-effectiveness analysis of the introduction of the human papillomavirus vaccine in Honduras.

BACKGROUND: Cervical cancer is the leading cause of cancer deaths in Honduras. With the availability of a vaccine to prevent human papillomavirus (HPV), the causative agent for cervical cancer, the Honduran Secretary of Health undertook a cost-effectiveness analysis of introducing the HPV vaccine to support their national decision-making process. METHODS: A national multidisciplinary team conducted this analysis with the CERVIVAC model, developed by the London School of Hygiene and Tropical Medicine in collaboration with the Pan American Health Organization's ProVac Initiative. The cumulative costs and health benefits of introducing the HPV vaccine were assessed over the lifetime of one single cohort of 11-year-old girls. We assumed a three-dose series with 95% vaccination coverage of the cohort using a mixture of school-based and facility-based delivery. To estimate national cervical cancer cases and deaths, we used United Nations demographic projections and GLOBOCAN estimates based on registry data from El Salvador, Guatemala, and Nicaragua. Based on estimates from the World Health Organization (WHO) and the Division of Intensified Cooperation with Countries (ICO), we assumed that 70% of cervical cancer would be due to vaccine types HPV16 and HPV18. We used a vaccine dose price of US$ 13.45 and evidence from the scientific literature to estimate vaccine effectiveness. National information was used to estimate health service utilization and costs of cervical cancer treatment. All costs and health benefits were discounted at 3%. RESULTS: Upon fully vaccinating 86,906 11-year old girls, 2250 (undiscounted) cervical cancer cases and 1336 (undiscounted) deaths would be prevented over the lifetime of the cohort. After discounting future health benefits at 3% per year, the equivalent cases and deaths prevented were 421 and 170. HPV vaccination is estimated to cost around US$ 5 million per vaccinated cohort, but this would be offset by around US$ 1 million in avoided costs borne by the government to treat cervical cancer. Furthermore, 4349 discounted disability adjusted life years (DALYs) could be avoided at a cost of US$ 926 per DALY avoided, making HPV vaccination in Honduras a highly cost-effective intervention. DISCUSSION: The net cost of HPV vaccination per DALY avoided is less than the WHO threshold for cost-effectiveness. However, at a cost of around US$ 5 million per vaccinated cohort, an important element to consider in this discussion is the budgetary implications that the introduction of the HPV vaccine would cause for the country. CONCLUSIONS: When comparing the costs and benefits of HPV vaccine introduction in Honduras, it is clear that this intervention would be highly cost-effective and that the intervention would greatly reduce cervical cancer disease. For these reasons, it is in the country's best interest to explore financing opportunities that could support the vaccine's introduction.

ProVac Global Initiative: a vision shaped by ten years of supporting evidence-based policy decisions.

INTRODUCTION: The Pan American Health Organization (PAHO) created the ProVac Initiative in 2004 with the goal of strengthening national technical capacity to make evidence-based decisions on new vaccine introduction, focusing on economic evaluations. In view of the 10th anniversary of the ProVac Initiative, this article describes its progress and reflects on lessons learned to guide the next phase. METHODS: We quantified the output of the Initiative's capacity-building efforts and critically assess its progress toward achieving the milestones originally proposed in 2004. Additionally, we reviewed how country studies supported by ProVac have directly informed and strengthened the deliberations around new vaccine introduction. RESULTS: Since 2004, ProVac has conducted four regional workshops and supported 24 health economic analyses in 15 Latin American and Caribbean countries. Five Regional Centers of Excellence were funded, resulting in six operational research projects and nine publications. Twenty four decisions on new vaccine introductions were supported with ProVac studies. Enduring products include the TRIVAC and CERVIVAC cost-effectiveness models, the COSTVAC program costing model, methodological guides, workshop training materials and the OLIVES on-line data repository. Ten NITAGs were strengthened through ProVac activities. DISCUSSION: The evidence accumulated suggests that initiatives with emphasis on sustainable training and direct support for countries to generate evidence themselves, can help accelerate the introduction of the most valuable new vaccines. International and Regional Networks of Collaborators are necessary to provide technical support and tools to national teams conducting analyses. Timeliness, integration, quality and country ownership of the process are four necessary guiding principles for national economic evaluations to have an impact on policymaking. It would be an asset to have a model that offers different levels of complexity to choose from depending on the vaccine being evaluated, the availability of data, and the time frame of the decision. CONCLUSION: Decision support for new vaccine introduction in low- and middle-income countries is critical to maximizing the efficiency and impact of vaccination programs. Global technical cooperation will be required. In the future, PAHO and WHO have an opportunity to expand the reach of the ProVac philosophy, models, and methods to additional regions and countries requiring real-time support. The ProVac Global Initiative is proposed as an effective mechanism to do so.

Examining the cost of delivering routine immunization in Honduras.

BACKGROUND: Many countries have introduced new vaccines and expanded their immunization programs to protect additional risk groups, thus raising the cost of routine immunization delivery. Honduras recently adopted two new vaccines, and the country continues to broaden the reach of its program to adolescents and adults. In this article, we estimate and examine the economic cost of the Honduran routine immunization program for the year 2011. METHODS: The data were gathered from a probability sample of 71 health facilities delivering routine immunization, as well as 8 regional and 1 central office of the national immunization program. Data were collected on vaccinations delivered, staff time dedicated to the program, cold chain equipment and upkeep, vehicle use, infrastructure, and other recurrent and capital costs at each health facility and administrative office. Annualized economic costs were estimated from a modified societal perspective and reported in 2011 US dollars. RESULTS: With the addition of rotavirus and pneumococcal conjugate vaccines, the total cost for routine immunization delivery in Honduras for 2011 was US$ 32.5 million. Vaccines and related supplies accounted for 23% of the costs. Labor, cold chain, and vehicles represented 54%, 4%, and 1%, respectively. At the facility level, the non-vaccine system costs per dose ranged widely, from US$ 25.55 in facilities delivering fewer than 500 doses per year to US$ 2.84 in facilities with volume exceeding 10,000 doses per year. Cost per dose was higher in rural facilities despite somewhat lower wage rates for health workers in these settings; this appears to be driven by lower demand for services per health worker in sparsely populated areas, rather than increased cost of outreach. CONCLUSIONS: These more-precise estimates of the operational costs to deliver routine immunizations provide program managers with important information for mobilizing resources to help sustain the program and for improving annual planning and budgeting as well as longer-term resource allocation decisions.

Cost-effectiveness analysis of 10- and 13-valent pneumococcal conjugate vaccines in Peru.

OBJECTIVE: To evaluate the cost-effectiveness of introducing the 10-valent pneumococcal conjugate vaccine (PCV10) versus the 13-valent PCV (PCV13) to the National Immunization Schedule in Peru for prevention of pneumococcal disease (PD) in children <5 years of age. METHODS: The integrated TRIVAC vaccine cost-effectiveness model from the Pan American Health Organization's ProVac Initiative (version 2.0) was applied from the perspective of the Government of Peru. Twenty successive cohorts of children from birth to 5 years were evaluated. Clinical outcomes were pneumococcal pneumonia (PP), pneumococcal meningitis (PM), pneumococcal sepsis (PS) and acute otitis media from any causes (AOM). Measures included prevention of cases, neurological sequelae (NS), auditory sequelae (AS), deaths and disability adjusted life years (DALYs). A sensitivity analyses was also performed. FINDINGS: For the 20 cohorts, net costs with PCV10 and PCV13 were US$ 363.26 million and US$ 408.26 million, respectively. PCV10 prevented 570,273 AOM; 79,937 PP; 2217 PM; 3049 PS; 282 NS; 173 AS; and 7512 deaths. PCV13 prevented 419,815 AOM; 112,331 PN; 3116 PM; 4285 PS; 404 NS; 248 AS; and 10,386 deaths. Avoided DALYs were 226,370 with PCV10 and 313,119 with PCV13. Saved treatment costs were US$ 37.39 million with PCV10 and US$ 47.22 million with PCV13. Costs per DALY averted were US$ 1605 for PCV10, and US$ 1304 for PCV13. Sensitivity analyses showed similar results. PCV13 has an extended dominance over PCV10. CONCLUSION: Both pneumococcal vaccines are cost effective in the Peruvian context. Although the net cost of vaccination with PCV10 is lower, PCV13 prevented more deaths, pneumococcal complications and sequelae. Costs per each prevented DALY were lower with PCV13. Thus, PCV13 would be the preferred policy; PCV10 would also be reasonable (and cost-saving relative to the status quo) if for some reason 13-valent were not feasible.

Progress in the establishment and strengthening of national immunization technical advisory groups: analysis from the 2013 WHO/UNICEF joint reporting form, data for 2012.

The majority of industrialized and some developing countries have established National Immunization Technical Advisory Groups (NITAGs). To enable systematic global monitoring of the existence and functionality of NITAGs, in 2011, WHO and UNICEF included related questions in the WHO/UNICEF Joint Reporting Form (JRF) that provides an official means to globally collect indicators of immunization program performance. These questions relate to six basic process indicators. According to the analysis of the 2013 JRF, data for 2012, notable progress was achieved between 2010 and 2012 and by the end of 2012, 99 countries (52%) reported the existence of a NITAG with a formal legislative or administrative basis (with a high of 86% in the Eastern Mediterranean Region - EMR), among the countries that reported data in the NITAG section of the JRF. There were 63 (33%) countries with a NITAG that met six process indicators (47% increase over the 43 reported in 2010) including a total of 38 developing countries. 11% of low income countries reported a NITAG that meets all six process criteria, versus 29% of middle income countries and 57% of the high income ones. Countries with smaller populations reported the existence of a NITAG that meets all six process criteria less frequently than more populated countries (23% for less populated countries versus 43% for more populated ones). However, progress needs to be accelerated to reach the Global Vaccine Action Plan (GVAP) target of ensuring all countries have support from a NITAG. The GVAP represents a major opportunity to boost the institutionalization of NITAGs. A special approach needs to be explored to allow small countries to benefit from sub-regional or other countries advisory groups.

Monitoring of progress in the establishment and strengthening of national immunization technical advisory groups.

The majority of industrialized and some developing countries have established technical advisory bodies to guide and formulate national immunization policies and strategies. These are referred to as National Immunization Technical Advisory Groups (NITAGs), WHO and its partners have placed a high priority on assisting in the establishment or strengthening of functional, sustainable, and independent NITAGs. To enable systematic global monitoring of the existence and functionality of NITAGs, in 2010, WHO and UNICEF included related questions in the WHO-UNICEF Joint Reporting Form (JRF) that provides an official means for WHO and UNICEF to collect indicators of immunization programme performance. This paper presents the status of NITAGs based on the analysis of the 2010 JRF. Although 115 countries (64% of responders) reported having a NITAG in 2010, only 50% of countries reported the existence of a NITAG with a formal administrative or legislative basis. Despite limitations in the ability to compare 2010 JRF data with that from a 2008 global survey, it appears that substantial progress has been achieved globally over with 43 committees reporting affirmatively about six NITAG process indicators, compared with 23 in the 2008 survey. Impressive progress has been observed in the proportion of countries reporting NITAGs with formal terms of reference (24% increase), a legislative or administrative basis (10% increase), and a requirement for members to disclose their interests (14% increase). Some of the poorest developing countries now enjoy support from a NITAG which meet all six process indicators. These may serve as examples for other countries.