Vaccine value profile for cytomegalovirus.

Cytomegalovirus (CMV) is the most common infectious cause of congenital malformation and a leading cause of developmental disabilities such as sensorineural hearing loss (SNHL), motor and cognitive deficits. The significant disease burden from congenital CMV infection (cCMV) led the US National Institute of Medicine to rank CMV vaccine development as the highest priority. An average of 6.7/1000 live births are affected by cCMV, but the prevalence varies across and within countries. In contrast to other congenital infections such as rubella and toxoplasmosis, the prevalence of cCMV increases with CMV seroprevalence rates in the population. The true global burden of cCMV disease is likely underestimated because most infected infants (85-90 %) have asymptomatic infection and are not identified. However, about 7-11 % of those with asymptomatic infection will develop SNHL throughout early childhood. Although no licensed CMV vaccine exists, several candidate vaccines are in development, including one currently in phase 3 trials. Licensure of one or more vaccine candidates is feasible within the next five years. Various models of CMV vaccine strategies employing different target populations have shown to provide substantial benefit in reducing cCMV. Although CMV can cause end-organ disease with significant morbidity and mortality in immunocompromised individuals, the focus of this vaccine value profile (VVP) is on preventing or reducing the cCMV disease burden. This CMV VVP provides a high-level, comprehensive assessment of the currently available data to inform the potential public health, economic, and societal value of CMV vaccines. The CMV VVP was developed by a working group of subject matter experts from academia, public health groups, policy organizations, and non-profit organizations. All contributors have extensive expertise on various elements of the CMV VVP and have described the state of knowledge and identified the current gaps. The VVP was developed using only existing and publicly available information.

Defining hard-to-reach populations for vaccination.

Extending the benefits of vaccination to everyone who is eligible requires an understanding of which populations current vaccination efforts have struggled to reach. A clear definition of "hard-to-reach" populations - also known as high-risk or marginalized populations, or reaching the last mile - is essential for estimating the size of target groups, sharing lessons learned based on consistent definitions, and allocating resources appropriately. A literature review was conducted to determine what formal definitions of hard-to-reach populations exist and how they are being used, and to propose definitions to consider for future use. Overall, we found that (1) there is a need to distinguish populations that are hard to reach versus hard to vaccinate, and (2) the existing literature poorly defined these populations and clear criteria or thresholds for classifying them were missing. Based on this review, we propose that hard-to-reach populations be defined as those facing supply-side barriers to vaccination due to geography by distance or terrain, transient or nomadic movement, healthcare provider discrimination, lack of healthcare provider recommendations, inadequate vaccination systems, war and conflict, home births or other home-bound mobility limitations, or legal restrictions. Although multiple mechanisms may apply to the same population, supply-side barriers should be distinguished from demand-side barriers. Hard-to-vaccinate populations are defined as those who are reachable but difficult to vaccinate due to distrust, religious beliefs, lack of awareness of vaccine benefits and recommendations, poverty or low socioeconomic status, lack of time to access available vaccination services, or gender-based discrimination. Further work is needed to better define hard-to-reach populations and delineate them from populations that may be hard to vaccinate due to complex refusal reasons, improve measurement of the size and importance of their impact, and examine interventions related to overcoming barriers for each mechanism. This will enable policy makers, governments, donors, and the vaccine community to better plan interventions and allocate necessary resources to remove existing barriers to vaccination.

Economic value of vaccinating geographically hard-to-reach populations with measles vaccine: A modeling application in Kenya.

BACKGROUND: Since special efforts are necessary to vaccinate people living far from fixed vaccination posts, decision makers are interested in knowing the economic value of such efforts. METHODS: Using our immunization geospatial information system platform and a measles compartment model, we quantified the health and economic value of a 2-dose measles immunization outreach strategy for children <24 months of age in Kenya who are geographically hard-to-reach (i.e., those living outside a specified catchment radius from fixed vaccination posts, which served as a proxy for access to services). FINDINGS: When geographically hard-to-reach children were not vaccinated, there were 1427 total measles cases from 2016 to 2020, resulting in $9.5 million ($3.1-$18.1 million) in direct medical costs and productivity losses and 7504 (3338-12,903) disability-adjusted life years (DALYs). The outreach strategy cost $76 ($23-$142)/DALY averted (compared to no outreach) when 25% of geographically hard-to-reach children received MCV1, $122 ($40-$226)/DALY averted when 50% received MCV1, and $274 ($123-$478)/DALY averted when 100% received MCV1. CONCLUSION: Outreach vaccination among geographically hard-to-reach populations was highly cost-effective in a wide variety of scenarios, offering support for investment in an effective outreach vaccination strategy.

Cost-effectiveness of inactivated seasonal influenza vaccination in a cohort of Thai children ≤60 months of age.

BACKGROUND: Vaccination is the best measure to prevent influenza. We conducted a cost-effectiveness evaluation of trivalent inactivated seasonal influenza vaccination, compared to no vaccination, in children ≤60 months of age participating in a prospective cohort study in Bangkok, Thailand. METHODS: A static decision tree model was constructed to simulate the population of children in the cohort. Proportions of children with laboratory-confirmed influenza were derived from children followed weekly. The societal perspective and one-year analytic horizon were used for each influenza season; the model was repeated for three influenza seasons (2012-2014). Direct and indirect costs associated with influenza illness were collected and summed. Cost of the trivalent inactivated seasonal influenza vaccine (IIV3) including promotion, administration, and supervision cost was added for children who were vaccinated. Quality-adjusted life years (QALY), derived from literature, were used to quantify health outcomes. The incremental cost-effectiveness ratio (ICER) was calculated as the difference in the expected total costs between the vaccinated and unvaccinated groups divided by the difference in QALYs for both groups. RESULTS: Compared to no vaccination, IIV3 vaccination among children ≤60 months in our cohort was not cost-effective in the introductory year (2012 season; 24,450 USD/QALY gained), highly cost-effective in the 2013 season (554 USD/QALY gained), and cost-effective in the 2014 season (16,200 USD/QALY gained). CONCLUSION: The cost-effectiveness of IIV3 vaccination among children participating in the cohort study varied by influenza season, with vaccine cost and proportion of high-risk children demonstrating the greatest influence in sensitivity analyses. Vaccinating children against influenza can be economically favorable depending on the maturity of the program, influenza vaccine performance, and target population.