The impact of vaccine procurement methods on public health in selected European countries.

Introduction: Across Europe, immunization programs have brought immense benefits to the prevention of infectious diseases. The vaccines used are procured through a variety of models such as tenders and Pricing & Reimbursement. However, to date, the impact of the procurement method on the performance and sustainability of vaccination programs and on public health has received little attention.Areas covered: Drawing on a review of the academic and policy literature, complemented by an interview program with stakeholders involved in the procurement of vaccines, the authors have documented the relationship between procurement method dynamics and the level of protection against vaccine-preventable diseases in Germany, Italy, Spain and Romania for, measles-containing vaccines, hexavalent and influenza vaccines.Expert opinion: Price-based tenders can contribute to vaccine supply issues, discourage the provision of value-added services supporting vaccination coverage and disincentives future R&D. Although it is observed that price-based tenders can intensify competition in the short term, there can be unintended consequences such as damage to long-term competition. As European countries are committed to strengthen their immunization programs, they should consider the implications of current vaccine procurement models on the vaccine ecosystem and on public health.

Current situation, causes, and countermeasures to NIP vaccine shortages in Guangzhou, China.

From 2017 to 2018, Guangzhou experienced a shortage in 3-6 types of National Immunization Program (NIP) vaccines. To evaluate the current situation and causes of the NIP vaccine shortage, we analysed the duration, intensity and causes of the shortage from data in the vaccine information system of the Guangzhou Center for Disease Control and Prevention; we also proposed countermeasures to resolve the shortage. In 2017, there were shortages of three types of NIP vaccines in Guangzhou. The most affected vaccines were inactivated poliovirus (IPV) vaccine and meningococcal group AC (MenAC) vaccine, accounting for 39.5% and 16.5% of the reported shortages, respectively. In 2018, the shortage extended to six vaccine types; the most affected were diphtheria, tetanus and pertussis (DTP) vaccine, MenAC vaccine, and Bacille Calmette Guerin (BCG) vaccine. The four main causes for the shortage were: 1) an insufficient production capacity; 2) a delay in batch issuance; 3) vaccine-related events; and 4) an extended bidding procurement cycle. Four solutions are proposed: 1) expand production output; 2) exempt creditworthy enterprises from batch inspections; 3) establish alternative enterprises and emergency use authorizations; and 4) establish public health funds and stockpile storage systems.

A pilot study of a novel, incentivised mHealth technology to monitor the vaccine supply chain in rural Zambia.

INTRODUCTION: The World Health Organization estimates that up to half of vaccines are wasted, however only a minority of mHealth programs in Africa have been directed at vaccine supply chain optimisation. We piloted a novel mHealth solution dependent only on short message services (SMS) technology that allowed workers in rural health centres in Zambia to report vaccine stock levels directly to an online platform. Small airtime incentives were offered to encourage users to engage with the system, as well as weekly reminder messages asking for stock updates. METHODS: The primary outcome measured was the percentage-of-doses-tracked, calculated over the study period. Each vaccine box was randomly allocated to offer either a standard or double airtime incentive and either weekly or daily reminders, in a 2 x 2 design; ANOVA was used to calculate if any of these factors affected time-to-reply. RESULTS: Over the study period, the total percentage-of-doses-tracked was 39.9%. Within the subset of users who sent at least one message to the platform, the percentage-of-doses-tracked was 93.8%. There was no significant difference in average time-to-reply between the standard airtime incentive and double airtime incentive groups, nor was there a significant difference between the standard reminder and daily follow-up reminder groups. CONCLUSION: This pilot study found that in an active subgroup of health workers, an incentivised mHealth solution was able to collect tracking data for 93.8% of doses. More research is needed to identify methods to encourage healthcare workers to engage in timely stock reporting practices.

Assessing the quality and accuracy of national immunization program reported target population estimates from 2000 to 2016.

BACKGROUND: A common means of vaccination coverage measurement is the administrative method, done by dividing the aggregated number of doses administered over a set period (numerator) by the target population (denominator). To assess the quality of national target populations, we defined nine potential denominator data inconsistencies or flags that would warrant further exploration and examination of data reported by Member States to the World Health Organization (WHO) and UNICEF between 2000 and 2016. METHODS AND FINDINGS: We used the denominator reported to calculate national coverage for BCG, a tuberculosis vaccine, and for the third dose of diphtheria-tetanus-pertussis-containing (DTP3) vaccines, usually live births (LB) and surviving infants (SI), respectively. Out of 2,565 possible reporting events (data points for countries using administrative coverage with the vaccine in the schedule and year) for BCG and 2,939 possible reporting events for DTP3, 194 and 274 reporting events were missing, respectively. Reported coverage exceeding 100% was seen in 11% of all reporting events for BCG and in 6% for DTP3. Of all year-to-year percent differences in reported denominators, 12% and 11% exceeded 10% for reported LB and SI, respectively. The implied infant mortality rate, based on the country's reported LB and SI, would be negative in 9% of all reporting events i.e., the country reported more SI than LB for the same year. Overall, reported LB and SI tended to be lower than the UN Population Division 2017 estimates, which would lead to overestimation of coverage, but this difference seems to be decreasing over time. Other inconsistencies were identified using the nine proposed criteria. CONCLUSIONS: Applying a set of criteria to assess reported target populations used to estimate administrative vaccination coverage can flag potential quality issues related to the national denominators and may be useful to help monitor ongoing efforts to improve the quality of vaccination coverage estimates.

Mapping diphtheria-pertussis-tetanus vaccine coverage in Africa, 2000-2016: a spatial and temporal modelling study.

BACKGROUND: Routine childhood vaccination is among the most cost-effective, successful public health interventions available. Amid substantial investments to expand vaccine delivery throughout Africa and strengthen administrative reporting systems, most countries still require robust measures of local routine vaccine coverage and changes in geographical inequalities over time. METHODS: This analysis drew from 183 surveys done between 2000 and 2016, including data from 881 268 children in 49 African countries. We used a Bayesian geostatistical model calibrated to results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017, to produce annual estimates with high-spatial resolution (5 ×    5 km) of diphtheria-pertussis-tetanus (DPT) vaccine coverage and dropout for children aged 12-23 months in 52 African countries from 2000 to 2016. FINDINGS: Estimated third-dose (DPT3) coverage increased in 72·3% (95% uncertainty interval [UI] 64·6-80·3) of second-level administrative units in Africa from 2000 to 2016, but substantial geographical inequalities in DPT coverage remained across and within African countries. In 2016, DPT3 coverage at the second administrative (ie, district) level varied by more than 25% in 29 of 52 countries, with only two (Morocco and Rwanda) of 52 countries meeting the Global Vaccine Action Plan target of 80% DPT3 coverage or higher in all second-level administrative units with high confidence (posterior probability ≥95%). Large areas of low DPT3 coverage (≤50%) were identified in the Sahel, Somalia, eastern Ethiopia, and in Angola. Low first-dose (DPT1) coverage (≤50%) and high relative dropout (≥30%) together drove low DPT3 coverage across the Sahel, Somalia, eastern Ethiopia, Guinea, and Angola. INTERPRETATION: Despite substantial progress in Africa, marked national and subnational inequalities in DPT coverage persist throughout the continent. These results can help identify areas of low coverage and vaccine delivery system vulnerabilities and can ultimately support more precise targeting of resources to improve vaccine coverage and health outcomes for African children. FUNDING: Bill & Melinda Gates Foundation.

Hexavalent vaccines: characteristics of available products and practical considerations from a panel of Italian experts.

Combination vaccines represent a valuable technological innovation in the field of infectious disease prevention and public health, because of their great health and economic value from the individual, societal, and healthcare system perspectives. In order to increase parents' and healthcare professionals' confidence in the vaccination programs and maintain their benefits to society, more information about the benefits of innovative vaccination tools such as combination vaccines is needed. Purpose of this work is an examination of available hexavalent vaccines, that protect against Diphtheria, Tetanus, Pertussis, Poliomyelitis, Hepatitis B and Haemophilus influenzae type b infections. From the epidemiological updates of vaccine preventable diseases to the vaccine development cycle, from the immunogenicity of antigenic components to the safety and co-administration with other vaccines, several aspects of available hexavalent vaccines are discussed and deepened. Also a number of practical considerations on schedules, age of employment, strategies for vaccination recovery, vaccination in at-risk births are issued, based on the recommendations of Italian Ministry of Health, Italian Society of Pharmacology (SIF), Italian Society for Pediatrics (SIP), Italian Federation of Family Paediatricians (FIMP) and Italian Society of Hygiene, Preventive Medicine and Public Health (SItI).

Estimated costs attributable to events of "out-of-temperature" in the stockpiling of hexavalent vaccines occurring in Italy.

BACKGROUND: Antigens contained in vaccines are inherently unstable biologically; such a characteristic is conferred by their three-dimensional structure. Preserving the ability of the vaccines to protect against disease is necessary to ensure the supervision and monitoring of all steps of the cold chain. DTPa-HBV-IPV/Hib vaccine (Infanrix hexaTM, GSK Vaccines, Belgium) is designed to prevent disease due to diphtheria, tetanus, pertussis (DTP), hepatitis B virus (HBV), poliomyelitis and Haemophilus influenzae type b (Hib); it was first licensed for use in Europe in 2000 and is currently licensed in at least 95 countries. Since October 2013, more than 102 million doses of GSK's DTPa-HBV-IPV/Hib vaccine have been distributed globally, with nearly 15 million doses distributed in Italy. DTPa-HBV-IPV/Hib components are stable up to a temperature of 25°C for 72 hours. Lacking of officially approved stability data may generate some concern in case of cold chain accidents. METHODS: An analysis based on collected data was carried out to estimate potential costs attributable to events of "out-of-temperature" in the stockpiling of hexavalent vaccines occurring in Italy in 2014. RESULTS: The analysis, based on real data, documented that the loss for the National Health Service (NHS) was in the range of 100,000 - 400,000 euros in one year. However, the amount of money that in principle could have been lost would have ranged between nearly half and one million euros/year. CONCLUSIONS: A substantial loss of money was avoided thanks to the availability of officially approved stability data for GSK's DTPa-HBV-IPV/Hib vaccine.

Strengthening routine immunization systems to improve global vaccination coverage.

BACKGROUND: Global coverage with the third dose of diphtheria-tetanus-pertussis vaccine among children under 1 year of age stagnated at ∼ 83-84% during 2008-13. SOURCES OF DATA: Annual World Health Organization and UNICEF-derived national vaccination coverage estimates. AREAS OF AGREEMENT: Incomplete vaccination is associated with poor socioeconomic status, lower education, non-use of maternal-child health services, living in conflict-affected areas, missed immunization opportunities and cancelled vaccination sessions. AREAS OF CONTROVERSY: Vaccination platforms must expand to include older ages including the second year of life. Immunization programmes, including eradication and elimination initiatives such as those for polio and measles, must integrate within the broader health system. GROWING POINTS: The Global Vaccine Action Plan (GVAP) 2011-20 is a framework for strengthening immunization systems, emphasizing country ownership, shared responsibility, equity, integration, sustainability and innovation. AREAS TIMELY FOR DEVELOPING RESEARCH: Immunization programmes should identify, monitor and evaluate gaps and interventions within the GVAP framework.

Immunisation coverage and its associations in rural Tanzanian infants.

INTRODUCTION: In Tanzania, vaccination rates (VRs) range from 80% to 90% for standard vaccines, but little information is available about rural populations and nomadic pastoralists. This study investigates levels and trends of the immunisation status of infants at eight mobile reproductive-and-child-health (RCH) clinics in a rural area in northern Tanzania (with a large multi-tribal population that has a significant population of nomadic pastoralists) for the years 1998, 1999, 2006 and 2007. In addition, the influence of tribal affiliation and health system-related factors on the immunisation status in this population is analysed. METHODS: Vaccination data of 3868 infants for the standard bacillus Calmette-Guérin (BCG), poliomyelitis, diphtheria, pertussis, tetanus and measles vaccines were obtained from the RCH clinic records retrospectively, and coverage for both single vaccines and full vaccination by the end of first year of life were calculated. These results were correlated with data on predominant tribal affiliation at the clinic site, skilled attendance at birth, service provision and vaccine availability as independent variables. RESULTS: In 1998, the full vaccination rate (FVR) across all RCH clinics was 72%, significantly higher than in the other years (1999: 58%; 2006: 58%; 2007: 57%) (p<0.0001). BCG and measles VRs were highest in 1998 and 1999, whereas VR was lowest for poliomyelitis in 1999, and for diphtheria-pertussis-tetanus in 2007 (all p<0.001). Measles VR showed a declining trend (1998: 72%; 1999: 73%; 2006: 62%; 2007: 59%) affecting the FVR, except in 1999 when poliomyelitis VR was lower (67%). FVR > 80% was only achieved at one clinic during 3 years. No clinic showed a consistent increase of VRs over time. In univariate analysis, predominant tribal affiliation (Datoga tribe) was associated with a low FVR (odds ratio (OR) 4.6 (95% confidence interval (CI) 3.8-5.5)), as were low rates of skilled attendance at birth (OR 3.6 (CI 2.9-4.4)). Other health system-related factors associated with low FVRs included interruption of scheduled monthly immunisation clinics (OR 9.8 (CI 2.1-45.5)) and lack of vaccines (OR 1.2-2.9, depending on vaccine). In multivariate analysis, predominant Datoga tribal affiliation and lack of vaccines retained their association with the risk of low rates of vaccination. CONCLUSIONS: Vaccination rates in this difficult-to-reach population are markedly lower than the national average for almost all years and clinics. Affiliation to the nomadic Datoga tribe and lack of vaccines determine VRs in this rural population. Improvements in immunisation service delivery, vaccine availability, stronger involvement of the nomadic communities and special outreach services for this population are required to improve VRs in these remote areas of Tanzania.

Determining the optimal vaccine vial size in developing countries: a Monte Carlo simulation approach.

Outreach immunization services, in which health workers immunize children in their own communities, are indispensable to improve vaccine coverage in rural areas of developing countries. One of the challenges faced by these services is how to reduce high levels of vaccine wastage. In particular, the open vial wastage (OVW) that result from the vaccine doses remaining in a vial after a time for safe use -since opening the vial- has elapsed. This wastage is highly dependent on the choice of vial size and the expected number of participants for which the outreach session is planned (i.e., session size). The use single-dose vials results in zero OVW, but it increases the vaccine purchase, transportation, and holding costs per dose as compared to those resulting from using larger vial sizes. The OVW also decreases when more people are immunized in a session. However, controlling the actual number of people that show to an outreach session in rural areas of developing countries highly depends on factors that are out of control of the immunization planners. This paper integrates a binary integer-programming model to a Monte Carlo simulation method to determine the choice of vial size and the optimal reordering point level to implement an (nQ, r, T) lot-sizing policy that provides the best tradeoff between procurement costs and wastage.

Effectiveness of planning and management interventions for improving age-appropriate immunization in rural India.

OBJECTIVE: To study the effectiveness of planning and management interventions for ensuring children in India are immunized at the appropriate age. METHODS: The study involved children aged less than 18 months recruited from Haryana, India, in 2005-2006: 4336 in a pre-intervention cohort and 5213 in a post-intervention cohort. In addition, immunization of 814 hospitalized children from outside the study area was also assessed. Operational barriers to age-appropriate immunization with diphtheria, pertussis and tetanus (DPT) vaccine were investigated by monitoring vaccination coverage, observing immunization sessions and interviewing parents and health-care providers. An intervention package was developed, with community volunteers playing a pivotal role. Its effectiveness was assessed by monitoring the ages at which the three DPT doses were administered. FINDINGS: The main reasons for delayed immunization were staff shortages, non-adherence to plans and vaccine being out of stock. In the post-intervention cohort, 70% received a third DPT dose before the age of 6 months, significantly more than in the pre-intervention cohort (62%; P = 0.002). In addition, the mean age at which the first, second and third DPT doses were administered decreased by 17, 21 and 34 days, respectively, in the study area over a period of 18 months (P for trend < 0.0001). No change was observed in hospitalized children from outside the study area. CONCLUSION: An intervention package involving community volunteers significantly improved age-appropriate DPT immunization in India. The Indian Government's intention to recruit village-based volunteers as part of a health sector reform aimed at decentralizing administration could help increase timely immunization.

Design and simulation study of the immunization Data Quality Audit (DQA).

The goal of the Data Quality Audit (DQA) is to assess whether the Global Alliance for Vaccines and Immunization-funded countries are adequately reporting the number of diphtheria-tetanus-pertussis immunizations given, on which the "shares" are awarded. Given that this sampling design is a modified two-stage cluster sample (modified because a stratified, rather than a simple, random sample of health facilities is obtained from the selected clusters); the formula for the calculation of the standard error for the estimate is unknown. An approximated standard error has been proposed, and the first goal of this simulation is to assess the accuracy of the standard error. Results from the simulations based on hypothetical populations were found not to be representative of the actual DQAs that were conducted. Additional simulations were then conducted on the actual DQA data to better access the precision of the DQ with both the original and the increased sample sizes.

Will more inputs improve the delivery of health services? Analysis of district vaccination coverage in Pakistan.

In order to determine whether physical resources or technical inputs can make a difference to the delivery of health services, we carried out a study that examined the large variation in district level vaccination coverage in Pakistan. Vaccination coverage was assessed by district-wise cluster surveys and the predictor variables were collected from census data and from a survey of 99 district health offices. Information was collected on basic supplies, physical infrastructure, management, training, socio-economic variables, and a variety of other indicators. Univariate and multivariate analyses were carried out. A model including female literacy rate, TV ownership, and provincial dummies explained 48% of the variation in DTP3 coverage. Very few of the other variables examined were significantly correlated to coverage. Possible explanatory variables like adequacy of syringe and vaccine supply, the number of vaccinators per capita, recent training of managers, frequency of supervision, availability of micro-plans, and turnover of managers were not correlated with coverage. While the Government of Pakistan has ensured that many physical resources and technical inputs have been provided to the district health offices, this does not appear able to explain the relatively low overall coverage or the variation between districts. Bolder initiatives and innovations are likely needed to improve delivery of basic health services.

Impact of vaccine economic programs on physician referral of children to public vaccine clinics: a pre-post comparison.

BACKGROUND: The Vaccines for Children (VFC) Program is a major vaccine entitlement program with limited long-term evaluation. The objectives of this study are to evaluate the effect of VFC on physician reported referral of children to public health clinics and on doses administered in the public sector. METHODS: Minnesota and Pennsylvania primary care physicians (n = 164), completed surveys before (e.g., 1993) and after (2003) VFC, rating their likelihood on a scale of 0 (very unlikely) to 10 (very likely) of referring a child to the health department for immunization. RESULTS: The percentage of respondents likely to refer was 60% for an uninsured child, 14% for a child with Medicaid, and 3% for a child with insurance that pays for immunization. Half (55%) of the physicians who did not participate in VFC were likely to refer a Medicaid-insured child, as compared with 6% of those who participated (P < 0.001). Physician likelihood to refer an uninsured child for vaccination, measured on a scale of 0 to 10 where 10 is very likely, decreased by a mean difference of 1.9 (P < 0.001) from pre- to post-VFC. The likelihood to refer a Medicaid-insured child decreased by a mean of 1.2 (P = 0.001). CONCLUSION: Reported out-referral to public clinics decreased over time. In light of increasing immunizations rates, this suggests that more vaccines were being administered in private provider offices.

Determinants of health status and the influence of primary health care services in Latin America, 1990-98.

Primary health care (PHC) services have been advocated as a means by which less developed countries may improve the health of their populations even in the face of poverty, low levels of literacy, poor nutrition and other factors that negatively influence health status. Using aggregated data from the World Bank and UNICEF this study examined which factors, both within the health care system and outside of it, are associated with under-5 mortality rates in 22 countries of Latin America and the Caribbean during the 1990s. In a multivariate analysis using generalized estimating equations for repeated measures, five factors were found to be independent predictors of lower under-5 mortality rates (U5MRs). These were vaccination levels, female literacy, the use of oral rehydration therapy, access to safe water and GNP per capita. When the magnitude of these associations were assessed, higher levels of GNP per capita was found to be very weakly associated with lower U5MRs, compared with female literacy and vaccination rates. These findings suggest that government policies which focus only on promoting economic growth, while not making important investments in PHC services, female education and access to safe water are unlikely to see large improvements in health status.