Informe especial: Coberturas de vacunación en residentes de la CABA en contexto Covid-19: 2 de octubre de 2020 / Special report: Vaccination coverage in CABA residents in context of Covid19

La vacunación es considerada una actividad esencial durante la pandemia de COVID-19 y se han desarrollado diferentes estrategias para el sostenimiento de la vacunación en el contexto actual, facilitar el acceso a través de la adaptación y reorganización de los servicios de salud, el no requerimiento de permisos de circulación para la vacunación, vacunación en instituciones fuera de salud, así como la elaboración de recomendaciones para realizar la vacunación de manera segura protegiendo tanto al vacunador como la persona a vacunar, entre otros. Con el objetivo de realizar la medición del impacto en las actividades de vacunación, se realiza el análisis comparativo de las vacunas aplicadas durante el primer semestre de los años 2018-2020, con la información recibida en el nivel central del Programa de Inmunizaciones. Se excluye del presente análisis la información referida a la vacuna antigripal ya que tiene una modalidad diferente de aplicación. (AU)

'It takes two to tango': Bridging the gap between country need and vaccine product innovation.

BACKGROUND: Despite a growing global commitment to universal health coverage, considerable vaccine coverage and uptake gaps persist in resource-constrained settings. One way of addressing the gaps is by ensuring product innovation is relevant and responsive to the needs of these contexts. Total Systems Effectiveness (TSE) framework has been developed to characterize preferred vaccine attributes from the perspective of country decision-makers to inform research and development (R&D) of products. A proof of concept pilot study took place in Thailand in 2018 to examine the feasibility and usefulness of the TSE approach using a rotavirus hypothetical test-case. METHODS: The excel-based model used multiple-criteria decision analysis (MCDA) to compare and evaluate five hypothetical rotavirus vaccine products. The model was populated with local data and products were ranked against decision criteria identified by Thai stakeholders. A one-way sensitivity analysis was performed to identify criteria that influenced vaccine ranking. Self-assessment forms were distributed to R&D stakeholders on the usability of the approach and were subsequently analysed. RESULTS: The model identified significant parameters that impacted on MCDA rankings. Self-assessment forms revealed that TSE was perceived as being able to encourage closer collaboration between country decision makers and vaccine developers. CONCLUSIONS: The pilot study demonstrates that it is feasible to use an MCDA approach to elicit stakeholder preferences and determine influential parameters to help identify the preferred product characteristics for R&D from the perspective of country decision-makers. It found that TSE can help steer manufacturers to develop products that are better aligned with country need. Findings will guide further development of the TSE concept.

The potential effects of introducing microneedle patch vaccines into routine vaccine supply chains.

BACKGROUND: Microneedle patch (MNP) technology is designed to simplify the process of vaccine administration; however, depending on its characteristics, MNP technology may provide additional benefits beyond the point-of-use, particularly for vaccine supply chains. METHODS: Using the HERMES modeling software, we examined replacing four routine vaccines - Measles-containing vaccine (MCV), Tetanus toxoid (TT), Rotavirus (Rota) and Pentavalent (Penta) - with MNP versions in the routine vaccine supply chains of Benin, Bihar (India), and Mozambique. RESULTS: Replacing MCV with an MNP (5 cm3-per-dose, 2-month thermostability, current single-dose price-per-dose) improved MCV availability by 13%, 1% and 6% in Benin, Bihar and Mozambique, respectively, and total vaccine availability by 1% in Benin and Mozambique, while increasing the total cost per dose administered by $0.07 in Benin, $0.56 in Bihar and $0.11 in Mozambique. Replacing TT with an MNP improved TT and total vaccine availability (3% and <1%) in Mozambique only, when the patch was 5 cm3 and 2-months thermostable but increased total cost per dose administered by $0.14. Replacing Rota with an MNP (at 5-15 cm3-per-dose, 1-2 month thermostable) improved Rota and total vaccine availability, but only improved Rota vaccine availability in Bihar (at 5 cm3, 1-2 months thermostable), while decreasing total vaccine availability by 1%. Finally, replacing Penta with an MNP (at 5 cm3, 2-months thermostable) improved Penta vaccine availability by 1-8% and total availability by <1-9%. CONCLUSIONS: An MNP for MCV, TT, Rota, or Penta would need to have a smaller or equal volume-per-dose than existing vaccine formulations and be able to be stored outside the cold chain for a continuous period of at least two months to provide additional benefits to all three supply chains under modeled conditions.

Economic impact of thermostable vaccines.

BACKGROUND: While our previous work has shown that replacing existing vaccines with thermostable vaccines can relieve bottlenecks in vaccine supply chains and thus increase vaccine availability, the question remains whether this benefit would outweigh the additional cost of thermostable formulations. METHODS: Using HERMES simulation models of the vaccine supply chains for the Republic of Benin, the state of Bihar (India), and Niger, we simulated replacing different existing vaccines with thermostable formulations and determined the resulting clinical and economic impact. Costs measured included the costs of vaccines, logistics, and disease outcomes averted. RESULTS: Replacing a particular vaccine with a thermostable version yielded cost savings in many cases even when charging a price premium (two or three times the current vaccine price). For example, replacing the current pentavalent vaccine with a thermostable version without increasing the vaccine price saved from $366 to $10,945 per 100 members of the vaccine's target population. Doubling the vaccine price still resulted in cost savings that ranged from $300 to $10,706, and tripling the vaccine price resulted in cost savings from $234 to $10,468. As another example, a thermostable rotavirus vaccine (RV) at its current (year) price saved between $131 and $1065. Doubling and tripling the thermostable rotavirus price resulted in cost savings ranging from $102 to $936 and $73 to $808, respectively. Switching to thermostable formulations was highly cost-effective or cost-effective in most scenarios explored. CONCLUSION: Medical cost and productivity savings could outweigh even significant price premiums charged for thermostable formulations of vaccines, providing support for their use.

Stability of live attenuated rotavirus vaccine with selected preservatives and primary containers.

Rotavirus infection, which can be prevented by vaccination, is responsible for a high burden of acute gastroenteritis disease in children, especially in low-income countries. An appropriate formulation, packaging, and delivery device for oral rotavirus vaccine has the potential to reduce the manufacturing cost of the vaccine and the logistical impact associated with introduction of a new vaccine, simplify the vaccination procedure, and ensure that the vaccine is safely and accurately delivered to children. Single-dose prefilled presentations can be easy to use; however, they are typically more expensive, can be a bottleneck during production, and occupy a greater volume per dose vis-à-vis supply chain storage and medical waste disposal, which is a challenge in low-resource settings. Multi-dose presentations used thus far have other issues, including increased wastage of vaccine and the need for separate delivery devices. In this study, the goals were to evaluate both the technical feasibility of using preservatives to develop a liquid multi-dose formulation and the primary packaging alternatives for orally delivered, liquid rotavirus vaccines. The feasibility evaluation included evaluation of commonly used preservatives for compatibility with rotavirus vaccines and stability testing of rotavirus vaccine in various primary containers, including Lameplast's plastic tubes, BD's oral dispenser version of Uniject™ (Uniject DP), rommelag's blow-fill-seal containers, and MEDInstill's multi-dose vial and pouch. These presentations were compared to a standard glass vial. The results showed that none of the preservatives tested were compatible with a live attenuated rotavirus vaccine because they had a detrimental effect on the viability of the virus. In the presence of preservatives, vaccine virus titers declined to undetectable levels within 1 month. The vaccine formulation without preservatives maintained a stability profile over 12 months in all primary containers that was similar to its profile in standard glass vials. This study demonstrates that there are multiple options for the primary container for rotavirus vaccines intended for oral delivery. Selection of an optimal primary container should take into consideration additional factors, including stability as well as cold chain volume, usability, cost, and manufacturing feasibility.

Calendario de vacunaciones de la Asociación Española de Pediatría: recomendaciones 2015 / Immunisation schedule of the Spanish Association of Paediatrics: 2015 Recommendations

El Comité Asesor de Vacunas de la Asociación Española de Pediatría actualiza anualmente su calendario de vacunaciones, tras un análisis tanto epidemiológico como de la seguridad, efectividad y eficiencia de las vacunas actuales, incluyendo grados de recomendación. Es el calendario que se estima idóneo actualmente para los niños residentes en España. En cuanto a las vacunas oficiales incluidas en el calendario común, se recalca la posibilidad de vacunar indistintamente frente a hepatitis B desde el nacimiento o desde los 2 meses; la recomendación de la primera dosis de triple vírica y de varicela a los 12 meses y la segunda a los 2-3 años; la administración de la vacuna DTPa o Tdpa a los 6 años, con refuerzo en la adolescencia; estrategias con Tdpa en embarazadas y convivientes del recién nacido, y la inmunización frente al papilomavirus en niñas a los 11-12 años con pauta de 2 dosis (0, 6 meses). Este comité insiste en la vacunación antineumocócica universal, tal y como se está llevando a cabo en todos los países de Europa Occidental. La vacuna frente al meningococo B, autorizada pero bloqueada actualmente en España, presenta un perfil de vacuna sistemática y se reivindica que, al menos, esté disponible en las farmacias comunitarias. Se propone, igualmente, la disponibilidad pública de las vacunas frente a la varicela, ya que han demostrado ser efectivas y seguras a partir del segundo año de vida. La vacunación frente al rotavirus es recomendable en todos los lactantes. La vacunación antigripal anual y la inmunización frente a la hepatitis A están indicadas en grupos de riesgo

The Advisory Committee on Vaccines of the Spanish Association of Paediatrics updates the immunisation schedule every year, taking into account epidemiological data as well as evidence on the safety, effectiveness and efficiency of current vaccines, including levels of recommendation. In our opinion, this is the optimal vaccination calendar for all children resident in Spain. Regarding the vaccines included in the official unified immunization schedule, the Committee emphasizes the administration of the first dose of hepatitis B either at birth or at 2 months of life; the recommendation of the first dose of MMR and varicella vaccine at the age of 12 months, with the second dose at the age of 2-3 years; DTaP or Tdap vaccine at the age of 6 years, followed by another Tdap booster dose at 11-12 years old; Tdap strategies for pregnant women and household contacts of the newborn, and immunization against human papillomavirus in girls aged 11-12 years old with a 2 dose scheme (0, 6 months). The Committee reasserts its recommendation to include vaccination against pneumococcal disease in the routine immunisation schedule, the same as it is being conducted in Western European countries. The recently authorised meningococcal B vaccine, currently blocked in Spain, exhibits the profile of a universal vaccine. The Committe insists on the need of having the vaccine available in communitary pharmacies. It has also proposed the free availability of varicella vaccines. Their efectiveness and safety have been confirmed when they are administred from the second year of life. Vaccination against rotavirus is recommended in all infants. The Committee stresses the need to vaccinate population groups considered at risk against influenza and hepatitis A

Rotavirus vaccines: successes and challenges.

Since 2006, the availability of two new rotavirus vaccines has raised enthusiasm to consider the eventual control and elimination of severe rotavirus diarrhea through the global use of vaccines. Rotavirus remains the most severe cause of acute diarrhea in children worldwide responsible for several hundred thousands of deaths in low income countries and up to half of hospital admissions for diarrhea around the world. The new vaccines have been recommended by WHO for all infants and in more than 47 countries, their introduction into routine childhood immunization programs has led to a remarkable decline in hospital admissions and even deaths within 3 years of introduction. Challenges remain with issues of vaccine finance globally and the problem that these live oral vaccines perform less well in low income settings where they are needed most. Ongoing research that will accompany vaccine introduction might help address these issues of efficacy and new vaccines and novel financing schemes may both help make these vaccines universally available and affordable in the decade.

National Vaccine Policy: ethical equity issues.

The ministry of health and family welfare published the national vaccination policy in April 2011. The policy document drew severe criticism from several public health experts. A review of the print and web-based literature on the national vaccine policy was done and the issues of ethics and equity involved in introducing new vaccines under the Universal Immunisation Programme (UIP) were studied. The average coverage of the UIP vaccines at the national level is below 50%. Despite this, the policy document did not state any concrete strategy for increasing the coverage. The main stumbling block for evidence-based vaccine policy in India is the lack of reliable epidemiological data, which makes it difficult for the National Technical Advisory Group on Immunisation to offer sound technical advice to the government. No attempts have been made to prioritise diseases or the selection of vaccines. The policy suggests the introduction of the following vaccines in the UIP: Haemophilus influenzae type b, pneumococcal vaccine, rotavirus vaccines and human papillomavirus (HPV). This selection is on the grounds of the vaccines' availability, not on the basis of epidemiological evidence or proven cost-effectiveness. This is a critical review of the current vaccination policy and the move to include the rotavirus and HPV vaccines in the UIP.

Distributional impact of rotavirus vaccination in 25 GAVI countries: estimating disparities in benefits and cost-effectiveness.

BACKGROUND: Other studies have demonstrated that the impact and cost effectiveness of rotavirus vaccination differs among countries, with greater mortality reduction benefits and lower cost-effectiveness ratios in low-income and high-mortality countries. This analysis combines the results of a country level model of rotavirus vaccination published elsewhere with data from Demographic and Health Surveys on within-country patterns of vaccine coverage and diarrhea mortality risk factors to estimate within-country distributional effects of rotavirus vaccination. The study examined 25 countries eligible for funding through the GAVI Alliance. METHODS: For each country we estimate the benefits and cost-effectiveness of vaccination for each wealth quintile assuming current vaccination patterns and for a scenario where vaccine coverage is equalized to the highest quintile's coverage. In the case of India, variations in coverage and risk proxies by state were modeled to estimate geographic distributional effects. RESULTS: In all countries, rates of vaccination were highest and risks of mortality were lowest in the top two wealth quintiles. However countries differ greatly in the relative inequities in these two underlying variables. Similarly, in all countries examined, the cost-effectiveness ratio for vaccination ($/Disability-Adjusted Life Year averted, DALY) is substantially greater in the higher quintiles (ranging from 2-10 times higher). In all countries, the greatest potential benefit of vaccination was in the poorest quintiles. However, due to reduced vaccination coverage, projected benefits for these quintiles were often lower. Equitable coverage was estimated to result in an 89% increase in mortality reduction for the poorest quintile and a 38% increase overall. CONCLUSIONS: Rotavirus vaccination is most cost-effective in low-income groups and regions. However in many countries, simply adding new vaccines to existing systems targets investments to higher income children, due to disparities in vaccination coverage. Maximizing health benefits for the poorest children and value for money require increased attention to these distributional effects.

Methodology and lessons-learned from the efficacy clinical trial of the pentavalent rotavirus vaccine in Bangladesh.

An efficacy clinical trial with pentavalent rotavirus vaccine (PRV), RotaTeq(®), was conducted at Matlab field site of ICDDR,B, Bangladesh from March 2007 to March 2009. The methodology, including operation logistics, and lessons-learned are described in this report. Vaccination was organized at 41 fixed-site clinics twice/month. A total of 1136 infants were randomized 1:1 to receive 3 doses of PRV/placebo at approximately 6-, 10-, and 14-weeks of age with routine vaccines of the Expanded Programme on Immunization (EPI) schedule. Twelve field-workers routinely visited study participants for safety and efficacy follow-up. The study was conducted following good clinical practices and maintaining cold-chain requirements. There were no temperature deviations of clinical vaccine supplies. Data entry was done using the source documents to a central database developed by the sponsor which was linked to web. Among enrolled infants, 1128 (99.3%) received 3 doses of PRV/placebo and efficacy follow-up was conducted for a median of 554 days. For the evaluation of immunogenicity, blood samples were collected from 150 participants predose 1 and from 147 (98%) of the same participants post dose 3. Stool samples were collected from 778 (99.9%) acute gastroenteritis episodes among children who reported to diarrhoea treatment centres. Thirty-nine serious adverse events, including 6 deaths, occurred among study participants. The efficacy of PRV against severe rotavirus gastroenteritis was 42.7% through the entire follow-up period; serum anti-rotavirus IgA response was 78.1%. Inclement weather, difficult transportation, and movement of study participants were some of the challenges identified. This is the first vaccine trial in rural Bangladesh with online data entry. The study was well accepted in the community and was completed successfully.

Use of formative research in developing a knowledge translation approach to rotavirus vaccine introduction in developing countries.

BACKGROUND: Rotavirus gastroenteritis is the leading cause of diarrheal disease mortality among children under five, resulting in 450,000 to 700,000 deaths each year, and another 2 million hospitalizations, mostly in the developing world. Nearly every child in the world is infected with rotavirus at least once before they are five years old. Vaccines to prevent rotavirus or minimize its severity are now becoming available, and have already been introduced into the public vaccine programs of several Latin American countries. The World Health Organization (WHO) has made rotavirus vaccine introduction in developing countries a high priority. The WHOs Guidelines for Vaccine Introduction indicates that a key determinant to achieving vaccine introduction is the public health priority of the disease, suggesting that where the disease is not a priority uptake of the vaccine is unlikely. WHO recommends conducting a qualitative analysis of opinions held by the public health community to determine the perceptions of the disease and the priority given to the vaccine. METHODS: This paper presents the formative research results of a qualitative survey of public health providers in five low- and middle-income countries to determine if and to what degree rotavirus is perceived to be a problem and the priority of a vaccine. Open-ended surveys were carried out through focus group discussions and one-on-one interviews. RESULTS: Researchers discovered that in all five countries knowledge of rotavirus was extremely low, and as a result was not considered a high priority. However, diarrhea among young children was considered a high priority among public health providers in the three poorest countries with relatively high levels of child mortality: India, Indonesia, and Nicaragua. CONCLUSION: In the poorest countries, advocacy and communication efforts to raise awareness about rotavirus sufficient for prioritization and accelerated vaccine introduction might benefit from a knowledge translation approach that delivers information and evidence about rotavirus through the broader context of diarrheal disease control, an existing priority, and including information about other new interventions, specifically low-osmolarity oral rehydration solution and zinc treatment.