Accelerating the Development of Measles and Rubella Microarray Patches to Eliminate Measles and Rubella: Recent Progress, Remaining Challenges.

Measles and rubella microarray patches (MR-MAPs) are critical in achieving measles and rubella eradication, a goal highly unlikely to meet with current vaccines presentations. With low commercial incentive to MAP developers, limited and uncertain funding, the need for investment in a novel manufacturing facility, and remaining questions about the source of antigen, product demand, and regulatory pathway, MR-MAPs are unlikely to be prequalified by WHO and ready for use before 2033. This article describes the current progress of MR-MAPs, highlights challenges and opportunities pertinent to MR-MAPs manufacturing, regulatory approval, creating demand, and timelines to licensure. It also describes activities that are being undertaken by multiple partners to incentivise investment in and accelerate the development of MR-MAPs.

The Operational Feasibility of Vaccination Programs Targeting Influenza Risk Groups in the World Health Organization (WHO) African and South-East Asian Regions.

BACKGROUND: Influenza vaccination is uncommon in low-resource settings. We evaluated aspects of operational feasibility of influenza vaccination programs targeting risk groups in the World Health Organization (WHO) African (AFR) and South-East Asian (SEAR) Regions. METHODS: We estimated routine immunization and influenza vaccination campaign doses, doses per vaccinator, and cold storage requirements for 1 simulated country in each region using evidence-based population distribution, vaccination schedule, and vaccine volumes. Influenza vaccination targeted persons <5 years, pregnant women, persons with chronic diseases, persons ≥65 years, and healthcare workers (HCW). For the AFR country, we compared vaccine volumes to actual storage capacities. RESULTS: Targeting HCW had a small operational impact, and subsequent findings exclude this group. During 3-month influenza vaccination campaigns, monthly doses delivered in the AFR country increased from 15.0% for ≥65 years to 93.1% for <5 years and in the SEAR country from 19.6% for pregnant women to 145.0% for persons with chronic diseases. National-level cold storage capacity requirements increased in the AFR country from 4.1% for ≥65 years to 20.3% for <5 years and in the SEAR country from 3.9% for pregnant women to 28.8% for persons with chronic diseases. Subnational-level cold storage capacity requirements increased in the AFR country from 5.9% for ≥65 years to 36.8% for <5 years and the SEAR country from 17.6% for pregnant women to 56.0% for persons with chronic diseases. CONCLUSIONS: Influenza vaccination of most risk groups will require substantial increases in doses, doses per vaccinator, and cold storage capacity in countries where infrastructure and resources are limited.

Estimating the future global dose demand for measles-rubella microarray patches.

Background: Progress toward measles and rubella (MR) elimination has stagnated as countries are unable to reach the required 95% vaccine coverage. Microarray patches (MAPs) are anticipated to offer significant programmatic advantages to needle and syringe (N/S) presentation and increase MR vaccination coverage. A demand forecast analysis of the programmatic doses required (PDR) could accelerate MR-MAP development by informing the size and return of the investment required to manufacture MAPs. Methods: Unconstrained global MR-MAP demand for 2030-2040 was estimated for three scenarios, for groups of countries with similar characteristics (archetypes), and four types of uses of MR-MAPs (use cases). The base scenario 1 assumed that MR-MAPs would replace a share of MR doses delivered by N/S, and that MAPs can reach a proportion of previously unimmunised populations. Scenario 2 assumed that MR-MAPs would be piloted in selected countries in each region of the World Health Organization (WHO); and scenario 3 explored introduction of MR-MAPs earlier in countries with the lowest measles vaccine coverage and highest MR disease burden. We conducted sensitivity analyses to measure the impact of data uncertainty. Results: For the base scenario (1), the estimated global PDR for MR-MAPs was forecasted at 30 million doses in 2030 and increased to 220 million doses by 2040. Compared to scenario 1, scenario 2 resulted in an overall decrease in PDR of 18%, and scenario 3 resulted in a 21% increase in PDR between 2030 and 2040. Sensitivity analyses revealed that assumptions around the anticipated reach or coverage of MR-MAPs, particularly in the hard-to-reach and MOV populations, and the market penetration of MR-MAPs significantly impacted the estimated PDR. Conclusions: Significant demand is expected for MR-MAPs between 2030 and 2040, however, efforts are required to address remaining data quality, uncertainties and gaps that underpin the assumptions in this analysis.

The potential effects of deploying SARS-Cov-2 vaccines on cold storage capacity and immunization workload in countries of the WHO African Region.

BACKGROUND: SARS-CoV-2 vaccines will be deployed to countries with limited immunization systems. METHODS: We assessed the effect of deploying SARS-Cov-2 vaccines on cold storage capacity and immunization workload in a simulated WHO African Region country using region-specific data on immunization, population, healthcare workers (HCWs), cold storage capacity (quartile values for national and subnational levels), and characteristics of an approved SARS-CoV-2 vaccine. We calculated monthly increases in vaccine doses, doses per vaccinator, and cold storage volumes for four-month SARS-CoV-2 vaccination campaigns targeting risk groups compared to routine immunization baselines. RESULTS: Administering SARS-CoV-2 vaccines to risk groups would increase total monthly doses by 27.0% for ≥ 65 years, 91.7% for chronic diseases patients, and 1.1% for HCWs. Assuming median nurse density estimates adjusted for absenteeism and proportion providing immunization services, SARS-CoV-2 vaccination campaigns would increase total monthly doses per vaccinator by 29.3% for ≥ 65 years, 99.6% for chronic diseases patients, and 1.2% for HCWs. When we applied quartiles of actual African Region country vaccine storage capacity, routine immunization vaccine volumes exceeded national-level storage capacity for at least 75% of countries, but subnational levels had sufficient storage capacity for SARS-CoV-2 vaccines for at least 75% of countries. CONCLUSIONS: In the WHO African Region, SARS-CoV-2 vaccination campaigns would substantially increase doses per vaccinator and cold storage capacity requirements over routine immunization baselines. Pandemic vaccination campaigns would increase storage requirements of national-level stores already at their limits, but sufficient capacity exists at subnational levels. Immediate attention to strengthening immunization systems is essential to support pandemic responses.

The operational impact of deploying SARS-CoV-2 vaccines in countries of the WHO African Region.

BACKGROUND: When available, SARS-CoV-2 vaccines will be deployed to countries with limited immunization systems. METHODS: We conducted an immunization capacity assessment of a simulated WHO African Region country using region-specific data on immunization, population, healthcare workers (HCWs), vaccine cold storage capacity (quartile values for national and subnational levels), and characteristics of influenza vaccines to represent future SARS-CoV-2 vaccines. We calculated monthly increases in vaccine doses, doses per vaccinator, and cold storage volumes for four-month SARS-CoV-2 vaccination campaigns targeting risk groups compared to routine immunization baselines. FINDINGS: Administering SARS-CoV-2 vaccines to risk groups would increase total monthly doses by 27.0% for ≥65 years, 91.7% for chronic diseases patients, and 1.1% for HCWs. Assuming median nurse density estimates adjusted for absenteeism and proportion providing immunization services, SARS-CoV-2 vaccination campaigns would increase total monthly doses per vaccinator by 29.3% for ≥65 years, 99.6% for chronic diseases patients, and 1.2% for HCWs. When we applied quartiles of actual African Region country vaccine storage capacity, routine immunization vaccine volumes exceeded national-level storage capacity for at least 75% of countries, but subnational levels had sufficient storage capacity for SARS-CoV-2 vaccines for at least 75% of countries. INTERPRETATION: In the WHO African Region, SARS-CoV-2 vaccination campaigns would substantially increase doses per vaccinator and cold chain capacity requirements over routine immunization baselines. Pandemic vaccination campaigns would add volume to national-level stores already at their limits, but sufficient capacity exists at subnational levels. Immediate attention to strengthening immunization systems is essential to support pandemic responses. FUNDING: None.

Strengthening routine immunization through measles-rubella elimination.

The 2016 mid-term review of the Global Measles-Rubella Strategic Plan 2012-20 for achieving measles-rubella elimination concluded that the full potential of strategies and activities to strengthen routine immunization (RI) service delivery had not been met. In December 2017, we contacted WHO and partner agency immunization staff in all six WHO Regions who identified 23 countries working on measles or rubella elimination that have implemented examples of recommended activities to improve RI, adapted to their needs. Among those examples, opportunities to strengthen RI through implementing supplementary immunization activities (SIAs) were reported most frequently, including advocacy for immunization and educational activities targeted at the public and skills training targeted at health professionals. The expansion of cold chain capacity to accommodate supplies required for SIAs facilitated widening RI service delivery to reach more communities, introduce new vaccines, and reduce the risk of vaccine stock-outs. Substantial numbers of under-vaccinated children, according to the national immunization schedule, have been identified during SIAs, but it is not possible to confirm whether these children actually received missing RI doses. Micro-planning exercises for SIAs have generated data that permitted the revision of catchment populations for fixed site and outreach RI services. Some countries reported using the opportunity afforded by measles/rubella elimination to strengthen overall vaccine-preventable disease surveillance and outbreak preparedness and to introduce mandatory school-entry vaccination requirements covering other vaccines in addition to measles and rubella. Unfortunately, we were unable to obtain information regarding the cost, impact or sustainability of these activities. The evaluation of the many other strategies that have been deployed in recent years to strengthen RI systems and raise vaccination coverage was beyond the scope of this survey. We conclude by providing recommendations to encourage more countries to adapt and implement a comprehensive set of RI-strengthening activities in association with the MR elimination goal.

The new World Health Organization recommendation on the 2-dose measles vaccine schedule and the way forward in African Region.

The new W.H.O. recommendation, which drops the coverage criterion for adoption of the 2-dose measles vaccine schedule, makes some African countries eligible for the 2-dose schedule which were previously ineligible. We look at the implications of the new recommendation for Ethiopia and Nigeria, the two largest African countries which are eligible under the new recommendation.

Slow Progress In Finalizing Measles And Rubella Elimination In The European Region.

All countries in the World Health Organization European Region committed to eliminating endemic transmission of measles and rubella by 2015, and disease incidence has decreased dramatically. However, there was little progress between 2012 and 2013, and the goal will likely not be achieved on time. Genuine political commitment, increased technical capacity, and greater public awareness are urgently needed, especially in Western Europe.

Supporting countries in establishing and strengthening NITAGs: lessons learned from 5 years of the SIVAC initiative.

To empower governments to formulate rational policies without pressure from any group, and to increase the use of evidence-based decision-making to adapt global recommendations on immunization to their local context, the WHO has recommended on multiple occasions that countries should establish National Immunization Technical Advisory Groups (NITAGs). The World Health Assembly (WHA) reinforced those recommendations in 2012 when Member States endorsed the Decade of Vaccines Global Vaccine Action Plan (GVAP). NITAGs are multidisciplinary groups of national experts responsible for providing independent, evidence-informed advice to health authorities on all policy-related issues for all vaccines across all populations. In 2012, according to the WHO-UNICEF Joint Reporting Form, among 57 countries eligible for immunization program financial support from the GAVI Alliance, only 9 reported having a functional NITAG. Since 2008, the Supporting Independent Immunization and Vaccine Advisory Committees (SIVAC) Initiative (at the Agence de Médecine Préventive or AMP) in close collaboration with the WHO and other partners has been working to accelerate and systematize the establishment of NITAGs in low- and middle-income countries. In addition to providing direct support to countries to establish advisory groups, the initiative also supports existing NITAGs to strengthen their capacity in the use of evidence-based processes for decision-making aligned with international standards. After 5 years of implementation and based on lessons learned, we recommend that future efforts should target both expanding new NITAGs and strengthening existing NITAGs in individual countries, along three strategic lines: (i) reinforce NITAG institutional integration to promote sustainability and credibility, (ii) build technical capacity within NITAG secretariats and evaluate NITAG performance, and (iii) increase networking and regional collaborations. These should be done through the development and dissemination of tools and guidelines, and information through a variety of adapted mechanisms.

Measles resurgence in southern Africa: challenges to measles elimination.

INTRODUCTION: In seven southern African countries (Botswana, Lesotho, Malawi, Namibia, South Africa, Swaziland and Zimbabwe), following implementation of a measles mortality reduction strategy starting in 1996, the number of annually reported measles cases decreased sharply to less than one per million population during 2006-2008. However, during 2009-2010, large outbreaks occurred in these countries. In 2011, a goal for measles elimination by 2020 was set in the World Health Organization (WHO) African Region (AFR). We reviewed the implementation of the measles control strategy and measles epidemiology during the resurgence in the seven southern African countries. METHODS: Estimated coverage with routine measles vaccination, supplemental immunization activities (SIA), annually reported measles cases by country, and measles surveillance and laboratory data were analyzed using descriptive analysis. RESULTS: In the seven countries, coverage with the routine first dose of measles-containing vaccine (MCV1) decreased from 80% to 65% during 1996-2004, then increased to 84% in 2011; during 1996-2011, 79,696,523 people were reached with measles vaccination during 45 SIAs. Annually reported measles cases decreased from 61,160 cases to 60 cases and measles incidence decreased to <1 case per million during 1996-2008. During 2009-2010, large outbreaks that included cases among older children and adults were reported in all seven countries, starting in South Africa and Namibia in mid-2009 and in the other five countries by early 2010. The measles virus genotype detected was predominantly genotype B3. CONCLUSION: The measles resurgence highlighted challenges to achieving measles elimination in AFR by 2020. To achieve this goal, high two-dose measles vaccine coverage by strengthening routine immunization systems and conducting timely SIAs targeting expanded age groups, potentially including young adults, and maintaining outbreak preparedness to rapidly respond to outbreaks will be needed.

Aligning new interventions with developing country health systems: target product profiles, presentation, and clinical trial design.

Many new interventions are being created to address health problems of the developing world. However, many developing countries have fragile health systems and find it difficult to accommodate change. Consequently, it is essential that new interventions are well aligned with health systems and their users. Establishing target product profiles (TPPs) is a critical, early step towards tailoring interventions to suit both of these constituencies. Specific analyses can help identify and establish relevant TPP criteria such as optimal formulation, presentation and packaging. Clinical trials for a new intervention should be designed to address both TPP-specific questions and anticipated use of the intervention in target countries. Examples are provided from research on malaria vaccines that are also applicable to other new public health interventions.

Researching routine immunization-do we know what we don't know?

BACKGROUND: The Expanded Programme on Immunization (EPI), launched in 1974, has developed and implemented a range of strategies and practices over the last three decades to ensure that children and adults receive the vaccines they need to help protect them against vaccine-preventable diseases. Many of these strategies have been implemented, resulting in immunization coverage exceeding 80% among children one year of age in many countries. Yet millions of infants remain under-immunized or unimmunized, particularly in poorer countries. In November 2009, a panel of external experts met at the United States Centers for Disease Control and Prevention (CDC) to review and identify areas of research required to strengthen routine service delivery in developing countries. METHODS: Research opportunities were identified utilizing presentations emphasizing existing research, gaps in knowledge and key questions. Panel members prioritized the topics, as did other meeting participants. FINDINGS: Several hundred research topics covering a wide range were identified by the panel members and participants. However there were relatively few topics for which there was a consensus that immediate investment in research is warranted. The panel identified 28 topics as priorities. 18 topics were identified as priorities by at least 50% of non-panel participants; of these, five were also identified as priorities by the panel. Research needs included identifying the best ways to increase coverage with existing vaccines and introduce new vaccines, integrate other services with immunizations, and finance immunization programmes. INTERPRETATION: There is an enormous range of research that could be undertaken to support routine immunization. However, implementation of strategic plans, rather than additional research will have the greatest impact on raising immunization coverage and preventing disease, disability, and death from vaccine-preventable diseases. The panel emphasized the importance of tying operational research to programmatic needs, with a focus on efforts to scale up proven best practices in each country, facilitating the full implementation of immunization strategies.

Rotavirus burden among children in the newly independent states of the former union of soviet socialist republics: literature review and first-year results from the rotavirus surveillance network.

BACKGROUND: Data on rotavirus burden among children in the 15 newly independent states of the former Union of Soviet Socialist Republics, particularly contemporary data from poorer countries, are not widely available. These data are desired by policy makers to assess the value of rotavirus vaccination, especially since the GAVI Alliance approved financial support for the region's eligible countries. The Rotavirus Surveillance Network was established to provide these data. METHODS: We reviewed the region's literature on rotavirus burden. We established an active surveillance network for rotavirus and analyzed data from 2007 from 4 sentinel hospitals in 3 countries (Georgia, Tajikistan, and Ukraine) that were collected using standardized enrollment and stool sample testing methods. RESULTS: Specimens for rotavirus testing were collected before 1997 in most studies, and the majority of studies were from 1 country, the Russian Federation. Overall, the studies indicated that approximately 33% of hospitalizations for gastroenteritis among children were attributable to rotavirus. The Rotavirus Surveillance Network documented that 1425 (42%) of 3374 hospitalizations for acute gastroenteritis among children aged <5 years were attributable to rotavirus (site median, 40%). Seasonal peaks (autumn through spring) were observed. Genotype data on 323 samples showed that G1P[8] was the most common type (32%), followed by G9P[8] (20%), G2P[4] (18%), and G4P[8] (18%). Infections due to G10 and G12 and mixed infections were also detected. CONCLUSIONS: The burden of rotavirus disease in the newly independent states is substantial. Vaccines should be considered for disease prevention.

Health systems and immunization financing for human papillomavirus vaccine introduction in low-resource settings.

This descriptive qualitative study synthesizes health system and immunization financing assessments performed through formative research in India, Peru, Uganda, and Vietnam using a non-probability sample of national and sub-national stakeholders; and recommends appropriate and effective strategies for HPV vaccine delivery in low-resource settings. We conclude that maximum feasibility and acceptability and lowest cost for delivering HPV vaccine can be achieved by implementing through national immunization programs; by partnering with other sectors, such as education and maternal-child health; by strengthening existing human resources and cold chain infrastructures where needed; and finally, by considering schools for reaching the target population.

Country recommendations on the inclusion of HPV vaccines in national immunization programmes among high-income countries, June 2006-January 2008.

We analysed country recommendations and funding plans finalized through January 2008 for the inclusion of quadrivalent and bivalent human papillomavirus (HPV) vaccines in national immunization programmes. Fifteen industrialized countries have recommended HPV vaccine use based on careful review of scientific evidence and cost-effectiveness. There was a strong consensus among the guidelines regarding assessment of vaccine safety and efficacy, selection of primary target populations for vaccination, vaccine delivery strategies, and the need for vaccinated females to seek cervical cancer screening. The analysis informs ongoing discussions in several countries considering HPV vaccines for national immunization programmes and discussions at the World Health Organization about global recommendations for HPV vaccine use for national immunization programmes.

Impact of alternative approaches to accelerated measles control: experience in the African region, 1996-2002.

From 1996 to 2000, several African countries accelerated measles control by providing a second opportunity for measles vaccine through supplemental campaigns. Fifteen countries completed campaigns in children aged 9 months to 14 years. Seven countries completed campaigns in children aged 9-59 months. In almost all countries that conducted campaigns in children aged 9 months to 14 years, measles deaths were reduced to near zero. In six countries, near-zero measles mortality has been maintained for 4-6 years. Supplemental immunization in children <5 years old was only partially effective (range, 0-67%) in reducing mortality. Measles cases decreased by 50% when routine vaccination coverage increased from 50% to 80%. Initial measles campaigns in children aged 9 months to 14 years, follow-up campaigns in those aged 9-59 months every 3-5 years, and increased routine coverage to 80% will be needed to reduce and maintain measles deaths in African countries at near zero.