The development of vaccines against one or all forms of human leishmaniasis remains hampered by a paucity of investment, at least in part resulting from the lack of well-evidenced and agreed ...estimates of vaccine demand. Starting from the definition of 4 main use cases (prevention of visceral leishmaniasis, prevention of cutaneous leishmaniasis, prevention of post-kala-azar dermal leishmaniasis and treatment of post-kala-azar dermal leishmaniasis), we have estimated the size of each target population, focusing on those endemic countries where incidence levels are sufficiently high to justify decisions to adopt a vaccine. We assumed a dual vaccine delivery strategy, including a wide age-range catch-up campaign before the start of routine immunisation. Vaccine characteristics and delivery parameters reflective of a target product profile and the likely duration of the clinical development effort were considered in forecasting the demand for each of the four indications. Over a period of 10 years, this demand is forecasted to range from 300-830 million doses for a vaccine preventing visceral leishmaniasis and 557-1400 million doses for a vaccine preventing cutaneous leishmaniasis under the different scenarios we simulated. In a scenario with an effective prophylactic visceral leishmaniasis vaccine, demand for use to prevent or treat post-kala-azar dermal leishmaniasis would be more limited (over the 10 years ~160,000 doses for prevention and ~7,000 doses for treatment). Demand would rise to exceed 330,000 doses, however, in the absence of an effective vaccine for visceral leishmaniasis. Because of the sizeable demand and potential for public health impact, a single-indication prophylactic vaccine for visceral or cutaneous leishmaniasis, and even more so a cross-protective prophylactic vaccine could attract the interest of commercial developers. Continuous refinement of these first-of-their kind estimates and confirmation of country willingness and ability to pay will be paramount to inform the decisions of policy makers and developers in relation to a leishmaniasis vaccine. Positive decisions can provide a much-needed contribution towards the achievement of global leishmaniasis control.
Abstract
Background
Despite group B Streptococcus (GBS) being a leading cause of maternal and infant morbidity and mortality, no vaccine is currently available. To inform vaccine developers, ...countries, and funders, we analyzed the key factors likely to influence the demand for a GBS vaccine and the long-term financial sustainability for a vaccine developer.
Methods
Using population-based forecasting, we estimated the demand for a GBS vaccine; using a discounted cash flow model we estimated the financial viability for a vaccine developer.
Results
Demand for this vaccine can be significant if countries adopt policy recommendations for use, in particular, the largest ones, most of which have a burden that justifies use of the vaccine, and if financing for the vaccine is made available either by countries or by funding mechanisms such as Gavi, the Vaccine Alliance.
Conclusions
This analysis suggests the potential for financial and commercial viability for a vaccine developer pursuing the commercialization of a GBS vaccine. Risks exists in relation to the clinical trial design and costs, the level of competition, countries’ ability to pay, the administration schedule, and the availability of policies that encourage use of the vaccine. To reduce those risks and ensure equitable access to a GBS vaccine, the role of donors or financers can prove very important, as can a coordinated operational research agenda that aims at clarifying those areas of uncertainty.
Highlights ► Vaccine introductions reduce disease and improve surveillance, training, cold chain, and injection safety. ► Opportunities to strengthen the health system are often missed with vaccine ...introductions. ► Weaknesses in planning for human and financial resource needs are a concern. ► Future vaccine introductions should explicitly plan to optimize impact on health systems. ► Donors and partners should provide sufficient and timely support to facilitate country planning.
Highlights ► We reviewed the impact of vaccine introduction on immunization and health systems. ► Existing vaccine delivery platforms and combination vaccines were most efficient. ► New vaccine ...introductions aided development of widespread vaccine safety policies. ► New vaccine introduction was often associated with lower health care costs. ► Future introductions should include health/immunization system impact assessments.
Pneumococcal conjugate vaccines (PCVs) are safe and effective for reducing illness and deaths caused by Streptococcus pneumoniae. Recommendations for PCV use from the World Health Organization (WHO) ...and funding from the GAVI Alliance have resulted in an increase in PCV introductions into national immunization programs, especially in lower-income countries. Additionally, new formulations that cover more serotypes commonly causing disease in lower- and middle-income countries have become available. This report uses WHO data from 2000-2012, stratified by country disease burden characteristics and World Bank country income groups, to describe global progress in PCV introduction. As of December 2012, a total of 86 (44%) WHO member states have added PCV to the routine infant immunization schedule of their national immunization programs; among those, 23 have introduced PCV with GAVI Alliance support. PCV introduction among WHO member states was most common in the Americas Region (60% of member states), followed by the Eastern Mediterranean Region (50%), European Region (49%), African Region (41%), and Western Pacific Region (33%); none of 11 WHO member states in the South-East Asia Region have introduced PCV. Proportions of low- and middle-income countries with PCV introductions were similar. The proportion of the world's birth cohort living in countries with PCV in national immunization programs increased from 1% in 2000 to 31% in 2012. These findings suggest that efforts to increase PCV introduction and use globally are succeeding; however, gaps in PCV use remain in Asia and countries with large birth cohorts, where concerted efforts should be focused.
AbstractHealth workers represent an important target group for seasonal influenza vaccination because of their increased risk of infection as well as the risk of transmitting infection to vulnerable ...patients in the health care setting. Moreover, seasonal vaccination of health workers contributes to pandemic preparedness. However, many countries, especially in Africa and Asia, do not have policies for health worker influenza vaccination. In countries where such policies exist, vaccination coverage is often low. The World Health Organization (WHO) is developing a manual to guide the introduction of seasonal influenza vaccination of health workers. An Independent External Advisory Group (IEAG) that is advising WHO on the content of the manual met to discuss issues that are relevant and often unique to health worker vaccination. This meeting report summarizes the main issues that were discussed and the outcomes of the discussion. The issues include policy considerations, including the evidence in support of health worker vaccination; categorization and prioritization of health workers; the choice of vaccination strategy; its integration into broader health worker vaccination and occupational health policies; planning and management of vaccination, particularly the approaches for communication and demand generation; and the challenges with monitoring and evaluation of health worker vaccination, especially in low and middle-income countries.
BackgroundMalaria, anemia, and malnutrition contribute substantially to childhood morbidity in sub-Saharan Africa, but their respective roles and interactions in conferring disease are complex. We ...aimed to investigate these interactions MethodsIn 2002, we assessed plasmodial infection, anemia, and nutritional indices in 2 representative surveys comprising >4000 children in northern Ghana ResultsInfection with Plasmodium species was observed in 82% and 75% of children in the rainy and dry season, respectively. The fraction of fever attributable to malaria was 77% in the rainy season and 48% in the dry season and peaked in children of rural residence. Anemia (hemoglobin level, <11 g/dL) was seen in 64% of children and was, in multivariate analysis, associated with young age, season, residence, parasitemia, P. malariae coinfection, and malnutrition (odds ratio OR, 1.68 95% confidence interval {CI}, 1.38–2.04). In addition, malnutrition was independently associated with fever (axillary temperature, ⩾37.5°C; OR, 1.59 95% CI, 1.13–2.23) and clinical malaria (OR, 1.67 95% CI, 1.10–2.50) ConclusionsMalnutrition is a fundamental factor contributing to malaria-associated morbidity and anemia, even if the latter exhibits multifactorial patterns. Our data demonstrate that malaria-control programs alone may not have the desired impact on childhood morbidity on a large scale without concomitant nutrition programs
Background TH 17 cells are of pathologic relevance in autoimmune disorders and presumably also in allergy and asthma. Regulatory T (Treg) cells, in contrast, suppress inflammatory and allergen-driven ...responses. Despite these disparate functions, both T-cell subsets have been shown to be dependent on TGF-β for their development. Objective The aim of the study was to analyze the differentiation and function of human TH 17 cells in comparison with other TH cell subsets. Methods Naive human CD4+ T cells were differentiated in vitro , and gene expression was analyzed by means of quantitative real-time PCR, ELISA, and immunofluorescence. The function of TH cell subsets was assessed by monitoring the response of primary bronchial epithelial cells in coculture experiments. Results In vitro differentiated TH 17 cells differ from Treg and other TH cells in their potency to induce IL-6 and IL-1β expression in primary bronchial epithelial cells. TGF-β, IL-1β, IL-6, and IL-23 are necessary during TH 17 cell differentiation to acquire these functions, including IL-17 production. In contrast, TGF-β alone is necessary and sufficient to induce the transcription factor RORC2. This transcription factor, previously thought to be specific for TH 17 cells, is also expressed in Treg cells, CD25+ cells, cytotoxic T cells, and natural killer T cells. Conclusion This study demonstrates mechanisms of differentiation to human TH 17 cells, a subset that effectively and uniquely modulates the function of primary bronchial epithelial cells.
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