Research and Development Agenda
The research and development agenda outlined below summarizes the priorities that have been established by advisory groups to the Initiative for Vaccine Research (vaccine intervention strategies) and the WHO Division of the Child and Adolescent Health (case-management strategies).
Vaccine Intervention Strategies
The GAVI task force on Hib immunization made a number of recommendations that vary depending on the country. Countries that have introduced Hib vaccine should focus on documenting its effect and should use the data to inform national authorities, development partners, and other agencies involved in public health to ensure sustained support to such vaccination programs. Countries eligible for GAVI support that have not yet introduced Hib vaccines are often hindered by a lack of local data and a lack of awareness of regional data. They can address these issues through subregional meetings at which country experts can pool data and review information from other countries. In addition, most of the countries need to carry out economic analyses that are based on a standardized instrument. Finally, all countries that face a high Hib disease burden need to develop laboratory facilities so that they can establish the incidence of Hib meningitis at selected sites. Countries in which the disease burden remains unclear may have limited capacity to document the occurrence of Hib disease using protocols that are based on surveillance for meningitis invasive disease. They will need to explore the possibilities of using alternative methods for measuring disease burden, including the use of vaccine-probe studies.
On the basis of experience with introducing Hib and hepatitis B vaccines, GAVI took a proactive approach and in 2003 established an initiative based at the Johns Hopkins School of Public Health in Baltimore to implement an accelerated development and introduction program for pneumococcal vaccines (the PneumoADIP; see http://www.preventpneumonia.org). The program's intent is to establish and communicate the value of pneumococcal vaccines and to support their delivery. Establishing the value of the vaccine involves developing local evidence about the burden of disease and the vaccines' potential effect on public health. This effort can be accomplished through enhanced disease surveillance and relevant clinical trials in a selected number of lead countries. Once established, the evidence base will be communicated to decision makers and key opinion leaders to ensure that data-driven decisions are made. Once the cost-effectiveness of routine vaccination is established, delivery systems will have to be established, and countries will need financial support so that the vaccines can be introduced into their immunization programs. These activities are being initiated before the launch of vaccine formulations designed for use in developing countries, so as to inform capacity planning, product availability, and pricing.
Case-Management Strategies
In 2003, WHO's Division of Child and Adolescent Health convened a meeting to review data and evidence from recent ARI case-management studies and to suggest the following revisions to case-management guidelines and future research priorities:
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Nonsevere pneumonia:
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Improve the specificity of clinical diagnostic criteria.
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Reassess WHO's current recommended criteria for detecting and managing treatment failure, given the high rates of therapy failure.
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Reanalyze data from short-course therapy studies to better identify determinants of treatment failure.
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Carry out placebo-controlled trials among children presenting with wheezing and pneumonia in selected settings that have a high prevalence of wheezing to determine whether such children need antibiotics.
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Severe pneumonia: In a randomized clinical trial in a controlled environment, Addo-Yobo and others (2004) showed that oral amoxicillin is as effective as parenteral penicillin or ampicillin; however, the following actions need to be undertaken before it can be recommended on a general basis:
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Analyze data on exclusions from the trial.
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Identify predictors that may help distinguish children who require hospitalization and who subsequently deteriorate.
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Reassess WHO's current recommended treatment failure criteria for severe pneumonia, given the overall high rates of therapy failure.
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Conduct descriptive studies in a public health setting in several centers worldwide, to evaluate the clinical outcomes of oral amoxicillin in children age 2 to 59 months who present with lower chest wall indrawing.
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Document the effectiveness of WHO's treatment guidelines for managing children with pneumonia and HIV infection.
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LRI deaths:
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To help develop more effective interventions to reduce LRI mortality, study the epidemiology of LRI deaths in various regions in detail, using routine and advanced laboratory techniques.
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Oxygen therapy:
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Carry out studies to show the effectiveness of oxygen for managing severe respiratory infections.
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Collect baseline information about the availability and delivery of oxygen and its use in hospital settings in low-income countries.
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Explore the utility of pulse oximetry for optimizing oxygen therapy in various clinical settings.
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Undertake studies to improve the specificity of clinical signs in the overlapping signs and symptoms of malaria and pneumonia.
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Study rapid diagnostic tests for malaria to assess their effectiveness in differentiating between malaria and pneumonia.
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Examine the effect of widespread use of co-trimoxazole on sulfadoxine-pyrimethamine resistance to Plasmodium falciparum.
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Etiology: Data on the etiology of pneumonia in children are somewhat out of date, and new etiological studies are needed that use modern technology to identify pathogens.
