Focus Area: Acute Respiratory Infection (ARI)
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| Photo: USAID/Chris Thomas |
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Statement of the Problem
A. Burden of Disease Due to ARI
Acute respiratory infection (ARI) is one of the leading causes of morbidity and mortality in children under 5 years of age in developing countries, and is responsible for an estimated 1.9 million deaths annually. Along with diarrhea, pneumonia accounts for the largest portion of infant deaths in developing areas. Among the 42 countries of the world with 90% of the child mortality burden, 14-24% of the under-5 mortality is due to pneumonia and nearly 70% of this pneumonia mortality occurs in the Africa and South and Southeast Asia regions. The majority of this burden is borne during early childhood with the greatest risk from mortality occurring during the neonatal period. The global incidence of ARI in children is estimated to be 154 million cases per year with each child suffering an estimated 4-6 episodes per year (ALRI ~0.4 per year). Nearly 10% of these episodes are severe enough to require hospitalization.
The impact of ARI can also be measured in terms of morbidity and co-morbidity. For every death directly attributable to ARI there are two-to-three further deaths where ARI is an associated cause. The morbidity associated with other serious diseases such as malnutrition and measles are made considerably worse in the presence of pneumonia, and pneumonia is the most common and deadly initial manifestation of HIV in children. In addition, several diseases such as asthma or malaria can mimic the symptoms of ARI. For example, respiratory distress is a presenting feature of 14% of all cases of malaria in Kenya and 34% of the severe malaria cases. Conversely, in areas of high malaria transmission, up to 45% of children admitted with respiratory signs indicative of severe ARI have malaria as the primary diagnosis.
Bacterial infection is believed to play a far greater role as a cause of pneumonia in children in developing countries than it does in developed ones, but etiologic diagnosis is difficult to determine and is shifting. Apart from measles, which is often complicated by pneumonitis, the main agents responsible for ARI in children include Streptococcus pneumoniae, Haemophilus influenzae, and respiratory syncytial virus (RSV). However, in areas of high HIV prevalence this pattern is changing to include pneumocystis jiroveci and a higher proportion of gram-negative bacterial organisms. It is estimated that 60 percent of ARI deaths can be prevented by the selective use of antibiotics but accurate diagnosis of pneumonia is difficult under the best of circumstances and not possible with current tools at the periphery of the health system in developing areas. Clinical diagnostic algorithms, while useful, lack specificity and potentially contribute to antimicrobial resistance (AMR).
Case management of ARI at the community level has been shown to be an effective means to achieve reductions in under-5 ARI mortality. An analysis of five community intervention studies using concurrent control communities showed that pneumonia-specific childhood mortality could be reduced 33% (L. Muhe, WHO/CAH, personal communication), and a recent meta analysis of nine community-based case management studies demonstrated a 25% reduction in under 5 mortality. However, program implementation of community Acute Lower Respiratory Infection (ALRI) treatment programs remains spotty and current rates of children with ARI being taken to a health provider are ~40% in Africa and South Asia. In nearly half of the 81 countries with available data, less than 50 per cent of the children with ARI were taken to an appropriate health care provider.
The increasing prevalence of HIV/AIDS has complicated the standard case management of ARI. While it is estimated that HIV has contributed as little as 3% to the overall global child mortality in the year 2000, HIV prevalence is increasing rapidly in many developing countries. For example, in India, which has the greatest number of HIV cases, adult seroprevalence is projected to increase from 4 million to 25 million in the next 7 years. In areas of high HIV prevalence a greater proportion of children presenting with ARI are HIV infected and these children cannot readily be distinguished from their uninfected counterparts. Importantly, high HIV prevalence complicates the treatment of ARI because of the need to add empiric cotrimoxazole to current ARI treatment recommendations and thus promotes selection of isolates resistant to cotrimoxazole, sulfadoxine-pyrimethamine (in malaria) and multiple unrelated classes of antibiotics. This is made an even more pressing problem with the WHO recommendation for 15 months of cotrimoxazole prophylaxis for all children exposed to HIV. Full implementation of the WHO/UNAIDS guidelines would necessitate daily cotrimoxazole prophylaxis for at least 2 million infants in Africa annually.
B. High Risk Groups
A number of factors may increase the risk of ALRI or mortality from infection. The risk of death is greater during infancy and particularly during the neonatal period. More than half of the deaths among children with community-acquired pneumonia is among neonates. Several co-morbid conditions can increase ARI morality, notably malnutrition (whether manifest as low birth weight or growth failure during childhood) and micronutrient deficiencies. Among the other conditions that may affect the risk of death are mixed or no breastfeeding, lack of access to referral or oxygen therapy, and co-occurrence of infectious diseases (e.g. malaria, HIV, measles). The clinical significance of antimicrobial resistance remains unresolved.
C. Major Public Health Consequences/Implications of Prevention
Childhood ARI contributed 67 million disability adjusted life years (DALYs) in 2000, more than any other disease entity including diarrhea (45 m) and malaria (32 m). In addition to the high mortality and suffering, it consumes significant health sector resources and the largely empiric treatment of ARI contributes to the worldwide pressure of emerging antimicrobial resistance. While significant progress has been made in the development of prophylactic measures (e.g. vaccines) and refinement of empiric treatment regimens, considerable research is still needed to maximize the implementation of known interventions, establish more supportive evidence for current practices and to develop novel tools and approaches for the prevention and treatment of childhood ARI.
It is accepted that RSV accounts for a significant amount of respiratory pathology in developing areas, although there are few population or community based estimates of the age-specific incidence of RSV disease. Some studies have shown that RSV is involved in 19-37% of severe respiratory illness among hospitalized children depending on age. Accurate information on incidence, seasonality, severity, case-fatality rates and local epidemiology across developing countries and at the community level are lacking and are needed to accurately gauge the potential value of RSV vaccination programs.
Wheezing and reactive airways disease are associated with or contributory to a significant proportion of childhood ARI. While an important component of the clinical presentation of RSV, its contribution to overall ARI morbidity is poorly understood. It is also in part responsible for the lack of specificity of the WHO clinical diagnostic for severe pneumonia. A better understanding of the role of wheezing in the pathophysiology of bacterial and viral ARI, particularly during infancy, would improve the WHO ARI diagnostic algorithm, minimize inappropriate antibiotic use and permit more rational use of bronchodilator therapy and prophylaxis.
Nutritional status and micronutrient supplementation have been established as being important determinants of the incidence and morbidity associated with both diarrhea and ARI. The optimal delivery strategy and combination of micronutrients needs to be determined.
HaRP Approach
The Health Research Program (HaRP) seeks to increase recognition, prevention and treatment of ARI by helping to improve health care provider's recognition and treatment approaches. Refinement of treatment strategies for the three categories of pneumonia include: non-severe (simple) pneumonia, severe pneumonia, and very severe pneumonia.
Harp also seeks to reduce the spread of antibiotic resistant pathogens and adverse drug reactions by:
- Assessing the necessity of antibiotic therapy for non-severe pneumonia
- Determining the etiology of very severe pneumonia, documenting antimicrobial resistance patterns, and identifying best treatment practices
- Demonstrating that oral therapy may be safely substituted for parenteral therapy in the treatment of children with severe pneumonia.
Related Links
- Report to Congress: Health-Related Research and Development Activities at USAID - May 2006 [PDF, 881MB] (requires Adobe Reader)
The U.S. Congress requested that USAID provide a report describing its role in the research, development, and application cycle and its efforts to coordinate research and development activities with other agencies. With this report USAID provides a proactive strategy for using research funds and a plan for stimulating the development and introduction of key products to address diseases affecting the developing world and countries in transition.
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