Introducing New Vaccines in Developing Countries: Concepts and Approaches to Estimating Burden of Haemophilus influenzae Type b-associated Disease

In the past 30 years, great strides have been made in immunizing infants and children routinely in developing countries under the Expanded Programme on Immunization. Despite this, the introduction of Haemophilus influenzae type b (Hib) vaccines has progressed rather slowly compared to previously-introduced vaccines for infant immunizations. This slower uptake has been attributed partly to the need for data on the burden of invasive Hib disease. To understand this need, conceptual underpinnings and prerequisites were explored for Hib disease-burden studies. Methodological approaches were also reviewed for conducting Hib disease-burden studies that may be considered in developing countries. Potential studies span a range of designs that provide varying levels of clinical, laboratory and epidemiologic evidence of the burden of invasive Hib disease. Carefully-conducted studies can lay the foundation for complementary studies of long-term disability due to invasive Hib disease, national economic analysis, and field evaluations of vaccine. Studies done in collaboration with national agencies and clinical investigators will maximize study value and provide critical data for national decision- makers who make choices regarding the introduction of Hib vaccines

Trends in Pneumonia and Influenza-associated Hospitalizations in South Korea, 2002-2005

Pneumonia and influenza are leading causes of morbidity and mortality across the globe. Korea has established the national health-insurance system to cover the entire Korean population since 1989. The aim of this study was to describe the epidemiologic trends in pneumonia and influenza-associated hospitalizations and deaths using the Korean National Health Insurance databases and national vital statistics. During 2002-2005, 989,472 hospitalizations and 10,543 deaths due to pneumonia and influenza were recorded. Eighty-one percent of the hospitalizations were related to diagnoses with unspecified aetiology. The average annual rate of hospitalizations due to pneumonia and influenza was 5.2 per 1,000 people [95% confidence interval (CI) 5.2-5.3], and the hospitalization rate increased by 28% (from 4.5 to 5.8 per 1,000 people) during the four-year study period. In addition, deaths due to pneumonia and influenza increased by 48% (2,829 during 2003, 3,522 during 2004, and 4,192 during 2005). Overall, the national burden of hospitalizations and deaths due to pneumonia and influenza in Korea was high, and it increased for all age-groups during the study period. A comprehensive review of potential interventions by the government authorities should aim to reduce the burden of pneumonia and influenza

Treatment Costs of Pneumonia, Meningitis, Sepsis, and Other Diseases among Hospitalized Children in Viet Nam

The aim of this study was to estimate the costs of treatment of children who present with the signs and symptoms of invasive bacterial diseases in Khanh Hoa province, Viet Nam. The study was an incidence-based cost-of-illness analysis from the health system perspective. The hospital costs included labour, materials and capital costs, both direct and indirect. Costs were determined for 980 children, with an average age of 12.67 months (standard deviation±11.38), who were enrolled in a prospective surveillance at the Khanh Hoa General Hospital during 2005-2006. Of them, 57% were male. By disease-category, 80% were suspected of having pneumonia, 8% meningitis, 3% very severe disease consistent with pneumococcal sepsis, and 9% other diseases. Treatment costs for suspected pneumonia, meningitis, very severe disease, and other diseases were US$31, US$ 57, US$73, and US$ 24 respectively. Costs ranged from US$24 to US$ 164 across different case-categories. Both type of disease and age of patient had statistically significant effects on treatment costs. The results showed that treatment costs for bacterial diseases in children were considerable and might differ by as much as seven times among invasive pneumococcal diseases. Changes in costs were sensitive to both age of patient and case-category. These cost-of-illness data will be an important component in the overall evidence base to guide the development of vaccine policy in Viet Nam

Trends in Pneumonia and Influenza-associated Hospitalizations in South Korea, 2002-2005

Pneumonia and influenza are leading causes of morbidity and mortality across the globe. Korea has established the national health-insurance system to cover the entire Korean population since 1989. The aim of this study was to describe the epidemiologic trends in pneumonia and influenza-associated hospitalizations and deaths using the Korean National Health Insurance databases and national vital statistics. During 2002-2005, 989,472 hospitalizations and 10,543 deaths due to pneumonia and influenza were recorded. Eighty-one percent of the hospitalizations were related to diagnoses with unspecified aetiology. The average annual rate of hospitalizations due to pneumonia and influenza was 5.2 per 1,000 people [95% confidence interval (CI) 5.2-5.3], and the hospitalization rate increased by 28% (from 4.5 to 5.8 per 1,000 people) during the four-year study period. In addition, deaths due to pneumonia and influenza increased by 48% (2,829 during 2003, 3,522 during 2004, and 4,192 during 2005). Overall, the national burden of hospitalizations and deaths due to pneumonia and influenza in Korea was high, and it increased for all age-groups during the study period. A comprehensive review of potential interventions by the government authorities should aim to reduce the burden of pneumonia and influenza

Influenza and Bacterial Coinfections in the 20th Century

To help understand the potential impact of bacterial coinfection during pandemic influenza periods, we undertook a far-reaching review of the existing literature to gain insights into the interaction of influenza and bacterial pathogens. Reports published between 1950 and 2006 were identified from scientific citation databases using standardized search terms. Study outcomes related to coinfection were subjected to a pooled analysis. Coinfection with influenza and bacterial pathogens occurred more frequently in pandemic compared with seasonal influenza periods. The most common bacterial coinfections with influenza virus were due to S. pneumoniae, H. influenzae, Staphylococcus spp., and Streptococcus spp. Of these, S. pneumoniae was the most common cause of bacterial coinfection with influenza and accounted for 40.8% and 16.6% of bacterial coinfections during pandemic and seasonal periods, respectively. These results suggest that bacterial pathogens will play a key role in many countries, as the H1N1(A) influenza pandemic moves forward. Given the role of bacterial coinfections during influenza epidemics and pandemics, the conduct of well-designed field evaluations of public health measures to reduce the burden of these common bacterial pathogens and influenza in at-risk populations is warranted

Influenza and Bacterial Pathogen Coinfections in the 20th Century

To help understand the potential impact of bacterial coinfection during pandemic influenza periods, we undertook a far-reaching review of the existing literature to gain insights into the interaction of influenza and bacterial pathogens. Reports published between 1950 and 2006 were identified from scientific citation databases using standardized search terms. Study outcomes related to coinfection were subjected to a pooled analysis. Coinfection with influenza and bacterial pathogens occurred more frequently in pandemic compared with seasonal influenza periods. The most common bacterial coinfections with influenza virus were due to S. pneumoniae, H. influenzae, Staphylococcus spp., and Streptococcus spp. Of these, S. pneumoniae was the most common cause of bacterial coinfection with influenza and accounted for 40.8% and 16.6% of bacterial coinfections during pandemic and seasonal periods, respectively. These results suggest that bacterial pathogens will play a key role in many countries, as the H1N1(A) influenza pandemic moves forward. Given the role of bacterial coinfections during influenza epidemics and pandemics, the conduct of well-designed field evaluations of public health measures to reduce the burden of these common bacterial pathogens and influenza in at-risk populations is warranted

Treatment costs of pneumonia, meningitis, sepsis, and other diseases among hospitalized children in Viet Nam

The aim of this study was to estimate the costs of treatment of children who present with the signs and symptoms of invasive bacterial diseases in Khanh Hoa province, Viet Nam. The study was an incidence-based cost-of-illness analysis from the health system perspective. The hospital costs included labour, ma-terials and capital costs, both direct and indirect. Costs were determined for 980 children, with an average age of 12. 67 months (standard deviation\ub1 11. 38), who were enrolled in a prospective surveillance at the Khanh Hoa General Hospital during 2005- 2006. Of them, 57% were male. By disease-category, 80% were suspected of having pneumonia, 8% meningitis, 3% very severe disease consistent with pneumococcal sep-sis, and 9% other diseases. Treatment costs for suspected pneumonia, meningitis, very severe disease, and other diseases were US$31, US$ 57, US$73, and US$ 24 respectively. Costs ranged from US$24 to US$ 164 across different case-categories. Both type of disease and age of patient had statistically significant effects on treatment costs. The results showed that treatment costs for bacterial diseases in children were consid-erable and might differ by as much as seven times among invasive pneumococcal diseases. Changes in costs were sensitive to both age of patient and case-category. These cost-of-illness data will be an important component in the overall evidence base to guide the development of vaccine policy in Viet Nam

Rapid assessment of Hib disease burden in Vietnam

<p>Abstract</p> <p>Background</p> <p>Several countries have applied the <it>Haemophilus influenzae </it>type b (Hib) rapid assessment tool (RAT) to estimate the burden of Hib disease where resources for hospital- or population-based surveillance are limited. In Vietnam, we used the Hib RAT to estimate the burden of Hib pneumonia and meningitis prior to Hib vaccine introduction.</p> <p>Methods</p> <p>Laboratory, hospitalization and mortality data were collected for the period January 2004 through December 2005 from five representative hospitals. Based on the WHO Hib RAT protocol, standardized MS Excel spreadsheets were completed to generate meningitis and pneumonia case and death figures.</p> <p>Results</p> <p>We found 35 to 77 Hib meningitis deaths and 441 to 957 Hib pneumonia deaths among children < 5 years of age annually in Vietnam. Overall, the incidence of Hib meningitis was estimated at 18/100,000 (95% confidence interval, CI, 15.1-21.6). The estimated Hib meningitis incidence in children < 5 years age was higher in Ho Chi Minh City (22.5/100,000 [95% CI, 18.4-27.5]) compared to Hanoi (9.8/100,000 [95% CI, 6.5-14.8]). The Hib RAT suggests that there are a total of 883 to 1,915 cases of Hib meningitis and 4,414 to 9,574 cases of Hib pneumonia per year in Vietnam.</p> <p>Conclusions</p> <p>In Hanoi, the estimated incidence of Hib meningitis for children < 5 years of age was similar to that described in previous population-based studies of Hib meningitis conducted from 1999 through 2002. Results from the Hib RAT suggest that there is a substantial, yet unmeasured, disease burden associated with Hib pneumonia in Vietnamese children.</p

Survey of childhood empyema in Asia: Implications for detecting the unmeasured burden of culture-negative bacterial disease

<p>Abstract</p> <p>Background</p> <p>Parapneumonic empyema continues to be a disease of significant morbidity and mortality among children despite recent advances in medical management. To date, only a limited number of studies have assessed the burden of empyema in Asia.</p> <p>Methods</p> <p>We surveyed medical records of four representative large pediatric hospitals in China, Korea, Taiwan and Vietnam using <it>ICD</it>-10 diagnostic codes to identify children <16 years of age hospitalized with empyema or pleural effusion from 1995 to 2005. We also accessed microbiology records of cultured empyema and pleural effusion specimens to describe the trends in the epidemiology and microbiology of empyema.</p> <p>Results</p> <p>During the study period, we identified 1,379 children diagnosed with empyema or pleural effusion (China, n = 461; Korea, n = 134; Taiwan, n = 119; Vietnam, n = 665). Diagnoses of pleural effusion (n = 1,074) were 3.5 times more common than of empyema (n = 305), although the relative proportions of empyema and pleural effusion noted in hospital records varied widely between the four sites, most likely because of marked differences in coding practices. Although pleural effusions were reported more often than empyema, children with empyema were more likely to have a cultured pathogen. In addition, we found that median age and gender distribution of children with these conditions were similar across the four countries. Among 1,379 empyema and pleural effusion specimens, 401 (29%) were culture positive. <it>Staphylococcus aureus </it>(n = 126) was the most common organism isolated, followed by <it>Streptococcus pneumoniae </it>(n = 83), <it>Pseudomonas aeruginosa </it>(n = 37) and <it>Klebsiella </it>(n = 35) and <it>Acinetobacter </it>species (n = 34).</p> <p>Conclusion</p> <p>The age and gender distribution of empyema and pleural effusion in children in these countries are similar to the US and Western Europe. <it>S. pneumoniae </it>was the second leading bacterial cause of empyema and pleural effusion among Asian children. The high proportion of culture-negative specimens among patients with pleural effusion or empyema suggests that culture may not be a sufficiently sensitive diagnostic method to determine etiology in the majority of cases. Future prospective studies in different countries would benefit from standardized case definitions and coding practices for empyema. In addition, more sensitive diagnostic methods would improve detection of pathogens and could result in better prevention, treatment and outcomes of this severe disease.</p