Temporal decline in diarrhea episodes and mortality in Kiribati children two years following rotavirus vaccine introduction, despite high malnutrition rates: a retrospective review.

BACKGROUND: Kiribati introduced rotavirus vaccine in 2015. To estimate the impact of rotavirus vaccine on acute gastroenteritis (AGE) and severe acute malnutrition (SAM) among children under 5 in Kiribati, a retrospective review of inpatient and outpatient AGE and hospitalized SAM was undertaken. METHODS: Inpatient data for admissions and hospital deaths due to AGE, SAM and all-causes were collected for children under 5 from all hospitals on the main island, Tarawa, from January 2010-December 2013 (pre-rotavirus vaccine) and January 2016-September 2017 (post-rotavirus vaccine). National outpatient diarrhea data were collected from January 2010 to August 2017 for under 5. An interrupted time-series analysis was undertaken to estimate the effect of rotavirus vaccine on the rates of inpatient and outpatient AGE, inpatient SAM; and inpatient case fatality rates for AGE and SAM, were calculated pre- and post-rotavirus vaccine introduction. RESULTS: The incidence rate of AGE admissions from Tarawa and national AGE outpatient presentations significantly declined by 37 and 44%, respectively, 2 years following rotavirus vaccine introduction. There was a significant decline in the percentage of AGE contributing to all-cause under 5 admissions (12·8% vs. 7·2%, p < 0·001) and all-cause under-five mortality (15·9% vs. 5·7%, p = 0·006) pre- and post-rotavirus vaccine introduction. The estimated incidence rate of inpatient SAM decreased by 24% in under 5 s, 2 years following rotavirus vaccine introduction. CONCLUSIONS: AGE morbidity and mortality and hospitalized SAM rates have declined following rotavirus vaccine introduction in Kiribati children.

Aetiology and incidence of diarrhoea requiring hospitalisation in children under 5 years of age in 28 low-income and middle-income countries: findings from the Global Pediatric Diarrhea Surveillance network.

INTRODUCTION: Diarrhoea remains a leading cause of child morbidity and mortality. Systematically collected and analysed data on the aetiology of hospitalised diarrhoea in low-income and middle-income countries are needed to prioritise interventions. METHODS: We established the Global Pediatric Diarrhea Surveillance network, in which children under 5 years hospitalised with diarrhoea were enrolled at 33 sentinel surveillance hospitals in 28 low-income and middle-income countries. Randomly selected stool specimens were tested by quantitative PCR for 16 causes of diarrhoea. We estimated pathogen-specific attributable burdens of diarrhoeal hospitalisations and deaths. We incorporated country-level incidence to estimate the number of pathogen-specific deaths on a global scale. RESULTS: During 2017-2018, 29 502 diarrhoea hospitalisations were enrolled, of which 5465 were randomly selected and tested. Rotavirus was the leading cause of diarrhoea requiring hospitalisation (attributable fraction (AF) 33.3%; 95% CI 27.7 to 40.3), followed by Shigella (9.7%; 95% CI 7.7 to 11.6), norovirus (6.5%; 95% CI 5.4 to 7.6) and adenovirus 40/41 (5.5%; 95% CI 4.4 to 6.7). Rotavirus was the leading cause of hospitalised diarrhoea in all regions except the Americas, where the leading aetiologies were Shigella (19.2%; 95% CI 11.4 to 28.1) and norovirus (22.2%; 95% CI 17.5 to 27.9) in Central and South America, respectively. The proportion of hospitalisations attributable to rotavirus was approximately 50% lower in sites that had introduced rotavirus vaccine (AF 20.8%; 95% CI 18.0 to 24.1) compared with sites that had not (42.1%; 95% CI 33.2 to 53.4). Globally, we estimated 208 009 annual rotavirus-attributable deaths (95% CI 169 561 to 259 216), 62 853 Shigella-attributable deaths (95% CI 48 656 to 78 805), 36 922 adenovirus 40/41-attributable deaths (95% CI 28 469 to 46 672) and 35 914 norovirus-attributable deaths (95% CI 27 258 to 46 516). CONCLUSIONS: Despite the substantial impact of rotavirus vaccine introduction, rotavirus remained the leading cause of paediatric diarrhoea hospitalisations. Improving the efficacy and coverage of rotavirus vaccination and prioritising interventions against Shigella, norovirus and adenovirus could further reduce diarrhoea morbidity and mortality.

Rapid assessment of Hib disease burden in Vietnam.

BACKGROUND: Several countries have applied the Haemophilus influenzae 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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.

Epidemiology of rotavirus diarrhea in mongolia and sri lanka, march 2005-february 2007.

BACKGROUND: Rotavirus is the most common cause of severe gastroenteritis among children. We conducted hospital-based surveillance to estimate the burden of hospitalizations for rotavirus among children aged <5 years and to describe strain distribution patterns during the 2-year study period. METHODS: Children aged <5 years with diarrhea were prospectively enrolled and evaluated by trained pediatricians at representative hospitals in Mongolia and Sri Lanka. Fecal specimens were tested by rotavirus antigen detection enzyme immunoassay. Specimens that tested positive for rotavirus were further characterized to determine the genotype of strains by reverse-transcriptase polymerase chain reaction. RESULTS: From 1 March 2005 through 28 February 2007, a total of 1277 hospitalized children with diarrhea were enrolled in Mongolia, and 1916 were enrolled in Sri Lanka. Of the 1152 children in Mongolia who had samples tested, 458 (40%) had results positive for rotavirus, and in Sri Lanka, 428 (24%) of 1806 children with samples tested had positive results. G3P[8] was the most common genotype among rotavirus strains in Mongolia (68%) and Sri Lanka (15%). CONCLUSIONS: Rotavirus causes 40% and 24% of hospitalizations for diarrhea among children in Mongolia and Sri Lanka, respectively. Each study site will continue surveillance of rotavirus, and additional laboratory testing will be performed to provide additional information on the distribution of rotavirus strains by G and P genotype.

Surveillance of pneumococcal-associated disease among hospitalized children in Khanh Hoa Province, Vietnam.

BACKGROUND: To understand the epidemiology of childhood bacterial diseases, including invasive pneumococcal disease, prospective surveillance was conducted among hospitalized children in Nha Trang, Vietnam. METHODS: From April 2005 through August 2006, pediatricians at the Khanh Hoa General Hospital used standardized screening criteria to identify children aged <5 years who had signs and symptoms of invasive bacterial disease. All cerebrospinal fluid (CSF) and blood specimens collected were tested by bacterial culture. Selected culture-negative specimens were tested for Streptococcus pneumoniae by antigen detection or for Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitidis, and S. pneumoniae by polymerase chain reaction (PCR). RESULTS: A total of 987 children were enrolled (794 with pneumonia, 76 with meningitis, and 117 with other syndromes consistent with invasive bacterial disease); 84% of children were aged 0-23 months, and 57% were male. Seven (0.71%) of 987 blood cultures and 4 (15%) of 26 CSF cultures were positive for any bacterial pathogen (including 6 for H. influenzae type b and 1 for S. pneumoniae). Pneumococcal antigen testing and PCR identified an additional 16 children with invasive pneumococcal disease (12 by antigen testing and 4 by PCR). Among children aged <5 years who lived in Nha Trang, the incidence rate of invasive pneumococcal disease was at least 48.7 cases per 100,000 children (95% confidence interval, 27.9-85.1 cases per 100,000 children). CONCLUSIONS: S. pneumoniae and H. influenzae type b were the most common causes of laboratory-confirmed invasive bacterial disease in children. PCR and antigen testing increased the sensitivity of detection and provided a more accurate estimate of the burden of invasive bacterial disease in Vietnam.

Global impact of rotavirus vaccine introduction on rotavirus hospitalisations among children under 5 years of age, 2008-16: findings from the Global Rotavirus Surveillance Network.

BACKGROUND: Rotavirus vaccine use in national immunisation programmes has led to declines in hospital admissions for rotavirus gastroenteritis among children; however, the global impact of rotavirus vaccine introduction has not been described using primary data. We describe the impact of rotavirus vaccine introduction on admissions for acute rotavirus gastroenteritis in primarily low-income and middle-income countries, using 9 years of data from the WHO-coordinated Global Rotavirus Surveillance Network (GRSN). METHODS: Between Jan 1, 2008, and Dec 31, 2016, children younger than 5 years of age who were admitted to hospital with acute gastroenteritis were prospectively enrolled in GRSN sites. We included sites that enrolled children and collected stool specimens monthly and tested at least 100 specimens annually in the impact analysis, with a separate analysis taking into account site continuity. We compared proportions of acute gastroenteritis cases positive for rotavirus in the pre-vaccine and post-vaccine periods and calculated mean proportion changes for WHO regions, with 95% CIs; these findings were then compared with interrupted time series analyses. We did further sensitivity analyses to account for rotavirus vaccination coverage levels and sites that collected specimens for at least 11 months per year and tested at least 80 specimens per year. We also analysed the age distribution of rotavirus-positive cases before and after vaccine introduction. FINDINGS: 403 140 children younger than 5 years of age admitted to hospital with acute gastroenteritis from 349 sites in 82 countries were enrolled over the study period, of whom 132 736 (32·9%) were positive for rotavirus. We included 305 789 children from 198 sites in 69 countries in the impact analysis. In countries that had not introduced rotavirus vaccine in their national immunisation programmes, rotavirus was detected in 38·0% (95% CI 4·8-73·4) of admissions for acute gastroenteritis annually whereas in those that have introduced the vaccine, rotavirus was detected in 23·0% (0·7-57·7) of admissions for acute gastroenteritis, showing a 39·6% (35·4-43·8) relative decline following introduction. Interrupted time series analyses confirmed these findings. Reductions by WHO regions ranged from 26·4% (15·0-37·8) in the Eastern Mediterranean Region to 55·2% (43·0-67·4) in the European Region and were sustained in nine countries (contributing up to 31 sites) for 6-10 years. The age distribution of children with rotavirus gastroenteritis shifted towards older children after rotavirus vaccine introduction. INTERPRETATION: A significant and sustained reduction in the proportion of hospital admissions for acute gastroenteritis due to rotavirus was seen among children younger than 5 years in GRSN sites following rotavirus vaccine introduction. These findings highlight the need to incorporate rotavirus vaccines into immunisation programmes in countries that have not yet introduced them and underline the importance of high-quality surveillance. FUNDING: The GRSN receives funding from Gavi, the Vaccine Alliance and the US Centers for Disease Control and Prevention. No specific funding was provided for this Article.

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

BACKGROUND: 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. METHODS: We surveyed medical records of four representative large pediatric hospitals in China, Korea, Taiwan and Vietnam using ICD-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. RESULTS: 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. Staphylococcus aureus (n = 126) was the most common organism isolated, followed by Streptococcus pneumoniae (n = 83), Pseudomonas aeruginosa (n = 37) and Klebsiella (n = 35) and Acinetobacter species (n = 34). CONCLUSION: The age and gender distribution of empyema and pleural effusion in children in these countries are similar to the US and Western Europe. S. pneumoniae 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.

Effectiveness of monovalent rotavirus vaccine in the Philippines.

Rotavirus (RV) is an important cause of diarrheal disease particularly in children aged under 5 years. Monovalent RV vaccine (RVV) was selectively introduced in 2012 in the Philippines and in July 2014 was introduced in the public health program of a province. Two RVV doses are recommended at 6 and 10 weeks of age. We conducted a test negative case-control evaluation to assess the effectiveness of RVV when given in a routine public health program in the Philippines. From September 2014 to August 2017, 967 children aged <5 years were hospitalized with diarrhea and of these, we enrolled 600 who were eligible to have received RVV and provided stool specimens for testing. Among children ≥8 months of age who were age-eligible to have received RVV, at least one dose of RVV had an adjusted vaccine effectiveness (VE) against RV hospitalization of 60% (95% confidence interval, CI: 24%, 79%), and against severe rotavirus diarrhea, VE was 64% (95% CI: 11%, 85%). These findings support the introduction of RVV into routine public health use in the Philippines. However, other factors such as costs, cost-effectiveness and operational issues must be considered prior to adoption of the vaccine into the countries' public immunization program.

Hospital-based surveillance for rotavirus diarrhea in Ulaanbaatar, Mongolia, April 2009 through March 2016.

BACKGROUND: Diarrheal disease is one of the leading causes of illness and death in young children in the world, especially the developing countries. Diarrheal disease results in about half a million childhood death per year, ranking second among all causes worldwide. Diarrheal disease due to rotavirus infection is currently the most common cause of severe diarrhea in infants and young children worldwide. Rotavirus immunization of infants is a safe and effective public health intervention for rotavirus infection control and expected to lead to a reduction of childhood morbidity and mortality. METHODS: We conducted hospital-based surveillance at two representative hospitals in Mongolia to estimate the burden of hospitalizations for rotavirus diarrhea among children aged <5 years and to describe strain distribution patterns during 6-year study period. Fecal specimens were tested by rotavirus antigen detection enzyme immunoassay (EIA). Specimens that tested positive for rotavirus were further characterized to determine the genotype of strains by reverse-transcriptase polymerase chain reaction. RESULTS: Between April 2009 and March 2016, among 7076 eligible children with diarrhea 6078 patients were enrolled nationally. Forty-six percent (2794/6078) of EIA a specimens were positive for rotavirus. Ninety-three percent (5649/6078) of hospitalizations for diarrhea involved children less than 2 years. No deaths were recorded due to rotavirus diarrhea. The most common genotype was G3P [8] (47.7%) followed by G9P [6] (14.4%), G2P [4] (12%), and G9P [8] (7.1%). CONCLUSIONS: This study found a relatively high prevalence of severe rotavirus-associated diarrhea disease in Mongolia and infants were the most affected. It highlights the urgent need for introduction of rotavirus vaccine into the national immunization program. Continued surveillance is crucial and pre-vaccine introduction rotavirus genotype patterns in Mongolia are valuable and can be followed post-introduction to assess vaccine impact.

Pediatric hospitalizations attributable to rotavirus gastroenteritis among Cambodian children: Seven years of active surveillance, 2010-2016.

BACKGROUND: Each year, approximately 1,066 Cambodian children under five years old die of diarrhea, and 51% of these deaths are due to rotavirus gastroenteritis. Quantifying childhood hospitalizations caused by severe rotavirus infections is also important in demonstrating disease burden caused by this virus. The objective of this study is to update and confirm the current burden of pediatric hospitalizations attributable to rotavirus gastroenteritis among Cambodian children using seven years of continuous active, prospective surveillance from 2010 to 2016. We also characterize the circulating rotavirus genotypic strains during this period. METHODS: Active surveillance for rotavirus gastroenteritis was conducted from January 2010 through December 2016 at a national hospital in Phnom Penh, Cambodia. Children <60 months of age who were hospitalized for acute gastroenteritis (AGE) were consented and enrolled. Information on gender, age, clinical characteristics, and month of onset were collected. Stool specimens were collected and tested by enzyme immunoassay for the presence of rotavirus antigen, and genotyping was performed on rotavirus test-positive specimens to characterize predominant rotavirus strains during the surveillance period. RESULTS: Of 7007 children enrolled with AGE and having specimens collected, 3473 (50%) were attributed to rotavirus gastroenteritis. The majority of rotavirus hospitalizations occurred in children younger than two years old (92%). Year-round rotavirus transmission was observed, with seasonal peaks during the cooler, dry months between November and May. Genotypic trends in rotavirus were observed over the surveillance period; the predominant rotavirus strains changed from G1P[8] (2010-2012), to G2P[4] (2013-2014), the emergence of genotype G8P[8] in 2015, and G3P[8] in 2016. CONCLUSIONS: Rotavirus is the leading cause of severe acute gastroenteritis hospitalizations in Cambodian children under five years old, with 50% of such hospitalizations attributable to rotavirus. Over 90% of rotavirus hospitalizations occurred in children under 2 years of age. Changes in the predominant rotavirus strains occurred over time among these unvaccinated children. This information is important to understand and prioritize the current potential impacts upon child health that could be achieved through the introduction of rotavirus vaccines in Cambodia.

Introduction of inactivated poliovirus vaccine in the Philippines: Effect on health care provider and infant caregiver attitudes and practices.

BACKGROUND: The introduction of inactivated poliovirus vaccine (IPV) to the Philippines' national immunization schedule meant the addition of a third injectable vaccine at a child's 14-week immunization visit. Although previous studies have shown that providing multiple vaccines at the same time affected neither the risk of severe adverse events nor vaccine efficacy, concerns were raised that providing three injections at a single visit, with two injections in one leg, might be unacceptable to health care providers (HCP) and infant caregivers. METHODS: We conducted pre- and post-IPV introduction surveys on the acceptance and acceptability of the additional injectable vaccine in three of the Philippines' 17 administrative regions. Regions 3 and 6 were included in the pre-introduction phase and Regions 3, 6 and 10 were included in the post-introduction phase. Thirty public health centers (PHCs) were randomly sampled from each region. HCPs and infant caregivers were interviewed. In addition, vaccination records from a minimum of 20 eligible children pre-introduction and 10 children post-introduction per PHC were reviewed. RESULTS AND DISCUSSION: We interviewed 89 HCPs and 286 infant caregivers during the pre-introduction phase and 137 HCPs and 455 caregivers during the post-introduction phase. Among 986 vaccination records reviewed post-introduction, 84% (n = 826) of children received all three recommended injections at one visit, with a range from 61% (209/342) in Region 10 to 100% (328/328) in Region 3. The proportion of HCPs reporting that they had administered three or more injectable vaccines and the proportion of caregivers that would be comfortable with their child receiving three or more injectable vaccines at one visit increased from pre- to post-introduction (p < 0.0001 for both). Eighty-seven percent of HCPs that had administered three or more injectable vaccines post-introduction reported being comfortable or very comfortable with the number of vaccines they had administered.

Rotavirus diarrhea in hospitalized children under 5 years of age in Vientiane, Lao PDR, 2009-2015.

BACKGROUND: Diarrhea is a leading cause of death in children <5 years worldwide, causing an estimated 215,000 deaths in 2013. This evaluation tracks the epidemiologic patterns and most common rotavirus genotypes among hospitalized children in this age group with acute gastroenteritis in Lao PDR. METHODS: Children <5 years in a central tertiary hospital in the capital city were prospectively enrolled into the surveillance platform during January 2009-December 2015. We collected information regarding clinical characteristics of enrolled children. Stool samples were obtained within 24 h of hospital admission and tested for rotavirus using rotavirus antigen detection enzyme immunoassay. Samples were sent to the regional reference laboratories in Australia and South Korea for genotyping. Bivariate analyses compared demographic and clinical characteristics between rotavirus positive and negative children using Chi-square statistical testing. Seasonality of rotavirus and annual genotype distribution are also described. RESULTS: We enrolled 1853 children <5 years with acute gastroenteritis during the surveillance period and collected 1772 fecal specimens, 982 (55%) of which tested positive for rotavirus. A higher proportion of rotavirus acute gastroenteritis was observed among children 12-23 months of age as compared to rotavirus negative children in the same age group, 41% vs 36%. Eighty-six percent of rotavirus positive children experienced vomiting, as compared to 65% of rotavirus negative children. Eighty-five percent (n = 830/982) of rotavirus positive specimens occurred during the dry season (January-April). The most common genotypes identified were G1, G2, G3 and P8 and P4. The most prevalent combined genotype differed annually during the surveillance period. CONCLUSION: Surveillance continues to be important in documenting the burden of rotavirus in children <5 years in Lao PDR as well as providing a baseline for determining the impact of rotavirus vaccine once it is introduced into Lao PDR's national immunization schedule.

Haemophilus influenzae type B meningitis among children in Hanoi, Vietnam: epidemiologic patterns and estimates of H. Influenzae type B disease burden.

From March 2000 to February 2002, a population-based study of Haemophilus influenzae type b (Hib) meningitis was conducted among children less than five years of age in Hanoi, Vietnam. Children with suspected bacterial meningitis were referred to hospitals and each patient underwent standardized clinical examination and microbiologic testing. In Hanoi, 580 children were evaluated for bacterial meningitis and 23 (4%) had confirmed or probable Hib meningitis. The incidence of all Hib meningitis was 12/100,000 child-years less than five years of age and 26/100,000 child-years less than two years of age. Nationally, an estimated 1,005 children less than five years of age are hospitalized for Hib meningitis and 5,107 are hospitalized for Hib pneumonia. Among children with Hib meningitis, at least 100 will develop severe neurologic sequelae and 40 will die. These data suggest there is a substantial burden of Hib disease in Vietnam. National leaders will be provided with these data to facilitate development of national vaccination policies for children in Vietnam.

Vaccine introduction in the Democratic People's Republic of Korea.

The feasibility of mass vaccination campaigns for Japanese encephalitis and Haemophilus influenzae type b infections was explored in the Democratic People's Republic of Korea using pilot vaccination studies. The experiences from these initial studies were then used to support larger vaccination campaigns in children at risk of these infections. We discuss the challenges and requirements for the inclusion of additional vaccines into the existing expanded program on immunization in the country.

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.

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.

The Supporting Independent Immunization and Vaccine Advisory Committees (SIVAC) initiative: a country-driven, multi-partner program to support evidence-based decision making.

Multiple health priorities, limited human resources and logistical capacities, as well as expensive vaccines with limited funds available increase the need for evidence-based decision making in immunization programs. The aim of the Supporting Independent Immunization and Vaccine Advisory Committees (SIVAC) Initiative is to support countries in the establishment or strengthening of National Immunization Technical Advisory Groups (NITAGs) that provide recommendations on immunization policies and programs (e.g., vaccination schedules, improvements of routine immunization coverage, new vaccine introduction, etc.). SIVAC, a program funded by the Bill & Melinda Gates Foundation, is based on a country-driven, step-by-step process that ensures its support is tailored to country needs and emphasizes NITAG sustainability. SIVAC supports countries by reinforcing the capacities of the NITAG scientific and technical secretariat and by providing specific support activities established in consultation with the country and other international partners. Additionally, SIVAC and partners have built an electronic platform, the NITAG Resource Center, that provides information, tools, and briefings to NITAGs and the immunization community.

Hospital-based surveillance for rotavirus diarrhoea in Phnom Penh, Cambodia, March 2005 through February 2007.

Globally rotavirus is the most common cause of severe gastroenteritis in children. From March 2005 through February 2007, a prospective hospital-based surveillance study was conducted at a national hospital in Phnom Penh, Cambodia, to estimate the burden of rotavirus hospitalizations among children aged <5 years old and to determine strain patterns. Children with diarrhoea underwent standard clinical evaluations. Parents were interviewed for demographic and family information. Faecal specimens were tested for rotavirus by enzyme immunoassay (EIA) and positive specimens were further characterized. Of 2817 hospitalized children with diarrhoea, 56% (n=1278) were positive for rotavirus antigen. The G1P[8] strain was the most common genotype (53%) followed by G2P[4] (10%). The findings suggest a need for improved prevention and control programs for rotavirus diarrhoea in Cambodia.