Paul E. Kilgore

First report from the Asian Rotavirus Surveillance Network.

Rotavirus remains the most common cause of severe, dehydrating diarrhea among children worldwide. Several rotavirus vaccines are under development. Decisions about new vaccine introduction will require reliable data on disease impact. The Asian Rotavirus Surveillance Network, begun in 2000 to facilitate collection of these data, is a regional collaboration of 36 hospitals in nine countries or areas that conduct surveillance for rotavirus hospitalizations using a uniform World Health Organization protocol. We summarize the Networks organization and experience from August 2001 through July 2002. During this period, 45% of acute diarrheal hospitalizations among children 0–5 years were attributable to rotavirus, higher than previous estimates. Rotavirus was detected in all sites year-round. This network is a novel, regional approach to surveillance for vaccine-preventable diseases. Such a network should provide increased visibility and advocacy, enable more efficient data collection, facilitate training, and serve as the paradigm for rotavirus surveillance activities in other regions.

Association between nasopharyngeal load of Streptococcus pneumoniae, viral coinfection, and radiologically confirmed pneumonia in Vietnamese children.

Background: The interplay between nasopharyngeal bacterial carriage, viral coinfection, and lower respiratory tract infections (LRTIs) is poorly understood. We explored this association in Vietnamese children aged less than 5 years. Methods: A hospital-based case-control study of pediatric LRTIs was conducted in Nha Trang, Vietnam. A total of 550 hospitalized children (274 radiologically confirmed pneumonia [RCP] and 276 other LRTIs) were enrolled and 350 healthy controls were randomly selected from the community. Polymerase chain reaction-based methods were used to measure bacterial loads of Streptococcus pneumoniae (SP), Haemophilus influenzae, and Moraxella catarrhalis and to detect 13 respiratory viruses and bacterial serotypes in nasopharyngeal samples of study participants. Results: The median nasopharyngeal bacterial load of SP was substantially higher in children with RCP compared with healthy controls or children with other LRTIs (P < 0.001). SP load was 15-fold higher in pneumonia children with viral coinfection compared with those children without viral coinfection (1.4 × 107/mL vs. 9.1 × 105/mL; P = 0.0001). SP load was over 200-fold higher in serotypeable SP compared with nontypeable SP (2.5 × 106/mL vs. 1 × 104/mL; P < 0.0001). These associations were independent of potential confounders in multiple regression models. No clear association was found between nasopharyngeal load of Haemophilus influenzae or Moraxella catarrhalis and viral coinfection in either RCP or other LRTIs groups. Conclusions: An increased load of SP in the nasopharynx was associated with RCP, viral coinfection, and presence of pneumococcal capsule.

Health Care Costs of Diarrheal Disease and Estimates of the Cost-Effectiveness of Rotavirus Vaccination in Vietnam

BACKGROUND Rotavirus disease causes a significant health and economic burden worldwide. Several rotavirus vaccines may soon be available for use. A countrys decision to introduce these vaccines will depend on its rotavirus disease burden, on the cost of the vaccine, and on the results of an economic assessment of the cost and effectiveness of a rotavirus vaccination program. METHODS Data on medical and nonmedical direct costs and indirect costs were established in Khanh Hoa Province, Vietnam, and extrapolated to national estimates on the basis of the birth cohort in 2004. The main outcome measures were economic burden and cost-effectiveness ratio (United States dollars per disability-adjusted life-year averted and dollars per life saved) of vaccination. RESULTS The disease burden is equivalent to an economic burden of an estimated 3.1 million US dollars in medical direct costs, 685,000 US dollars in nonmedical direct costs, and 1.5 million US dollars in indirect costs. From a societal perspective, treatment of rotavirus disease costs an estimated 5.3 million US dollars per year. From the health care system perspective, universal vaccination of infants at a cost of < or = 7.26 US dollars/vaccine dose would be a cost-effective public health intervention, according to the World Bank cost-effectiveness standard for low-income countries (140 US dollars/disability-adjusted life-year). CONCLUSIONS Vaccination can effectively reduce the disease burden and health care costs of rotavirus-specific diarrhea in Vietnam.

Incidence and Burden of Rotavirus Gastroenteritis in Japan, as Estimated from a Prospective Sentinel Hospital Study

We assessed the burden of rotavirus infection-related disease, in terms of hospitalization and associated costs, at 3 sentinel hospitals in Akita prefecture, Japan. From January 2001 through December 2002, a total of 443 children <5 years of age were hospitalized for acute gastroenteritis. Of 422 stool specimens collected, 244 (58%) tested positive for rotavirus. Only 7.8% of the rotavirus disease-associated hospitalizations involved infants <6 months of age, whereas most cases of disease (39%) were reported in the second year of life, and 89% of cases had occurred by 36 months of age. The mean severity score for rotavirus gastroenteritis resulting in hospitalization was 16.5, according to the modified 20-point severity scoring system. The average associated direct medical cost was 136,000 yen (1236 US dollars) per case and was similar among the 3 hospitals. The estimated incidence of rotavirus disease-associated hospitalizations among children <5 years of age was 7.9-17.6 hospitalizations/1000 person-years, and the estimated cumulative incidence by 5 years of age was 6.6%. Thus, approximately 1 in 15 children will require hospitalization due to rotavirus diarrhea by their fifth year of life. In Japan, this would mean that 78,000 children <5 years of age would be hospitalized each year, resulting in a direct medical cost of 10 billion yen (96 US dollars million). The burden associated with rotavirus gastroenteritis in Japan is substantial and might be reduced through the introduction of vaccines.

Visualizing geographic and temporal trends in rotavirus activity in the United States, 1991 to 1996

BACKGROUND Rotavirus is the leading cause of severe pediatric gastroenteritis worldwide. A vaccine may soon be licensed for use in the United States to prevent this disease. To characterize US geographic and temporal trends in rotavirus activity, we made contour maps showing the timing of peak rotavirus activity. METHODS From July, 1991, through June, 1996, 79 laboratories participating in the National Respiratory and Enteric Virus Surveillance System reported on a weekly basis the number of stool specimens that tested positive for rotavirus. The peak weeks in rotavirus detections from each laboratory were mapped using kriging, a modeling technique originally developed for geostatistics. RESULTS During the 5-year period 118,716 fecal specimens were examined, of which 27,616 (23%) were positive for rotavirus. Timing of rotavirus activity varied by geographic location in a characteristic pattern in which peak activity occurred first in the Southwest from October through December and last in the Northeast in April or May. The Northwest exhibited considerable year-to-year variability (range, December to May) in the timing of peak activity, whereas the temporal pattern in the remainder of the contiguous 48 states was relatively constant. CONCLUSION Kriging is a useful method for visualizing geographic and temporal trends in rotavirus activity in the United States. This analysis confirmed trends reported in previous years, and it also identified unexpected variability in the timing of peak rotavirus activity in the Northwest. The causes of the seasonal differences in rotavirus activity by region are unknown. Tracking of laboratory detections of rotavirus may provide an effective surveillance tool to assess the impact of a rotavirus vaccination campaign in the United States.

Sentinel Hospital Surveillance for Rotavirus Diarrhea in the People's Republic of China, August 2001–July 2003

China has the second largest birth cohort in the world and the second highest number of deaths due to rotavirus infection. It is also the only country with a licensed rotavirus vaccine. Chinese policy makers now need credible estimates of the burden of rotavirus disease, to decide about vaccine use. From August 2001 through July 2003, prospective hospital-based surveillance for rotavirus diarrhea among children <5 years of age was conducted in 6 sentinel hospitals. Rotavirus isolates were characterized to determine the G and P genotypes circulating during the study. Of 3149 children who were admitted to the hospitals for diarrhea and for whom screening for rotavirus was performed, 1590 (50%) had positive results of an antigen detection assay. Of all episodes of rotavirus diarrhea, 95% occurred during the first 2 years of life. The most common rotavirus strain was P[8]G3 (49% of episodes), and all the common strains were detected, including G9 strains (4% of episodes). Ongoing efforts are under way to more precisely define the burden of rotavirus diarrhea in urban and rural populations, to assess the proportion of episodes that may be due to unusual or emerging strains, and to estimate the economic burden of rotavirus disease.

Epidemiological Profile of Rotavirus Infection in the Republic of Korea: Results from Prospective Surveillance in the Jeongeub District, 1 July 2002 through 30 June 2004

To facilitate future decisions regarding the usefulness of rotavirus vaccines in the Republic of Korea, active surveillance was conducted in a network of clinics, emergency departments, and hospitals serving Jeongeub District, Korea. Children with diarrhea underwent standard clinical evaluations, and stool specimens were collected to test for the presence of rotavirus. Parents were interviewed to collect demographic and family information. From 1 July 2002 through 30 June 2004, a total of 4106 children, representing 1 (50%) of every 2 children <5 years old in the study population, were evaluated for rotavirus diarrhea. Of the 2232 stool specimens obtained throughout the year, 460 (20.6%) were rotavirus positive; however, the monthly prevalence of rotavirus infection peaked at 49.5% in February 2004. Of the 460 rotavirus-positive stool specimens, 366 were obtained from children who visited outpatient clinics, and 94 were obtained from children who were hospitalized. By extrapolating the proportion of rotavirus-positive patients to all children with diarrhea in the surveillance system, we calculate that 882 children in Jeongeub District had rotavirus infection (which would predict that there would be 702 associated clinic visits and 180 hospitalizations). Genotyping of rotavirus strains showed that 39% of strains were type G9P[8], 24% were type G1P[8], 17% were type G3P[8], and 13% were type G2P[4]. The incidence of rotavirus diarrhea peaked at age 13-24 months, and 94% of cases occurred during the first 3 years of life. The annual incidence of all rotavirus disease-associated outcomes was 56.9 cases/1000 children <5 years old (95% confidence interval [CI], 51.9-62.2 cases/1000 children <5 years old). The incidence of rotavirus disease-associated hospitalizations was 11.6 cases/1000 children <5 years old (95% CI, 9.5-14.2 cases/1000 children <5 years old). In Korea, diarrhea is common during childhood, and the incidence of diarrhea due to rotavirus infection suggests that improved programs for the prevention and control of both rotavirus diarrhea and diarrhea due to other causes are needed.

Anticipating rotavirus vaccines : hospital-based surveillance for rotavirus diarrhea and estimates of disease burden in Bangladesh

OBJECTIVES Rotavirus is the most common cause of severe diarrhea in children worldwide, and a vaccine may soon be licensed and available for use in immunization programs. To assess the need for a rotavirus vaccine in Bangladesh, we estimated the disease burden of rotavirus diarrhea from national vital statistics for births and diarrheal deaths, together with hospital surveillance data on the proportion of severe childhood diarrhea attributed to rotavirus. METHODS From 1990 through 1993, hospital surveillance was conducted of a systematic, random 4% sample of >80,000 patients with diarrhea who sought care each year at the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B). RESULTS Rotavirus was detected in 20% (1561 of 7709) of fecal specimens from children with diarrhea <5 years of age; 92% of all cases (1436) occurred in children <2 years of age, but only 3% (50) of cases occurred in infants <3 months of age. Children infected with rotavirus were more likely to have watery stools (P < 0.001), severe vomiting (P < 0.001) but less severe dehydration (P = 0.007) than children infected with other enteropathogens. CONCLUSIONS We estimate that in this setting, where 18% of children die by age 5 and about 25% of these succumb to diarrhea, between 14,850 and 27,000 of the 3 million Bangladeshi children born in 1994 will die of rotavirus by the age of 5 years, equivalent to 1 rotavirus death per 111 to 203 children. The estimated burden of rotavirus diarrhea in Bangladesh is sufficiently great to warrant field testing of rotavirus vaccines for possible inclusion in the current immunization program.

Association of environmental tobacco smoking exposure with an increased risk of hospital admissions for pneumonia in children under 5 years of age in Vietnam

Background: The association between environmental tobacco smoking (ETS) and childhood pneumonia has not been established in developed or developing countries. A study was conducted to assess the effect and impact of ETS exposure on pneumonia among children in central Vietnam. Methods: A population-based large-scale cross-sectional survey was conducted covering all residents of 33 communes in Khanh Hoa Province, the central part of Vietnam. Information on demographics, socioeconomic status and house environment, including smoking status of each household member, was collected from householders. Hospital admissions for pneumonia among children aged <5 years in each household in the previous 12 months were recorded based on caregiver’s report. Results: A total of 353 525 individuals living in 75 828 households were identified in the study areas. Of these, 24 781 (7.0%) were aged <5 years. The prevalence of ETS was 70.5% and the period prevalence of hospital admissions for pneumonia was 2.6%. Multiple logistic regression analysis showed that exposure to ETS was independently associated with hospital admissions for pneumonia (adjusted odds ratio 1.55, 95% CI 1.25 to 1.92). The prevalence of tobacco smoking was higher among men than women (51.5% vs 1.5%). It is estimated that 28.7% of childhood pneumonia in this community is attributable to ETS. Conclusions: Children in Vietnam are exposed to substantial levels of ETS which results in 44 000 excess hospital admissions due to pneumonia each year among children aged <5 years.

Viral pathogens associated with acute respiratory infections in central Vietnamese children.

Hospitalized Vietnamese children with acute respiratory infection were investigated for 13 viral pathogens using multiplex-polymerase chain reaction. We enrolled 958 children of whom 659 (69%) had documented viral infection: rhinovirus (28%), respiratory syncytial virus (23%), influenza virus (15%), adenovirus (5%), human metapneumo virus (4.5%), parainfluenza virus (5%), and bocavirus (2%). These Vietnamese children had a range of respiratory viruses which underscores the need for enhanced acute respiratory infection surveillance in tropical developing countries.