Rosalyn J. Singleton

Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis

Summary Background The global burden of disease attributable to respiratory syncytial virus (RSV) remains unknown. We aimed to estimate the global incidence of and mortality from episodes of acute lower respiratory infection (ALRI) due to RSV in children younger than 5 years in 2005. Methods We estimated the incidence of RSV-associated ALRI in children younger than 5 years, stratified by age, using data from a systematic review of studies published between January, 1995, and June, 2009, and ten unpublished population-based studies. We estimated possible boundaries for RSV-associated ALRI mortality by combining case fatality ratios with incidence estimates from hospital-based reports from published and unpublished studies and identifying studies with population-based data for RSV seasonality and monthly ALRI mortality. Findings In 2005, an estimated 33·8 (95% CI 19·3–46·2) million new episodes of RSV-associated ALRI occurred worldwide in children younger than 5 years (22% of ALRI episodes), with at least 3·4 (2·8–4·3) million episodes representing severe RSV-associated ALRI necessitating hospital admission. We estimated that 66 000–199 000 children younger than 5 years died from RSV-associated ALRI in 2005, with 99% of these deaths occurring in developing countries. Incidence and mortality can vary substantially from year to year in any one setting. Interpretation Globally, RSV is the most common cause of childhood ALRI and a major cause of admission to hospital as a result of severe ALRI. Mortality data suggest that RSV is an important cause of death in childhood from ALRI, after pneumococcal pneumonia and Haemophilus influenzae type b. The development of novel prevention and treatment strategies should be accelerated as a priority. Funding WHO; Bill & Melinda Gates Foundation.

Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis.

Summary Background The annual number of hospital admissions and in-hospital deaths due to severe acute lower respiratory infections (ALRI) in young children worldwide is unknown. We aimed to estimate the incidence of admissions and deaths for such infections in children younger than 5 years in 2010. Methods We estimated the incidence of admissions for severe and very severe ALRI in children younger than 5 years, stratified by age and region, with data from a systematic review of studies published between Jan 1, 1990, and March 31, 2012, and from 28 unpublished population-based studies. We applied these incidence estimates to population estimates for 2010, to calculate the global and regional burden in children admitted with severe ALRI in that year. We estimated in-hospital mortality due to severe and very severe ALRI by combining incidence estimates with case fatality ratios from hospital-based studies. Findings We identified 89 eligible studies and estimated that in 2010, 11·9 million (95% CI 10·3–13·9 million) episodes of severe and 3·0 million (2·1–4·2 million) episodes of very severe ALRI resulted in hospital admissions in young children worldwide. Incidence was higher in boys than in girls, the sex disparity being greatest in South Asian studies. On the basis of data from 37 hospital studies reporting case fatality ratios for severe ALRI, we estimated that roughly 265 000 (95% CI 160 000–450 000) in-hospital deaths took place in young children, with 99% of these deaths in developing countries. Therefore, the data suggest that although 62% of children with severe ALRI are treated in hospitals, 81% of deaths happen outside hospitals. Interpretation Severe ALRI is a substantial burden on health services worldwide and a major cause of hospital referral and admission in young children. Improved hospital access and reduced inequities, such as those related to sex and rural status, could substantially decrease mortality related to such infection. Community-based management of severe disease could be an important complementary strategy to reduce pneumonia mortality and health inequities. Funding WHO.

Bronchiectasis in Alaska Native children: Causes and clinical courses†

Although bronchiectasis has become a rare condition in U.S. children, it is still commonly diagnosed in Alaska Native children in the Yukon Kuskokwim Delta. The prevalence of bronchiectasis has not decreased in persons born during the 1980s as compared with those born in the 1940s. We reviewed case histories of 46 children with bronchiectasis.

The Relationship Between In-Home Water Service and the Risk of Respiratory Tract, Skin, and Gastrointestinal Tract Infections Among Rural Alaska Natives

OBJECTIVES We investigated the relationship between the presence of in-home piped water and wastewater services and hospitalization rates for respiratory tract, skin, and gastrointestinal tract infections in rural Alaska. METHODS We determined in-home water service and hospitalizations for selected infectious diseases among Alaska Natives by region during 2000 to 2004. Within 1 region, infant respiratory hospitalizations and skin infections for all ages were compared by village-level water services. RESULTS Regions with a lower proportion of home water service had significantly higher hospitalization rates for pneumonia and influenza (rate ratio [RR] = 2.5), skin or soft tissue infection (RR = 1.9), and respiratory syncytial virus (RR = 3.4 among those younger than 5 years) than did higher-service regions. Within 1 region, infants from villages with less than 10% of homes served had higher hospitalization rates for pneumonia (RR = 1.3) and respiratory syncytial virus (RR = 1.2) than did infants from villages with more than 80% served. Outpatient Staphylococcus aureus infections (RR = 5.1, all ages) and skin infection hospitalizations (RR = 2.7, all ages) were higher in low-service than in high-service villages. CONCLUSIONS Higher respiratory and skin infection rates were associated with a lack of in-home water service. This disparity should be addressed through sanitation infrastructure improvements.

Reemergence of invasive Haemophilus influenzae type b disease in a well-vaccinated population in remote Alaska.

Before vaccination, Alaska Natives experienced very high rates of invasive Haemophilus influenzae type b (Hib) disease and carriage. Vaccination with Hib conjugate vaccine PRP-OMP (polyribosylribitol phosphate Neisseria meningitidis outer membrane protein) began in 1991 and resulted in a sharp decline in cases. In 1996, after switching to a different Hib conjugate vaccine, DTP-HbOC (which combines diphtheria-tetanus-whole cell pertussis vaccines with HbOC [Hib oligosaccharide CRM197]), cases of invasive Hib disease increased, suggesting ongoing Hib transmission despite widespread vaccination. To determine the prevalence of and risk factors for carriage, a cross-sectional study of oropharyngeal Hib carriage was conducted among Alaska Native children aged 1-5 years in remote southwestern Alaska. Of 496 children with swabs taken, 46 (9.3%) were colonized with Hib. Carriage rates varied by village from 2.2% to 13.2% and by age from 6.1% in 1-year-olds to 14.7% in 5-year-olds. Crowding was associated with Hib carriage. Widespread vaccination with PRP-OMP Hib conjugate vaccine did not eliminate carriage in this population of Alaska Natives, and ongoing carriage contributed to disease resurgence.

Viral respiratory infections in hospitalized and community control children in Alaska

Respiratory syncytial virus (RSV) in Alaska Native children from the Yukon Kuskokwim (YK) Delta is associated with a hospitalization rate five times higher than that reported for the general US child population. The role of other viral respiratory pathogens has not been studied in this population. YK Delta children <3 years of age hospitalized with respiratory infections and same aged community control children were prospectively enrolled between October 2005 and September 2007. Polymerase chain reaction detection of viruses was performed on nasopharyngeal samples. Characteristics of hospitalized and asymptomatic control children were analyzed. From October 2005 to September 2007, 440 hospitalized and 425 control children were analyzed. Respiratory viruses were detected in 90% (395) of hospitalized children: 194 (44%) rhinovirus, 131 (30%) adenovirus, 102 (23%) RSV, 77 (18%) para influenza viruses (PIV), 66 (15%) human metapneumovirus (hMPV), 23 (5%) influenza, and 25 (6%) coronavirus. Fifty‐two percent (221) of control children had a virus detected, most commonly rhinovirus (33%), and adenovirus (16%). RSV, PIV, hMPV, and influenza were significantly more common in hospitalized cases than control children, but rhinovirus, adenovirus, and coronavirus were not. RSV and hMPV were associated with higher severity of illness. In this study, RSV remains the most important virus associated with respiratory hospitalization, although hMPV and PIV were also common. RSV and hMPV were associated with more severe illness. Rhinovirus and adenovirus were detected in two‐thirds of hospitalized children, but their frequent detection in control children made their role in respiratory hospitalization uncertain. J. Med. Virol. 82:1282–1290, 2010.

Severe Respiratory Syncytial Virus Disease in Alaska Native Children

Hospitalization rates for respiratory syncytial virus (RSV) infection range from 1 to 20/1000 infants. To determine the rate and severity of RSV infections requiring hospitalization for infants in the Yukon-Kuskokwim (YK) Delta of Alaska, a 3-year prospective surveillance study was conducted. The annual rate of RSV hospitalization for YK Delta infants <1 year of age was 53-249/1000. RSV infection was the most frequent cause of infant hospitalization. RSV disease severity did not differ among non-high-risk infants in the YK Delta and at Johns Hopkins Hospital (JHH). On average, 1/125 infants born in the YK Delta required mechanical ventilation for RSV infection. During the peak season, approximately

Elimination of hepatocellular carcinoma and acute hepatitis B in children 25 years after a hepatitis B newborn and catch‐up immunization program

1034/child <3 years of age was spent on RSV hospitalization in the YK Delta. In YK Delta infants </=6 months old, RSV microneutralizing antibody titers <1200 were associated with severe disease (odds ratio=6.2, P=.03). In the YK Delta and at JHH, newborns may be at greater risk for severe RSV illness than previously thought.

Lower respiratory tract infections among american Indian and Alaska Native children and the general population of U.S. Children.

Alaska Native people experience the highest rates of acute and chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) in the United States. We examined the effect of a universal newborn immunization with hepatitis B vaccine and mass population screening immunization program initiated in 1984 on rates of HBV and HCC in children 25 years later. During this time, the population of Alaska Native people grew from an estimated 75,000 to 130,000 persons. A surveillance system to detect acute HBV infection in Alaska Native facilities was established in 1981. Cases of HCC in children under 20 years of age were identified using a National Cancer Institute (NCI)‐funded Cancer Registry established in 1969 coupled with an active surveillance program of screening persons with chronic HBV semiannually for alpha‐fetoprotein since 1982. The incidence of acute symptomatic HBV infection in persons <20 years of age fell from cases 19/100,000 in 1981‐1982 to 0/100,000 in 1993‐1994. No cases of acute HBV have occurred in children since 1992. The incidence of HCC in persons <20 years decreased from 3/100,000 in 1984‐1988 to zero in 1995‐1999 and no cases have occurred since 1999. The number of identified hepatitis B surface antigen‐positive children <20 years in the Alaska Native population declined from 657 in 1987 to two in 2008. Conclusion: Universal newborn vaccination coupled with mass screening and immunization of susceptible Alaska Natives has eliminated HCC and acute symptomatic HBV infection among Alaska Native children and this approach is the best way to prevent HBV‐related disease in children. (HEPATOLOGY 2011;)

Respiratory Syncytial Virus Hospitalizations Among American Indian and Alaska Native Infants and the General United States Infant Population

Background and Objective: Lower respiratory tract infections (LRTIs) cause substantial childhood morbidity. This study characterizes and compares LRTI-associated morbidity among American Indian/Alaska Native (AI/AN) children and the general population of U.S. children. Methods: Hospitalization and outpatient records with a diagnosis indicating LRTIs were evaluated for children aged younger than 5 years during 1990–2001. Results: For 1999–2001, the LRTI-associated hospitalization rate was significantly higher for AI/AN children than for U.S. children (116.1 versus 63.2/1000, respectively), with the disparity being greater for infants than for 1- to 4-year-old children. Also the rate of LRTI-associated outpatient visits among AI/AN infants was higher than that for all U.S. infants (737.7 versus 207.2/1000, respectively). LRTI hospitalization and outpatient visit rates were highest in the Alaska and Southwest Indian Health Service regions. During 1990–2001, the LRTI hospitalization rate among AI/AN infants in the Alaska region and among the general U.S. infant population increased. Bronchiolitis-associated hospitalization rates increased for AI/AN and U.S. infants, whereas the pneumonia-associated hospitalization rate decreased among AI/AN infants and remained stable among U.S. infants. Conclusions: LRTIs continue to be an important cause of morbidity in children, especially among AI/AN infants in the Alaska and Southwest regions. Strategies to reduce LRTI hospitalizations and outpatient visits are warranted for all infants, but the greatest potential impact would be among AI/AN infants.