Effectiveness of influenza vaccination of day care children in reducing influenza-related morbidity among household contacts.

CONTEXT: A growing proportion of young children in the United States participate in day care, and these children are considered to be at high risk for influenza infection. Whether vaccinating day care children reduces household transmission of influenza is not known. OBJECTIVE: To evaluate the effect of vaccinating day care children on reducing influenza-related morbidity among their household contacts. DESIGN: Single-blind, randomized controlled trial conducted during the 1996-1997 influenza season. SETTING: Ten day care centers for children of US Navy personnel in San Diego, Calif. PARTICIPANTS: A total of 149 day care attendees (aged 24-60 months) and their families were randomized; 127 children and their 328 household contacts received 2 vaccine doses and were included in the analysis. INTERVENTIONS: Inactivated influenza vaccine was administered to 60 children with 162 household contacts, and hepatitis A vaccine as a control was administered to 67 age-matched children with 166 household contacts. MAIN OUTCOME MEASURES: Information regarding febrile respiratory illnesses and related morbidity for household contacts of influenza-vaccinated vs control children (subgrouped by influenza-vaccinated and unvaccinated contacts), obtained by telephone interviews with parents every 2 weeks from November 1996 through April 1997. RESULTS: Influenza-unvaccinated household contacts (n = 120) of influenza-vaccinated day care children had 42% fewer febrile respiratory illnesses (P =.04) compared with unvaccinated household contacts of control children. Among school-aged household contacts (aged 5-17 years), there was an 80% reduction among contacts of vaccinated children (n = 28) vs contacts of unvaccinated children (n = 31) in febrile respiratory illnesses (P =.01), as well as reductions of more than 70% in school days missed (P =.02), reported earaches (P =.02), physician visits (P =.007), physician-prescribed antibiotics (P =.02), and adults who missed work to take care of ill children (P =.04). CONCLUSIONS: These results indicate that vaccinating day care children against influenza helps reduce influenza-related morbidity among their household contacts, particularly among school-aged contacts. Future studies should be conducted in civilian populations to assess the full effect of vaccinating day care children against influenza. JAMA. 2000;284:1677-1682.

Studies of the 1996-1997 inactivated influenza vaccine among children attending day care: immunologic response, protection against infection, and clinical effectiveness.

A randomized, blinded, pilot study of influenza vaccine administered to children attending day care centers was conducted during the 1996-1997 winter. Vaccine efficacy in preventing serologically proven influenza virus infection was 0.45 (95% confidence limit [CL]: -0.02, 0.69) for influenza B and 0.31 (95% CL: -0.95, 0.73) for influenza A(H3N2). For both influenza A(H3N2) and B, children without preexisting hemagglutination inhibition (HI) antibody to these antigens had lower antibody responses to vaccine, were less likely to develop a serological response, and were more likely to develop serological evidence of influenza infection. Although there were no reductions in respiratory or febrile respiratory illnesses among all vaccinated children, there was a trend for reductions in such illnesses among vaccinated children with preexisting HI antibodies to influenza A(H3N2) and B. Therefore, immunologic priming in young children may be important for vaccine response and for protection against infection. Larger studies are needed in other influenza seasons to assess vaccine efficacy and clinical effectiveness.

Chronic liver disease mortality in the United States, 1979 through 1989.

OBJECTIVES: Rates and trends for chronic liver disease mortality in the United States were examined. METHODS: National Center for Health Statistics data on underlying cause of death for chronic liver disease for the United States from 1979 through 1989 were analyzed. Four groups of diseases and conditions included under the International Classification of Diseases, 9th Revision, code for chronic liver disease were assessed separately. RESULTS: From 1979 through 1989, there were 303,875 deaths from chronic liver disease; 48% were in the cirrhosis without alcohol group, 42% in the alcohol-related liver disease group, 8% in the liver disease without alcohol group, and 1.5% in the biliary cirrhosis group. Chronic liver disease death rates for Blacks were more than 1.5 times greater than those for Whites and for other races. Chronic liver disease mortality declined 22% overall among both sexes. The largest decreases were for liver disease without alcohol (42%) and cirrhosis without alcohol (25%), followed by alcohol-related liver disease (14%) and biliary cirrhosis (12%). CONCLUSION: Although declines in US chronic liver disease deaths have been attributed to declining alcohol consumption, these analyses suggest that greater declines have occurred in deaths not coded as alcohol related.

Measles immunity in a population of healthcare workers.

OBJECTIVES: To evaluate measles seroprevalence among cohorts of new employees and to evaluate vaccine responses of susceptible adult healthcare workers. DESIGN: New employees were screened for measles susceptibility as part of employee evaluations. Anti-IgG measles antibody tests were completed on 2,473 workers. Demographic, measles history, and measles vaccination information was collected using a short questionnaire. Susceptible workers were vaccinated and screened for vaccine responses following vaccination. RESULTS: Ninety-three workers (4%) were seronegative, and 56 (2%) were equivocal. Individuals in the youngest cohort (born after 1956) were significantly more likely to be susceptible than those in the middle cohort (born 1951 to 1956) and those in the oldest cohort (born before 1951) (P < 0.01). The middle cohort included eight (5%) of the 149 seronegative or equivocal workers. Among the members of the youngest cohort, those from the United States were more likely to be susceptible (P < 0.01) than those from outside the United States. Of the 106 vaccinated susceptible workers whose follow-up serologies were determined, 90 (85%) developed positive IgG serologies, six had equivocal results, and 10 were seronegative. Eleven of the 16 non- or hyporesponders were revaccinated and re-evaluated; nine developed low positive IgG antimeasles levels, one exhibited an equivocal response, and one failed to respond. CONCLUSIONS: A small but important proportion of healthcare workers are susceptible to measles. Whenever feasible, measles immunity programs for healthcare workers should include workers born before 1957. Of workers born after 1956, those from outside the United States are more likely to be immune than workers from inside the United States. Using the currently available vaccine, revaccination of initial non- or hyporesponders appears to be effective.

Nodular regenerative hyperplasia of the liver in idiopathic hypereosinophilic syndrome.

We report a 52-year-old man with idiopathic hypereosinophilic syndrome and nodular regenerative hyperplasia of the liver. We postulate that nodular regenerative hyperplasia may be the result of an eosinophil-induced vascular lesion.

Outbreak of Kawasaki syndrome in Denver, Colorado: association with rug and carpet cleaning.

Between October 1984 and January 1985, the largest outbreak of Kawasaki syndrome reported to date in the continental United States (62 cases) occurred in the Front Range of the Rocky Mountains, extending from Colorado Springs, Colorado, to Cheyenne, Wyoming. Fifty-two (84%) of these Kawasaki syndrome patients lived in the Denver metropolitan area. A case-control study revealed that 16 (62%) of 26 Kawasaki syndrome patients compared with 10 (20%) of 49 matched control subjects had a history of exposure to shampooed (19%) or spot-cleaned (81%) rugs or carpets within 30 days of the Kawasaki syndrome onset date (odds ratio = 5, P less than .01). The time of exposure to shampooed or spot-cleaned rugs or carpets for 9 of 10 Kawasaki syndrome patients who had a single exposure and for all 6 Kawasaki syndrome patients who had multiple exposures were clustered within an interval 13 to 30 days before the onset of illness. Although the reason for this unusually large outbreak remains obscure, it is the third in which a statistically significant association between Kawasaki syndrome and rug or carpet cleaning has been found.

Risk of respiratory illness associated with day-care attendance: a nationwide study.

The risk of respiratory and other illnesses in children (age groups: 6 weeks through 17 months, 18 through 35 months, and 36 through 59 months) in various types of day-care facilities was studied. Children considered exposed to day care were those who were enrolled in day care with at least one unrelated child for at least 10 hours per week in each of the 4 weeks before the interview; unexposed children were not enrolled in any regular child care with unrelated children and did not have siblings younger than 5 years of age receiving regular care with unrelated children. Although an increased risk of respiratory illness was associated with attending day care for children in all three age groups, this risk was statistically significant only for children 6 weeks through 17 months of age (odds ratio = 1.6; 95% confidence interval = 1.1 to 2.4) and children 18 through 35 months of age who had no older siblings (odds ratio = 3.4; 95% confidence interval = 2.0 to 6.0). In contrast, day-care attendance was not associated with an increased risk of respiratory illness in children 18 through 35 months of age with older siblings (odds ratio = 1.0). For children aged 6 weeks through 17 months, the exposure to older siblings was associated with an increased risk of respiratory illness; however, for children aged 36 through 59 months, older siblings were protective against respiratory illness. In addition, for the children in each age group currently in day care, increased duration of past exposure to day care was associated with a decreased risk of respiratory illness.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk of infection following exposures to human parvovirus B19.

In response to concern about the effect of human parvovirus B19 infection of the fetus, we have developed estimates of the risk of adults becoming infected following B19 exposures at home, in schools or day-care centers, and in hospitals. These estimates can then be used with other data to estimate the risk to the fetus of a B19 exposure during pregnancy. The risk to the fetus equals the rate of maternal susceptibility to infection times the rate of maternal infection following the specific type of exposure times the rate of fetal death following maternal infection. Data from studies of outbreaks of B19 associated erythema infectiosum and aplastic crisis suggest that the risk of infection among susceptible adults following household exposure to a B19 infected person is approximately 50% and following school exposures during outbreaks of erythema infectiosum is 20% to 30%. All susceptible school staff members, not just teachers, appear to be at risk for infection during outbreaks. Additional study is needed to determine the risk of infection following exposure to B19 infected patients in the hospital. Based on these and other data we can estimate that pregnant women whose serologic status is unknown have less than 2.5% chance of suffering fetal loss after household exposure and less than 1.5% chance after school exposure.

Occupational risk of human parvovirus B19 infection for school and day-care personnel during an outbreak of erythema infectiosum.

Human parvovirus B19, the cause of erythema infectiosum, has recently been associated with adverse fetal outcomes. During a large outbreak of erythema infectiosum in Connecticut, a survey was conducted on 571 (90%) of 634 school and day-care personnel to determine the risk of acquiring B19 infection. Serologic evidence of B19 infection was determined by using an enzyme-linked immunosorbent assay. Of the school and day-care personnel, 58% had evidence of previous B19 infection. The minimal rate of B19 infection in susceptible personnel during the outbreak was 19%. The risk was increased for teachers and day-care providers who had contact with younger children and with greater numbers of ill children. These results suggest that B19 infection is an occupational risk for school and day-care personnel.

Respiratory syncytial virus outbreak on American Samoa. Evaluation of risk factors.

Acute respiratory illness is one of the leading causes of childhood mortality in developing nations. We investigated an increase in hospitalizations of children less than 2 years old for severe lower respiratory tract illness (LRI) from October 1986 through December 1986 on the island of American Samoa. Hospitalization rates were highest in children less than 6 months of age (60 of 1000 compared with 22 of 1000 for those 6 to 11 months of age, and seven of 1000 for those 12 to 24 months of age). The outbreak was more severe than in previous years, with ten (19%) of 54 patients admitted to the intensive care unit (ICU) compared with three (7%) of 42 and one (3%) of 40 during the same months of 1985 and 1984. Two patients died. Most patients had clinical bronchiolitis; of 34 patients tested, serologic or nasal aspirate evidence of recent respiratory syncytial virus (RSV) infection was found in 18 (53%). A study of patients younger than 1 year of age demonstrated that patients hospitalized with LRI were more likely to have a household member who smoked cigarettes (18/20, 90%) than outpatient controls without recent respiratory illness (8/15, 53%). Maternal sera obtained between December 1985 and October 1986 showed no protective effect of either detectable IgG or neutralizing antibody to two major groups of RSV. Our study documents the involvement of RSV in an outbreak of severe LRI among infants in a tropical area and further suggests that exposure to cigarette smoke is a risk factor for LRI infants.

Reye's syndrome.

The most important recent development in our understanding of Reye's syndrome is the epidemiologic evidence linking this disease to aspirin in the United States. Assessment of epidemiologic issues of concern raised in prior studies did not explain the extremely high odds ratios observed in more recent studies. The observation of a dose-response relation between risk of Reye's syndrome and dose of aspirin ingested during the antecedent illness provides further supportive evidence for a causal link between Reye's syndrome and aspirin. Additional evidence for this association in the United States is provided by a marked decline in the use of aspirin among children in the United States, which has been accompanied by a dramatic decline in the incidence of Reye's syndrome. In contrast to experience in the United States, Reye's syndrome affecting primarily children aged 5-15 years has been relatively rare in Great Britain and Australia where acetaminophen rather than aspirin is the primary analgesic/antipyretic used. With the declining incidence of aspirin use in the United States, Reye's syndrome among children aged 5-15 years is becoming increasingly rare in the United States as well and, as in Great Britain and Australia, an increasing proportion of cases are being reported in children aged less than five years. Recent reports have suggested that many children younger than age five years who are thought to have the disease may be shown to have other metabolic disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Reye's syndrome and aspirin. Evidence for a dose-response effect.

Data collected from the Public Health Service Main Study of Reye's Syndrome and Medications were analyzed to assess the relationship between the development of Reye's syndrome and the dose of aspirin received during the antecedent respiratory or chickenpox illness. Among those exposed to aspirin, case-patients were found to have received greater average daily and maximum daily doses of aspirin and greater doses of aspirin on the first four days of the antecedent illness (median, 25.1 mg/kg; 33.0 mg/kg; and 65.4 mg/kg; respectively) than did controls (median, 14.5 mg/kg; 19.0 mg/kg; and 27.0 mg/kg; respectively). The excess risk associated with increasing aspirin doses was due primarily to intermediate levels of dose (eg, 15 to 27 mg/kg per day) rather than higher levels (greater than 27 mg/kg per day). The dose difference between exposed case-patients and controls was greatest on days 3 and 4 of the antecedent illness.

Human parvovirus B19 and pregnancy.

Although B19 infection during pregnancy usually has no adverse effect on the fetus, it can cause fetal death. Recent studies make it possible to estimate risk of infection following different types of exposure and the risk of fetal death after infection. The most common clinical manifestations of B19 infection are erythema infectiosum and aplastic crisis in patients with chronic hemolytic anemias.

Kawasaki syndrome clusters in Harris County, Texas, and eastern North Carolina. A high endemic rate and a new environmental risk factor.

Sixty-one cases of Kawasaki syndrome (KS) occurred in Harris County, Texas, during the three-year period from January 1982 through December 1984. Fifty-five (90%) of these 61 patients were under 5 years old, for an annual endemic rate in children under 5 years old of 9.1 cases per 100,000 per year. To our knowledge this is the highest endemic rate reported to date in the continental United States. Between Aug 26 and Sept 19, 1984, seven children with KS were hospitalized in Harris County. The seven children were between 5 months and 5 years old. The number of cases in this cluster was unusual for late summer, which is generally a low-incidence season for KS in Harris County. More important, a case-control study of these children revealed that they resided significantly closer to a bayou or drainage ditch than did randomly selected matched control subjects. A similar association with drainage ditches or creeks was observed in a subsequent cluster of 13 cases of KS in seven eastern North Carolina counties. To our knowledge, this is the first report of a possible association between KS and residing near water.

Risk of adverse outcomes of pregnancy after human parvovirus B19 infection.

Human parvovirus B19 (B19) infection during pregnancy has been associated with fetal deaths. We conducted several studies to develop data needed to make recommendations for preventing fetal death associated with infection. In the first study, after an outbreak of B19 infection, specimens of cord blood from 47 infants with congenital anomalies, 10 with suspected intrauterine infection, and gestational age-matched controls were tested for IgG and IgM antibodies to B19. None had evidence of recent infection. Next, 192 women with unknown exposure to B19 who had stillbirths or spontaneous abortions were studied. Two patients and two controls had evidence of recent B19 infection. In a second case-control study of women who had stillbirths after outbreaks of erythema infectiosum in area schools, none of the 20 patients or 26 controls were IgM positive at the time of delivery. The rate of infection, as demonstrated by IgM positivity, among 267 pregnant control subjects was approximately 1%. These studies suggest that among pregnant women unselected for exposure to B19, neither infection nor stillbirths are common.

Community outbreak of thyrotoxicosis: epidemiology, immunogenetic characteristics, and long-term outcome.

Between January and March 1984, the first community outbreak of transient thyrotoxicosis in the United States was documented in a seven-county area of southeastern Nebraska; 36 of the total 49 patients resided in York County (2.4 cases per 1,000 population). The median age of patients was 36 years, range six to 82 years; 51 percent were women. By definition, all patients were symptomatic, visited a physician, and had a newly identified elevated serum concentration of thyroxine or triiodothyronine of unknown cause. None had a goiter or a painful thyroid gland. Low 131I uptake measurements were found in all nine patients studied. Six patients were hospitalized; none died. Investigation of all 12 household contacts of eight selected patients revealed five additional persons with thyrotoxicosis and four with asymptomatic hyperthyroxinemia. A case-control study revealed that illness was associated with a significantly higher frequency of a reported recent respiratory viral-like condition. In another case-control study, the HLA-DR3 antigen was present in more case subjects (39 percent) than control subjects (14 percent). In addition, a significantly higher proportion of patients than control subjects purchased beef from one of the three supermarkets in York Country. Concomitant with the outbreak, the supermarket implicated in the outbreak purchased an unusually large quantity of beef (7,000 pounds) from a nonregular supplier in Nebraska, which had reportedly instituted the practice of trimming gullets (a procedure that removes the muscles from bovine larynx for beef) about three months earlier. Thus, it is concluded that the Nebraska outbreak, like one in Minnesota that occurred 18 months later, probably resulted from patients having eaten ground beef that was contaminated with bovine thyroid gland. This form of thyrotoxicosis, perhaps misdiagnosed as painless thyroiditis in the past, probably represents a previously under-recognized public health problem.