Prevention of Hemophilus influenzae type b disease

To determine the efficacy of rifampin prophylaxis in eradication of oropharyngeal carriage of Hemophilus influenzae type b and prevention of secondary H influenzae type b disease, we conducted a multicenter placebo-controlled trial among selected persons with invasive H influenzae type b disease. Households and day-care classrooms were randomized so that their members received either rifampin (initially at a dose of 10 mg/kg/dose for two to four days [rifampin-10], but subsequently at 20 mg/kg/dose for four days [rifampin-20]) or placebo. Pretherapy H influenzae type b colonization rates were similar in the treatment groups. Therapy with either rifampin regimen significantly reduced carriage (rifampin-20, 97%; rifampin-10, 63%; placebo, 28%). New acquisition of carriage was also significantly reduced by either rifampin regimen (rifampin-20 or rifampin-10, 2% v placebo, 6%). No rifampin-resistant H influenzae type b isolates emerged after treatment. Four of 765 placebo-treated contacts experienced secondary disease in contrast to zero of 1,112 rifampin-treated contacts. Because chemoprophylaxis of close contacts with rifampin seems to reduce significantly the risk of secondary H influenzae type b disease, we recommend the administration of prophylaxis in households or day-care classrooms where children younger than 4 years have been exposed to the disease.     

Hemophilus influenzae type b disease. An epidemiologic study with special reference to day-care centers

Day-care centers are a relatively new phenomena of American society that bring together large numbers of young children susceptible to contagious disease. This study examines the incidence and risk factors of endemic Hemophilus influenzae type b disease both in the general population and in day-care attendees in Monroe County, New York, for 1982 and 1983. The attack rate in the general population (excluding day-care attendees) was highest in children younger than 1 year (131.9 cases per 100,000 per year) and in those 1 to 2 years old (75.7 cases per 100,000 per year) compared with older children. The relative risk for day-care attendees was much greater than that of the general population. It was 12.3 times greater for children younger than 1 year, 7.2 times greater for those 1 to 2 years old, and 3.8 times greater for those 2 to 3 years old. We conclude that children attending day-care facilities face a substantial increased risk of contracting invasive H influenzae type b disease. Efforts to prevent susceptibility and contagious spread of this disease in this population seem necessary.     

A day care-based study of the efficacy of Haemophilus b polysaccharide vaccine

To assess the efficacy of the Haemophilus b polysaccharide vaccine following licensure and to evaluate the risk of Haemophilus influenzae type b (Hib) disease in the week following vaccination, we conducted a day care-based case-control efficacy study using cases of invasive Hib disease ascertained through active surveillance in areas with a total population of 34 million. For each patient 18 to 59 months old, up to three 18- to 59-month-old controls were chosen from the same day care classroom. Using conditional logistic regression, the vaccine efficacy was estimated to be 45% (95% confidence interval = -1% to 70%) and did not change significantly after accounting for potential biases. In addition, three (3%) of 104 patients vs five (2%) of 207 controls were vaccinated within seven days before the patients' dates of admission (odds ratio = 1.8, 95% confidence interval = 0.3 to 10.2), which does not suggest an increased risk of Hib disease in the week following immunization. This study suggests that the efficacy of the currently used HBPV is less than expected from previous studies and points out the usefulness of case-control studies for monitoring vaccine efficacy following licensure.     

Protective efficacy of Haemophilus influenzae type b polysaccharide and conjugate vaccines in children 18 months of age and older

To evaluate the protective efficacy of polyribosylribitol phosphate (PRP) and polyribosylribitol phosphate-diphtheria toxoid (PRP-D) vaccines in children 18 to 59 months of age, we conducted a case-control study in Los Angeles (Calif) County between July 1, 1988, and July 31, 1989. Seventy-nine children with invasive Haemophilus influenzae type b disease 18 to 59 months of age were identified, and 212 controls were selected by random-digit telephone dialing methods. Cases and controls were stratified by age and month of disease onset of the case. Seventeen PRP vaccine failures and two PRP-D vaccine failures occurred more than 2 weeks after vaccination. The PRP vaccine was shown not to be effective (point estimate--47%; 95% confidence interval,--307% to 47%), but the PRP-D vaccine was 88% protective (95% confidence interval, 42% to 97%). Adjustment of the efficacy estimates for potential confounding variables did not change the results significantly. The PRP-D vaccine provided significantly better protection than the PRP vaccine against invasive H influenzae type b disease in this population.     

Lack of efficacy of Haemophilus b polysaccharide vaccine in Minnesota

We evaluated the efficacy of Haemophilus b polysaccharide vaccine in children in Minnesota using a case-control study. The vaccine became available in Minnesota in August 1985. During the subsequent 28 months, 88 cases of invasive H influenzae type b disease were identified in children 24 to 71 months of age, the group targeted for vaccination. Of the 88 cases, 36 (41%) occurred in vaccinated children. Fifty-eight (33%) of 176 controls were vaccinated during a similar period. The vaccine's protective efficacy for children with any history of vaccination was -58% (95% confidence interval = -204% to 18%). The vaccine's protective efficacy for children who were most likely to be protected by vaccination was -55% (95% confidence interval = -238% to 29%). Our results indicate that vaccination with Haemophilus b polysaccharide vaccine had no effect in preventing H influenzae type b disease in Minnesota children.     

The occupational risk of cytomegalovirus infection among day-care providers.

We prospectively studied day-care providers at six day-care centers in south-eastern Iowa to determine their occupational risk for primary cytomegalovirus infection and to define epidemiologic risk factors. Ninety-six (38%) of 252 day-care providers were seropositive for cytomegalovirus by latex agglutination at entry into the study. Among 82 seronegative providers available for follow-up, seven seroconversions occurred at only two of the six participating centers, yielding an annualized seroconversion rate of 7.9%. Median time to seroconversion among these providers was 13 months. Using Kaplan-Meier estimates of risk, we determined that the overall risk of seroconversion among providers at various centers ranged from 0% to 22% by 12 months and from 0% to 40% by 16 months. Risk of cytomegalovirus acquisition by providers was independent of race, age, education, the presence of a child at home, or caring for children younger than 2 or 3 years in the day-care center. However, the risk of seroconversion among day-care providers appeared to parallel rates of cytomegalovirus excretion and acquisition among children at each center.     

The protective efficacy of Haemophilus b polysaccharide vaccine

To assess the protective efficacy of the Haemophilus b polysaccharide vaccine, a case-control study was conducted in Connecticut, Dallas County, and greater Pittsburgh. Seventy-six children 24 to 72 months of age who had H influenzae type b isolated from normally sterile sites from August 1985 through July 1987 were enrolled. For each case two controls, matched by age and place of residence, were randomly selected from the records of all live births in the area. Antecedent receipt of the Haemophilus b polysaccharide vaccine was ascertained from the records of all physicians and clinics at which the subjects received medical care. Overall, 12% of the cases and 39% of the controls had received the vaccine. The estimate of the protective efficacy of the vaccine was 88% overall (95% confidence interval, 74% to 96%) and 91% (95% confidence interval, 71% to 99%), 92% (95% confidence interval, 76% to 99%), and 81% (95% confidence interval, 45% to 96%) in Connecticut, Dallas County, and greater Pittsburgh, respectively. The estimates were not substantially affected by adjusting with logistic regression for differences between the cases and controls in race and the attendance of group day care. We conclude that the Haemophilus b polysaccharide vaccine is highly effective in these areas among children who receive the vaccine when they are 24 months of age or older.     

Outbreak of measles in a highly vaccinated secondary school population.

OBJECTIVE: To examine the factors associated with measles vaccine effectiveness and the effect of two doses of vaccine on measles susceptibility during an outbreak. DESIGN: Retrospective cohort study. SETTING: A secondary school in the City of Toronto. SUBJECTS: The entire school population (1135 students 14 to 21 years of age). MAIN OUTCOME MEASURES: Risk of measles during an outbreak associated with age at first measles vaccination, length of time since vaccination, vaccination before 1980 and whether date of vaccination was estimated; vaccine efficacy of one dose versus two doses. RESULTS: Eighty-seven laboratory-confirmed or clinically confirmed cases of measles were identified (for an attack rate of 7.7%). The measles vaccination rate was 94.2%, and 10% of the students had received two doses of measles vaccine before the outbreak. Among those who had received only one dose of vaccine, vaccination at less than 15 months of age was associated with vaccine failure (relative risk 3.62, 95% confidence interval 2.32 to 5.66). There was no increased risk of vaccine failure associated with length of time since vaccination once the relative risk was adjusted for age at vaccination in a stratified analysis. Vaccination before 1980 and an estimated date of vaccination were not associated with increased risk of vaccine failure. Administration of a second dose of vaccine during the outbreak was not protective. Two doses of vaccine given before the outbreak conferred significant protection, and the relative risk of failure after one dose versus two doses was 5.0 (95% confidence interval 1.25 to 20.15). Of the 87 cases, 76 (87%) could have been prevented had all the students received two doses of measles vaccine before the outbreak, with the first at 12 months of age or later. CONCLUSIONS: Delayed primary measles vaccination (at 15 months of age or later) significantly reduced measles risk at later ages. However, revising the timing of the current 12-month dose would leave children vulnerable during a period in which there is increased risk of complications. The findings support a population-based two-dose measles vaccination strategy for optimal measles control and eventual disease elimination.     

Risk factors for ectopic pregnancy. A population-based study

To evaluate the association between ectopic pregnancy and 22 potential risk factors, we conducted a population-based case-control study. The investigation included 274 cases diagnosed from 1935 through 1982 in residents of Rochester, Minn, and 548 matched controls selected from live-birth deliveries. Risk factor information documented prior to the last index menstrual period was obtained via medical record abstract. Univariate matched analyses revealed nine variables associated with a significantly elevated relative risk of ectopic pregnancy. Following conditional logistic regression, four variables remained as strong and independent risk factors for ectopic pregnancy: current intrauterine device use (relative risk, 13.7; 95% confidence interval, 1.6 to 120.6), a history of infertility (relative risk, 2.6; 95% confidence interval, 1.6 to 4.2), a history of pelvic inflammatory disease (relative risk, 3.3; 95% confidence interval, 1.6 to 6.6), and prior tubal surgery (relative risk, 4.5; 95% confidence interval, 1.5 to 13.9). Theoretically, any condition that prevents or retards migration of the fertilized ovum to the uterus could predispose a woman to ectopic gestation. Further research is needed to clarify the impact of other potential risk factors in the etiology of ectopic pregnancy.     

Person-to-person transmission of Giardia lamblia in day-care nurseries.

In an outbreak of giardiasis at two day-care nurseries in metropolitan Toranto Giardia lamblia appeared to be transmitted person to person. No common source of infection could be found. The proportions of children infected in the two nurseries were 39% and 17%; infection was spread to 7% and 23% of their household contacts. Of the infected children and household contacts 26% and 30% respectively of those for whom detailed information could be obtained were symptomatic. Canadian children were more likely to be infected and symptomatic than were immigrant children attending the nurseries. The most susceptible ages for infection were 1 to 3 years. The results of this study suggest that all children in day-care nurseries who are infected with G. lamblia should be treated, regardless of whether they are symptomatic.     

Effect of immunoglobulin on hepatitis A in day-care centers

Over a 21-month interval, we investigated the effectiveness of immunoglobulin (lg) in preventing hepatitis A spread in day-care centers. Immunoglobulin was given to all center and employees whenever hepatitis occurred in one center child or employee or parents in two families. Immunoglobulin programs were completed in 91 centers during the trial within an average of 17 days of onset of illness in the index case. Immunoglobulin intervention caused significant reduction in the average size of a day-care hepatitis outbreaks, from 7.3 cases in historically untreated centers to 6.0 cases in Ig-treated centers. Cases in center children and employees virtually ceased two weeks after Ig intervention, while those in household contacts decreased significantly within six weeks. Reported cases of hepatitis type A or unspecified in the community decreased 75%, and the number of new hepatitis outbreaks decreased 77% during the trial. A decrease occurred not only in day-care-associated cases, but in cases not directly associated with centers, probably due to decreased tertiary spread from day-care families into the community. Use of Ig to prevent hepatitis spread in day-care centers seems to be an excellent means of controlling this disease, both within the centers and the general community.     

Haemophilus influenzae type b disease. Incidence in a day-care center.

Haemophilus influenzae type b (HIB) disease was observed during a 14-month period in seven of 48 infants attending a day-care center. Surveillance studies showed that 28 (58%) infants had positive nasopharyngeal cultures for HIB; four infants were colonized with HIB for nine to 12 months. Ampicillin trihydrate prophylaxis failed to reduce the HIB carrier rate. Haemophilus influenzae type b polysaccharide vaccine was administered to 34 of the children. Sera obtained prior to immunization showed detectable antibody in all infants. Only nine (26%) infants had twofold or greater rises in serum HIB antibody titers after vaccination. Antibody response was independent of age, preimmunization antibody concentration, and HIB carrier status. In one infant, HIB meningitis developed four months after she received polysaccharide vaccine. This outbreak emphasizes that HIB is highly contagious in closed populations of young, susceptible infants.     

Immunoglobulin deficiency and idiotype expression in children developing Haemophilus influenzae type b disease after vaccination with conjugate vaccine. The Collaborative Study Group

OBJECTIVE.--Haemophilus influenzae type b (Hib) conjugate vaccines are effective in preventing Haemophilus disease in most children. The reasons why the vaccination fails in some children are unknown. This study investigated host factors in children who developed the disease despite conjugate vaccination. DESIGN, PATIENTS, OUTCOME MEASURES.--A convenience sample of 23 patients in whom Hib disease developed 14 days or more after conjugate vaccination was investigated for the presence of subnormal serum immunoglobulin concentrations and anticapsular antibody responses to Hib disease. We also investigated expression of the Hib idiotype 1 (Hibld-1), a serological marker of a VKII chain that comprises a major portion of the normal variable region repertoire of the antibody response to Hib polysaccharide. The results were compared with those of 149 patients in whom the unconjugated Hib polysaccharide vaccine failed and of 90 unvaccinated patients who developed the disease. RESULTS.--Compared with children in whom the unconjugated polysaccharide vaccination failed, the relative risk of a subnormal serum concentration of IgM, IgA, IgG, and/or IgG2 in the children in whom the conjugate vaccination failed was 4.9 (95% confidence interval [CI], 1.8 to 14; P less than .003) and of IgG2 was 22 (95% CI, 3.5 to 146; P less than .001). With the exception of the children with subnormal serum immunoglobulin concentrations, most of the children with conjugate vaccination failure showed normal or high anticapsular antibody responses to the disease, whereas the children with polysaccharide vaccination failure showed impaired responses. The Hibld-1 was expressed by the majority of the children in both vaccination failure groups and of the unvaccinated patients. CONCLUSIONS.--In most patients, vaccination failure is not attributable to lack of expression of the variable region gene encoding Hibld-1. However, children in whom conjugate vaccination has failed frequently have subnormal serum immunoglobulin concentrations and should be evaluated for immunodeficiency.     

Menstrual disorders in a Paediatric and Adolescent Gynaecology Clinic: patient presentations and longitudinal outcomes

OBJECTIVE. To study the presentations, diagnoses, and outcomes in adolescents with menstrual disorders. DESIGN. Prospective cohort study. SETTING. Paediatric and Adolescent Gynaecology Clinic, Hong Kong. PARTICIPANTS. A total of 577 adolescents aged 14 to 19 years. MAIN OUTCOME MEASURES. The presentations and diagnoses of adolescents with menstrual disorders were reviewed and their menstrual outcomes determined by a telephone survey. RESULTS. In all, 47% presented with menorrhagia, prolonged menstruation, and short menstrual cycles; 27% had secondary amenorrhoea, 12% had dysmenorrhoea, 11% had oligomenorrhoea, and 3% had primary amenorrhoea. Significant diagnoses included congenital genital tract anomalies, premature ovarian failure, anorexia nervosa, and polycystic ovarian syndrome. Polycystic ovarian syndrome was diagnosed in 16% of the cohort. In all, 24% of these 577 patients had abnormal menstrual cycles 4 years later. Direct logistic regression analysis indicated a cycle length of more than 35 days at presentation (adjusted odds ratio=2.8; 95% confidence interval, 1.8-4.5), previous diagnosis of polycystic ovarian syndrome (adjusted odds ratio=2.0; 95% confidence interval, 1.1-3.4), and current body mass index of 23 kg/m(2) or higher (adjusted odds ratio=1.8; 95% confidence interval, 1.0-3.0) were risk factors for persistently long menstrual cycle exceeding 35 days. Adolescents who were screened out with a definitive diagnosis after initial assessment were at low risk of persistently long menstrual cycles at follow-up (adjusted odds ratio=0.3; 95% confidence interval, 0.1-0.8). CONCLUSIONS. Adolescent menstrual disorders should not be ignored. Long cycle, diagnosis of polycystic ovarian syndrome at first consultation, and a current body mass index of 23 kg/m(2) or higher were statistically associated with persistent problems.     

阿司匹林预防再发静脉血栓栓塞症的研究

目的：探讨阿司匹林预防再发静脉血栓栓塞症的有效性和安全性。方法：初次发作无激惹原因的静脉血栓栓塞症患者在完成6~18个月华法林治疗后随机分为阿司匹林组（100 mg·d-1）或安慰剂组,观察治疗2年。主要有效性终点为再发静脉血栓栓塞症,主要安全性终点为严重出血。结果：在研究中位期23.8个月时,103例给予阿司匹林治疗的患者有14例发生了再发静脉血栓栓塞症,99例给予安慰剂的患者有21例发生了再发静脉血栓栓塞症（13.6%vs 21.2%,危险比0.59,95%可信区间0.37~0.95;P=0.02）。阿司匹林组和安慰剂组各有1例患者发生了严重出血事件。结论：对已停用抗凝治疗的无激惹原因静脉血栓栓塞症患者给予阿司匹林治疗可减少再发静脉血栓栓塞风险,并且不增加严重出血风险。     

Risk factors for measles in a previously vaccinated population and cost-effectiveness of revaccination strategies

Using data from a large measles outbreak that occurred in Dane County (Wisconsin) in 1986, we conducted a case-control study to evaluate risk factors for vaccine failure and assessed the cost-effectiveness of school-based revaccination strategies. Vaccination before a change in the measles vaccine stabilizer in 1979 (odds ratio, 5.5; 95% confidence interval, 1.05 to 28.9) and vaccination before age 15 months (odds ratio, 13.9; 95% confidence interval, 5.9 to 32.6) were identified as risk factors. Revaccination strategies for all students ($3444 per case prevented), students vaccinated before 1980 ($3166 per case prevented), and students vaccinated before age 15 months ($2546 per case prevented) were evaluated, assuming use of measles-mumps-rubella vaccine after the initial case was detected in a school. However, a large proportion of cases (43% to 53%) may not have been preventable using these strategies. Therefore, revaccination in all schools assessed to be at risk for measles may be necessary to prevent large outbreaks until a two-dose vaccination schedule is fully implemented.     

Research letter: Factors influencing childhood influenza immunization

FOLLOWING THE LAUNCH OF A PUBLICLY FUNDED influenza immunization program for all residents of Ontario over the age of 6 months, we evaluated 203 parents of children who presented to our emergency department between January and March of the following year (2001). Overall, 54 (27%) of the children had been vaccinated. Parents of non-immunized children were more likely to believe that immunization resulted in a flu-like illness (42% v. 17%; p = 0.001), caused side effects that were more severe than having influenza (36% v. 17%; p = 0.010) and weakened the immune system (52% v. 24%; p < 0.001). Parents of both immunized and non-immunized children incorrectly identified gastrointestinal symptoms as symptoms of influenza. The primary reason for deciding against immunization was the belief that their child was not at risk. After adjustment, children with a chronic disease were more likely than those without a chronic disease to be immunized (adjusted odds ratio [OR] 4.7, 95% confidence interval [CI] 1.8–12.6). Children of parents who discussed immunization with a physician were more likely to be immunized than those who had not discussed immunization with a physician (OR 6.8, 95% CI 2.4–19.2).     

Prevalence of HTLV-III/LAV in household contacts of patients with confirmed AIDS and controls in Kinshasa, Zaire

Household members of 46 patients with confirmed acquired immunodeficiency syndrome (AIDS) and 43 human T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV)-seronegative controls from Kinshasa, Zaire, were identified and sought for serologic testing for evidence of HTLV-III/LAV infection. Twenty (9.8%) of 204 case-household members and three (1.9%) of 155 control-household members were HTLV-III/LAV seropositive (relative risk = 5.1; 95% confidence interval, 1.7 to 15.2). Eleven (61.1%) of 18 spouses of patients with AIDS were HTLV-III/LAV seropositive, compared with one (3.7%) of 27 control spouses (relative risk = 16.5; 95% confidence interval, 3.7 to 75.0). Except for spouses, the rate of HTLV-III/LAV seropositivity did not differ significantly between case and control households. Furthermore, for adults in case households who were not spouses, the number seropositive for HTLV-III/LAV was identical to that predicted from sex- and age-specific HTLV-III/LAV seroprevalence rates. These data from Zaire confirm the results of US and European studies of household contacts of infected hemophiliacs and pediatric patients with AIDS.     

Viral hepatitis associated with day-care centers.

From September 1976 through March 1978, we investigated 11 outbreaks of non-B viral hepatitis associated with Louisiana day-care centers. The outbreaks included 168 cases, most of which were erroneously considered "sporadic" cases of non-B viral hepatitis prior to the investigations. Thirteen percent of all non-B viral hepatitis cases reported in the New Orleans metropolitan area during 1977 were associated with one of the outbreaks. Most of the cases in each outbreak and 85% overall were in older, usually adult, contacts of children attending the day-care centers. Within the household, parents appeared to be at greatest risk, particularly those who had 1- to 2-year-old children in the day-care center. Day-care center outbreaks of non-B hepatitis are easily overlooked and may be more widespread than is currently appreciated.     

Rifampin alone or with trimethoprim for contacts of children with Haemophilus influenzae type b infections.

We carried out a nonrandomized, unblinded study to compare the efficacy of rifampin alone with that of rifampin in combination with trimethoprim in the eradication of the Haemophilus influenzae type b (HIB) carrier state among contacts of patients with invasive HIB infection. The study population comprised 17 index patients admitted to hospital with severe HIB infections and 233 contacts, 43 of whom had nasopharyngeal colonization with HIB of the same biotype as that of the index patient. Rifampin in a daily dose of 20 mg/kg (maximum 600 mg) for 4 days eradicated the carrier state in 86% of cases, as did the combination of rifampin at the same dosage and trimethoprim in a daily dose of 5 mg/kg (maximum 160 mg) for 4 days.