Jay D. Wenger

Bacterial Meningitis in the United States in 1995

BACKGROUNDnBefore the introduction of the conjugate vaccines, Haemophilus influenzae type b was the major cause of bacterial meningitis in the United States, and meningitis was primarily a disease of infants and young children. We describe the epidemiologic features of bacterial meningitis five years after the H. influenzae type b conjugate vaccines were licensed for routine immunization of infants.nnnMETHODSnData were collected from active, population-based surveillance for culture-confirmed meningitis and other invasive bacterial disease during 1995 in laboratories serving all the acute care hospitals in 22 counties of four states (total population, more than 10 million). The rates were compared with those for 1986 obtained by similar surveillance.nnnRESULTSnOn the basis of 248 cases of bacterial meningitis in the surveillance areas, the rates of meningitis (per 100,000) for the major pathogens in 1995 were Streptococcus pneumoniae, 1.1; Neisseria meningitidis, 0.6; group B streptococcus, 0.3; Listeria monocytogenes, 0.2; and H. influenzae, 0.2. Group B streptococcus was the predominant pathogen among newborns, N. meningitidis among children 2 to 18 years old, and S. pneumoniae among adults. Pneumococcal meningitis had the highest case fatality rate (21 percent) and in 36 percent of cases was caused by organisms that were not susceptible to penicillin. From these data, we estimate that 5755 cases of bacterial meningitis were caused by these five pathogens in the United States in 1995, as compared with 12,920 cases in 1986, a reduction of 55 percent. The median age of persons with bacterial meningitis increased greatly, from 15 months in 1986 to 25 years in 1995, largely as a result of a 94 percent reduction in the number of cases of H. influenzae meningitis.nnnCONCLUSIONSnBecause of the vaccine-related decline in meningitis due to H. influenzae type b, bacterial meningitis in the United States is now a disease predominantly of adults rather than of infants and young children.

A population-based assessment of invasive disease due to group B Streptococcus in nonpregnant adults.

BACKGROUNDnGroup B streptococci (Streptococcus agalactiae) are a major cause of meningitis and septicemia in neonates and pregnant women, but the importance of group B streptococcal disease in nonpregnant adults has not been clearly defined.nnnMETHODSnWe conducted a prospective surveillance of the pathogens responsible for meningitis for a period of 24 months in 35 hospitals and a referral laboratory in metropolitan Atlanta. We reviewed the clinical and laboratory records of all the nonpregnant adults identified as having invasive group B streptococcal disease during this period.nnnRESULTSnDuring 1989 and 1990 there were 424 patients with invasive group B streptococcal disease (annual incidence, 9.2 cases per 100,000 population). Of these patients, 46 percent were 1 month of age or younger, 6 percent were older than 1 month but younger than 18 years of age, and 48 percent were 18 or older. Men and nonpregnant women accounted for 68 percent (n = 140) of all cases among adults (annual incidence, 4.4 per 100,000). Clinical and laboratory records were available for 137. In the nonpregnant adult patients (age, 18 to 99 years), the most common clinical diagnoses were skin, soft-tissue, or bone infection (in 36 percent); bacteremia with no identified source (30 percent); urosepsis (14 percent); pneumonia (9 percent); and peritonitis (7 percent). Risk factors included older age (> or = 60 years), the presence of diabetes mellitus, the presence of malignant neoplasms, and infection with the human immunodeficiency virus. The mortality rate in nonpregnant adults was 21 percent, accounting for 67 percent of all deaths related to group B streptococcal infection during the surveillance period.nnnCONCLUSIONSnInvasive group B streptococcal infection is a major problem not only in pregnant women and neonates but also in nonpregnant adults, especially those who are elderly and those who have chronic diseases.

Cat Scratch Disease in Connecticut -- Epidemiology, Risk Factors, and Evaluation of a New Diagnostic Test

BACKGROUNDnAlthough cat scratch disease is commonly diagnosed in patients who have unexplained regional lymphadenopathy after encounters with cats, its epidemiology and the risk factors for disease are not clearly defined, and there is no generally accepted diagnostic test.nnnMETHODSnWe conducted a physician survey to identify cases of cat scratch disease occurring over a 13-month period in cat owners in Connecticut. We interviewed both the patients (or their parents) and controls matched for age who owned cats. Serum from the patients was tested for antibodies to Rochalimaea henselae with a new, indirect fluorescent-antibody test.nnnRESULTSnWe identified 60 patients with cat scratch disease and 56 age-matched subjects. Patients were more likely than controls to have at least one pet kitten 12 months old or younger (odds ratio, 15), to have been scratched or bitten by a kitten (odds ratio, 27), and to have had at least one kitten with fleas (odds ratio, 29). A conditional logistic-regression analysis found that in kitten-owning households, patients were more likely than controls to have been scratched or bitten by a cat or kitten (odds ratio, 12.4; 95 percent confidence interval, 1.0 to 150). Of 45 patients, 38 had serum samples with titers of 1:64 or higher for antibody to R. henselae, as compared with 4 of 112 samples from controls (P < 0.001). The positive predictive value of the serologic test was 91 percent. Of 48 serum samples from patients cats, 39 were positive for antibodies to R. henselae, as compared with positive samples from 11 of 29 control cats (P < 0.001).nnnCONCLUSIONSnCat scratch disease is strongly associated with owning a kitten, and fleas may be involved in its transmission. The serologic test for rochalimaea may be useful diagnostically, and our results suggest an etiologic role for this genus.

Protective efficacy of a serogroup B meningococcal vaccine in Sao Paulo, Brazil

Serogroup B Neisseria meningitidis is the most common cause of epidemic meningococcal disease in developed countries. Until recently no vaccine has been available for prevention of infection with this organism. In an attempt to control epidemic serogroup B meningococcal disease in greater Sao Paulo, Brazil, during 1989 and 1990, a Cuban-produced outer-membrane-protein-based serogroup B meningococcal vaccine was given to about 2.4 million children aged from 3 months to 6 years. We have done a case-control study to estimate the efficacy of the vaccine in greater Sao Paulo. Microbiologically confirmed cases of serogroup B meningococcal disease were identified through hospital-based surveillance. Controls were matched by neighbourhood and age. Vaccination status was confirmed by inspection of vaccination cards. Between June, 1990, and June, 1991, 112 patients and 409 matched controls with confirmed vaccine status were enrolled. Estimated vaccine efficacy varied by age: 48 months or older = 74% (95% Cl 16 to 92%), 24 to 47 months = 47% (-72 to 84%), and less than 24 months = -37% (< -100 to 73%). Our results suggest that the Cuban-produced vaccine may be effective for prevention of serogroup B meningococcal disease in older children and adults.

Risk Factors for Group B Streptococcal Disease in Adults

Group B streptococcus (Streptococcus agalactiae), a major cause of neonatal sepsis and meningitis in the United States, is an important cause of invasive bacterial infection in adults. An estimated 7600 cases of group B streptococcal disease occur annually among persons 15 years of age and older in the United States [1]; the incidence among those 60 years of age or older is 18/100 000 persons per year [2]. Among nonpregnant adults, skin and soft-tissue infections and bacteremia of uncertain source are the most common manifestations of invasive disease. The clinical spectrum also includes urosepsis, pneumonia, peritonitis, meningitis, septic arthritis, and endocarditis [2]. Despite nearly universal sensitivity of the organism to penicillin [3, 4], approximately 20% of cases of adult group B streptococcal disease are fatal [2]. Previous case series have indicated that chronic underlying conditions such as diabetes mellitus, cancer, and alcoholism are common among adults with group B streptococcal disease [5-11]. Reports of population-based studies have indicated that the rate of disease is significantly higher among persons with diabetes mellitus [2, 12], human immunodeficiency virus (HIV) infection [2], and cancer [2, 12]. These studies have also indicated that a substantial proportion of adult infections are nosocomially acquired. However, the magnitude of risk associated with specific patient characteristics has not been evaluated in a controlled study adjusting for the effect of multiple factors. In addition, specific determinants of community-acquired and nosocomial disease have not been assessed. Vaccines currently being developed for the prevention of neonatal group B streptococcal disease [13-16] may also be considered for the prevention of invasive infection in adults. Better knowledge of determinants of adult disease could be used to target such preventive efforts most effectively. We therefore did a casecontrol study comparing nonpregnant adults who had invasive group B streptococcal disease with patients hospitalized for other conditions. We report specific underlying conditions that were associated with community-acquired and nosocomial group B streptococcal infection and discuss the implications of these findings for the potential use of future vaccines. Methods Identification of Cases Active surveillance for invasive group B streptococcal infection was done in 1991 and 1992 in an aggregate population of 6.6 million persons using previously described methods [1]. The population included all residents of three counties in California (Alameda, Contra Costa, and San Francisco); eight counties in Georgia (Cobb, Clayton, Dekalb, Douglas, Fulton, Gwinnett, Newton, and Rockdale); and Baltimore City and Baltimore County, Maryland. Briefly, regional surveillance staff made biweekly calls to infection-control practitioners or designated contacts in the microbiology laboratories serving all acute-care hospitals in the surveillance areas for reports of sterile-site (for example, blood or cerebrospinal fluid) isolates of group B streptococcus. A case report form requesting information on demographic characteristics, site of isolation, and clinical syndrome was completed for each identified case. To ensure complete reporting, periodic audits of all laboratories were done. A case of invasive adult group B streptococcal disease was defined as isolation of group B streptococcus from a normally sterile site in a resident of a surveillance area who was 18 years of age or older and who was not pregnant or postpartum. If group B streptococcus was first isolated from a specimen obtained 2 or more days after hospital admission, the case was defined as nosocomial. Cases with positive cultures obtained from 1 June 1991 to 30 June 1992 in California and Georgia and from 1 November 1991 to 31 October 1992 in Maryland were eligible for inclusion. Selection of Controls For each case-patient, a listing of all patients hospitalized on the same day and of the hospital service to which they were admitted was obtained and reviewed. Controls were selected by identifying the three preceding patients admitted to the same general service (for example, medicine instead of oncology or surgery instead of orthopedic surgery) as the case-patient. If three appropriate controls could not be identified, admission lists for previous days were sequentially reviewed until three controls for each case-patient were enrolled. Data Collection We used standardized forms to abstract medical records for case-patients and controls. Information on demographic variables, outcome, outpatient medications, presenting signs and symptoms, underlying conditions, and the clinical syndrome associated with group B streptococcal infection was collected. For all cases, isolation of group B streptococcus from a sterile site was documented and information on isolation of other organisms from blood was obtained. For nosocomial cases, additional information was obtained on medications administered and procedures done in the hospital before the first positive group B streptococcal specimen was collected. For controls matched to case-patients with nosocomial infection, this additional information was abstracted for the same number of days after admission as for the matched case-patient. Statistical Analysis We used the chi-square test to compare proportions of categorical variables among case-patients. We did matched univariate and multiple conditional logistic regression analyses [17] using the Statistical Analysis System procedure PHREG [18] to estimate the risk for group B streptococcal disease associated with individual underlying conditions and exposures. Potential interaction among the variables associated with disease was evaluated by including two-way interaction and main-effect terms in multivariate models. We used stepwise selection, incorporating variables that were significant (P < equals 0.05) in the univariate analysis, to identify a final model for nosocomial disease. To ensure that the risk associated with the underlying conditions was assessed after we controlled for age, we forced a categorical variable that coded for age into the community-acquired model and then used stepwise selection to determine the other variables in the final model. Results Chart abstractions were completed for 219 of the 290 (76%) case-patients identified by surveillance (97 from Baltimore, 72 from the San Francisco metropolitan area, and 50 from the Atlanta metropolitan area) and for 645 matched controls from 54 hospitals (2.9 controls per case-patient). Seventy-one case-patients identified by surveillance were not included in the study for the following reasons: the hospital chart was not available for review (50 case-patients), the hospital did not participate in the study (9 case-patients), a sterile-site group B streptococcal culture could not be documented (5 case-patients), the patient was not admitted to the hospital (3 case-patients), the hospital closed (2 case-patients), or the patient died in the emergency department (2 case-patients). Information from the surveillance case report form indicates that the age and sex distribution and mortality rate of the cases not included did not significantly differ from those of the case-patients included in the study. Proportions of case-patients and controls with selected demographic characteristics and underlying medical conditions are listed in Table 1. The age range for case-patients was 22 to 99 years (median age, 68 years), and the age range for controls was 18 to 99 years (median age, 60 years). Case-patients who died during the hospitalization that was studied died a median of 5 days after collection of the specimen from which group B streptococcus was isolated (range, 0 to 187 days). Table 1. Characteristics and Selected Underlying Medical Conditions Reported for Nonpregnant Adults with Invasive Group B Streptococcal Infection and Hospital-Matched Controls Characteristics of Invasive Group B Streptococcal Disease Site of Isolation Group B streptococcus was isolated from blood in 201 cases (92%). Other sites of isolation included synovial fluid (6 cases), peritoneal fluid (6 cases), pleural fluid (4 cases), and cerebrospinal fluid (2 cases). It was also isolated from an abscess, bone, bone marrow, bronchial washing, intervertebral disc-space fluid, gall bladder, and liver tissue (1 case each). More than one site of isolation could be reported for each case. Polymicrobial Bacteremia Polymicrobial bacteremia, defined as the isolation of other bacterial species from blood cultures collected on the same day as a positive blood culture for group B streptococcus, was identified in 53 of 201 case-patients (26%) with group B streptococcal bacteremia. Staphylococcus aureus was isolated from 24 case-patients and was the only additional organism isolated from 17 case-patients. The age distribution, mortality rate, and proportion of nosocomial cases were similar between case-patients with polymicrobial bacteremia and those with bacteremia caused only by group B streptococcus. Clinical Syndromes The clinical syndromes associated with group B streptococcal infection in case-patients are listed in Table 2. Seven of the 19 case-patients with cellulitis were women with a history of breast cancer in whom cellulitis was associated with invasive group B streptococcal infection. Five of these 7 case-patients had cellulitis of the arm or chest wall on the side of a mastectomy done 3 months to 12 years before admission, 1 had cellulitis of the chest wall opposite the site of the previous mastectomy, and 1 had cellulitis of the arm after axillary node dissection. Table 2. Clinical Syndromes Associated with Group B Streptococcal Infection among 219 Nonpregnant Adults Characteristics Associated with In-Hospital Death Age was associated with in-hospital mortality. Case-patients 65 years of age or older were significantly more likely to die of group

Cat scratch disease in the United States: an analysis of three national databases.

OBJECTIVESnCurrent knowledge of the epidemiology of cat scratch disease is based primarily on information from case series. We used three national databases to obtain more representative data to determine the incidence and demographics of cat scratch disease.nnnMETHODSnRecords coded with the diagnosis of cat scratch disease from two hospital discharge databases and an ambulatory care database were analyzed. Costs of diagnostic tests and hospitalization were obtained from a sample of providers and published data.nnnRESULTSnThe incidence of patients discharged from hospitals with a diagnosis of cat scratch disease was between 0.77 and 0.86 per 100,000 population per year. Fifty-five percent of the case patients were 18 years of age or younger. Males accounted for 60% of cases. Incidence varied by season; approximately 60% of case patients were discharged in the months September through January. The estimated incidence of disease in ambulatory patients was 9.3 per 100,000 population per year. On the basis of these rates, we estimated the annual health care cost of the disease to be more than

Tobacco smoke as a risk factor for meningococcal disease

12 million.nnnCONCLUSIONSnThe rates and seasonality of cat scratch disease found in this study were consistent with previous reports. Adults represented a higher percentage of the total than reported in previous case series, suggesting that the disease may affect more adults than previously recognized.

MULTISTATE CASE-CONTROL STUDY OF MATERNAL RISK FACTORS FOR NEONATAL GROUP B STREPTOCOCCAL DISEASE

BACKGROUNDnSince 1992 the US Pacific Northwest has experienced a substantial increase in the incidence of serogroup B meningococcal disease. The current meningococcal polysaccharide vaccine is poorly immunogenic in young children and does not protect against N. meningitidis serogroup B. Defining alternative approaches to the prevention and control of meningococcal disease is of considerable public health importance.nnnMETHODSnWe performed a case-control study comparing 129 patients in Oregon and southwest Washington with 274 age- and area-matched controls. We used conditional logistic regression analysis to determine which exposures remained associated with disease after adjusting for other risk factors and confounders and calculated the proportion of disease attributable to modifiable exposures.nnnRESULTSnAfter adjustment for all other significant exposures identified, having a mother who smokes was the strongest independent risk factor for invasive meningococcal disease in children < 18 years of age [odds ratio (OR), 3.8; 95% confidence interval (CI) 1.6 to 8.9)], with 37% (CI 15 to 65) of all cases in this age group potentially attributable to maternal smoking. Adult patients were more likely than controls to have a chronic underlying illness (OR 10.8, CI 2.7 to 43.3), passive tobacco smoke exposure (OR 2.5, CI 0.9 to 6.9) and to smoke tobacco (OR 2.4, CI 0.9 to 6.6). Dose-response effects were seen for passive smoke exposure and risk of disease in all age groups.nnnCONCLUSIONnTobacco smoke exposure independently increases the risk of developing meningococcal disease.

Carriage of Haemophilus influenzae type b in children after widespread vaccination with conjugate Haemophilus influenzae type b vaccines.

Risk factors for early onset disease (EOD) caused by Group B streptococci (GBS) that are the foundation of prevention guidelines were identified in studies conducted in a few hospital centers. We investigated cases of EOD identified through laboratory-based active surveillance during 1991 and 1992 in a multistate population of 17 million. Ninety-nine cases were compared with 253 controls matched for hospital, date of birth and birth weight. Prematurity (< 37 weeks of gestation) was present in 28% of cases; 53% of case mothers had rupture of membranes > 12 hours; and 48% reported intrapartum fever. The incidence of EOD in each surveillance area was higher among blacks. By multivariate analysis, case mothers were more likely than controls to have rupture of membranes before labor onset (adjusted odds ratio 8.7, P < 0.001), intrapartum fever (adjusted odds ratio 11.9, P < 0.001), and history of urinary infection during pregnancy (adjusted odds ratio 4.3, P < 0.05). Young maternal age was also associated with risk of disease. Three-fourths of case mothers had intrapartum fever, < 37 weeks of gestation and/or prolonged rupture of membranes, indicators previously used to select high risk women for intrapartum chemoprophylaxis. Our findings extend data from single hospitals and suggest prenatal screening and selective intrapartum chemoprophylaxis of high-risk mothers could potentially prevent the majority of EOD in the United States.

Epidemiology of Haemophilus influenzae type b disease and impact of Haemophilus influenzae type b conjugate vaccines in the United States and Canada

Rates of invasive Haemophilus influenzae type b (Hib) disease in children decreased very rapidly after licensure of Hib conjugate vaccines. A role for a vaccine-related reduction in nasopharyngeal carriage of Hib has been suggested. We studied oropharyngeal carriage of Hib and vaccination rates in a population of 2− to 5-year-old children in metropolitan Atlanta. Among 584 children 75% were vaccinated with an Hib conjugate vaccine, 17% had not been vaccinated and 8% had no vaccination records available. Forty-one percent of the children were colonized with H. influenzae. One child was colonized with Hib. Hib carriage (0.17%; upper 95% confidence interval boundary, 0.97%) was substantially lower than the estimates of Hib carriage from prior studies of children who had not received Hib conjugate vaccines. Our data are consistent with a decline in Hib carriage induced by widespread use of conjugate Hib vaccines, which may have contributed to the decline of Hib disease in United States children.