Jay C. Butler

Cigarette Smoking and Invasive Pneumococcal Disease

Background Approximately half of otherwise healthy adults with invasive pneumococcal disease are cigarette smokers. We conducted a population-based case–control study to assess the importance of cigarette smoking and other factors as risk factors for pneumococcal infections. Methods We identified immunocompetent patients who were 18 to 64 years old and who had invasive pneumococcal disease (as defined by the isolation of Streptococcus pneumoniae from a normally sterile site) by active surveillance of laboratories in metropolitan Atlanta, Baltimore, and Toronto. Telephone interviews were conducted with 228 patients and 301 control subjects who were reached by random-digit dialing. Results Fifty-eight percent of the patients and 24 percent of the control subjects were current smokers. Invasive pneumococcal disease was associated with cigarette smoking (odds ratio, 4.1; 95 percent confidence interval, 2.4 to 7.3) and with passive smoking among nonsmokers (odds ratio, 2.5; 95 percent confidence interval, 1.2 ...

Hantavirus Pulmonary Syndrome: A Clinical Description of 17 Patients with a Newly Recognized Disease

Background In May 1993 an outbreak of severe respiratory illness occurred in the southwestern United States. A previously unknown hantavirus was identified as the cause. In Asia hantaviruses are associated with hemorrhagic fever and renal disease. They have not been known as a cause of human disease in North America. Methods We analyzed clinical, laboratory, and autopsy data on the first 17 persons with confirmed infection from this newly recognized strain of hantavirus. Results The mean age of the patients was 32.2 years (range, 13 to 64); 61 percent were women, 72 percent were Native American, 22 percent white, and 6 percent Hispanic. The most common prodromal symptoms were fever and myalgia (100 percent), cough or dyspnea (76 percent), gastrointestinal symptoms (76 percent), and headache (71 percent). The most common physical findings were tachypnea (100 percent), tachycardia (94 percent), and hypotension (50 percent). The laboratory findings included leukocytosis (median peak cell count, 26,000 per cu...

Investigation of bioterrorism-related anthrax, United States, 2001: epidemiologic findings.

In October 2001, the first inhalational anthrax case in the United States since 1976 was identified in a media company worker in Florida. A national investigation was initiated to identify additional cases and determine possible exposures to Bacillus anthracis. Surveillance was enhanced through health-care facilities, laboratories, and other means to identify cases, which were defined as clinically compatible illness with laboratory-confirmed B. anthracis infection. From October 4 to November 20, 2001, 22 cases of anthrax (11 inhalational, 11 cutaneous) were identified; 5 of the inhalational cases were fatal. Twenty (91%) case-patients were either mail handlers or were exposed to worksites where contaminated mail was processed or received. B. anthracis isolates from four powder-containing envelopes, 17 specimens from patients, and 106 environmental samples were indistinguishable by molecular subtyping. Illness and death occurred not only at targeted worksites, but also along the path of mail and in other settings. Continued vigilance for cases is needed among health-care providers and members of the public health and law enforcement communities.

Serological criteria for evaluation and licensure of new pneumococcal conjugate vaccine formulations for use in infants

The World Health Organization (WHO) is undertaking a series of consultations on serological criteria for the evaluation and licensure of new formulations/combinations or different vaccination schedules of pneumococcal conjugate vaccines. The lack of a definitive serological correlate of protection and the multiplicity of antigens involved, especially since the clinical efficacy of most of the individual serotypes represented in the only licensed vaccine has not been established, are hindering the formulation of criteria for licensure of new formulations or combinations of the vaccine. This report analyses the various options with their relative merits and drawbacks and provides preliminary recommendations as guidance to regulatory agencies in evaluating these vaccines for the purposes of licensure. More detailed recommendations for production and control of pneumococcal conjugate vaccines, including criteria for evaluation for licensure, are currently being drafted.

Temporal and Geographic Stability of the Serogroup-Specific Invasive Disease Potential of Streptococcus pneumoniae in Children

A meta-analysis study design was used to analyze 7 data sets of invasive and carriage pneumococcal isolates recovered from children, to determine whether invasive disease potential differs for each serotype and, if so, whether it has changed over time or differs geographically. Serotype- and serogroup-specific odds ratios (ORs) were calculated for each study and as a pooled estimate, with use of serotype 14 as the reference group. ORs varied widely: the serotypes with the highest ORs (1, 5, and 7) were 60-fold more invasive than those with the lowest ORs (3, 6A, and 15). There was a significant inverse correlation between invasive disease and carriage prevalence for the serotypes that we considered, which implies that the most invasive serotypes and serogroups were the least commonly carried and that the most frequently carried were the least likely to cause invasive disease. There was no evidence of any temporal change or major geographical differences in serotype- or serogroup-specific invasive disease potential.

Community-Onset Methicillin-Resistant Staphylococcus aureus Associated with Antibiotic Use and the Cytotoxin Panton-Valentine Leukocidin during a Furunculosis Outbreak in Rural Alaska

BACKGROUND Community-onset methicillin-resistant Staphylococcus aureus (CO-MRSA) reports are increasing, and infections often involve soft tissue. During a CO-MRSA skin infection outbreak in Alaska, we assessed risk factors for disease and whether a virulence factor, Panton-Valentine leukocidin (PVL), could account for the high rates of MRSA skin infection in this region. METHODS We conducted S. aureus surveillance in the outbreak region and a case-control study in 1 community, comparing 34 case patients with MRSA skin infection with 94 control subjects. An assessment of traditional saunas was performed. S. aureus isolates from regional surveillance were screened for PVL genes by use of polymerase chain reaction, and isolate relatedness was determined by use of pulsed-field gel electrophoresis (PFGE). RESULTS Case patients received more antibiotic courses during the 12 months before the outbreak than did control subjects (median, 4 vs. 2 courses; P=.01) and were more likely to use MRSA-colonized saunas than were control subjects (44% vs. 13%; age-adjusted odds ratio, 4.6; 95% confidence interval, 1.7-12). The PVL genes were present in 110 (97%) of 113 MRSA isolates, compared with 0 of 81 methicillin-susceptible S. aureus isolates (P<.001). The majority of MRSA isolates were closely related by PFGE. CONCLUSION Selective antibiotic pressure for drug-resistant strains carrying PVL may have led to the emergence and spread of CO-MRSA in rural Alaska.

An Outbreak of Multidrug-Resistant Pneumococcal Pneumonia and Bacteremia among Unvaccinated Nursing Home Residents

BACKGROUND Outbreaks of pneumococcal disease are uncommon and have occurred mainly in institutional settings. Epidemic, invasive, drug-resistant pneumococcal disease has not been seen among adults in the United States. In February 1996, there was an outbreak of multidrug-resistant pneumococcal pneumonia among the residents of a nursing home in rural Oklahoma. METHODS We obtained nasopharyngeal swabs for culture from residents and employees. Streptococcus pneumoniae isolates were serotyped and compared by pulsed-field gel electrophoresis. A retrospective cohort study was conducted to identify factors associated with colonization and disease. RESULTS Pneumonia developed in 11 of 84 residents (13 percent), 3 of whom died. Multidrug-resistant S. pneumoniae, serotype 23F, was isolated from blood and sputum from 7 of the 11 residents with pneumonia (64 percent) and from nasopharygeal specimens from 17 of the 74 residents tested (23 percent) and 2 of the 69 employees tested (3 percent). All the serotype 23F isolates were identical according to pulsed-field gel electrophoresis. Recent use of antibiotics was associated with both colonization (relative risk, 2.3; 95 percent confidence interval, 1.3 to 4.2) and disease (relative risk, 3.6; 95 percent confidence interval, 1.2 to 10.8). Only three residents (4 percent) had undergone pneumococcal vaccination. After residents received pneumococcal vaccine and prophylactic antibiotics, there were no additional cases of pneumonia, and the rates of carriage decreased substantially. CONCLUSIONS In this outbreak a single pneumococcal strain was disseminated among the residents and employees of a nursing home. The high prevalence of colonization with a virulent organism in an unvaccinated population contributed to the high attack rate. Clusters of pneumococcal disease may be underrecognized in nursing homes, and wider use of pneumococcal vaccine is important to prevent institutional outbreaks of drug-resistant S. pneumoniae infection.

Potential interventions for the prevention of childhood pneumonia: geographic and temporal differences in serotype and serogroup distribution of sterile site pneumococcal isolates from children—implications for vaccine strategies

Streptococcus pneumoniae is a leading cause of fatal bacterial pneumonia in young children. Pneumococcal polysaccharide vaccines have not been promoted for use in young children because many constituent serotypes are not immunogenic in children < 2 years old. Conjugating pneumococcal polysaccharide epitopes to a protein carrier would likely increase vaccine immunogenicity in children. We reviewed published and unpublished pneumococcal serotype and serogroup data from 16 countries on 6 continents to determine geographic and temporal differences in serotype and serogroup distribution of sterile site pneumococcal isolates among children and to estimate coverage of proposed and potential pneumococcal conjugate vaccine formulas. The most common pneumococcal serotypes or groups from developed countries were, in descending order, 14, 6, 19, 18, 9, 23, 7, 4, 1 and 15. In developing countries the order was 6, 14, 8, 5, 1, 19, 9, 23, 18, 15 and 7. Development of customized heptavalent vaccine formulas, one for use in all developed countries and one for use in all developing countries, would not provide substantially better coverage against invasive pneumococcal disease than two currently proposed heptavalent formulas. An optimal nanovalent vaccine for global use would include serotypes 1, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Geographic and temporal variation in pneumococcal serotypes demonstrates the need for a species-wide pneumococcal vaccine.

Indirect Effect of Conjugate Vaccine on Adult Carriage of Streptococcus pneumoniae: An Explanation of Trends in Invasive Pneumococcal Disease

BACKGROUND Use of heptavalent protein-polysaccharide pneumococcal conjugate vaccine (PCV7) has been associated with decreases in PCV7-type invasive pneumococcal disease and nasopharyngeal (NP) carriage in children. Vaccine use has also indirectly decreased the rate of invasive disease in adults, presumably through decreased transmission of pneumococci from vaccinated children to adults. METHODS We conducted NP carriage surveys in 8 villages in Alaska in 1998-2004. Streptococcus pneumoniae isolates were characterized by serotype and antimicrobial susceptibility. We analyzed trends in serotype distribution, antibiotic resistance, and factors associated with adult carriage of PCV7-serotype pneumococci before and after the introduction of PCV7 in 2001. RESULTS We collected 15,598 NP swabs; overall, 52% of adults living in the villages surveyed participated in the colonization study. The proportion of adult carriers with PCV7-type pneumococcal carriage decreased from 28% of carriers in 1998-2000 to 4.5% of carriers in 2004 (P<.0001). Among adults, the proportion of colonizing isolates that were resistant to penicillin decreased from 13% in 1998-2000 to 6% in 2004 (P=.05), whereas the percentage of isolates with intermediate susceptibility to penicillin increased from 12% in 1998-2000 to 19% in 2004 (P<.01). Adults were more likely to carry PCV7-type pneumococci if they lived with a child <5 years old or if they lived with a child who had not been age-appropriately vaccinated with PCV7. CONCLUSIONS Pediatric vaccination with PCV7 has resulted in decreased PCV7-type pneumococcal carriage among adults and helps to explain recent decreases in the rate of PCV7-type invasive pneumococcal disease among adults.

A cluster of anaphylactic reactions in children with spina bifida during general anesthesia: Epidemiologic features, risk factors, and latex hypersensitivity

BACKGROUND Anaphylactic reactions (ARs) in high-risk pediatric patients undergoing general anesthesia, especially those with spina bifida, have been attributed to anesthetics, muscle relaxants, antimicrobials, ethylene oxide, and latex. METHODS To identify risk factors for AR during general anesthesia and to investigate the role of latex allergy, we studied epidemiologic and immunologic characteristics of patients with ARs during general anesthesia during a 13-month cluster of such reactions at Childrens Hospital of Wisconsin (case patients). Patients with AR were compared with patients with spina bifida undergoing uneventful general anesthesia during the same period (control patients). For each case patient and control patient, we conducted a chart review; a parental interview; skin prick testing with latex, anesthetics, aeroallergens, and banana extract; ELISA and RAST for latex-specific IgE; a total serum IgE; and an ELISA for IgE antibody to ethylene oxide. RESULTS Anaphylactic reactions occurred exclusively in patients with spina bifida (n = 10) or patients with a congenital urinary tract anomaly (n = 1). Case-patients were more likely than control patients to have a history of asthma (p = 0.002), rubber contact allergy (p = 0.001), food allergy (p = 0.001), rash caused by adhesive tape (p = 0.05), daily rectal disimpaction (p < 0.001), nine or more prior surgical procedures (p < 0.002), latex-specific IgE (p = 0.027), or elevated total serum IgE levels (p = 0.002). Multivariate analysis identified non-white race, rubber contact allergy, history of food allergy, and nine or more surgical procedures as significant independent risk factors. Logistic model equation identified the predicted probability of AR with a sensitivity, specificity, and positive predictive value of 82%, 97%, and 82%, respectively. CONCLUSIONS These findings demonstrate that atopy, especially symptomatic latex allergy, is associated with AR during anesthesia in patients with spina bifida. Until a standardized latex test is available, a medical history of immediate rubber contact allergy, non-white race, food allergy, or nine or more prior surgical procedures can identify patients with spina bifida at highest risk for ARs. A complete history, including rubber contact and food allergy, should be compiled on all patients with spina bifida before surgery.