PspA family typing and PCR-based DNA fingerprinting with BOX A1R primer of pneumococci from the blood of patients in the USA with and without sickle cell disease.

Disease and mortality rates for Streptococcus pneumoniae infections are much higher in patients with sickle cell disease (SCD) than in age-matched patients without SCD. Pneumococcal surface protein A (PspA) has been proposed as a component in human vaccines against S. pneumoniae to provide greater breadth of coverage than can be obtained with the 7-valent conjugate vaccine. The cross-reactivity of PspA is associated with the 'PspA family' structure. In this study we examined strains of S. pneumoniae from patients with and without SCD to determine whether the strains infecting the hypersusceptible population of SCD patients were limited to the same two PspA families already known to comprise over 95% of strains infecting non-SCD patients. Each strain was also evaluated according to the presence or absence of specific PCR fragments based on repetitive BOX elements to screen for possible SCD-associated clonal structure. Strains from SCD and non-SCD patients were similarly dispersed among the most common BOX PCR groups and strains from both groups expressed a similar distribution of PspA variants. Thus, a PspA vaccine designed for the population at large should also be appropriate for patients with SCD.

Pontiac fever due to Legionella micdadei from a whirlpool spa: possible role of bacterial endotoxin.

During January 1998, a cluster of illnesses occurred among hotel guests in Wisconsin. Ill persons had been exposed to the hotel's whirlpool spa and swimming pool. Symptoms included headache, fever, chills, myalgia, shortness of breath, and fatigue. A diagnosis of Pontiac fever was made, based on serologic evidence of acute infection with Legionella micdadei. High concentrations of heterotrophic bacteria were recovered from the spa, despite apparently high disinfectant levels. L. micdadei was isolated from the swimming pool filter and water from the spa after heat enrichment but not from pools and spas at nearby hotels. Water from hotel pools and spas was tested to determine endotoxin levels; water from the spa of the implicated hotel contained the highest concentration of endotoxin (14,400 endotoxin units/mL). Additional studies are needed to determine the role of endotoxin from legionellae or other bacteria in the pathogenesis of Pontiac fever.

Randomized trial of the quantitative and functional antibody responses to a 7-valent pneumococcal conjugate vaccine and/or 23-valent polysaccharide vaccine among HIV-infected adults.

In a double-blinded, randomized trial, human immunodeficiency virus (HIV)-infected adults with > or = 200 CD4 cells/microl received placebo (PL), 7-valent conjugate, or 23-valent pneumococcal polysaccharide (PS) vaccine in one of the following two-dose combinations given 8 weeks apart: conjugate-conjugate, conjugate-polysaccharide, placebo-polysaccharide, placebo-placebo. A total of 67 persons completed the study. Neither significant increases in HIV viral load nor severe adverse reactions occurred in any group. After controlling for confounders, when compared with persons receiving placebo-polysaccharide, persons receiving conjugate-conjugate and conjugate-polysaccharide had higher antibody concentrations (serotypes 4, 6B, 9V and serotype 23F, respectively) and opsonophagocytic titers (functional antibody assay, serotypes 9V, 23F and serotypes 4, 6B, 9V, respectively) after the second dose (P<0.05). The second dose with either conjugate or polysaccharide following the first conjugate dose, however, produced no further increase in immune responses.

Rethinking recommendations for use of pneumococcal vaccines in adults.

Streptococcus pneumoniae remains a major cause of disease worldwide; the emergence of antibiotic-resistant strains emphasizes the importance of disease prevention by use of vaccines. Recent studies have provided information that is useful for the evaluation of current vaccine recommendations. Recommendations target most people who are at high risk for invasive pneumococcal disease. However, higher risk has also been identified for African Americans and smokers, but these groups are not specifically targeted by current recommendations. The vaccine is effective against invasive disease in immunocompetent people, although studies in immunocompromised subjects have found few subgroups in which the vaccine appears to be effective. Questions with regard to optimal timing and indications for revaccination remain a challenge, because the duration of protection and effectiveness of revaccination remain unknown. New pneumococcal vaccines appear promising but will need to be tested against the performance of the polysaccharide vaccine. Improving delivery of the currently available pneumococcal polysaccharide vaccine to adults who will benefit should be a high priority.

Treating cardiovascular disease with antimicrobial agents: a survey of knowledge, attitudes, and practices among physicians in the United States.

To assess physicians' knowledge, attitudes, and prescribing behaviors with regard to the association between Chlamydia pneumoniae and cardiovascular disease, we surveyed 750 physicians in Alaska, 1172 in West Virginia, and 569 infectious disease (ID) specialists in a nationwide network during February-May 1999. Eighty-five percent knew of the association between C. pneumoniae and atherosclerosis, but this awareness was more common among ID specialists and cardiologists than among generalists (96% vs. 77%; P<.001). Knowledge scores were significantly higher among ID specialists and cardiologists (P<.001) and among physicians who saw relatively more patients who had myocardial infarction and/or were at risk of atherosclerotic disease. Four percent of physicians had treated or recommended treating cardiovascular diseases with antimicrobial agents; this percentage was significantly higher among cardiologists, physicians who empirically treat patients with peptic ulcers with antimicrobial agents, and physicians with a relatively high knowledge score.

Streptococcus pneumoniae serotype 4 outbreak in a home for the aged: report and review of recent outbreaks.

OBJECTIVE: To describe a pneumonia outbreak caused by Streptococcus pneumoniae among residents of a home for the aged and to review contemporary pneumococcal outbreaks. DESIGN: Epidemiological investigation. METHODS: S pneumoniae isolates were serotyped and analyzed by pulsed-field gel electrophoresis. Paired sera were tested for antibodies to pneumococcal surface adhesin A protein (PsaA, a 37-kDa cell-wall protein). Pneumococcal outbreaks reported in the last decade in English were reviewed. RESULTS: Pneumonia developed in 18 of 200 residents. In 11 (61%), a pneumococcal etiology was demonstrated. S pneumoniae, serotype 4, was isolated from the blood cultures of 3 patients; all isolates were indistinguishable by pulsed-field gel electrophoresis. Pneumococcal involvement was established in 2 by sputum culture and latex agglutination of parapneumonic fluid and in 6 others by a twofold rise in optical density of serum antibody reactive to PsaA. Pneumococcal immunization had not previously been received by any patient; mortality was 22%. No additional cases were noted following administration of pneumococcal vaccine and antibiotic prophylaxis with penicillin or erythromycin. Twenty-six outbreaks of invasive pneumococcal disease since 1990 were reviewed. Twelve occurred in the United States, and serotypes 23F, 14, and 4 accounted for 8 (67%) of 12 outbreaks. All confirmed serotypes in US outbreaks are included in the 23-valent vaccine. More than one half of pneumococcal outbreaks worldwide involved elderly persons in hospitals or long-term-care facilities. CONCLUSIONS: A pneumococcal pneumonia outbreak occurred among unvaccinated residents of a residential facility for the aged. Institutionalized elderly persons are at risk of outbreaks of pneumococcal disease and should be vaccinated.

Experience with the prevention of invasive Haemophilus influenzae type b disease by vaccination in Alaska: the impact of persistent oropharyngeal carriage.

OBJECTIVES: To report the epidemiology of invasive Haemophilus influenzae type b (Hib) disease in high-risk Alaska Native infants before and after universal infant Hib vaccination and evaluate an increase in invasive Hib disease in 1996 after changing Hib vaccine type. STUDY DESIGN: Statewide laboratory surveillance for invasive Hib disease has been conducted since 1980. Three cross-sectional Hib carriage studies were conducted in 1997 and 1998. RESULTS: The invasive Hib disease rate in Alaska Natives decreased from 332 cases per 100,000 children <5 years old in 1980-1991 to 17:100,000 in 1992-1995 but increased primarily in rural areas to 57.9:100,000 after a switch in Hib vaccine types. Carriage studies in 5 rural Alaska Native villages showed oropharyngeal Hib carriage as high as 9.3% in children aged 1 to 5 years; in contrast, carriage in urban Alaska Native children was <1%. CONCLUSIONS: Although Hib disease has decreased in Alaska, the rate of Hib disease and carriage in rural Alaska Natives did not decrease to the same extent as in non-Natives and urban Alaska Natives. Use of polyribosylribitol phosphate-outer-membrane protein conjugate vaccine for the first vaccine dose is critical to disease control in this population with continued transmission in infants <6 months of age. The ability to eliminate Hib carriage and disease may be affected by population characteristics, vaccination coverage, and Hib vaccine type used. This may pose a challenge to global elimination of Hib.

Serotype distribution and antimicrobial resistance patterns of invasive isolates of Streptococcus pneumoniae: Alaska, 1991-1998.

From January 1991 through December 1998, a total of 1046 pneumococcal isolates were received from 23 laboratories participating in the statewide surveillance system. Of these, 1037 were recovered from normally sterile sites (blood and cerebrospinal and pleural fluid) and were available for serotyping and susceptibility testing. Ninety-two percent of these isolates were serotypes represented in the 23-valent pneumococcal polysaccharide vaccine. Serotypes in the 7-valent pneumococcal conjugate vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F) were recovered from 72% of Alaska Natives and 84% of non-Native children <5 years old with invasive disease. Statewide, 7.3% and 3.2% of isolates had intermediate and high levels of resistance to penicillin, respectively; 9.2% were resistant to erythromycin (minimal inhibitory concentration, >/=1 microg/mL) and 19% to trimethoprim/sulfamethoxazole (minimal inhibitory concentration, >/=4/76 microg/mL). Twelve percent of invasive isolates were resistant to >/=2 classes of antibiotics; of these, serotype 6B accounted for 33%, and 63% were recovered from children <5 years old.

Screening for hepatitis C virus in a health maintenance organization.

BACKGROUND: Chronic infection with hepatitis C virus (HCV) is a major public health problem and is associated with over 10,000 deaths a year in the United States. In its early stages, HCV tends to be asymptomatic and can be detected only through screening. OBJECTIVES: To develop and validate a database risk algorithm for HCV infection using electronic data at HealthPartners, a health maintenance organization (HMO) in Minnesota. A secondary objective was to evaluate the benefit of screening health care workers for HCV. METHODS: A database risk algorithm was developed using diagnostic and procedure codes in the administrative database to identify at-risk enrollees. One thousand three hundred eighty enrollees (an at-risk sample and a control sample) and 502 health care workers participated in anonymous screening. Both descriptive statistics and logistic regression were used to examine the frequency of HCV infection, associations with risk factors, self-selection factors in participation, and concordance between the database risk algorithm and the risk profile questionnaire. RESULTS: Eleven enrollees tested positive for HCV, 9 from the at-risk sample and 2 from the control sample. All health care workers tested negative for HCV. Both lifestyle and medical risk factors were associated with positive test results for HCV. Enrollees with alcohol-drug diagnoses were less likely to participate in screening. A substantial proportion of enrollees with risk factors was identified either by the database risk algorithm or the risk profile questionnaire, but not by both. CONCLUSION: While the frequency of HCV infection was lower than previous estimates for the US population, the strong correlation with risk factors suggests that using the database risk algorithm for screening is a useful approach. Managed care plans with suitable data on their enrollee populations are in a key position to serve an important public health role in detecting asymptomatic patients who are infected with HCV.

Projected cost-effectiveness of pneumococcal conjugate vaccination of healthy infants and young children.

CONTEXT: Pneumococcal conjugate vaccine for infants has recently been found effective against meningitis, bacteremia, pneumonia, and otitis media. OBJECTIVE: To evaluate the projected health and economic impact of pneumococcal conjugate vaccination of healthy US infants and young children. DESIGN: Cost-effectiveness analysis based on data from the Northern California Kaiser Permanente randomized trial and other published and unpublished sources. SETTING AND PATIENTS: A hypothetical US birth cohort of 3.8 million infants. INTERVENTIONS: Hypothetical comparisons of routine vaccination of healthy infants, requiring 4 doses of pneumococcal conjugate vaccine (at 2, 4, 6, and 12-15 months), and catch-up vaccination of children aged 2 to 4.9 years requiring 1 dose, with children receiving no intervention. MAIN OUTCOME MEASURES: Cost per life-year saved and cost per episode of meningitis, bacteremia, pneumonia, and otitis media prevented. RESULTS: Vaccination of healthy infants would prevent more than 12000 cases of meningitis and bacteremia, 53000 cases of pneumonia, 1 million episodes of otitis media, and 116 deaths due to pneumococcal infection. Before accounting for vaccine costs, the vaccination program would save $342 million in medical and $415 million in work-loss and other costs from averted pneumococcal disease. Vaccination of healthy infants would result in net savings for society if the vaccine cost less than $46 per dose, and net savings for the health care payer if the vaccine cost less than $18 per dose. At the manufacturer's list price of $58 per dose, infant vaccination would cost society $80000 per life-year saved or $160 per otitis media episode prevented (other estimated costs would be $3200 per pneumonia case prevented, $15000 for bacteremia, and $280000 for meningitis). The cost-effectiveness of an additional program to administer 1 dose of vaccine to children aged 2 to 4.9 years would vary depending on the children's ages, relative risks of pneumococcal disease, and vaccine cost. CONCLUSIONS: Pneumococcal conjugate vaccination of healthy US infants has the potential to be cost-effective. To achieve cost savings, its cost would need to be lower than the manufacturer's list price. In addition to tangible costs, the vaccine should be appraised based on the less tangible value of preventing mortality and morbidity from pneumococcal disease.

Cigarette smoking and invasive pneumococcal disease. Active Bacterial Core Surveillance Team.

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 to 5.1) after adjustment by logistic-regression analysis for age, study site, and independent risk factors such as male sex, black race, chronic illness, low level of education, and living with young children who were in day care. There were dose-response relations for the current number of cigarettes smoked per day, pack-years of smoking, and time since quitting. The adjusted population attributable risk was 51 percent for cigarette smoking, 17 percent for passive smoking, and 14 percent for chronic illness. CONCLUSIONS: Cigarette smoking is the strongest independent risk factor for invasive pneumococcal disease among immunocompetent, nonelderly adults. Because of the high prevalence of smoking and the large population attributable risk, programs to reduce both smoking and exposure to environmental tobacco smoke have the potential to reduce the incidence of pneumococcal disease.

Epidemiologic relation between HIV and invasive pneumococcal disease in San Francisco County, California.

BACKGROUND: Patients with AIDS have a high incidence of invasive pneumococcal disease, but no population-based data are available on secular trends or rates of this disease in specific demographic groups. OBJECTIVE: To compare clinical characteristics, rates, and trends of pneumococcal disease in HIV-infected and non-HIV-infected persons. DESIGN: Population-based laboratory surveillance and chart review. SETTING: All of the 13 microbiology laboratories in San Francisco County, California. PATIENTS: Persons who had a sterile site culture that was positive for Streptococcus pneumoniae between October 1994 and June 1997. MEASUREMENTS: Stratified incidence rates and adjusted rate ratios, serotyping of isolates, and comparison of secular trends and rates according to census tract by Poisson regression. RESULTS: Persons infected with HIV accounted for 54.2% of 399 patients 18 to 64 years of age who had pneumococcal disease. The incidence of pneumococcal disease per 100 000 person-years was 35.0 cases overall and 802.9 cases in patients with AIDS. Compared with persons who were not known to be HIV-infected, the rate ratio for patients with AIDS was 46:0 (95% CI, 36.0 to 58.9); 55.2% of cases were attributable to HIV. In HIV-infected patients, 82.5% of isolates were serotypes that are included in the pneumococcal polysaccharide vaccine. The incidence of pneumococcal disease in black patients with AIDS (2384.6 cases per 100 000 person-years) was 5.4 times that in nonblack patients with AIDS. Rates by census tract were inversely associated with income (P < 0.001), During the study period, the incidence of pneumococcal disease decreased from 10.6 cases per 1000 person-years to 4.2 cases per 1000 person-years in patients with AIDS (P = 0.004, Poisson regression). CONCLUSIONS: In a community with a high prevalence of HIV infection, much of the burden of pneumococcal disease was attributable to AIDS. High incidence rates were seen in young adults and especially in black persons. Efforts to increase pneumococcal vaccination rates should target HIV-infected adults, particularly those living in poor urban areas.

Strengths and limitations of molecular subtyping in a community outbreak of Legionnaires' disease.

An epidemiological and microbiological investigation of a cluster of eight cases of Legionnaires' disease in Los Angeles County in November 1997 yielded conflicting results. The epidemiological part of the investigation implicated one of several mobile cooling towers used by a film studio in the centre of the outbreak area. However, water sampled from these cooling towers contained L. pneumophila serogroup 1 of another subtype than the strain that was recovered from case-patients in the outbreak. Samples from two cooling towers located downwind from all of the case-patients contained a Legionella strain that was indistinguishable from the outbreak strain by four subtyping techniques (AP-PCR, PFGE, MAb, and MLEE). It is unlikely that these cooling towers were the source of infection for all the case-patients, and they were not associated with risk of disease in the case-control study. The outbreak strain also was not distinguishable, by three subtyping techniques (AP-PCR, PFGE, and MAb), from a L. pneumophila strain that had caused an outbreak in Providence, RI, in 1993. Laboratory cross-contamination was unlikely because the initial subtyping was done in different laboratories. In this investigation, microbiology was helpful for distinguishing the outbreak cluster from unrelated cases of Legionnaires' disease occurring elsewhere. However, multiple subtyping techniques failed to distinguish environmental sources that were probably not associated with the outbreak. Persons investigating Legionnaires' disease outbreaks should be aware that microbiological subtyping does not always identify a source with absolute certainty.

Effectiveness of pneumococcal polysaccharide vaccine for preschool-age children with chronic disease.

To estimate the effectiveness of pneumococcal polysaccharide vaccine, we serotyped isolates submitted to the Pneumococcal Sentinel Surveillance System from 1984 to 1996 from 48 vaccinated and 125 unvaccinated children 2 to 5 years of age. Effectiveness against invasive disease caused by serotypes included in the vaccine was 63%. Effectiveness against serotypes in the polysaccharide vaccine but not in a proposed seven-valent protein conjugate vaccine was 94%.

An outbreak of acute respiratory disease caused by Mycoplasma pneumoniae and adenovirus at a federal service training academy: new implications from an old scenario.

Outbreaks of Mycoplasma pneumoniae and adenovirus have been reported in military institutions for several decades. During a recent outbreak in a federal service training academy, we performed an epidemiological and laboratory investigation to better characterize and control the outbreak. Of 586 students responding to a questionnaire, 317 (54%) reported having a respiratory illness during the outbreak period. Among 42 students who underwent complete laboratory testing, 24 (57%) had evidence of M. pneumoniae infection, 8 (19%) had evidence of adenovirus infection, and 4 (10%) had evidence of both. Polymerase chain reaction testing of oropharyngeal swabs revealed more acute M. pneumoniae infections (57% positive) than did serology or culture. Multivariate analysis revealed that visiting the campus health clinic >3 times for a nonrespiratory condition, such as injury, was a significant risk factor for illness among freshmen early in the course of the outbreak, whereas having an ill roommate was a risk factor throughout the duration of the outbreak.

Hospital characteristics associated with colonization of water systems by Legionella and risk of nosocomial legionnaires' disease: a cohort study of 15 hospitals.

OBJECTIVE: To investigate an increase in reports of legionnaires' disease by multiple hospitals in San Antonio, Texas, and to study risk factors for nosocomial transmission of legionnaires' disease and determinants for Legionella colonization of hospital hot-water systems. SETTING: The 16 largest hospitals in the cities of San Antonio, Temple, and Austin, Texas. DESIGN: Review of laboratory databases to identify patients with legionnaires' disease in the 3 years prior to the investigation and to determine the number of diagnostic tests for Legionella performed; measurement of hot-water temperature and chlorine concentration and culture of potable water for Legionella. Exact univariate calculations, Poisson regression, and linear regression were used to determine factors associated with water-system colonization and transmission of Legionella. RESULTS: Twelve cases of nosocomial legionnaires' disease were identified; eight of these occurred in 1996. The rise in cases occurred shortly after physicians started requesting Legionella urinary antigen tests. Hospitals that frequently used Legionella urinary antigen tests tended to detect more cases of legionnaires' disease. Legionella was isolated from the water systems of 11 of 12 hospitals in San Antonio; the 12th had just experienced an outbreak of legionnaires' disease and had implemented control measures. Nosocomial legionellosis cases probably occurred in 5 hospitals. The number of nosocomial legionnaires' disease cases in each hospital correlated better with the proportion of water-system sites that tested positive for Legionella (P=.07) than with the concentration of Legionella bacteria in water samples (P=.23). Hospitals in municipalities where the water treatment plant used monochloramine as a residual disinfectant (n=4) and the hospital that had implemented control measures were Legionella-free. The hot-water systems of all other hospitals (n=11) were colonized with Legionella. These were all supplied with municipal drinking water that contained free chlorine as a residual disinfectant. In these contaminated hospitals, the proportion of sites testing positive was inversely correlated with free residual chlorine concentration (P=.01). In all hospitals, hot-water temperatures were too low to inhibit Legionella growth. CONCLUSIONS: The increase in reporting of nosocomial legionnaires' disease was attributable to increased use of urinary antigen tests; prior cases may have gone unrecognized. Risk of legionnaires' disease in hospital patients was better predicted by the proportion of water-system sites testing positive for Legionella than by the measured concentration of Legionella bacteria. Use of monochloramine by municipalities for residual drinking water disinfection may help prevent legionnaires' disease.

The challenge of ongoing Haemophilus influenzae type B carriage and transmission in Alaska.

Cases of invasive Haemophilus influenzae type b disease in Alaskan children quickly dropped 10-fold after widespread vaccination with a conjugate vaccine (PRP-OMP) began in 1991. However, reemergence of invasive disease in 1996-97 soon followed a change to a combination diphtheria-tetanus toxoid-pertussis/H. influenzae type b vaccine which incorporates a different conjugate vaccine (HbOC). Previously unrecognized persistence of H. influenzae type b carriage in rural Alaska, coupled with characteristics of the immune response to HbOC, are the likely explanations for disease reemergence. The current vaccine recommendation--PRP-OMP for the first dose, followed by HbOC to complete the vaccination series--appears to protect Alaskan infants even in the face of continuing carriage and transmission. Successful control of invasive H. influenzae type b disease in Alaskan children will require not only appropriate immunization, but also continuing surveillance for both disease and carriage, identification of factors associated with carriage, and investigation into the feasibility of using vaccination plus antimicrobial drugs to eliminate this pathogen.

Acute otitis media: management and surveillance in an era of pneumococcal resistance. Drug-Resistant Streptococcus Pneumoniae Therapeutic Working Group.

Experts in the management of otitis media and the Drug-resistant Streptococcus pneumoniae Therapeutic Working Group were convened by the Centers for Disease Control and Prevention to respond to changes in antimicrobial susceptibility among pneumococci. The objective was to provide consensus recommendations for the management of acute otitis media (AOM) and for the surveillance of drug-resistant Streptococcus pneumoniae. After summarizing published and unpublished data from the scientific literature and the experience of the panel members, the group concluded that oral amoxicillin should remain the first-line antimicrobial agent for treating AOM. For patients with clinically defined treatment failure after 3 days of therapy, useful alternative agents include amoxicillin-clavulanate, cefuroxime axetil, and intramuscular ceftriaxone. The group also made recommendations to improve surveillance and to obtain antimicrobial susceptibility patterns for local geographic areas.