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R F Breiman

Publications and source records attributed to R F Breiman.

At least 37 records · Page 2Linked to original sources

Accuracy of ICD-9-CM codes in detecting community-acquired pneumococcal pneumonia for incidence and vaccine efficacy studies.

Studies have used medical record discharge data as coded by the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) to estimate pneumococcal pneumonia incidence and vaccine efficacy. However, the accuracy of coding data to identify laboratory-confirmed pneumococcal pneumonia is not known. With the use of information collected in Ohio for a community-based pneumonia incidence study, the authors calculated the sensitivities, specificities, positive predictive values (PPV), and negative predictive values (NPV) of specific codes for pneumococcal pneumonia among hospitalized patients with community-acquired pneumonia. Sensitivities of the most common ICD-9-CM codes listed in the first five positions for patients with laboratory-confirmed pneumococcal pneumonia were 58.3% (code 481.0, pneumococcal pneumonia), 20.4% (38.0, streptococcal septicemia), 19.2% (38.2, pneumococcal septicemia), 15.0% (518.81, respiratory failure), 14.2% (486.0, pneumonia, organism unspecified), and 11.3% (482.3, streptococcal pneumonia). Using the first five listed ICD-9-CM codes rather than just the first listed code increased sensitivity without causing substantial change in specificity, PPV, and NPV. Sensitivity, PPV, and NPV of individual and groups of codes varied with different case definitions of pneumococcal pneumonia. Incidence and vaccine efficacy studies with the ability to validate diagnoses by medical chart review can use a combination of many ICD-9-CM codes to maximize sensitivity. However, without the ability to review medical charts, researchers must carefully decide which codes would best suit their studies.

Adolescent↗

Molecular characterization of a globally distributed lineage of serotype 12F Streptococcus pneumoniae causing invasive disease.

These studies have identified a major genetic lineage of capsule serotype 12F Streptococcus pneumoniae, which has maintained two different types of the pneumococcal surface protein A (PspA) virulence factor and caused invasive disease in geographically disjoint locations. Twenty outbreak strains from a Texas jail and Maryland day care center and 16 reference strains from Texas, Maryland, Washington, Michigan, Oklahoma, Missouri, Alaska, and Australia were examined. Although the Texas and Maryland outbreak strains were indistinguishable by IS1167 and boxA genotyping procedures, all strains examined were members of a genetically similar lineage. The microevolutionary history of pspA differed from that of the overall genetic background of the strains. Taken together, these findings suggested that the Texas and Maryland outbreaks were caused by different clones of a major genetic lineage of serotype 12F pneumococci, within which at least one PspA has been acquired via localized genetic recombination.

Amino Acid Sequence↗

Parainfluenza virus infection among adults hospitalized for lower respiratory tract infection.

To better define the contribution of human parainfluenza viruses (HPIVs) to lower respiratory tract infection in adults, we tested acute- and convalescent-phase serum specimens from hospitalized adults participating in a population-based prospective study of lower respiratory tract infection during 1991-1992. We tested all available specimens from the epidemic seasons for each virus and approximately 300 randomly selected specimens from the corresponding off-seasons for antibodies to HPIV-1, HPIV-2, or HPIV-3. During the respective epidemic season, HPIV-1 infection was detected in 18 (2.5%) of 721 and HPIV-3 infection in 22 (3.1%) of 705 patients with lower respiratory tract infection. Only 2 (0.2%) of 1,057 patients tested positive for HPIV-2 infection. No HPIV-1 infections and only 2 (0.7% of 281 patients tested) HPIV-3 infections were detected during the off-seasons. HPIV-1 and HPIV-3 were among the four most frequently identified infections associated with lower respiratory tract infection during their respective outbreak seasons.

Adult↗

Clinical characteristics of Chlamydia pneumoniae infection as the sole cause of community-acquired pneumonia.

The clinical characteristics of 26 patients with community-acquired pneumonia due to Chlamydia pneumoniae as the only identified pathogen who required hospitalization were evaluated. Most patients (18) had reinfection based on serological results. The mean age of the patients was 55 years (38 years, patients with primary infection; 63 years, patients with reinfection), and the gender representation was equal. Generally, illness was mild and associated with limited temperature elevation and nonspecific symptoms. The presence of comorbid illnesses and the requirement of supplemental oxygen therapy were the most common criteria for hospital admission.

Adult↗

A community outbreak of Legionnaires' disease linked to hospital cooling towers: an epidemiological method to calculate dose of exposure.

BACKGROUND: From July to September 1994, 29 cases of community-acquired Legionnaires' disease (LD) were reported in Delaware. The authors conducted an investigation to a) identify the source of the outbreak and risk factors for developing Legionella pneumophila serogroup 1 (Lp-1) pneumonia and b) evaluate the risk associated with the components of cumulative exposure to the source (i.e. distance from the source, frequency of exposure, and duration of exposure). METHODS: A case-control study matched 21 patients to three controls per case by known risk factors for acquiring LD. Controls were selected from patients who attended the same clinic as the respective case-patients. Water samples taken at the hospital, from eight nearby cooling towers, and from four of the patient's homes were cultured for Legionella. Isolates were subtyped using monoclonal antibody (Mab) analysis and arbitrarily primed polymerase chain reaction (AP-PCR). RESULTS: Eleven (52%) of 21 case-patients worked at or visited the hospital compared with 17 (27%) of 63 controls (OR 5.0, 95% CI : 1.1-29). For those who lived, worked, or visited within 4 square miles of the hospital, the risk of illness decreased by 20% for each 0.10 mile from the hospital; it increased by 80% for each visit to the hospital; and it increased by 8% for each hour spent within 0.125 miles of the hospital. Lp-1 was isolated from three patients and both hospital cooling towers. Based on laboratory results no other samples contained Lp-1. The clinical and main-tower isolates all demonstrated Mab pattern 1,2,5,6. AP-PCR matched the main-tower samples with those from two case-patients. CONCLUSION: The results of our investigation suggested that the hospital cooling towers were the source of a community outbreak of LD. Increasing proximity to and frequency of exposure to the towers increased the risk of LD. New guidelines for cooling tower maintenance are needed. Knowing the location of cooling towers could facilitate maintenance inspections and outbreak investigations.

Adult↗

Vaccines to prevent respiratory infection: opportunities on the near and far horizon.

Illnesses caused by respiratory pathogens result in great loss of life, suffering and commitment of resources for treatment. That the suffering and loss of life can be prevented through immunization has already been clearly shown with existing vaccines, such as those for Haemophilus influenzae type b, Streptococcus pneumoniae, and influenza. The emergence of drug-resistant pathogens is making reliance on therapy more expensive and perhaps less successful, accentuating the need to focus on prevention. Although several effective vaccines to prevent respiratory infections currently exist, they are underutilized globally. Improvements in immunogenicity, efficacy, and ease of administration, and lowering the costs of some of the existing vaccines would augment the potential for prevention worldwide. The greatest opportunities for the prevention of respiratory infections will rest with vaccines that will become available in the future.

Journal Article↗

Lessons learned from a review of the development of selected vaccines. National Vaccine Advisory Committee.

BACKGROUND: Although the vaccine research and development network in the United States remains vibrant, its continued success requires maintaining harmonious interaction among its many components. Changing one component is likely to affect the system overall. An examination of case studies of the development of selected vaccines would allow an examination of the network as a whole. This article presents conclusions drawn from the case study review undertaken. OBJECTIVE: Successful development of vaccines is a time-intensive process requiring years of commitment from a network of scientists and a continuum of regulatory and manufacturing entities. We undertook this work to shed light on how well the vaccine development system in the United States performs. METHOD: The National Vaccine Advisory Committee examined the research and development pathways of several vaccines that reached licensure expeditiously (hepatitis B vaccine, Haemophilus influenzae type b conjugate vaccines); some that became licensed only after considerable delay (oral typhoid Ty21a vaccine, varicella vaccine); some that are at the point of imminent or recent licensure (reassortant Rhesus rotavirus vaccine, which was licensed by the Food and Drug Administration on August 30, 1998) or near submission for licensure (intranasal cold adapted influenza vaccine); and one for which clinical development is slow because of hurdles that must be overcome (respiratory syncytial virus vaccines). RESULTS: Some common themes emerged from the reviews of these vaccine "case histories": the expediting influence of a strong scientific base and rationale; the need for firm quantitation of disease burden and clear identification of target populations; the critical role played by individuals or teams who act as "champions" to overcome the inevitable obstacles; availability of relevant animal models, high-quality reagents and standardized assays to measure immune response; the absolute requirement for well designed, meticulously executed clinical trials of vaccine safety, immunogenicity, and efficacy; postlicensure measurements of the public health impact of the vaccine and a track record of the vaccine's safety and acceptance with large-scale use; and the critical need for international collaborations to evaluate vaccines against diseases of global importance that are rare in the United States (eg, typhoid fever). It was clear that the critical step-up from bench scale to pilot lots and then to large-scale production, which depends on a small group of highly trained individuals, is often a particularly vulnerable point in the development process. CONCLUSIONS: One fundamental lesson learned is that within the varied and comprehensive US vaccine development infrastructure, multiple and rather distinct paths can be followed to reach vaccine licensure. The National Vaccine Advisory Committee review process should be conducted periodically in the future to ascertain that the US vaccine development network, which has been enormously productive heretofore and has played a leadership role globally, is adapting appropriately to ensure that new, safe, and efficacious vaccines become available in a timely manner.

Drug Approval↗

Geocoding and linking data from population-based surveillance and the US Census to evaluate the impact of median household income on the epidemiology of invasive Streptococcus pneumoniae infections.

The emergence of drug-resistant Streptococcus pneumoniae poses new clinical challenges and may also reflect a change in the epidemiology of S. pneumoniae infections. A variety of studies have shown that drug-resistant S. pneumoniae infections are linked to antimicrobial use. It has been hypothesized that persons of high socioeconomic status are at increased risk for a drug-resistant infection because of greater access to antimicrobial drugs. To assess whether median household income is associated with increased risk of penicillin-nonsusceptible S. pneumoniae infections, the authors geocoded and linked data from population-based surveillance for invasive pneumococcal disease with data from the 1990 US Census. Among invasive pneumococcal isolates from Atlanta, Georgia, in 1994, increasing proportions of penicillin-nonsusceptible isolates were associated with higher median household incomes (chi2 for trend, 15.17; p=0.002). Despite higher rates of invasive pneumococcal disease among blacks and persons who resided within lower median household income areas, white patients in areas with higher median household income had a higher risk of being infected with strains that were not susceptible to penicillin (Wilcoxon rank sum, Z=2.66, p=0.008). These findings demonstrated the utility of geocoding and US Census data in describing the epidemiology of drug-resistant S. pneumoniae and also provided more evidence that socioeconomic factors may influence the development of drug resistance.

Adolescent↗

Epidemiology of emerging pneumococcal drug resistance: implications for treatment and prevention.

Drug-resistant Streptococcus pneumoniae infection are becoming increasingly common throughout the world. These strains pose new challenges in the treatment of suspected pneumococcal infections, and they highlight the importance of limiting selection for resistant strains through judicious antibiotic use and preventing infection by immunization of persons at high risk. The clinical impact of drug-resistant S. pneumoniae infection has not been fully defined, but anecdotal reports suggest that outcome is poor for persons with drug-resistant pneumococcal meningitis. The American Academy of Pediatrics has recommended adding vancomycin to the treatment of suspected pneumococcal meningitis cases until the results of culture and susceptibility testing are available. Additional data are needed to determine the optimal empiric antibiotic regimen for nonmeningeal invasive pneumococcal infections. A 23-valent pneumococcal capsular polysaccharide vaccine can prevent many drug-resistant and susceptible invasive pneumococcal infections. The vaccine is recommended in the United States for persons at increased risk of pneumococcal infection due to certain medical conditions and for all persons > or = 65 years old. Vaccine efficacy for immunocompetent persons > or = 65 years is 75%. However, the vaccine is underutilized, and a substantial reduction in the morbidity and mortality associated with invasive pneumococcal infections is unlikely until the vaccine is used more widely among persons at risk for disease.

Adolescent↗

Community-acquired pneumonia in adults: guidelines for management. The Infectious Diseases Society of America.

This is part of the series of practice guidelines commissioned by the Infectious Diseases Society of America through its Practice Guidelines Committee. The purpose of this guideline is to provide assistance to clinicians in the diagnosis and treatment of community-acquired pneumonia. The targeted providers are internists and family practitioners. The targeted groups are immunocompetent adult patients. Criteria are specified for determining whether the inpatient or outpatient setting is appropriate for treatment. Differences from other guidelines written on this topic include use of laboratory criteria for diagnosis and approach to antimicrobial therapy. Panel members and consultants are experts in adult infectious diseases. The guidelines are evidence based where possible. A standard ranking system is used for the strength of the recommendations and the quality of the evidence cited in the literature reviewed. The document has been subjected to external review by peer reviewers as well as by the Practice Guidelines Committee and was approved by the IDSA Council. An executive summary and tables highlight the major recommendations. The guidelines will be listed on the IDSA home page at http://www.idsociety.org.

Adult↗

More than 10 years of unrecognized nosocomial transmission of legionnaires' disease among transplant patients.

OBJECTIVE: To investigate a cluster of cases of legionnaires' disease among patients at a hospital. SETTING: A university hospital that is a regional transplant center. DESIGN: Retrospective review of microbiology and serology data from the hospital laboratories and prospective surveillance via the radiology department; a case-control study and environmental sampling within the hospital and from nearby cooling towers. RESULTS: Diagnosis of seven cases of legionnaires' disease in the first 9 months of 1996 led to recognition of a nosocomial outbreak that may have begun as early as 1979. Review of charts from 1987 through September 1996 identified 25 culture-confirmed cases of nosocomial or possibly nosocomial legionnaires' disease, including 18 in bone marrow and heart transplant patients. Twelve patients (48%) died. During the first 9 months of 1996, the attack rate was 6% among cardiac and bone marrow transplant patients. For cases that occurred before 1996, intubation was associated with increased risk for disease. High-dose corticosteroid medication was strongly associated with the risk for disease, but other immunosuppressive therapy or cancer chemotherapy was not. Several species and serogroups of Legionella were isolated from numerous sites in the hospital's potable water system. Six of seven available clinical isolates were identical and were indistinguishable from environmental isolates by pulsed-field gel electrophoresis. Initial infection control measures failed to interrupt nosocomial acquisition of infection. After extensive modifications to the water system, closely monitored repeated hyperchlorinations, and reduction of patient exposures to aerosols, transmission was interrupted. No cases have been identified since September 1996. CONCLUSIONS: Legionella can colonize hospital potable water systems for long periods of time, resulting in an ongoing risk for patients, especially those who are immunocompromised. In this hospital, nosocomial transmission possibly occurred for more than 17 years and was interrupted in 1996, after a sudden increase in incidence led to its recognition. Hospitals specializing in the care of immunocompromised patients (eg, transplant centers) should prioritize surveillance for cases of legionnaires' disease. Aggressive control measures can interrupt transmission of this disease successfully.

Case-Control Studies↗

Outbreak of pneumonia in a long-term care facility: antecedent human parainfluenza virus 1 infection may predispose to bacterial pneumonia.

OBJECTIVES: To determine the causes of an outbreak of lobar pneumonia. DESIGN: Matched (1:2) case-control study. SETTING: A 70-bed chronic care facility for older people. PARTICIPANTS: Residents of the facility. RESULTS: Ten residents developed pneumonia over a 10-day period. Two residents died. One case-patient had Streptococcus pneumoniae bacteremia; another had polymerase chain reaction evidence of S. pneumoniae infection. No other etiologic agent was identified. Only four of 10 case-patients had received routine diagnostic cultures of blood or sputum before the administration of antibiotics. Symptoms of upper respiratory illness (URI) among residents before the pneumonia outbreak corresponded with elevation of antibodies to human parainfluenza virus 1 (HPIV1). In a matched case-control study, six of 10 case-patients, compared with five of 20 controls, had symptoms of URI during the preceding month (matched odds ratio (MOR) = 4.5, 95% CI = 0.8-33). Nine case-patients had serum available, and five of these had both serologic evidence of recent HPIV1 infection and recent URI, compared with two of 18 controls (MOR = 9.0, 95% CI = 1.2-208). Only three residents had documentation of pneumococcal vaccination. CONCLUSIONS: Noninfluenza viral infections may play a role in the pathogenesis of some bacterial pneumonias. S. pneumoniae was the cause of at least two pneumonias; lack of preantibiotic cultures may have interfered with isolation of S. pneumoniae in others. Recent HPIV1 infection was epidemiologically linked to subsequently developing pneumonia. Spread of HPIV1 in the facility may have contributed to increased susceptibility to S. pneumoniae and, potentially, to other bacterial pathogens.

Aged↗

Comparison of a pneumococcal common protein (PsaA) antibody ELISA and a PsaA immune complex ELISA for detection of pneumococcal serum antibody.

We examined and compared results from three assays, an enzyme-linked immunosorbent assay (ELISA) and two immune complex ELISAs for analysis of the serum antibody response to a native pneumococcal 37-kD common cell-wall protein by using acute- and convalescent-phase sera from 56 patients with community-acquired pneumonia. The sensitivities of the ELISA, the undissociated and dissociated immune complex assays were 85% (23 of 27), 78% (21 of 27) and 67% (18 of 27), respectively. To determine specificity, paired sera from patients with pneumonia of other bacterial etiologies were tested. The specificities were 83, 83 and 72% for the ELISA, undissociated immune complex, and dissociated immune complex, respectively. Based on this study, the sensitivities of the three assays were not statistically different. These tests could be used retrospectively to confirm invasive pneumococcal disease.

Adhesins, Bacterial↗

Legionnaires' disease: clinical, epidemiological, and public health perspectives.

Legionnaires' disease is a modern environmental infectious disease. It stems from the capacity of the causative agent, Legionella, to multiply within amoebae in warm water and the use, during the 20th century, of devices that maintain water at warm temperatures and produce aerosols. When contaminated with Legionella, aerosols consisting of respirable droplets place the bacteria in juxtaposition with alveolar macrophages, which, as with amoebae, they may parasitize, resulting in illness in susceptible persons. The disease is much more common than previously appreciated with at least 13,000 cases estimated to occur per year in the United States, based on prospective studies. Two highly specific tests, urinary antigen detection and sputum culture, are available for diagnosis during illness. With 60% to 80% sensitivity, urinary antigen tests rapidly detect antigens of Legionella pneumophila serogroup 1, which are responsible for 70% of the cases of legionnaires' disease; results can be available within a few hours. Culture of sputum is 50% to 60% sensitive, but several days are required for growth, and many patients do not produce sputum. Serologic testing, although useful for epidemiologic studies when convalescent-phase antibody titers can be compared with acute-phase titers, is not helpful for clinical decision making because of the low positive predictive value of commercially available acute-phase serologic tests. Erythromycins, intravenous azithromycin, and levofloxacin are currently approved by the US Food and Drug Administration for treatment of legionnaires' disease. However, clarithromycin and several other fluoroquinolones are active against Legionella and may also provide effective therapy. Recent recommendations from the Centers for Disease Control and Prevention's Hospital Infection Control Practices Advisory Committee should be helpful in reducing nosocomial legionnaires' disease. Recommendations are in place or are being developed to minimize the risk of disease in a variety of other settings.

Communicable Disease Control↗

Stability of Legionella urinary antigens over time.

Twenty-two urine samples positive for Legionella pneumophila serogroup 1 antigen by EQUATE radioimmunoassay (RIA) (Binax, Portland, ME, USA) were stored at various temperatures and the RIA repeated at 1, 7, 30, 90, and 120 days to evaluate stability of the urinary antigens. The mean ratios of patient/negative control remained stable. Although there was a 10% decrease in the mean ratios after 1 month, changes were not significant. However, individual samples with ratios close to 3 may fall to < 3.

Antigens, Bacterial↗

Emergence of antibody to capsular polysaccharides of Streptococcus pneumoniae during outbreaks of pneumonia: association with nasopharyngeal colonization.

Antibody to pneumococcal capsular polysaccharides (PPS) of Streptococcus pneumoniae plays a major role in protecting the host against pneumococcal infection. A variable proportion of healthy adults have antibody to PPS, often in the absence of recognized pneumococcal infection. To determine whether exposure to pneumococci or colonization by pneumococci, or both, stimulates the emergence of antibody to PPS, we studied outbreaks of pneumonia at two military camps. Of the men who were present at a military training camp during an outbreak of pneumonia due to S. pneumoniae serotype 1 but who did not develop pneumonia, 27.8% had IgG antibody to PPS 1, whereas only 3.6% of controls had this antibody. In another outbreak caused by S. pneumoniae serotypes 7F and 8, 35.9% of asymptomatic soldiers who had nasopharyngeal colonization by one of these strains had antibody to the relevant PPS, and another 30.8% who originally did not have antibody developed it within 30 days; thus, 66.7% of these soldiers had antibody to the relevant PPS. These data show that serotype-specific antibody promptly appears following exposure to an outbreak of pneumococcal pneumonia and is probably mediated through acquisition of nasopharyngeal pneumococcal carriage.

Adult↗

The role of arbitrarily primed PCR in identifying the source of an outbreak of Legionnaires' disease.

An outbreak of community-acquired Legionnaires' disease (LD) occurred in Providence, R.I., in fall 1993. To find the outbreak source, exposures of 17 case patients were compared to those of 33 matched controls. Case patients were more likely than controls to have visited a section of downtown (area A) during the 2 weeks before illness (11 [65%] versus 9 [27%]; matched odds ratio, 6.5; P = 0.01). Water samples were cultured from 27 aerosol-producing devices within area A. Legionella pneumophila serogroup 1 isolates underwent monoclonal antibody (MAb) subtyping and arbitrarily primed PCR (AP-PCR). All four L. pneumophila serogroup 1 isolates available from case patients who visited area A had identical MAb and AP-PCR patterns. Among 14 environmental isolates, 5 had MAb patterns that matched the case patient isolates, but only 1 had a matching AP-PCR pattern. This investigation implicates a cooling tower in area A as the outbreak source and illustrates the usefulness of AP-PCR for identifying sources of LD outbreaks.

Disease Outbreaks↗