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Biomedical subjects

R F Breiman

Publications and source records attributed to R F Breiman.

At least 19 recordsLinked to original sources
PubMed2006

Risk factors for typhoid fever in a slum in Dhaka, Bangladesh.

We systematically investigated risk factors for typhoid fever in Kamalapur, a poor urban area of Bangladesh, to inform targeted public health measures for its control. We interviewed patients with typhoid fever and two age-matched controls per case about exposures during the 14 days before the onset of illness. The municipal water supply was used by all 41 cases and 81of 82 controls. In multivariate analysis, drinking unboiled water at home was a significant risk factor [adjusted odds ratio (aOR) 12.1, 95% CI 2.2-65.6]. Twenty-three (56%) cases and 21 (26%) controls reported that water from the primary source was foul-smelling (aOR 7.4, 95% CI 2.1-25.4). Eating papaya was associated with illness (aOR 5.2, 95% CI 1.2-22.2). Using a latrine for defecation was significantly protective (aOR 0.1, 95% CI 0.02-0.9). Improved chlorination of the municipal water supply or disinfecting drinking water at the household level may dramatically reduce the risk of typhoid fever in Kamalapur. The protective effect of using latrines, particularly among young children, should be investigated further.

Adolescent↗
PubMed2006

Prevalence of sputum smear-positive tuberculosis in a rural area in Bangladesh.

The objective of the study was to determine the prevalence of smear-positive tuberculosis (TB) in a rural area in Bangladesh at Matlab. A TB surveillance system was established among 106,000 people in rural Bangladesh at Matlab. Trained field workers interviewed all persons aged > or = 15 years to detect suspected cases of TB (cough > 21 days) and sputum specimens of suspected cases were examined for acid-fast bacilli (AFB). Of 59,395 persons interviewed, 4235 (7.1%) had a cough for > 21 days. Sputum specimens were examined for AFB from 3834 persons, 52 (1.4%) of them were positive for AFB. The prevalence of chronic cough and sputum positivity were significantly higher among males compared to females (P < 0.001). The population-based prevalence rate of smear-positive TB cases was 95/100,000 among persons aged > or = 15 years. Cases of TB clustered geographically (relative risk 5.53, 95% CI 3.19-9.59). The high burden of TB among rural population warrants appropriate measures to control TB in Bangladesh. The higher prevalence of persistent cough and AFB-positive sputum among males need further exploration. Factors responsible for higher prevalence of TB in clusters should be investigated.

Adolescent↗
PubMed2006

Emergence of multidrug-resistant Salmonella enterica serotype Typhi with decreased ciprofloxacin susceptibility in Bangladesh.

During 1989-2002, we studied the antimicrobial resistance of 3928 blood culture isolates of Salmonella enterica serotype Typhi (S. Typhi) in Dhaka, Bangladesh. Overall 32% (1270) of the strains were multidrug-resistant (MDR, resistant to chloramphenicol, ampicillin and trimethoprim-sulphamethoxazole); first detected in 1990 (rate of 8%), increased in 1994 (44%), declined in 1996 (22%, P<0.01 compared to 1994) and re-emerged in 2001 (36%) and 2002 (42%, P<0.01 compared to 1996). An increased MIC of ciprofloxacin (0.25 microg/ml) indicating decreased susceptibility to ciprofloxacin was detected in 24 (18.2%) out of 132 randomly selected strains during 1990-2002; more frequently in MDR than susceptible strains (46.3% vs. 5.5%, P<0.001), and the proportion of them rose to 47% in 2002 from 8% in 2000 (P<0.01). Ciprofloxacin (5 microg) disk diffusion zone diameters of < or =24 mm as break-point had 98% sensitivity and 100% specificity when compared with a ciprofloxacin MIC of 0.25 microg/ml as break-point for decreased susceptibility; being a useful and easy screen test. All strains were susceptible to ceftriaxone. The emergence of MDR S. Typhi with decreased ciprofloxacin susceptibility will further complicate the therapy of typhoid fever because of the lack of optimum treatment guidelines.

Anti-Infective Agents↗
PubMed2005

Application of an improved method for the recombinant k 39 enzyme-linked immunosorbent assay to detect visceral leishmaniasis disease and infection in Bangladesh.

Several serology-based immunoassays are used to diagnose visceral leishmaniasis (VL), a chronic protozoan parasitic disease caused by the Leishmania donovani complex. These tests are primarily designed to diagnose the most severe clinical form of VL, known as kala-azar. However, leishmanial infection is frequently asymptomatic and may manifest only as a positive serologic response or positive leishmanin skin test. We modified a previously described enzyme-linked immunosorbent assay (ELISA) that detects patient antibodies reactive with the recombinant Leishmania protein K39 (rK39) to confirm suspected kala-azar and to detect asymptomatic infection in a community study in Bangladesh. With the inclusion of a standard curve on each ELISA plate, the rK39 ELISA was more repeatable (kappa coefficient of agreement=0.970) and more reliable compared to the original method (kappa=0.587, P<0.001). The cutoff point for a positive antibody response was chosen based on the 99th percentile of the ELISA distribution for the negative-control sera. However, we found that sera from all patients with active kala-azar yielded values more than twice the magnitude of this cutoff. Using receiver-operator characteristic curves, we determined a second cutoff value predictive of kala-azar. Using these criteria, the sensitivity and specificity of the modified ELISA for kala-azar were 97.0% and 98.9%, respectively, for sera from our study population. We hypothesize that individuals with antibody levels greater than the 99th percentile of the negative controls but less than the cutoff point for kala-azar have asymptomatic leishmanial infections.

Animals↗
PubMed2001

Challenges in the development, licensure, and use of combination vaccines.

Before substantial public health benefits associated with use of combination vaccines can be realized, a variety of challenges must be addressed. In February 2000, the National Vaccine Program Office convened the International Symposium on Combination Vaccines to explore solutions for barriers to development, licensure, and use of safe and effective combination vaccines. The symposium focused on the following questions: (1) What immunologic standards should be used to evaluate new combination vaccines? (2) How should correlates of protection be developed, and how should the data they provide be interpreted? (3) What sample size is adequate for prelicensure safety trials of combination vaccines? (4) Should standards for evaluation of combination vaccines containing licensed components be different from standards for evaluation of combinations containing unlicensed components? (5) How can the "great expectations" of postlicensure surveillance be realized? Available data relevant to these issues were presented, providing a foundation for furthering the science of combination vaccines.

Clinical Trials as Topic↗
PubMed2001

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.

Adult↗
PubMed2001

Clinical outcomes of bacteremic pneumococcal pneumonia in the era of antibiotic resistance.

Limited data are available about the impact of antimicrobial resistance on clinical outcomes in cases of pneumococcal pneumonia. This was studied in 146 persons hospitalized with invasive pneumonia due to Streptococcus pneumoniae (minimum inhibitory concentration of cefotaxime, > or = .25 microg/mL) who were identified through population-based active surveillance for the period of November 1994 through April 1996. Compared with matched control subjects who had infection with more-susceptible S. pneumoniae, the proportion of subjects who died or who were admitted to an intensive care unit did not differ significantly. Multivariable analysis showed no significant contribution of antimicrobial resistance to mortality or the requirement for care in an intensive care unit. The ability to detect an effect of antimicrobial resistance on these important outcome measures may have been influenced by aggressive multidrug empirical therapy in this group of hospitalized patients. Factors other than resistance, such as severity of illness at presentation and advance directive status ("do not resuscitate" orders), appear to have a stronger influence on pneumococcal pneumonia outcomes.

Adolescent↗
PubMed2001

Vaccines as tools for advancing more than public health: perspectives of a former director of the National Vaccine Program office.

With application of new technologies and licensing of new vaccines, vaccines will soon be better by several orders of magnitude. Yet barriers impede the introduction and wide use of new vaccines. Most of the diseases for which we will have vaccines in the future have not evoked enthusiasm from public health professionals, but not consumer demand, despite ongoing high rates of disease and death. Furthermore, the public's attention turns from the now rarely occurring vaccine-preventable diseases to reports of fears and confirmed adverse events associated with the same vaccines that so effectively continue to prevent disease. New vaccines will be held to a much higher standard; thus we will need more capacity for disease studies, vaccine trials, and surveillance systems. Vaccines and immunization programs contribute to the societal fabric and are an expression of social responsibility. Vaccine research and implementation programs must have the foundation and capacity to keep pace with evolving scientific and societal realities so that their broad benefits can be fully realized.

Altruism↗
PubMed2001

Intussusception, infection, and immunization: summary of a workshop on rotavirus.

This article summarizes the proceedings of a workshop sponsored by the National Institutes of Health and the National Vaccine Program Office, and held in Bethesda, Maryland, on January 21, 2000. The objective of the meeting was to focus research toward an understanding of the basis for the possible association between intussusception and the reassortant rhesus-human rotavirus vaccine tetravalent (RRV-TV). After numerous reports of intussusception after administration of RRV-TV, the manufacturers of this vaccine voluntarily withdrew it from the United States market. The American Academy of Pediatrics, the Advisory Committee on Immunization Practices, and the American Academy of Family Physicians also withdrew their original recommendations for administration of RRV-TV to children at 2, 4, and 6 months of age. These actions will have global implications for the prevention of morbidity and mortality attributable to rotavirus infection. Benefit-cost ratios for the use of RRV-TV will be substantially different in developing countries compared with developed countries. Therefore, extensive research is needed in both of these settings, to further our understanding of the epidemiology, pathogenesis, and pathology of both rotavirus disease and intussusception to enable optimal prevention. The workshop reviewed the current understanding of the possible association between RRV-TV and intussusception, as well as the possible association between a variety of viral infections and intussusception. The workshop also identified critical areas of research regarding this possible association. This research will be essential not only for the development of safe and effective rotavirus vaccines, but for the development of other oral vaccines as well.

Child, Preschool↗
PubMed2000

Evaluation of effectiveness of the 23-valent pneumococcal capsular polysaccharide vaccine for HIV-infected patients.

BACKGROUND: We conducted a retrospective case-control study to evaluate effectiveness of pneumococcal vaccine against invasive disease among adults with human immunodeficiency virus (HIV) infection in San Francisco, Calif, and Atlanta, Ga. METHODS: Case patients were 18- to 55-year-old subjects with HIV infection who were admitted to selected hospitals in Atlanta or San Francisco from February 1992 to April 1995 from whom Streptococcus pneumoniae was isolated from a normally sterile site. Controls were HIV-infected patients of similar age matched to cases by hospital of admission and CD4 lymphocyte count (<0.20, 0.20-0.499, >/=0.50 x 10(9)/L [<200, 200-499, >/=500 cells/mm(3)]) or clinical stage of acquired immunodeficiency syndrome. Case and control subjects were restricted to persons known to have HIV infection before hospital admission. Analysis used matched univariate and conditional logistic regression. RESULTS: One hundred seventy-six case patients and 327 controls were enrolled. By univariate analysis, persons with pneumococcal disease were more likely to be black, be current smokers, and have close contact with children. Adjusted for these factors and CD4 cell count, pneumococcal vaccine effectiveness was 49% (95% confidence interval [CI], 12%-70%). Adjusting for all variables and key interaction terms, vaccine effectiveness among whites was 76% (95% CI, 35%-91%), whereas effectiveness among blacks was 24% (95% CI, -50% to 61%). Among controls, vaccination was significantly less common among blacks (29% vs 45%; P<.005). CONCLUSIONS: Pneumococcal vaccine demonstrated protection against invasive pneumococcal infections among white but not black HIV-infected adults. Failure to demonstrate effectiveness among blacks may be due to limited power because of low use of the vaccine in this population, immunization at more advanced stages of immunosuppression, or unmeasured factors. These data support current recommendations for use of pneumococcal vaccine in HIV-infected persons and highlight a clear need for strategies to improve vaccine-induced protection.

AIDS-Related Opportunistic Infections↗
PubMed2000

Adult immunization programs in nontraditional settings: quality standards and guidance for program evaluation.

This report provides a summary of the National Vaccine Advisory Committee's (NVAC) workshop on adult immunization programs in nontraditional settings, quality standards for such programs, and guidance for program evaluation. Throughout the United States, an increasing number of adults are receiving vaccine in nontraditional settings (e.g., pharmacies and churches). Immunization programs in nontraditional settings are often more accessible and convenient than a health-care provider's office or a public health clinic, especially for medically underserved adults (e.g., economically disadvantaged, inner city, and minority populations). Medically underserved adults might be at particular risk for undervaccination because they are often without a medical home (i.e., a regular point of contact where their health-care needs are met). Immunization programs in nontraditional settings might enhance the capacity of the health-care system to effectively deliver vaccine to adults by increasing the number and types of sites where adults can receive vaccine. NVAC has recognized that strategies need to be developed to make vaccines available to all adults and that the number of immunization programs in nontraditional settings is increasing. Therefore, the Committee issues the following report, including quality standards and guidance for program evaluation.

Adult↗
PubMed2000

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.

Bacterial Vaccines↗
PubMed2000

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.

Adolescent↗
PubMed2000

Clinical outcomes of meningitis caused by Streptococcus pneumoniae in the era of antibiotic resistance.

Limited data are available on clinical outcomes of meningitis due to cefotaxime-nonsusceptible Streptococcus pneumoniae. We analyzed data from 109 cases of pneumococcal meningitis in Atlanta, Baltimore, and San Antonio, which were identified through population-based active surveillance from November 1994 to April 1996. Pneumococcal isolates from 9% of the cases were resistant to cefotaxime, and isolates from 11% had intermediate susceptibility. Children were more likely to have cephalosporin-nonsusceptible pneumococcal meningitis, but mortality was significantly higher among adults aged 18-64 years. Vancomycin was given upon admission to 29% of patients, and within 48 h of admission to 52%. Nonsusceptibility to cefotaxime was not associated with the following outcomes: increased mortality, prolonged length of hospital or intensive care unit (ICU) stay, requirement of intubation or oxygen, ICU care, discharge to another medical or long-term-care facility, or neurological deficit. Empirical use of vancomycin, current prevalence of drug-resistant S. pneumoniae, and degree of nonsusceptibility to cefotaxime may have influenced these findings.

Adolescent↗
PubMed2000

Impact of penicillin susceptibility on medical outcomes for adult patients with bacteremic pneumococcal pneumonia.

The impact of penicillin susceptibility on medical outcomes for adult patients with bacteremic pneumococcal pneumonia was evaluated in a retrospective cohort study conducted during population-based surveillance for invasive pneumococcal disease in the greater Atlanta region during 1994. Of the 192 study patients, 44 (23%) were infected with pneumococcal strains that demonstrated some degree of penicillin nonsusceptibility. Compared with patients infected with penicillin-susceptible pneumococcal strains, patients whose isolates were nonsusceptible had a significantly greater risk of in-hospital death due to pneumonia (relative risk [RR], 2.1; 95% confidence interval [CI], 1-4.3) and suppurative complications of infection (RR, 4.5; 95% CI, 1-19.3), although only risk of suppurative complications remained statistically significant after adjustment for baseline differences in severity of illness. Among adults with bacteremic pneumococcal pneumonia, infection with penicillin-nonsusceptible pneumococci is associated with an increased risk of adverse outcome.

Adult↗
PubMed2000

Outbreak of Legionnaires' disease associated with a display whirlpool spa.

BACKGROUND: Recognized outbreaks of Legionnaires' disease (LD) are rare; when they occur, they provide opportunities to understand the epidemiology of the illness and improve prevention strategies. We investigated a population-based outbreak. METHODS: After the confirmation of LD in October 1996 in five people in neighbouring towns in southwest Virginia, active surveillance for additional cases was undertaken. A case-control study was conducted to identify exposures associated with illness, followed by a cohort study among employees of the facility at which the source of the outbreak was located in order to assess unrecognized exposure and illness. Samples of likely sources of LD in the facility were cultured for LEGIONELLA: RESULTS: In all, 23 laboratory-confirmed cases of LD were eventually identified. Of the 15 cases in the case-control study, 14 (93%) reported visiting a home-improvement store, compared with 12 (27%) of 45 controls (matched odds ratio [MOR] = 23.3; 95% CI : 3-182). Among home-improvement centre patrons, 10 (77%) of 13 cases questioned recalled either visiting or walking by a display whirlpool spa, compared with 3 (25%) of 12 controls (MOR = 5.5; 95% CI : 0.7-256.0). Two cases' sputum isolates were an exact match, by monoclonal antibody subtyping and arbitrarily primed polymerase chain reaction, to a whirlpool spa filter isolate from the store. Employees reporting more exposure to the display spas were more likely to report symptoms of LD or to have an elevated titre. CONCLUSIONS: This investigation shows that LD can be transmitted from a whirlpool spa used for display only, and highlights the need for minimizing the risk of transmission of LD from all water-filled spas. Key messages This paper describes an investigation of a population-based outbreak of Legionnaires' disease (LD). A case-control study first identified a home-improvement store as the likely source of the outbreak. An environmental investigation later confirmed that finding, as two cases' sputum isolates were an exact match, by monoclonal antibody subtyping and arbitrarily primed polymerase chain reaction, to a whirlpool spa filter isolate from the store. The spa was intended and used for display only.

Adult↗
PubMed2000

The radiologic manifestations of Legionnaire's disease. The Ohio Community-Based Pneumonia Incidence Study Group.

STUDY OBJECTIVES: To study the serial radiographic manifestations of Legionnaire's disease from the initial presentation on admission to recovery using strict criteria for the diagnosis of infection. MATERIALS AND METHODS: We prospectively studied the chest radiographs of patients hospitalized with a diagnosis of community-acquired pneumonia in Summit County, Ohio between November 1990 and November 1992. Forty-three patients fulfilled strict criteria for legionellosis. The diagnosis of infection was based on the criteria of "definite" diagnosis as defined by the Ohio Community-Based Pneumonia Incidence Study Group report. The criteria included the isolation of the microorganism, the presence of a significant antibody rise, or the presence of Legionella antigen in the urine. RESULTS: Forty of 43 patients had admission radiographs interpreted as compatible with pneumonia. In spite of appropriate antimicrobial therapy, worsening of the infiltrates was found in more than half of the patients within the first week. Twenty-seven patients were observed to have pleural effusion during the course of hospitalization: 10 effusions were found on admission, another 14 developed during the first week, and 3 new effusions were discovered after the first week. Cavitation was found in only one patient. None of the patients had apical involvement. CONCLUSION: This study confirms previous reports using less stringent etiologic diagnosis criteria that chest radiographic findings in Legionnaire's disease are not specific. Even with appropriate therapy, more than half of the patients will have worsening of the infiltrates during the first week. Pleural effusion is common among our patients, and it is frequently detected during the serial radiographic studies during the first week of hospitalization. Chest radiography in Legionnaire's disease is useful only for the monitoring of disease progression and not for diagnostic purposes. In addition, worsening of infiltrates and pleural effusion are seen in more than half of the patients in spite of appropriate therapy and clinical improvement.

Adult↗