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Biomedical subjects

R F Breiman

Publications and source records attributed to R F Breiman.

At least 91 records · Page 5Linked to original sources

Pneumococcal disease during HIV infection. Epidemiologic, clinical, and immunologic perspectives.

OBJECTIVE: To characterize the epidemiology, clinical manifestations, and immunologic risk factors for infections with Streptococcus pneumoniae among persons infected with human immunodeficiency virus (HIV); and to delineate a practical approach for diagnosis, treatment, and prevention of these infections. DATA SOURCES: English-language articles from Index Medicus and their references as well as abstracts from conference proceedings that compared rates as well as clinical and microbiologic features of S. pneumoniae infections in HIV-infected patients. STUDY SELECTION: All human studies that included denominators, appropriate control groups, or sufficient clinical descriptions and animal studies with key immunologic observations were cited. DATA EXTRACTION: We compared epidemiologic and clinical responses to pneumococcal disease in HIV-infected patients and control subjects and correlated clinical and experimental data on immunologic defects associated with HIV infection with those on regulation of pneumococcal infections. DATA SYNTHESIS: Among patients with HIV infection, the incidence of invasive pneumococcal disease is high, bacteremia is a common complication of pneumonia, and relapses occur frequently. However, the clinical presentation, response to therapy, and serotypes isolated are similar to those in persons without HIV infection, and mortality is similar or lower. Specific local and systemic defects in host defense, particularly humoral immunity, may contribute to the high incidence of invasive pneumococcal disease. CONCLUSIONS: Streptococcus pneumoniae is the leading cause of invasive bacterial respiratory disease in adults and children with HIV infection. Prompt diagnosis and antimicrobial therapy are associated with a favorable clinical outcome. Characterizing the specific immunologic defects associated with invasive pneumococcal disease in HIV-infected patients may facilitate development of successful, cost-effective strategies for prophylaxis.

HIV Infections↗

Communitywide outbreak of Legionnaires' disease associated with a grocery store mist machine.

From 10 October through 13 November 1989, 33 patients were hospitalized with legionnaires' disease in Bogalusa, Louisiana. A case-control study revealed case-patients were more likely than controls to have shopped at grocery store A (93% vs. 52%; odds ratio [OR], 11.6; 95% confidence interval [CI], 2.3-78.7) in the 10 days before illness. Among those who shopped at grocery store A, case-patients were more likely to shop for greater than 30 min (OR, 18.0; CI, 2.0-407.8) and to buy produce items located close to an ultrasonic mist machine (OR, 7.4; CI, 1.3-56.2). Employees of grocery store A were more likely than employees of other grocery stores in Bogalusa to have antibody titers of greater than or equal to 1:128 to Legionella pneumophila serogroup 1 (Lp-1; relative risk, 2.9; CI, 1.3-6.8). Lp-1 was isolated from water in the reservoir of the mist machine. The monoclonal antibody subtype of the isolate was identical to organisms identified in two patients. Viable Lp-1 was isolated from mist produced by the machine. Aerosols from a grocery store mist machine were the source of this outbreak.

Adult↗

The spread of multiply resistant Streptococcus pneumoniae at a day care center in Ohio.

Streptococcus pneumoniae, type 23F, resistant to penicillin (MIC, 2 micrograms/mL) and multiple other antimicrobic agents, was isolated from middle ear fluid of a child with otitis media attending a day care center in Ohio. To determine the extent of spread of this strain, nasopharyngeal culture surveys were done, and 52 carriers were identified among 250 children attending the index day care center. No carriers were found among 121 children at two other day care centers in the same urban area. Use of prophylactic doses of antibiotics (P < .001) and frequent use of antibiotics (P < 0.001) were risk factors for nasopharyngeal carriage. Carriers were more likely to have had frequent otitis media episodes (P < .02) and otitis media not responsive to antimicrobial therapy (P < .001). Strategies to limit the spread of highly resistant pneumococcal strains should include encouraging judicious use of antimicrobic agents and reevaluating indications for prophylactic use of antimicrobic agents.

Adult↗

Incubation of water samples containing amoebae improves detection of legionellae by the culture method.

Some protozoans isolated from aquatic habitats, including domestic water supplies, can support the intracellular replication of autochthonous legionellae in vitro. We studied the effect of incubating water samples containing amoebae on the sensitivity of culture for legionellae. Samples collected during investigations of legionellosis epidemics and shown by conventional culture procedures to contain amoebae, but not legionellae, were incubated at 35 degrees C and replated. Legionellae were recovered from 59 of 144 such samples. Species isolated included L. pneumophila, L. anisa, L. bozemanii, L. gormanii, L. micdadei, L. rubrilucens, L. sainthelensi, L. steigerwaltii, and an unnamed species. Acanthamoeba polyphaga, Acanthamoeba hatchetti, a Rosculus sp., Hartmannella vermiformis, and Vahlkampfia spp. were among the autochthonous amoebae identified. Legionellae were recovered by this procedure from only 3 of 63 samples that were negative for amoebae by conventional culture procedures. These results show that water samples negative for legionellae, but positive for amoebae, by standard culture techniques should be incubated and replated to maximize the sensitivity of culture for legionellae.

Amoeba↗

Imported leprosy in the United States, 1978 through 1988: an epidemic without secondary transmission.

OBJECTIVES: Leprosy remains a major health problem in many regions of the world. In the United States, although leprosy continues to be reported, approximately 90% of cases are imported (i.e., occur among immigrants and refugees). An increase in imported cases began in 1978. This study was conducted to analyze this trend and to characterize the contributing cases. METHODS: Centers for Disease Control leprosy surveillance data from 1971 through 1988 were analyzed. RESULTS: The number of imported cases reported annually was relatively constant from 1971 through 1977 (mean = 119 per year), increased to 307 in 1985, and then decreased to 102 in 1988. Of the 957 excess cases reported from 1978 through 1988, 73.4% were among persons from Southeast Asia, including 51.3% from Vietnam, Cambodia, and Laos (Indochina). There was no coincident increase in indigenous cases of leprosy; the mean annual number of such cases was 17.7 (range = 10 to 29). Leprosy remains endemic in Texas, Hawaii, Louisiana, and possibly California. CONCLUSIONS: An epidemic of imported leprosy began in the United States in 1978, peaked in 1985, and ended by 1988. This increase was primarily due to cases among refugees from Indochina and was limited by a decrease in the influx of Indochinese refugees in the mid-1980s. There is no evidence that these cases resulted in transmission in the United States.

Adult↗

Outbreak of invasive group A streptococcal infections in a nursing home. Lessons on prevention and control.

OBJECTIVE: Nine outbreaks of group A streptococcal (GAS) infections in nursing homes were reported to the Centers for Disease Control (Atlanta, Ga) during the past two winters. We conducted an intensive epidemiologic and laboratory investigation of one of these outbreaks to determine clinical characteristics, risk factors for transmission and infection, and methods of control and prevention. METHODS: Cases were detected using cultures and serologic tests. Matched case-control and retrospective cohort studies were performed to determine risk factors for infection. RESULTS: Between December 13, 1989, and January 31, 1990, 16 (20%) of 80 residents, and three (7%) of 45 staff, were infected with GAS. Eleven of the residents had invasive disease and four died. Isolates were available from four persons; all were serotype M-1, T-1. There was strong spatial clustering of cases within the nursing home; having a roommate with prior infection was the most important risk factor. Residents with preexisting decubiti had a reduced risk of infection, perhaps because of stricter infection control practices in their care. No evidence was found for common-source transmission of infection. No further cases occurred after improvement of infection control practices and administration of prophylactic antimicrobials to all residents and staff. CONCLUSIONS: Invasive GAS disease is increasing nationwide, and is a potentially serious problem in the growing and high-risk setting of nursing homes. These data suggest that, in this outbreak, a virulent GAS strain was introduced, with subsequent person-to-person transmission. Adherence to infection control practices can prevent or control GAS outbreaks. Prophylactic antimicrobials may be an effective adjunct to control severe or ongoing outbreaks.

Aged↗

Current trends in bacterial respiratory pathogens.

The relationship of virulence and antimicrobial susceptibility with morbidity due to bacterial respiratory pathogens is complex and evolving. Ultimately, decreasing the incidence of pneumonia due to bacterial pathogens will be dependent on successful preparation and distribution of effective vaccines. Until effective vaccines are widely available, control of a majority of respiratory infections will depend on promotion of rational therapeutic strategies. Though limited to a few specific serotypes and strains, changes in virulence of bacterial respiratory pathogens have been noted. Co-infections due to multiple respiratory pathogens may increase morbidity; however, the epidemiology of co-infections is not clear. Relationships between respiratory viruses and bacteria may exist that increase virulence of both agents, but information regarding these relationships awaits further investigation. Resistance of respiratory pathogens to the more commonly used antimicrobials, such as penicillin, erythromycin, chloramphenicol, and cotrimoxazole, is being documented globally with increasing frequency. The evolution of antimicrobic resistance, especially among strains of Streptococcus pneumoniae, the most common and deadly agent of lower respiratory tract infections, provides impetus to develop and promote effective pneumococcal vaccines and to search for new and effective antimicrobials.

Bacterial Infections↗

Nosocomial Legionnaires' disease and use of medication nebulizers.

Guidelines for the prevention of nosocomial pneumonia specify that only sterile fluids should be used for aerosol therapy; however, this recommendation may not be uniformly followed. Thirteen patients with nosocomial pneumonia due to Legionella pneumophila serogroup 3 (Lp3) were identified at a community hospital in the period from 1984 through 1988; 12 patients (92%) had chronic obstructive pulmonary disease; and 9 patients (69%) died. An epidemiologic investigation suggested that the use of nebulizers to deliver medication was associated with acquiring legionnaires' disease. The hospital potable water system was contaminated with Lp3, and a survey indicated that tap water was commonly used to wash medication nebulizers. Lp3 in respirable-size droplets was isolated from aerosols generated by a nebulizer containing Lp3 at one-tenth the concentration found in the hospital potable water. These findings support the recommendation that only sterile fluids be used for filling or cleaning respiratory care equipment and suggest that this guideline is not universally followed.

Administration, Inhalation↗

Changing epidemiology of group A streptococcal infection in the USA.

To see whether changes in the epidemiology of group A streptococcal disease in the USA have been accompanied by a corresponding change in serotype distribution, epidemiological and M-typing and T-typing data for 5193 strains sent to the Centers for Disease Control, Atlanta, between 1972 and 1988 were analysed. The proportions of M-types 1, 3, and 18 increased significantly during the study period. These M-types were more likely to be invasive, to cause fatal infection, and to occur in a cluster of infections than were other types. By contrast, the proportions of M-types 4 and 12 decreased; they were less invasive and were less likely to be found in clusters than were other types. These data suggest that changes in the epidemiology of group A streptococcal disease may be related to changes in the distribution of M-types causing infection.

Adult↗

Role of air sampling in investigation of an outbreak of legionnaires' disease associated with exposure to aerosols from an evaporative condenser.

Epidemiologic studies have suggested that legionnaires' disease can be transmitted to susceptible hosts by contaminated aerosolized water from cooling towers and evaporative condensers; however, epidemic strains of Legionella have not been isolated by air sampling at such sites during epidemiologic investigations. An outbreak of legionnaires' disease occurred at a retirement hotel; Legionella pneumophila serogroup 1 was isolated from an evaporative condenser and from potable water. A case-control study showed that the only significant exposure risk was in area A. L. pneumophila serogroup 1 was isolated during air sampling near the evaporative condenser exhaust site, the air conditioning intake vent, and an air vent in area A, but not in shower stalls. Monoclonal antibody subtype patterns of L. pneumophila serogroup 1 isolates from patients matched those from the evaporative condenser but not from shower water. Air sampling and monoclonal antibody subtyping results support epidemiologic evidence that the evaporative condenser was the source of this outbreak.

Aerosols↗

Pneumococcal bacteremia in Charleston County, South Carolina. A decade later.

Since nationwide surveillance for pneumococcal bacteremia in the United States is not done, community-based studies are useful alternative methods to monitor trends in this disease. Data on the incidence of pneumococcal bacteremia in Charleston County, South Carolina, from 1974 to 1976, have been used to support cost-effective pneumococcal vaccine programs for the elderly. We reevaluated the incidence of pneumococcal bacteremia in Charleston County in 1986 and 1987 to assess whether earlier estimates remained valid given changes in medical practice. During 1986 and 1987, overall annual incidence of pneumococcal bacteremia in Charleston County was 18.7 per 100,000 (95% confidence limits, 13.7 to 23.6 per 100,000), which represents a 2.3-fold increase over the earlier rate. The increase coincided with a 2.2-fold increase in the annual number of blood cultures processed at four Charleston County hospital laboratories from 1975 to 1987 despite only a 1.1-fold increase in the number of patients discharged from these hospitals. Annualized rates increased 2.3-fold for adults more than or equal to 65 years old to 53 per 100,000 and 4.6-fold for children less than 2 years old to 162 per 100,000. The case-fatality rate of bacteremic patients was 18%, compared with 21% in the earlier study. The case-fatality rate for adults more than or equal to 65 years of age was 44%. Ninety-one percent of adults 19 to 64 years old with bacteremia had underlying medical conditions for which pneumococcal vaccine is recommended; all persons 55 to 64 years old had at least one underlying condition. The marked increases in pneumococcal bacteremia rates detected are likely due to more routine culturing of blood from symptomatic patients with pneumococcal disease. These findings emphasize the need for effective programs promoting use of pneumococcal vaccine in high-risk groups, particularly those more than or equal to 65 years old, and the development of a more immunogenic vaccine for children less than 2 years old.

Adult↗

A live avirulent mutant Legionella pneumophila vaccine induces protective immunity against lethal aerosol challenge.

We have examined the capacity of a live avirulent mutant form of the intracellular bacterial pathogen Legionella pneumophila to induce immune responses and protective immunity in guinea pigs. The mutant L. pneumophila is nonlethal to guinea pigs and does not revert to virulence with passage through guinea pigs. In contrast, exposure of guinea pigs to aerosols containing wild-type L. pneumophila induces a pneumonic illness that clinically and pathologically resembles Legionnaires' disease in humans. Guinea pigs immunized by aerosol exposure to mutant L. pneumophila developed a strong humoral immune response to wild-type L. pneumophila antigens with reciprocal antibody titers of 32-512 (median 256) by the indirect fluorescent antibody assay, compared with titers of less than 2 for control (sham immunized) guinea pigs. Mutant immunized but not control guinea pigs also developed strong cell-mediated immune responses to wild-type L. pneumophila antigens, as demonstrated in assays of cutaneous delayed-type hypersensitivity and in vitro splenic lymphocyte proliferation. Mutant immunized guinea pigs developed strong protective immunity to lethal aerosol challenge with wild-type L. pneumophila. In four independent experiments 40-83% of mutant immunized guinea pigs survived compared with 0% of control guinea pigs. Overall, 13 of 21 (62%) mutant immunized guinea pigs survived compared with 0 of 21 (0%) control guinea pigs (P = 0.00002, Fisher's exact test, two-tailed). Mutant immunization induced protection comparable to wild-type immunization in these studies; 8 of 14 (57%) guinea pigs immunized by wild-type L. pneumophila survived. This study demonstrates that guinea pigs immunized with a live avirulent mutant L. pneumophila vaccine (a) develop a strong humoral immune response to wild-type L. pneumophila antigens; (b) develop a strong cell-mediated immune response to wild-type L. pneumophila antigens; and (c) develop protective immunity to lethal aerosol challenge with wild-type L. pneumophila. This study demonstrates the feasibility of a vaccine against Legionnaires' disease.

Aerosols↗

Guinea pigs sublethally infected with aerosolized Legionella pneumophila develop humoral and cell-mediated immune responses and are protected against lethal aerosol challenge. A model for studying host defense against lung infections caused by intracellular pathogens.

We have employed the guinea pig model of L. pneumophila infection, which mimics Legionnaires' disease in humans both clinically and pathologically, to study humoral and cell-mediated immune responses to L. pneumophila and to examine protective immunity after aerosol exposure, the natural route of infection. Guinea pigs exposed to sublethal concentrations of L. pneumophila by aerosol developed strong humoral immune responses. By the indirect fluorescent antibody assay, exposed guinea pigs had a median serum antibody titer (expressed as the reciprocal of the highest positive dilution) of 32, whereas control guinea pigs had a median titer of less than 1. Sublethally infected (immunized) guinea pigs also developed strong cell-mediated immune responses. In response to L. pneumophila antigens, splenic lymphocytes from immunized but not control animals proliferated strongly in vitro, as measured by their capacity to incorporate [3H]thymidine. Moreover, immunized but not control guinea pigs developed strong cutaneous delayed-type hypersensitivity to intradermally injected L. pneumophila antigens. Sublethally infected (immunized) guinea pigs exhibited strong protective immunity to L. pneumophila. In two independent experiments, all 22 immunized guinea pigs survived aerosol challenge with one or three times the lethal dose of L. pneumophila whereas none of 16 sham-immunized control guinea pigs survived (p less than 0.0001 in each experiment). Immunized guinea pigs were not protected significantly from challenge with 10 times the lethal dose. Immunized but not control animals cleared the bacteria from their lungs. This study demonstrates that guinea pigs sublethally infected with L. pneumophila by the aerosol route develop strong humoral immune responses to this pathogen, develop strong cell-mediated immune responses and cutaneous delayed-type hypersensitivity to L. pneumophila antigens, are protected against subsequent lethal aerosol challenge, and are able to clear the bacteria from their lungs. The guinea pig model of L. pneumophila pulmonary infection is as an excellent one for studying general principles of host defense against pulmonary infections caused by intracellular pathogens.

Aerosols↗