Of floors and ceilings--defining, assuring, and communicating vaccine safety.
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Biomedical subjects
Publications and source records attributed to R F Breiman.
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The objective of this report is to summarize the medical literature relevant to the epidemiology, diagnosis, treatment, and control of hantavirus pulmonary syndrome (HPS). The English language literature was searched from January 1993 through March 1995, manually and using Medline, including conference proceedings and reference lists. We selected relevant articles on clinical aspects of HPS. HPS is a newly described illness that progresses through three phases: prodromal, cardiopulmonary, and convalescent. Its hallmark is the rapid progression from nonspecific prodromal symptoms to respiratory insufficiency caused by noncardiogenic pulmonary edema. Unlike other hantavirus infections, renal involvement and hemorrhagic manifestations are not dominant features in HPS. Treatment is based on close intensive care monitoring, oxygen, and cardiovascular support with inotropic and vasopressor drugs. Preventive measures include avoiding contact with rodents and their excrement. Peromyscus maniculatus is the primary rodent vector for the Sin Nombre virus, which caused the epidemic of HPS in the southwest United States in May 1993. HPS has a unique set of clinical findings and is caused by a genetically distinct hantavirus. Physicians and other health professionals should consider this disease when evaluating patients with unexplained respiratory insufficiency after a febrile prodrome, especially when history suggests possible rodent contact. Sporadic cases and possibly epidemics of HPS are likely in the future, particularly when ecological changes increase the population of infected rodent vectors in an area.
OBJECTIVE: To determine the incidence and mortality rates of patients with bacteremic infections with Streptococcus pneumoniae, and to determine the serotypes and antimicrobial susceptibilities of the pneumococcal isolates. DESIGN: Prospective case ascertainment and procurement of S pneumoniae isolates between January 1991 and April 1994. SETTING: Ten adult care hospitals in Franklin County, Ohio. PATIENTS: Patients (N = 590) in whom S pneumoniae was isolated from blood cultures. MEASUREMENTS: Demographic data from patients with pneumococcal bacteremia were obtained by chart review. Pneumococcal serotyping and antimicrobial susceptibility testing were performed on 499 bacteremic isolates. RESULTS: Among residents of Franklin County, the annual incidence of pneumococcal bacteremia was higher in patients at least 65 years old (83.0 per 100,000 population) compared with younger adults (9.6 per 100,000 population) (odds ratio [OR], 8.74; 95% confidence interval [CI], 7.19 to 10.62) and more common among African Americans than whites (OR, 1.36; 95% CI, 1.06 to 1.75). The relative risk of pneumococcal bacteremia among persons infected with the human immunodeficiency virus was 41.8 times (CI, 19.0 to 92.0) that of county residents 18 to 64 years of age. The overall mortality rate was 19% and was age-dependent, reaching 38% in patients at least 85 years old. The distribution of pneumococcal serotypes causing bacteremia was remarkably consistent over time. The incidence of drug-resistant strains increased during the study period; by 1994 14% were resistant to penicillin, 12% to ceftazidime, and 24% to trimethoprim-sulfamethoxazole. The resistant strains included several serotypes of S pneumoniae. Most serotypes (89.8%) of S pneumoniae causing bacteremia are contained in the pneumococcal vaccine. CONCLUSIONS: Increased use of pneumococcal vaccine and recognition of antimicrobial resistance patterns may assist physicians in treating patients with S pneumoniae bacteremia. Educational programs to discourage unnecessary antimicrobial drug use should be developed for patients and physicians.
Emergence of drug-resistant Streptococcus pneumoniae (DRSP) presents a challenge to the medical and public health communities since the magnitude of the problem is not known, the clinical impact of DRSP infections is not well described, national vaccination rates are low, and antimicrobial drugs are often used excessively and inappropriately. To address the problem of DRSP, a working group by Centers for Disease Control and Prevention was formed in June 1994 consisting of public health practitioners, health care providers, and clinical laboratorians representing state and federal agencies and various professional organizations. Through periodic open meetings, the working group has developed a strategy for surveillance, investigation, prevention, and control of infections due to DRSP. The strategy focuses on (1) implementing an electronic laboratory-based surveillance (ELBS) system for reporting invasive DRSP infections and providing clinically relevant feedback to clinicians, (2) identifying risk factors and outcomes of DRSP infection, (3) increasing pneumococcal vaccination, and (4) promoting judicious antimicrobial drug use. Data received through ELBS will be used to make timely estimates of the community-specific prevalence of drug-resistant pneumococci. National, regional, and local trends will be made available to health care providers and clinicians to promote optimal antimicrobial drug use and increased vaccination in targeted areas. Once in operation, the ELBS network will be adaptable to other diseases, improving the comprehensiveness and timeliness of public health surveillance. The intended outcome of the strategy is to reduce complications of DRSP infection, such as long-term sequelae of infection, health care expenditures, morbidity, and mortality.
OBJECTIVES: To determine risk factors for carriage of drug-resistant Streptococcus pneumoniae to understand better the factors promoting spread of these isolates. STUDY DESIGN: We obtained medical and demographic information and nasopharyngeal swab specimens from 216 children less than 6 years old with upper respiratory tract infections, seeking medical care at five Memphis, Tenn, study sites. We evaluated risk factors for carriage of penicillin-nonsusceptible S. pneumoniae (NSSP) among 100 children with S. pneumoniae isolates. Patterns of antimicrobial prescription were recorded for enrolled children. RESULTS: Independent risk factors for carriage of NSSP included an increased number of antimicrobial treatment courses during the previous 3 months and white race. Day care attendance approached statistical significance (p = 0.07). Most children with upper respiratory tract infection received a prescription for antimicrobial drugs. These prescriptions were more common for white children than for black children. CONCLUSIONS: Increased use of antimicrobial drugs enhances the risk of carriage of NSSP. This may contribute to the higher risk among white children of NSSP infection; however, after control for antimicrobial use, white children were still at an increased risk of infection with NSSP, possibly through greater exposure to resistant strains.
In August and September 1993, we investigated an outbreak of legionnaires' disease in Fall River, Massachusetts, that involved 11 persons; the attack rate was highest in Flint, a community of Fall River. All cases were infected with Legionella pneumophila serogroup 1 (Lp-1). A case-control study revealed that cases were more likely than matched controls to have visited sites in neighborhood A of Flint. Environmental sampling in Flint found that four of nine aerosol-producing devices sampled contained legionellae; only two, conjoined cooling towers on building A, contained Lp-1. Three independent methods of subtyping--monoclonal antibody subtyping, arbitrary primer polymerase chain reaction, and pulsed-field gel electrophoresis--revealed that Lp-1 isolates from three cases with culture-positive legionnaires' disease matched those from the cooling towers on building A. Water samples from the homes of cases with culture-positive legionnaires' disease contained no legionellae. The results of this epidemiologic and laboratory investigation indicate that the cooling towers on building A were the source of the outbreak of legionnaires' disease and confirm the importance of cooling towers in the transmission of legionnaires' disease.
Unusual, primarily pulmonary, manifestations of hantaviral illness occurring in the southwestern United States raised the possibility of person-to-person transmission of a recently recognized hantavirus, Sin Nombre virus. To determine whether such transmission had occurred among health care workers (HCWs) exposed to patients with confirmed hantavirus pulmonary syndrome, we evaluated HCWs who had cared for patients with hantavirus pulmonary syndrome or who had processed specimens from these patients. Information about exposure to these patients and about recent illnesses was obtained via a standardized questionnaire. Serum specimens were tested for IgM and IgG antibodies to hantaviruses with use of ELISAs. Of the 396 HCWs, 266 (67%) reported that they had been exposed to patients with hantavirus pulmonary syndrome or to their body fluids or that they had processed laboratory specimens from these patients. Although 108 (27%) of the HCWs reported fever, myalgias, or respiratory illnesses during the 3 months before the serum specimens were obtained, hantavirus antibodies were not detected in any HCW. These data suggest that person-to-person transmission of Sin Nombre virus is unlikely to occur in health care settings.
To determine if individuals with extensive exposure to rodent habitats were infected with Sin Nombre hantavirus (SNV), we evaluated forest and park service personnel from the region of endemicity in the southwestern United States. Information about work and recreational activities, including exposure to rodents and a history of recent illnesses, was obtained via a standardized questionnaire. Serum specimens were also collected. Of 140 participating workers, 84 (60%) were primarily engaged in outdoor work activities, 14 (10%) were office-based supervisors, and 42 (30%) were office workers. Of the 140 employees, 89 (64%) reported repeated exposures to rodents, rodent nests, and/or rodent droppings; 22 (16%) reported trapping or handling wild rodents. Hantavirus antibodies were not detected in any park employee. These data suggest that transmission of SNV is a rare event even among persons in the southwestern United States who have a high level of exposure to this virus. Although park employees and visitors in this region are at low risk of infection with SNV, these persons should continue to use recommended measures for risk reduction.
A multidrug-resistant serotype 14 strain of Streptococcus pneumoniae was isolated from sterile-site specimens and nasopharyngeal secretions from > 200 children in Slovakia between 1985 and 1990. Nasopharyngeal culture surveys were done to determine the extent of spread and means of transmission of this strain. The resistant strain was isolated from cultures of 8 (33.0%) of 24 children at hospital A and from 1 (0.8%) of 130 children attending outpatient clinics or day care centers (P < .001). One-quarter of the initially uncolonized children at hospital A acquired the resistant strain during hospitalization. Among hospitalized children, frequent antimicrobial drug use (P < .01), prior hospitalization (P < .005), and length of hospital stay (P < .001) were associated with infection with the resistant strain. These findings support limiting broad-spectrum antimicrobial drug use and nonessential hospitalizations in settings were drug-resistant pneumococci are prevalent. Development of a pneumococcal vaccine that is immunogenic in young children is urgently needed.
Respiratory syncytial virus (RSV), the most important cause of lower respiratory disease in infants and young children, is rarely considered among the causes for community-acquired lower respiratory infection in adults. All noninstitutionalized adults hospitalized with community-acquired pneumonia in two Ohio counties were evaluated between December 1990 and May 1992. Fifty-three (4.4%) of 1195 adults admitted during the RSV seasons and 4 (1.0%) of 390 in the off-season had serologic evidence of RSV infection, making RSV one of the four most common pathogens identified. RSV-infected patients had clinical features (e.g., wheezing and rhonchi) that distinguished them from all non-RSV-infected patients and other features (e.g., nonelevated white blood cell counts) that distinguished them from those infected with bacterial or atypical agents. However, RSV infection was not diagnosed during hospitalization for any of the 57 RSV-infected patients. RSV should be considered in the differential diagnosis for adults hospitalized between November and April with community-acquired lower respiratory infection.
As part of ongoing national surveillance, serotyping and antimicrobial susceptibility testing were done on all pneumococcal isolates recovered from normally sterile body sites of patients at 12 hospitals in 11 states during 1993-1994. Of 740 isolates, 14.1% were penicillin-nonsusceptible Streptococcus pneumoniae (PNSP; MIC > or = 0.1 microgram/mL), 3.2% were penicillin-resistant (MIC > or = 2.0 micrograms/mL), and 25.5% were nonsusceptible to more than one antimicrobial agent. PNSP were more prevalent among children < 6 years old (18.4%) than patients > or = 18 years old (11.7%) and among white persons (16.2%) than black persons (12.1%). PNSP represented 15 serotypes, but 89% of PNSP were serotypes in the 23-valent pneumococcal vaccine. The proportion of isolates with reduced susceptibility and the number of serotypes of nonsusceptible strains are increasing in the United States. Improved local surveillance for PNSP infections, judicious use of antibiotics, and development and use of effective pneumococcal vaccines will be required to treat and prevent disease caused by these strains.
Not all new threats from microorganisms result from changes within the microorganisms themselves. Innovative, progressive changes introduced by humans can provide advantages to microbes which, in turn, threaten the population. In most cases, advantages are provided unwittingly as a by-product of technology, and can be corrected when the problem is recognized. An end to progress is neither a practical nor desirable solution. Alertness (i.e., surveillance) for the emergence of new diseases and to changes in disease patterns will continue to be critical to ensure timely implementation of public health measures.
BACKGROUND: Children < 2 years old living in the Yukon-Kuskokwim Delta (YKD) region of Alaska have one of the highest pneumococcal bacteremia rates of in the world. METHODS: To determine the prevalence of and risk factors for infection with intermediate or resistant Streptococcus pneumoniae in the YKD, we cultured nasopharyngeal secretions of healthy children < or = 5 years old, reviewed their hospital records and administered questionnaires to accompanying parents. RESULTS: Of 185 children evaluated we obtained 95 pneumococcal isolates; drug susceptibility patterns and serotyping results were available for 92. Of these, 33 (36%) were intermediate or resistant to at least one drug class tested; 27 isolates were intermediate (minimum inhibitory concentration 0.1 to 1.0 mg/l) and none were resistant to penicillin. Compared with other isolates, capsular serotype 6B isolates were more likely to be intermediate or resistant to at least one drug (relative risk, 5.3; P < 0.001) and to more than one drug (relative risk, 17.0; P < 0.001). The majority of 6B isolates had identical pneumococcal surface protein A patterns. Carriage of intermediate or resistant pneumococcus was associated with age < 2 years (relative risk, 3.0; P < 0.001) but not with antibiotic use or other evaluated risk factors. CONCLUSIONS: Young age but not antibiotic use was associated with carriage of intermediate or resistant S. pneumoniae in the YKD region of Alaska. Much of the intermediate or resistant pneumococcus in the YKD may have resulted from the proliferation of a single capsular serotype 6B clone.
The Legionella Urinary Antigen EIA kit (Binax, Portland, Maine) was compared with the EQUATE RIA Legionella Urinary Antigen kit (Binax) for its ability to detect the presence of urinary antigens to Legionella pneumophila serogroup 1. Urine specimens from patients without Legionnaires' disease (n = 33) were negative by both methods (specificity, 100%). Twenty (77%) of 26 urine specimens from patients with Legionnaires' disease positive by the radioimmunoassay kit were also positive by the enzyme immunoassay (EIA) kit. If the cutoff for a positive EIA result were lowered to a ration of > or = 2.5, 23 of 26 (88%) urine specimens would have been positive by EIA and the specificity would remain 100%. Use of the EIA kit is an acceptable method for detecting L. pneumophila serogroup 1 urinary antigens by laboratories that do not want to handle radioactive materials.
BACKGROUND: Streptococcus pneumoniae is a major cause of illness, and the emergence of drug-resistant strains threatens to complicate the management of pneumococcal infections. We conducted a laboratory-based surveillance for drug-resistant S. pneumoniae among patients with invasive pneumococcal infections in Atlanta. METHODS: From January through October 1994, pneumococcal isolates from 431 patients with invasive disease in metropolitan Atlanta were serotyped and tested to determine their susceptibility to various antimicrobial agents. Susceptibility to the antimicrobial agents was defined according to guidelines established by the National Committee for Clinical Laboratory Standards. RESULTS: The annual incidence of invasive pneumococcal infection was 30 cases per 100,000 population. Isolates from 25 percent of the patients were resistant to penicillin (7 percent were highly resistant), and isolates from 26 percent were resistant to trimethoprim-sulfamethoxazole (7 percent highly resistant). Fifteen percent of the isolates were resistant to erythromycin, 9 percent to cefotaxime (4 percent were highly resistant), and 25 percent to multiple drugs. Drug-resistant pneumococci were found in both children and adults. Children under six years of age were more likely than older children and adults to have isolates resistant to multiple drugs or cefotaxime. Whites were more likely than blacks to have invasive pneumococcal infections caused by drug-resistant organisms. Among white children younger than six years, 41 percent of the S. pneumoniae isolates were resistant to penicillin. CONCLUSIONS: Drug-resistant strains of S. pneumoniae are common among both children and adults in Atlanta. Although blacks had a higher incidence of invasive pneumococcal infections than whites, whites were more likely to be infected with a drug-resistant isolate. Control of drug-resistant pneumococci will require more judicious use of antimicrobial agents and wider use of the pneumococcal polysaccharide vaccine.
Cases of Legionnaires' disease have been categorized as definitive and presumptive. The sensitivity and specificity of antibody titers of > or = 256 and of urinary antigen ratios of > or = 3 were evaluated in 68 patients with "definitive" Legionnaires' disease and in 636 patients with pneumonia who had negative cultures and did not have fourfold rises in titers of antibody to Legionella pneumophila. An acute-phase antibody titer of > or = 256 did not discriminate between cases and noncases (10% vs. 6%; P = .29). The urinary antigen assay gave a positive result in fewer than 1% of noncases but was positive in 55.9% of all cases. This assay was most sensitive (80%) in cases in which L. pneumophila serogroup 1 was isolated. We propose that the case definition for definitive Legionnaires' disease be expanded to include positive urinary antigen assays and that the category of presumptive Legionnaires' disease--based on acute-phase or standing antibody titers of > or = 256 in the nonoutbreak setting--be discarded. The urinary antigen assay will be a valuable tool in the prompt diagnosis of Legionnaires' disease.
Bacterial respiratory tract infections occur frequently in persons infected with human immunodeficiency virus (HIV) and may be caused by a wide variety of pathogens. Pneumonia is the most commonly diagnosed respiratory infection in HIV-infected persons and is more common in those persons than in non-HIV-infected ones. HIV-infected persons have a much higher risk of pneumococcal disease than do noninfected controls, and disease may occur relatively early in the course of HIV infection. While mortality associated with the disease does not seem to be high among HIV-infected persons, there is a higher rate of recurrence of the disease in that population. Risk factors for pneumococcal disease in HIV-infected persons are not well characterized. Though efficacy data are limited, the 23-valent polysaccharide pneumococcal vaccine is recommended for use early in the course of HIV infection. There are no data suggesting that HIV-infected persons should be revaccinated routinely. Antiretroviral agents may enhance the immunologic response to the polysaccharide vaccine. Prophylactic antibiotics may have a role in preventing recurrences of severe bacterial respiratory infections, and intravenous immunoglobulin may be useful in preventing serious bacterial infections in HIV-infected children. HIV-infected persons are also at greater risk for serious infections with Haemophilus influenzae than are non-HIV-infected persons. Vaccination against H. influenzae type b (Hib) is recommended for HIV-infected children but not for adults. Antimicrobial drug-resistant strains of Streptococcus pneumoniae and H. influenzae have become more prevalent recently and consequently have impacted on strategies for prevention and treatment of those infections.
Conjugation of pneumococcal polysaccharide antigens to a protein carrier may improve protective immunity after vaccination of young children, an age group with high incidence of Streptococcus pneumoniae infection and poor immune responses to polysaccharide vaccines. To identify serotypes most commonly associated with infection in young children, pneumococcal isolates were serotyped from 3884 children < 6 years old (including 3007 < 2 years old) with pneumococcal bacteremia (n = 3169), meningitis (n = 401), or otitis media (n = 314). The isolates were submitted as part of a national surveillance during 1978-1994. Seven serotypes (14, 6B, 19F, 18C, 23F, 4, and 9V) accounted for 3045 isolates (78%). A conjugate pneumococcal vaccine protecting against these seven serotypes and serologically cross-reactive serotypes could potentially prevent 86% of bacteremia and 83% of meningitis but only 65% of otitis media cases. The proportion of isolates covered by such a vaccine increased from 78% to 87% during 1978-1994. Surveillance for pneumococcal serotypes causing infection is needed to detect shifts in serotype distribution over time.