[Show abstract][Hide abstract] ABSTRACT: A novel Legionella species was identified based on analysis of 16S rRNA and mip (macrophage infectivity potentiator) gene sequences, cellular fatty acids, isoprenoid quinones, biochemical reactions, antigens and quantitative DNA-DNA hybridization. Strain CDC-1796-JAP-E(T) was isolated from well water at the Nagasaki Municipal Medical Center, Japan. Two strains, CDC-3041-AUS-E and CDC-3558-AUS-E, were isolated from water samples during an outbreak of legionellosis in South Australia. Strain CDC-5427-OH-H was isolated from a 66-year-old female patient diagnosed with Legionnaires' disease in the US. Cells from these four strains were gram-negative, non-fluorescent, rod-shaped, and positive for alkaline phosphatase, esterase, leucine arylamidase, catalase, gelatinase, β-lactamase and tyrosine browning assay. Phylogenetic analysis of 16S rRNA and mip genes revealed that the four strains formed a distinct cluster within the genus Legionella. The bacteria contained branched-chain fatty acids and quinones that are typical of members of the genus Legionella. Slide agglutination tests demonstrated no cross-reaction with 52 previously described members of the Legionellaceae. DNA-DNA hybridization studies indicated that DNAs from the four strains were highly related (78-84 %) but they showed 29 % relatedness to Legionella oakridgensis ATCC 33761(T) and less than 10 % to strains of other Legionella species tested. These characterizations suggest that the isolates represent a novel species, for which the name Legionella nagasakiensis sp. nov. is proposed; the type strain is CDC-1796-JAP-E(T) ( = ATCC BAA-1557(T) = JCM 15315(T)).
INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY 03/2011; 62(Pt 2):284-8. · 2.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although pneumonia is a leading cause of death from infectious disease worldwide, comprehensive information about its causes and incidence in low- and middle-income countries is lacking. Active surveillance of hospitalized patients with pneumonia is ongoing in Thailand. Consenting patients are tested for seven bacterial and 14 viral respiratory pathogens by PCR and viral culture on nasopharyngeal swab specimens, serology on acute/convalescent sera, sputum smears and antigen detection tests on urine. Between September 2003 and December 2005, there were 1730 episodes of radiographically confirmed pneumonia (34·6% in children aged <5 years); 66 patients (3·8%) died. A recognized pathogen was identified in 42·5% of episodes. Respiratory syncytial virus (RSV) infection was associated with 16·7% of all pneumonias, 41·2% in children. The viral pathogen with the highest incidence in children aged <5 years was RSV (417·1/100,000 per year) and in persons aged ≥50 years, influenza virus A (38·8/100,000 per year). These data can help guide health policy towards effective prevention strategies.
Epidemiology and Infection 03/2010; 138(12):1811-22. · 2.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Legionella longbeachae causes most cases of legionellosis in Australia and may be underreported worldwide due to the lack of L. longbeachae-specific diagnostic tests. L. longbeachae displays distinctive differences in intracellular trafficking, caspase 1 activation, and infection in mouse models compared to Legionella pneumophila, yet these two species have indistinguishable clinical presentations in humans. Unlike other legionellae, which inhabit freshwater systems, L. longbeachae is found predominantly in moist soil. In this study, we sequenced and annotated the genome of an L. longbeachae clinical isolate from Oregon, isolate D-4968, and compared it to the previously published genomes of L. pneumophila. The results revealed that the D-4968 genome is larger than the L. pneumophila genome and has a gene order that is different from that of the L. pneumophila genome. Genes encoding structural components of type II, type IV Lvh, and type IV Icm/Dot secretion systems are conserved. In contrast, only 42/140 homologs of genes encoding L. pneumophila Icm/Dot substrates have been found in the D-4968 genome. L. longbeachae encodes numerous proteins with eukaryotic motifs and eukaryote-like proteins unique to this species, including 16 ankyrin repeat-containing proteins and a novel U-box protein. We predict that these proteins are secreted by the L. longbeachae Icm/Dot secretion system. In contrast to the L. pneumophila genome, the L. longbeachae D-4968 genome does not contain flagellar biosynthesis genes, yet it contains a chemotaxis operon. The lack of a flagellum explains the failure of L. longbeachae to activate caspase 1 and trigger pyroptosis in murine macrophages. These unique features of L. longbeachae may reflect adaptation of this species to life in soil.
Journal of bacteriology 12/2009; 192(4):1030-44. · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Approximately 84% of legionellosis cases are due to Legionella pneumophila serogroup 1. Moreover, a majority of L. pneumophila serogroup 1 clinical isolates react positively with monoclonal antibody 2 (MAb2) of the international standard panel. Over 94% of the legionellosis outbreaks investigated by the Centers for Disease Control and Prevention are due to this subset of L. pneumophila serogroup 1. To date, there is no complete explanation for the enhanced ability of these strains to cause disease. To better characterize these organisms, we subtyped 100 clinical L. pneumophila serogroup 1 isolates and 50 environmental L. pneumophila serogroup 1 isolates from the United States by (i) reactivity with MAb2, (ii) presence of a lag-1 gene required for the MAb2 epitope, and (iii) sequence-based typing analysis. Our results showed that the MAb2 epitope and lag-1 gene are overrepresented in clinical L. pneumophila serogroup 1 isolates. MAb2 recognized 75% of clinical isolates but only 6% of environmental isolates. Similarly, 75% of clinical isolates but only 8% of environmental isolates harbored lag-1. We identified three distinct lag-1 alleles, referred to as Philadelphia, Arizona, and Lens alleles, among 79 isolates carrying this gene. The Arizona allele is described for the first time in this study. We identified 59 different sequence types (STs), and 34 STs (58%) were unique to the United States. Our results support the hypothesis that a select group of STs may have an enhanced ability to cause legionellosis. Combining sequence typing and lag-1 analysis shows that STs tend to associate with a single lag-1 allele type, suggesting a hierarchy of virulence genotypes. Further analysis of ST and lag-1 profiles may identify genotypes of L. pneumophila serogroup 1 that warrant immediate intervention.
Journal of clinical microbiology 07/2009; 47(8):2525-35. · 4.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although the majority of cases of Legionnaires' disease (LD) are caused by Legionella pneumophila, an increasing number of other Legionella species have been reported to cause human disease. There are no clinical presentations unique to LD and hence accurate laboratory tests are required for early diagnosis. Therefore, we designed a real-time PCR assay that targets the 23S-5S rRNA intergenic spacer region (23S-5S PCR) and allows for detection of all Legionella species and discrimination of L. pneumophila from other Legionella species. In total, 271 isolates representing 50 Legionella species were tested and the assay was validated using 39 culture-positive and 110 culture-negative patient specimens collected between 1989 and 2006. PCR-positive results were obtained with all 39 culture-positive samples (100% sensitivity). Specimens that tested positive according to 23S-5S PCR, but were culture-negative, were further analysed by DNA sequencing of the amplicon or the macrophage infectivity potentiator (mip) gene. In addition to L. pneumophila, Legionella longbeachae, Legionella cincinnatiensis and Legionella micdadei were identified in the specimens. The assay showed a 7-log dynamic range displaying a sensitivity of 7.5 CFU/mL or three genome equivalents per reaction. Sixty-one specimens containing viruses or bacteria other than Legionellae were negative according to 23S-5S PCR, demonstrating its specificity. Use of this assay should contribute to the earlier detection of respiratory disease caused by Legionella species, as well as to increased rates of detection.
Clinical Microbiology and Infection 05/2009; 16(3):255-61. · 4.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The ResPlex I assay (Qiagen) was designed to amplify and detect DNA of six bacterial respiratory pathogens. This assay was compared with real-time PCR assays based upon the same target sequences for the ability detect the target bacteria by use of both stock strains and specimens from respiratory disease patients. The ResPlex I assay is somewhat less sensitive than real-time PCR assays but offers the advantage of multiple assays in a single reaction.
Journal of clinical microbiology 07/2008; 46(6):2074-7. · 4.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Legionella species, Mycoplasma pneumoniae, and Chlamydia pneumoniae are recognized as important causes of pneumonia in high-income countries, but their significance in middle-income countries, such as Thailand, is unknown.
Population-based surveillance identified inpatient 3489 cases of clinically-defined pneumonia in a rural Thai province for 1 year. Patients who had a chest radiograph performed (for 2059 cases of pneumonia) were enrolled in an etiology study (which included 755 cases of pneumonia among 738 patients). Paired serum, nasopharyngeal swab, and urine specimens were obtained for diagnostic immunologic and molecular tests. Patients aged <18 years were not systematically tested for Legionella species. We report a lower limit of incidence (observed incidence) and an upper limit extrapolated to persons not tested or not enrolled in the study.
The incidence of pneumonia due to Legionella longbeachae requiring hospitalization was 5-29 cases per 100,000 population. No case of Legionella pneumophila pneumonia was observed. The definite C. pneumoniae pneumonia incidence was 3-23 cases per 100,000 population; rates were highest among patients aged <1 year (18-166 cases per 100,000 population) and those aged >or=70 years (23-201 cases per 100,000 population). M. pneumoniae pneumonia had a similar age distribution, with an overall incidence of 6-44 cases per 100,000 population. These pathogens were associated with 15% of all cases of pneumonia. A nonsignificantly higher proportion of patients with pneumonia associated with L. longbeachae, compared with patients with pneumonia associated with M. pneumoniae or C. pneumoniae, required supplemental oxygen or mechanical ventilation (45% vs. 18%; P<.1). Among patients with atypical pneumonia, only 15% received antibiotics with activity against the associated pathogen.
M. pneumoniae, C. pneumoniae, and L. longbeachae, but not L. pneumophila, are frequently associated with severe pneumonia in rural Thailand. Few patients receive antibiotics that cover atypical pathogens.
[Show abstract][Hide abstract] ABSTRACT: A long-term care facility (LTCF) reported an outbreak of Legionnaires' disease (LD) in September 2004.
We conducted case finding through enhanced surveillance, medical record review (n = 131), and community surveys (n = 258). We cultured water samples from the LTCF and assayed their outdoor air-intake filters for Legionella DNA. We also investigated a cooling tower, the only nearby outdoor aerosol source.
Among 7 confirmed cases, 2 LTCF residents never exited, and 2 community residents never entered the LTCF during the incubation period. Among 63 water and biofilm samples collected from throughout the LTCF, we found no evidence of Legionella colonization, either in the potable water or air-handling systems. Conversely, we isolated a common outbreak-causing strain of Legionella pneumophila serogroup 1 from an industrial cooling tower located 0.4 km from the LTCF and recovered L pneumophila DNA from the LTCF's outdoor air-intake filters, suggesting that aerosolized Legionella from the cooling tower most likely entered the LTCF through the air-intake system or, possibly, through open windows.
Residents of LTCFs can acquire LD from community sources. A cluster of LD cases among LTCF residents does not necessarily indicate transmission from within the LTCF.
American Journal of Infection Control 07/2007; 35(5):319-23. · 2.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: From June to November 2005, 18 cases of community-acquired Legionnaires' disease (LD) were reported in Rapid City South Dakota. We conducted epidemiologic and environmental investigations to identify the source of the outbreak.
We conducted a case-control study that included the first 13 cases and 52 controls randomly selected from emergency department records and matched on underlying illness. We collected information about activities of case-patients and controls during the 14 days before symptom onset. Environmental samples (n = 291) were cultured for Legionella. Clinical and environmental isolates were compared using monoclonal antibody subtyping and sequence based typing (SBT).
Case-patients were significantly more likely than controls to have passed through several city areas that contained or were adjacent to areas with cooling towers positive for Legionella. Six of 11 case-patients (matched odds ratio (mOR) 32.7, 95% CI 4.7-infinity) reported eating in Restaurant A versus 0 controls. Legionella pneumophila serogroup 1 was isolated from four clinical specimens: 3 were Benidorm type strains and 1 was a Denver type strain. Legionella were identified from several environmental sites including 24 (56%) of 43 cooling towers tested, but only one site, a small decorative fountain in Restaurant A, contained Benidorm, the outbreak strain. Clinical and environmental Benidorm isolates had identical SBT patterns.
This is the first time that small fountain without obvious aerosol-generating capability has been implicated as the source of a LD outbreak. Removal of the fountain halted transmission.
[Show abstract][Hide abstract] ABSTRACT: During March 2004, a large outbreak of legionnaires disease and Pontiac fever occurred among hotel guests in Oklahoma. An investigation was conducted to identify the source and evaluate the utility of the Legionella urine antigen assay and serologic testing for the identification of Pontiac fever.
A retrospective cohort investigation of hotel guests and employees and an environmental evaluation were performed. Participants were interviewed, and clinical specimens were collected from consenting individuals.
Six cases of legionnaires disease and 101 cases of Pontiac fever were identified. Exposure to the indoor pool and hot tub area was associated with legionellosis (relative risk, 4.4; 95% confidence interval, 2.8-6.9). Specimens from the pool and hot tub tested positive for Legionella pneumophila serogroup 1 by polymerase chain reaction. For Pontiac fever, the sensitivity and positive predictive value were 35.7% and 100%, respectively, for the urine antigen assay, and 46.4% and 90%, respectively, for serologic testing. The specificity and negative predictive value were 100% and 47.8%, respectively, for the urine antigen assay, and 89.3% and 45.5%, respectively, for serologic testing.
Urine antigen testing, with or without serologic testing, can be used to confirm outbreak-associated cases of Pontiac fever caused by L. pneumophila serogroup 1.
[Show abstract][Hide abstract] ABSTRACT: Background: Etiologic data are critical for developing evidence-based standards for diagnosing and treating pneumonia. M. pneumoniae (MP), C. pneumoniae (CP), and Legionella are increasingly recognized as important causes of pneumonia in upper-income countries, but their significance in middle-income countries, such as Thailand, is unknown.
Methods: Active, population-based surveillance identified all inpatients with pneumonia in Sa Kaeo Province during a 1-year period (n=3489). Patients with a chest x-ray (n=2059) were approached for enrollment in an etiology study (n=762). Infection was defined as seroconversion for MP; a ≥4-fold antibody rise for CP or L. longbeachae (LL); a single IgM ≥1:16 for CP; or positive PCR for CP or MP from nasopharyngeal swabs. Patients <18 years were not tested for LL.
Results: CP incidence was 19/100,000. Rates were highest in patients <1 year (53/100,000) and ≥75 years (241/100,000). MP had a similar age distribution, with an overall incidence of 6/100,000. LL incidence was 5/100,000. CP, MP, and LL infections accounted for 15% of all pneumonias. Clinical presentation and x-ray findings did not differ by etiology; however, a higher proportion of LL cases then MP/CP cases required intubation or oxygen (45% vs.18%, p<0.1). Among those with atypical infection, 93% received antibiotics but only 15% received optimal therapy.
Conclusions: CP, MP, and LL are frequently associated with pneumonia in rural Thailand. LL has not been described in SE Asia and the risk of infection is underappreciated. Atypical infections cannot be distinguished clinically and few patients receive antibiotics that cover these pathogens.
Infectious Diseases Society of America 2006 Annual Meeting; 10/2006
[Show abstract][Hide abstract] ABSTRACT: To characterize illness and identify the etiology for two nursing home outbreaks of respiratory illness.
Multisite outbreak investigations; cohort. Setting: Two nursing homes in Pennsylvania.
Facility A residents (n = 170), Facility B residents (n = 124), and employees (n = 91).
Medical records for Facility A and B residents were reviewed, and employees from Facility B self-administered a questionnaire to identify risk factors for illness. Serological, oropharyngeal, and nasopharyngeal specimens were collected for both outbreaks, and testing for respiratory pathogens was performed.
In Facility A, 40 (24%) of 170 residents were identified with respiratory illness; 13 (33%) case-patients had radiographically confirmed pneumonia, 15 (38%) were taken to a hospital, and two (5%) died. Of 10 specimens collected from symptomatic Facility A case-patients, four (40%) tested positive using reverse transcription polymerase chain reaction for rhinovirus. In Facility B, 77 (62%) of 124 residents had respiratory illness, and 40 (52%) had radiographically confirmed pneumonia; 12 (16%) case-patients were hospitalized, and five (6%) died. Of 19 respiratory specimens collected from symptomatic Facility B case-patients, six (32%) were positive for rhinovirus; one was from an employee. Five (50%) of 10 rhinovirus-positive cases in both outbreaks had clinical and radiographic evidence of pneumonia.
These investigations suggest that rhinoviruses may be an underrecognized cause of respiratory outbreaks in nursing homes, capable of causing pneumonia and perhaps death.
Journal of the American Geriatrics Society 03/2006; 54(2):284-9. · 4.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated 3 cases of legionnaires disease (LD) that developed in travelers who stayed at a hotel in the United States Virgin Islands where cases of LD occurred in 1981-1982 and in 1998. The temperature of the potable water at the hotel was in a range that could optimally support the growth of Legionella species, and the potable water was colonized with Legionella pneumophila in 1981-1982 and in 2002-2003.
[Show abstract][Hide abstract] ABSTRACT: In response to the emergence of severe acute respiratory syndrome (SARS), the United States established national surveillance using a sensitive case definition incorporating clinical, epidemiologic, and laboratory criteria. Of 1,460 unexplained respiratory illnesses reported by state and local health departments to the Centers for Disease Control and Prevention from March 17 to July 30, 2003, a total of 398 (27%) met clinical and epidemiologic SARS case criteria. Of these, 72 (18%) were probable cases with radiographic evidence of pneumonia. Eight (2%) were laboratory-confirmed SARS-coronavirus (SARS-CoV) infections, 206 (52%) were SARS-CoV negative, and 184 (46%) had undetermined SARS-CoV status because of missing convalescent-phase serum specimens. Thirty-one percent (124/398) of case-patients were hospitalized; none died. Travel was the most common epidemiologic link (329/398, 83%), and mainland China was the affected area most commonly visited. One case of possible household transmission was reported, and no laboratory-confirmed infections occurred among healthcare workers. Successes and limitations of this emergency surveillance can guide preparations for future outbreaks of SARS or respiratory diseases of unknown etiology.
[Show abstract][Hide abstract] ABSTRACT: Several isolates, belonging to two new species of the same novel genus of gamma-proteobacteria, were recovered from drilled well (borehole) and spa water at São Gemil in central Portugal. These organisms are phylogenetically most closely related to the strictly intracellular uncultured species of the genus Rickettsiella, which cause disease in arthropods, and to the facultatively intracellular species of the genus Legionella, some of which cause Legionnaires' disease and Pontiac fever. The São Gemil strains grew only on media containing charcoal, as is also true of the species of the genus LEGIONELLA: Unlike the vast majority of Legionella isolates, the new isolates did not require L-cysteine or ferric pyrophosphate for growth but like the legionellae had an absolute requirement for alpha-ketoglutarate. Strains SGT-39(T) and SGT-56 grew consistently between 30 and 43 degrees C, while strains SGT-108(T) and SGT-109 grew between 30 and 40 degrees C. The pH ranges for growth of these organisms were surprisingly narrow: strains SGT-39(T) and SGT-56 grew between pH 6.3 and 7.3, while strains SGT-108(T) and SGT-109 grew between pH 6.3 and 7.0. Both organisms proliferated in the amoeba Hartmannella vermiformis but did not grow in U937 human cells. Based on 16S rRNA gene sequence analysis and physiological, biochemical, and chemical analysis we describe two new species of one novel genus; one species is represented by strain SGT-39(T), for which we propose the name Aquicella lusitana, while strain SGT-108(T) represents a second species of the same genus, for which we propose the name Aquicella siphonis.
Applied and Environmental Microbiology 12/2003; 69(11):6533-40. · 3.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This case-control study investigated a cluster of respiratory illness among patrons of a restaurant. Of 173 patrons interviewed, 117 (68%) were ill. Symptoms included myalgias (93%), headache (87%), and fatigue (79%). The mean incubation period was 49 h and the mean duration of illness was 71 h. Patrons aged >15 years were more likely to have been ill than younger patrons (odds ratio [OR], 2.96; P=.002); 58% of persons who were ill sat near a large fountain, compared with 18% of respondents who were not ill (OR, 7.5; P=.005). Legionella anisa was cultured from water samples obtained from the fountain pool. Of 22 individuals who were ill, 11 (50%) had a > or =4-fold increase in the titer of antibody to that strain of L. anisa from acute-phase to convalescent-phase serum samples; 3 others (14%) had persistently elevated titers of > or =512; of a group of 20 individuals who had not been exposed to the restaurant, none had titers of >128. Pontiac fever should be considered as a diagnosis during acute outbreaks of influenza-like illness with a high attack rate and no other identified etiology.
[Show abstract][Hide abstract] ABSTRACT: Legionnaires disease (LD) is a severe pneumonia usually transmitted by aerosolized Legionella-contaminated water. Although numerous hospital-associated outbreaks have been reported, LD outbreaks in nursing homes are rarely described. Legionella colonization of plumbing systems is most common in older buildings. In June 2002, a LD outbreak occurred among residents of a newly constructed nursing home. We conducted a cohort study and environmental investigation to identify sources of and opportunities to prevent transmission.
Residents exposures to potential transmission sources were assessed by chart review and staff interviews. Multivariable regression was used to calculate risk ratios (RR) for associations between exposures to potential transmission sources and laboratory-confirmed (positive culture or urine antigen) LD, controlling for smoking and underlying disease. Water samples for Legionella culture were collected throughout the facility. Environmental Legionella isolates were sub-typed and compared to a clinical isolate.
Eleven LD cases, two of them fatal, occurred among 259 facility residents (attack rate 4.2%) over a 17-day period. LD risk was significantly greater (RR=7.1, 95%CI=2.2-30.8) among residents who bathed or showered during a two-day period nine days (one incubation period) before the outbreak peak. Going outside near the cooling tower and history of dysphagia were not associated with disease. Legionella isolates from a case-patient and the facilitys potable water were identical by monoclonal antibody subtyping and amplified fragment length polymorphism. Potable water temperatures and biocide concentrations were conducive to Legionella growth.
LD transmission likely occurred via aerosolized potable water. Increased LD risk associated with bathing during a particular two-day period suggests a concentrated release of Legionella from the potable water system occurred at that time. LD transmission can occur even in newly constructed nursing homes. LD testing should be performed for nursing home residents with pneumonia to allow early detection of an outbreak. Water systems should be maintained to limit potential for Legionella growth.
Infectious Diseases Society of America 2003 Annual Meeting; 10/2003
[Show abstract][Hide abstract] ABSTRACT: We investigated 4 cases of legionnaires' disease (LD) reported among workers at an Ohio automotive plant in March 2001. A "confirmed" case of LD was defined as x-ray-confirmed pneumonia and a confirmatory laboratory test. A "possible" case of LD was defined as elevated titers of antibody and respiratory symptoms. Legionella pneumophila serogroup 1 (LP1) was isolated from 1 case patient. Legionella was isolated from 18 (9%) of 197 environmental samples; 3 isolates were LP1 but did not match the case isolate. We conducted a case-control study; 17 case patients with confirmed or possible LD and 86 control subjects (workers with low antibody titers and without symptoms) were enrolled. Visiting a specific cleaning line (odds ratio, [OR], 7.29; 95% confidence interval [CI], 2.31-23.00) and working in the cleaning region of the plant (OR, 3.22; 95% CI, 1.11-9.38) were associated with LD. LD can be transmitted in industrial settings in which aerosols are produced. Clinicians should consider LD when treating persons from these settings for pneumonia.
The Journal of Infectious Diseases 04/2003; 187(6):1015-8. · 5.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: New diagnostic tests and empirical therapy for pneumonia may have important ramifications for the identification, treatment, and control of legionnaires disease (LD). To determine trends in the epidemiology of LD, we analyzed data for 1980-1998 from the passive surveillance system of the Centers for Disease Control and Prevention. During this time period, there were 6757 confirmed cases of LD (median annual number, 360 cases/year). Diagnosis by culture and by direct fluorescent antibody and serologic testing decreased significantly; diagnosis by urine antigen testing increased from 0% to 69%. The frequency of isolates other than Legionella pneumophila serogroup 1 (LP1) decreased from 38% to 4% (P=.003). The case-fatality rate decreased significantly, from 34% to 12% (P<.001) for all cases, from 46% to 14% (P<.0001) for nosocomial cases, and from 26% to 10% (P=.05) for community-acquired cases. LD-related mortality has decreased dramatically. The decrease in culture-based diagnosis limits the recognition of non-LP1 disease and impairs outbreak investigation, because fewer Legionella isolates are provided for further examination.
[Show abstract][Hide abstract] ABSTRACT: The bioterrorism-associated human anthrax epidemic in the fall of 2001 highlighted the need for a sensitive, reproducible, and specific laboratory test for the confirmatory diagnosis of human anthrax. The Centers for Disease Control and Prevention developed, optimized, and rapidly qualified an enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G (IgG) antibodies to Bacillus anthracis protective antigen (PA) in human serum. The qualified ELISA had a minimum detection limit of 0.06 micro g/mL, a reliable lower limit of detection of 0.09 micro g/mL, and a lower limit of quantification in undiluted serum specimens of 3.0 micro g/mL anti-PA IgG. The diagnostic sensitivity of the assay was 97.8%, and the diagnostic specificity was 97.6%. A competitive inhibition anti-PA IgG ELISA was also developed to enhance diagnostic specificity to 100%. The anti-PA ELISAs proved valuable for the confirmation of cases of cutaneous and inhalational anthrax and evaluation of patients in whom the diagnosis of anthrax was being considered.