Diagnosis Of Legionnaires Research Articles

Legionnaires' Disease: Update on Diagnosis and Treatment.

Legionellosis is the infection caused by bacteria of the genus Legionella, including a non-pneumonic influenza-like syndrome, and Legionnaires’ disease is a more serious illness characterized by pneumonia. Legionellosis is becoming increasingly important as a public health problem throughout the world; although it is an underreported disease, studies have consistently documented a high incidence. In addition, health costs associated with the disease are high. Diagnosis of Legionnaires’ disease is based mainly on the detection of Legionella pneumophila serogroup 1 antigen in urine. However, there have been advances in detection tests for patients with legionellosis. New methodologies show greater sensitivity and specificity, detect more species and serogroups of Legionella spp., and have the potential for use in epidemiological studies. Testing for Legionella spp. is recommended at hospital admission for severe community-acquired pneumonia, and antibiotics directed against Legionella spp. should be included early as empirical therapy. Inadequate or delayed antibiotic treatment in Legionella pneumonia has been associated with a worse prognosis. Either a fluoroquinolone (levofloxacin or moxifloxacin) or a macrolide (azithromycin preferred) is the recommended first-line therapy for Legionnaires’ disease; however, little information is available regarding adverse events or complications, or about the duration of antibiotic therapy and its association with clinical outcomes. Most published studies evaluating antibiotic treatment for Legionnaires’ disease are observational and consequently susceptible to bias and confounding. Well-designed studies are needed to assess the usefulness of diagnostic tests regarding clinical outcomes, as well as randomized trials comparing fluoroquinolones and macrolides or combination therapy that evaluate outcomes and adverse events.

Sensitivity and Positive Predictive Value of Death Certificate Data Among Deaths Caused by Legionnaires' Disease in New York City, 2008-2013.

Death certificates are an important source of information for understanding life expectancy and mortality trends; however, misclassification and incompleteness are common. Although deaths caused by Legionnaires' disease might be identified through routine surveillance, it is unclear whether Legionnaires' disease is accurately recorded on death certificates. We evaluated the sensitivity and positive predictive value of death certificates for identifying deaths from confirmed or suspected Legionnaires' disease among adults in New York City. We deterministically matched death certificate data from January 1, 2008, through December 31, 2013, on New York City residents aged ≥18 years to surveillance data on confirmed and suspected cases of Legionnaires' disease from January 1, 2008, through October 31, 2013. We estimated sensitivity and positive predictive value by using surveillance data as the reference standard. Of 294 755 deaths, 27 (<0.01%) had an underlying cause of death of Legionnaires' disease and 33 (0.01%) had any mention of Legionnaires' disease on the death certificate. Of 1211 confirmed or suspected cases of Legionnaires' disease, 267 (22.0%) matched to a record in the death certificate data set. The sensitivity of death certificates that listed Legionnaires' disease as the underlying cause of death was 17.3% and of death certificates with any mention of Legionnaires' disease was 20.9%. The positive predictive value of death certificates that listed Legionnaires' disease as the underlying cause of death was 70.4% and of death certificates with any mention of Legionnaires' disease was 69.7%. Death certificates had limited ability to identify confirmed or suspected deaths with Legionnaires' disease. Provider trainings on the diagnosis of Legionnaires' disease, particularly hospital settings, and proper completion of death certificates might improve the sensitivity of death certificates for people who die of Legionnaires' disease.

A Case of Pulmonary-Renal Syndrome Leading to the Diagnosis of Legionnaires' Disease.

We report a case of a 51-year-old Caucasian man referred at our department due to acute renal failure (ARF) complicating respiratory failure during hospitalization in a regional hospital. The patient was previously started on steroids due to the suspicion of rapidly progressive glomerulonephritis (RPGN) in the context of Goodpasture syndrome. However, clinical and laboratory findings did not support this diagnosis; instead a careful evaluation limited differential diagnosis of the renal insult to acute tubular necrosis or acute interstitial nephritis (AIN) following respiratory infection. With lung function fully improved but renal function not recovering, a renal biopsy revealed AIN, a finding leading to further diagnostic testing and finally to the diagnosis of Legionnaires' disease as a cause of this patient's pulmonary-renal syndrome. The management consisted of progressive tapering of oral steroids associated with full recovery of the patient's renal function. This is a rare case of Legionnaires' disease causing immune-mediated AIN and highlights the possibility of Legionella infection as a cause of pulmonary-renal syndrome.

Diagnostic Accuracy of PCR Alone and Compared to Urinary Antigen Testing for Detection of Legionella spp.: a Systematic Review.

The diagnosis of Legionnaires' disease (LD) is based on the isolation of Legionella spp., a 4-fold rise in antibodies, a positive urinary antigen (UA), or direct immunofluorescence tests. PCR is not accepted as a diagnostic tool for LD. This systematic review assesses the diagnostic accuracy of PCR in various clinical samples with a direct comparison versus UA. We included prospective or retrospective cohort and case-control studies. Studies were included if they used the Centers for Disease Control and Prevention consensus definition criteria of LD or a similar one, assessed only patients with clinical pneumonia, and reported data for all true-positive, false-positive, true-negative, and false-negative results. Two reviewers abstracted data independently. Risk of bias was assessed using Quadas-2. Summary sensitivity and specificity values were estimated using a bivariate model and reported with a 95% confidence interval (CI). Thirty-eight studies were included. A total of 653 patients had confirmed LD, and 3,593 patients had pneumonia due to other pathogens. The methodological quality of the studies as assessed by the Quadas-2 tool was poor to fair. The summary sensitivity and specificity values for diagnosis of LD in respiratory samples were 97.4% (95% CI, 91.1% to 99.2%) and 98.6% (95% CI, 97.4% to 99.3%), respectively. These results were mainly unchanged by any covariates tested and subgroup analysis. The diagnostic performance of PCR in respiratory samples was much better than that of UA. Compared to UA, PCR in respiratory samples (especially in sputum samples or swabs) revealed a significant advantage in sensitivity and an additional diagnosis of 18% to 30% of LD cases. The diagnostic performance of PCR in respiratory samples was excellent and preferable to that of the UA. Results were independent on the covariate tested. PCR in respiratory samples should be regarded as a valid tool for the diagnosis of LD.

PCR method for the rapid detection and discrimination of Legionella spp. based on the amplification of pcs, pmtA, and 16S rRNA genes.

Legionella bacteria are organisms of public health interest due to their ability to cause pneumonia (Legionnaires' disease) in susceptible humans and their ubiquitous presence in water supply systems. Rapid diagnosis of Legionnaires' disease allows the use of therapy specific for the disease. L. pneumophila serogroup 1 is the most common cause of infection acquired in community and hospital environments. The non-L. pneumophila infections are likely under-detected because of a lack of effective diagnosis. In this work, simplex and duplex PCR assays with the use of new molecular markers pcs and pmtA involved in phosphatidylcholine synthesis were specified for rapid and cost-efficient identification and distinguishing Legionella species. The sets of primers developed were found to be sensitive and specific for reliable detection of Legionella belonging to the eight most clinically relevant species. Among these, four primer sets I, II, VI, and VII used for duplex-PCRs proved to have the highest identification power and reliability in the detection of the bacteria. Application of this PCR-based method should improve detection of Legionella spp. in both clinical and environmental settings and facilitate molecular typing of these organisms.

Lab Diagnosis of Legionnaires’ Disease

Legionnaires’ disease is a multi-system disease which causes atypical pneumonia due to Legionella bacteria, most commonly of the species Legionella pneumophila. About one out of every 10 people who get sick from Legionnaires’ disease will die. Most common source of infection-contaminated water supply through inhalation of contaminated water droplets (aerosols). A laboratory diagnosis of Legionnaires’ disease can be made using a variety of laboratory tests including: culture/isolation of the causative organism, antigen detection in urine, a significant rise in antibody titres or PCR methods. Determination of the monoclonal subtype and molecular sequence typing can support linking between strains from the sampled environment and from patients. The control measures available to reduce the amount of Legionella in a water system include structural adaptations to the water system, temperature control, disinfection using chemicals or other oxidizing materials, and use of biocides or installation of filters. JMS 2014;17(2):50-54

Research advances of Legionella and Legionnaires’ disease

Legionella is a causative agent of legionellosis or Legionnaires’ disease. Infection with Legionella spp. is an important cause of community and hospital-acquired pneumonia. Moreover, infection with Legionella is one of the most common causes of severe pneumonia in community settings, and Legionella is isolated in 40% of hospital-acquired pneumonia cases. The clinical features of legionellosis or Legionnaires’ disease are not unique, which makes the diagnosis challenging. Macrolides and fluoroquinolones are the most widely used drugs in treatment. Early recognition, treatment and effective measures for prevention and control of the disease are important and required. Although there have been a lot of methods for diagnosis of Legionella infection, they were often time-consuming or complex, not suitable for clinical purposes. This review summarizes available information regarding the microbiology, taxonomy, epidemiology, pathogenesis and diagnosis of Legionnaires’ disease, with an emphasis on the laboratory diagnosis of infection with Legionella spp.

The Chest Radiographic Manifestations of Legionnaires' Disease in Taiwan: A Retrospective Study

Objective To evaluate the chest radiographic manifestations of Legionnaires' disease in Taiwan. Materials and Methods From January 2003 to August 2008, we reviewed the chest X-rays of 53 patients from a medical center in east Taiwan with a diagnosis of Legionnaires' disease, confirmed by the Center for Disease Control and Prevention of Taiwan. We compared our results with those found in the current literature. Results Among the 53 patients, 44 (83%) had positive findings—shown by initial chest radiographs. Thirty patients (68%) were classified as having patchy airspace opacities, four (16%) had confluent opacities, and 11 (25%) had interstitial infiltrates. Three patients (7%) had mixed alveolar and interstitial patterns. In terms of distribution of the lesion, 23 (52%) were unilobar, 16 (36%) were multilobar and five (11%) were bilateral. The lower lobes were the most common location of involvement ( n = 32, 73%). Five patients (11%) had pleural effusion on presentation, but none of our patients had cavitations. Nine patients (17%) in our study had negative chest X-ray findings on initial presentation. Conclusion The radiographic manifestation of Legionnaires' disease in Taiwan is variable, ranging from normal to airspace consolidation, interstitial infiltrates, or mixed patterns. Although previously classified as atypical pneumonia, the most common radiographic findings are airspace consolidation, particularly unilobar, and located in the lower lobes.

Severe Q fever community-acquired pneumonia (CAP) mimicking Legionnaires' disease: Clinical significance of cold agglutinins, anti-smooth muscle antibodies and thrombocytosis

Atypical community-acquired pneumonia (CAP) may be caused by zoonotic or nonpulmonary pathogens. However, atypical pathogens are systemic infectious disease accompanied by pneumonia in contrast with typical bacterial pathogens with infection limited to the lungs and absent extrapulmonary findings. Clinically and radiologically, the atypical CAP pathogens that most closely resemble each other are psittacosis, Q fever, and Legionnaires' disease. Psittacosis can usually be readily suspected or eliminated on the basis of a recent psittacine bird contact history. The 2 atypical pneumonias that most closely resemble each other clinically are Q fever and Legionnaires' disease. The epidemiology of Q fever is related to livestock, and sporadic cases are related to contact to parturient cats. In nonendemic areas, Q fever CAP mimics Legionnaires' disease most closely. Both Q fever and Legionella CAP have several clinical and laboratory features in common. However, there are subtle but important differences that allow the astute clinician to differentiate between these 2 disorders on the basis of clinical and nonspecific laboratory findings before definitive diagnostic tests results are reported. We report a case of severe Q fever CAP mimicking Legionnaires' disease in a young adult normal host. Her initial zoonotic contact history was negative, and her clinical presentation suggested Legionnaires' disease as the most likely diagnosis. Against the diagnosis of Legionnaires' disease was the patient's age and occurrence of the disease in spring time. In contrast, Legionnaires' disease is usually an infection of older individuals and occurs in late summer/fall. Although the patient did not have splenomegaly, a common finding in Q fever CAP, she did have mild hepatomegaly. Hepatomegaly is a uncommon in Q fever CAP but is not a feature of Legionnaires' disease. In the absence of a positive zoonotic contact history, the cardinal findings pointing to the diagnosis of Q fever in this case were "multiple round opacities" on chest computed tomography scan and thrombocytosis during her hospitalization. Against the diagnosis of Legionnaires' disease was the absence of hypophosphatemia and highly elevated ferritin levels. In patients with atypical pneumonias in whom the clinical presentation and nonspecific laboratory findings suggest Legionnaires' disease, but in addition have findings not associated with Legionnaires' (eg, hepatomegaly, thrombocytosis), Q fever serology should be ordered. We conclude that Q fever may closely mimic Legionnaires' disease. Severe atypical CAP with "multiple round opacities" on chest x-ray/computed tomography chest scan with elevated anti-smooth muscle antibodies or thrombocytosis should suggest the diagnosis of Q fever and prompt specific testing for Q fever. Rarely, Q fever CAP may be associated with elevated cold agglutinin titers.

Clinical Relevance of Positive NOWTMLegionellaUrinary Antigen Test in a Tertiary-Care Hospital in Korea

The morbidity and mortality of Legionnaires' disease are not established in Korea, because patients with community-acquired pneumonia (CAP) have rarely been investigated for Legionella. An assay for Legionella antigen in urine has been approved as one of the diagnostic criteria of Legionnaires' disease. Binax Now(TM) Legionella Urinary Antigen Test (LUA) was introduced in Asan Medical Center in July 2002. The purpose of this study was to evaluate the clinical relevance of positive LUA. During the 39-month period from July 2002 to September 2005, the medical records of LUA-positive patients were reviewed for demographic findings, laboratory findings, clinical diagnosis, antimicrobial treatment, outcome, and acquisition of infections. Diagnosis of Legionnaires' disease was based on National Nosocomial Infections Surveillance (NNIS) criteria for defining nosocomial pneumonia. Seven (0.3%) of the 2443 patients tested for LUA were positive. All 7 patients were consistent with the diagnostic criteria of Legionnaires' disease; six patients were diagnosed with CAP and one patient was admitted due to nosocomial pneumonia. Six patients were treated with azithromycin or ciprofloxacin but one patient was not treated for Legionella infection. With the report of LUApositive results, a Legionella-targeted treatment was started in two patients and an inappropriate empirical therapy was ceased in one patient. All patients treated with Legionella-targeted treatment improved clinically except one who died of adult respiratory distress syndrome at the first hospital day. Positive LUA is useful in diagnosing Legionnaire's disease at an early stage and in helping to initiate appropriate treatments in a tertiary-care hospital in Korea.

Legionnaires' Disease Associated with Habitual Drinking of Hot Spring Water.

A 57-year-old man presented with pneumonia, respiratory distress, and myelodysplastic syndrome. A diagnosis of Legionnaires' disease due to Legionella pneumophila (L. pneumophila) was established. The patient had long been drinking tap water via a conduit from a hot spring resource, from which L. pneumophila was also isolated. Both the patient's strain and the water strain of L. pneumophila were identified as serogroup 1, and the genetic relatedness between the two strains as seen by pulsed-field gel electrophoresis was 87%. The patient was successfully treated with erythromycin, fluoroquinolone, and rifampicin. This case raises an important issue on public health represented by legionellosis in Japan.

Laboratory diagnosis of Legionnaires' disease: The expanding role of the Legionella urinary antigen test

Introduction Legionnaires’ disease is pneumonia, caused by Legionella species. At least 39 Legionella species have been identified, but L. pneumophila causes approximately 90% of the reported cases of Legionnaires’ disease in the U.S. (1). Legionnaires’ disease has been aptly described as under-diagnosed but overtreated (2). The Centers for Disease Control and Prevention in Atlanta, GA (CDC) estimates that 18,000 to 25,000 cases of Legionnaires’ disease occur annually in the U.S. However, these figures underestimate the true incidence of Legionnaires’ disease (I ). Cases of Legionnaires’ disease go unrecognized because it is not possible to clinically distinguish Legionnaires’ disease from other causes of pneumonia, and the diagnostic tests for Legionella are not ordered routinely. The tests currently available for making the diagnosis of Legionnaires’ disease include culture isolation, visualization of the bacterium by direct fluorescent antibody (DFA) staining of respiratory secretions, serum antibody testing, and Legionella urinary antigen testing. The reported sensitivities of these tests vary widely depending on the study. The sensitivity of culture, DFA, serology, and the urinary antigen test has been reported to be between 40 to 80,25 to 75,40 to 75, and 70 to 90%. respectively (3-5). These tests should be performed by experienced microbiologists to achieve optimal results. Since many laboratories have inadequate experience with these tests, specimens for Legionella testing are often sent to a reference laboratory. Those laboratories that do perform Legionella diagnostic testing in-house may not do it well. A College of American Pathologists survey of laboratories showed that only 32% of laboratories successfully identified a pure culture of L. pneumophila (3). At the V.A. Medical Center Special Pathogens Laboratory, Pittsburgh, PA, we have found culture to be the most sensitive diagnostic method. We optimize the recovery of Legionella from culture by using multiple selective media and acid-buffer pretreatment of sputum specimens, but for many smaller laboratories this approach may be impractical (6). For pneumonia caused by L. pneumophifa serogroup 1, the urinary antigen test is a practical alternative to culture for the diagnosis of Legionnaires’ disease. The urinary antigen test has several advantages over culture. For many patients with Legionnaires’ disease, obtaining an adequate sputum specimen is difficult; urine, on the other hand, is easily obtained. The results of urinary antigen testing can be available within hours, whereas culture results require three to five days. The disadvantage of the urinary antigen test is that it is specific for L. pneumophila, serogroup 1 only. Since the vast majority of cases of Legionnaires’ disease are caused by this species and serogroup, this limitation has not been considered a major disadvantage of the test.

Surveillance for Legionnaires' Disease

To augment available information about the epidemiology of legionnaires' disease, we analyzed data reported to the passive surveillance system at the Centers for Disease Control and Prevention, Atlanta, Ga, from 1980 through 1989. Risk of disease associated with specific demographic characteristics and health conditions was calculated by comparing the surveillance group with the US population. Risk of death was calculated using multivariate logistic regression models. A diagnosis of legionnaires' disease was confirmed on the basis of clinical and laboratory criteria for 3254 patients. Disease rates did not vary by year, but were higher in the northern states and during the summer. Legionella pneumophila, serogroup 1, constituted 71.5% of fully identified isolates. This study confirmed previously identified risk factors for legionnaires' disease. In addition, a markedly elevated risk was identified for persons with acquired immunodeficiency syndrome (rate ratio, 41.9; 95% confidence interval, 12.9, 71.0), or hematologic malignancy (rate ratio, 22.4; 95% confidence interval, 19.0, 25.9). Likelihood of death was increased in patients who were elderly or male; those with hospital-acquired infection, renal disease, malignancy, or immunosuppression; and those from whom L pneumophila, serogroup 6, was isolated. Infection with Legionella remains an important cause of disease and death in the United States. Diagnosis and treatment of legionnaires' disease should be targeted at patients at increased risk for illness and complications due to Legionella infection. Diagnostic tests for legionnaires' disease based on species other than L pneumophila, serogroup 1, should be developed and tested. Recommendations for prevention of legionnaires' disease should be focused on settings where there are persons at greatest risk for illness or serious outcome.

Microbiological aspects of an outbreak of Legionnaires’ disease in South Western Sydney

In April 1992 an outbreak of Legionnaires' disease occurred in south western Sydney. Twenty four patients were diagnosed as having Legionnaires' disease either on the basis of a positive culture of Legionella pneumophila serogroup I from a respiratory specimen (14 patients) or a four-fold or greater rise in antibody titre or isolated convalescent titre > 1024 with IgM antibodies present (10 patients). This is the largest outbreak in New South Wales since 44 cases of Legionnaires' disease were reported in Wollongong in 1987. Culture and direct immunofluorescent staining (DFA) were performed for early laboratory diagnosis. The DFA test and a set of defined clinical criteria were then used to classify patients as probable cases of Legionnaires' disease for subsequent Public Health investigations. The DFA test had a predictive value for a positive culture of 45.8% and for a negative culture of 97.1%. Its positive predictive value for a definite diagnosis of Legionnaires' disease (either positive culture or seroconversion), however, was 78.3% with a negative predictive valve of 95.1%. During a 27 day period DFA and culture for Legionella species were performed on 198 specimens from 127 patients. Cultures became positive after a mean of 5 days incubation (range 1-11 days). The use of both selective and non-selective media is recommended for optimal recovery of L. pneumophila since some isolates were obtained on only one culture plate. After an initial evaluation of heat decontamination of specimens this process was abandoned, since in 8/63 specimens so treated, L. pneumophila was recovered prior to but not following heat decontamination and was not grown only in heated specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefamandole-susceptible strains of Legionella pneumophila serogroup 1: implications for diagnosis and utility as an epidemiological marker.

The standard selective Legionella medium that contains cefamandole failed to grow legionella pneumophila serogroup 1, subtype Bellingham, from a sputum sample from a patient with nosocomial Legionnaires' disease; the isolate did grow on a similar selective medium that substitutes vancomycin for cefamandole. Two Bellingham isolates from this patient's hospital environment also failed to grow when tested on the cefamandole medium. We tested 106 additional L. pneumophila serogroup 1 isolates that belonged to nine different monoclonal antibody subtypes and demonstrated that susceptibility to cefamandole was rare (10%) and limited to the Bellingham subtype. The diagnosis of Legionnaires' disease may be missed unless the culture protocol includes both a nonselective medium and a selective medium that does not contain cefamandole. In vitro susceptibility to cefamandole also provided an epidemiologic marker that linked a water source for a patient to nosocomial Legionnaires' disease.

Diagnosis of Legionnaires' Disease by Radioimmunoassay of Legionella Antigen in Pleural Fluid

We describe a case of culture-proven Legionnaires' disease (serogroup 1) in which a rapid diagnosis was made by detection of Legionella antigen in pleural fluid by use of the Binax radioimmunoassay for urine.

Nosocomial Legionnaires' disease—advances in diagnosis and typing

The impact of new methodologies on the routine diagnosis of legionella pneumonia has been limited but the potential for advance is considerable. Antigen detection immunoassays have not yet reached the stage where they are used in routine practice. Monoclonal antibodies have been successfully used for direct fluorescence of bronchial aspirates. Nucleic acid hybridization techniques have yet to find a role in diagnosis. Serology remains the most commonly used method in the diagnosis of Legionnaires' disease. Methods of typing Legionella pneumophila include monoclonal antibodies and isoenzyme, plasmid and nucleic acid analysis. Biotyping methods have not been found to be of value. The use of monoclonal antibodies has permitted the comparison of clinical and environmental isolates and allowed the separation of serogroup 1 into subgroups of differing virulence. The subgroup of serogroup 1 called Pontiac is responsible for the majority of sporadic and epidemic legionella pneumonia in the UK. An internationally accepted panel of monoclonal antibodies is used to define these strains. The extent to which other subgroups of serogroup 1 and other serogroups of L. pneumophila cause disease appear to reflect their environmental prevalence.

The rapid microagglutination test in the diagnosis of Legionnaires' disease

The rapid microagglutination test (RMAT) is a simple method for the detection of antibody to Legionella pneumophila serogroup 1. This test was compared with the indirect fluorescent antibody test (IFAT) in a group of 19 patients who had Legionnaires' disease, and also in a group of 491 individuals who did not have the disease. The RMAT correlated well with the IFAT in the Legionnaires' group of patients. All patients with diagnostic titres by the IFAT had RMAT titres of 8 or greater. In the group who did not have Legionnaires' disease, 434 were negative by both tests. However, in the 57 individuals who gave a positive test by the RMAT and/or the IFAT, the correlation between the two tests was poor. It is suggested that the RMAT could reliably be adopted by routine laboratories for serological detection of possible cases of Legionnaires' disease.

Hairy cell leukaemia and legionnaires' disease

A 69-year-old man who had recently returned from a holiday in Majorca, presented with haemoptysis and fever. Chest radiograph showed right lower lobe consolidation. A diagnosis of Legionnaires' disease was made. He was treated with erythromycin and made an uneventful recovery.

Rapid diagnosis of Legionnaires' disease by bronchoalveolar lavage.

Legionella pneumophila has, in recent years, emerged as a common pulmonary pathogen in the normal and immuno-compromised patient (ICP). Making a specific etiologic diagnosis of pneumonia in the latter group is a common clinical dilemma often complicated by poor specimen availability and risks of invasive procedures. Improved staining and isolation techniques for L pneumophila would suggest that early diagnosis could be possible if adequate specimens were available. This report summarizes our experience with bronchoalveolar lavage (BAL) with which we have diagnosed L pneumophila in eight immunocompromised patients, well in advance of more traditional methods. On the basis of this experience, we would advocate early BAL in the ICP as a rapid, safe, moderately sensitive and specific diagnostic test to aid in the identification of L pneumophila.