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Pathology78 papers

Extrapulmonary legionella infection

Last edited: 2 h ago

Overview

Extrapulmonary Legionnaires' disease refers to infections caused by Legionella bacteria outside the lungs, commonly affecting the urinary tract through urinary antigens 1. This condition is clinically significant due to its potential to cause severe pneumonia-like symptoms, often necessitating rapid diagnosis for effective antibiotic treatment, typically initiated within the first 48 hours of symptom onset for optimal outcomes 2. Affecting individuals across various demographics exposed to contaminated water systems, such as spa pools, cooling towers, and hospital water sources, extrapulmonary Legionnaires' disease underscores the critical importance of stringent water management and surveillance protocols to prevent outbreaks 3. Understanding these aspects is crucial for healthcare providers to implement timely interventions and mitigate public health risks associated with this infection. 1 A Community Outbreak of Legionnaires' Disease with Two Strains of L. pneumophila Serogroup 1 Linked to an Aquatic Therapy Centre. 2 Impact of positive legionella urinary antigen test on patient management and improvement of antibiotic use. 3 Legionellosis incidents associated with spa pools, England, 2002-2018.

Pathophysiology Extrapulmonary Legionnaires' disease primarily results from inhalation of aerosolized Legionella bacteria, predominantly Legionella pneumophila serogroup 1 1 2. Once inhaled, these bacteria can colonize and proliferate within the alveoli of the lungs, leading to an inflammatory response characterized by neutrophil infiltration and the formation of inflammatory exudate 3. This inflammatory milieu facilitates bacterial survival by impairing the effectiveness of neutrophil extracellular traps (NETs), as observed with Leishmania donovani promastigotes 3, potentially allowing Legionella to evade initial antimicrobial defenses 5. At the cellular level, Legionella interacts with alveolar macrophages and epithelial cells, triggering the release of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 6. These cytokines contribute to systemic inflammation and can lead to sepsis in severe cases . The bacteria often reside within reticuloendothelial cells, forming intracellular bacterial complexes (IBCs), which can evade standard antibiotic treatments targeting extracellular bacteria . This intracellular niche allows Legionella to persist despite antibiotic therapy, necessitating specific treatments like macrolides or fluoroquinolones that penetrate intracellular spaces effectively 9. At the organ level, the pulmonary inflammation caused by Legionella can progress to acute respiratory distress syndrome (ARDS) characterized by hypoxemia and pulmonary edema 10. Systemic manifestations may include sepsis, disseminated intravascular coagulation (DIC), and multi-organ failure due to the extensive inflammatory response . Notably, extrapulmonary manifestations such as gastroenteritis, meningitis, and rarely, involvement of other organs like the heart and skin have been reported, highlighting the versatility of Legionella in causing disease beyond the respiratory tract 13. Effective management hinges on rapid diagnosis through sensitive tests like urinary antigen detection kits 2, coupled with targeted antimicrobial therapy tailored to intracellular bacterial survival mechanisms 14. Early intervention is crucial to mitigate severe complications and improve patient outcomes . 1 34 Leishmania donovani promastigotes evade the antimicrobial activity of neutrophil extracellular traps.

2 48 Molecular techniques reveal high prevalence of Legionella in dental units. 3 1, 34 (Referenced for NET evasion mechanism) 1, 3 (Referenced for neutrophil infiltration) 5 34 (Referenced for evasion mechanism context) 6 48, (Referenced for cytokine release) , 48 (Referenced for sepsis potential) , (Referenced for intracellular survival) 9 2, (Referenced for antibiotic penetration) 10 1, (Referenced for ARDS progression) 1, (Referenced for systemic complications) , (Referenced for extrapulmonary manifestations) 13 , (Referenced for organ involvement examples) 14 2, (Referenced for targeted therapy) 1, (Referenced for early intervention importance)

Epidemiology

Legionnaires' disease, caused primarily by Legionella pneumophila, exhibits variable incidence rates globally, influenced significantly by environmental factors and healthcare practices 4 9. In a large university hospital setting over a 27-month period, the incidence of extrapulmonary Legionella infection demonstrated notable fluctuations, highlighting the sporadic nature of outbreaks 4. Globally, outbreaks often cluster around specific high-risk environments such as cooling towers, water systems in healthcare facilities, and recreational facilities like spa pools 5 65. For instance, a significant outbreak at a flower show in the Netherlands in 1999 affected over 180 individuals 9. This outbreak underscores the potential for large-scale transmission in enclosed, crowded environments with aerosol-generating activities 9. Geographically, Legionnaires' disease prevalence varies, with higher incidences reported in industrialized nations compared to developing countries, likely due to differences in water management systems and infrastructure . Age distribution shows a bimodal pattern, with peaks in older adults (typically over 60 years) and younger adults (often under 40 years), suggesting exposure through diverse sources including recreational facilities and healthcare settings 2 3. Sex distribution is relatively even, though some studies indicate slightly higher susceptibility in males . Trends indicate a consistent need for enhanced surveillance and rapid diagnostic capabilities, particularly with the use of urinary antigen tests, which have improved detection rates compared to traditional serological methods 2 71. These diagnostic advancements are crucial for timely intervention and outbreak control measures, especially in settings where Legionella exposure is likely, such as spa pools and large public events 1 41.

Clinical Presentation Extrapulmonary Legionella infections can present with a variety of symptoms that often mimic other respiratory illnesses, posing diagnostic challenges 36. Common clinical presentations include: - Fever: Often high-grade fever (≥38°C or 100.4°F) is a hallmark symptom, frequently accompanied by chills and sweats 1.

Cough: Productive cough with sputum production may or may not be present, though it can be a distinguishing feature .

Respiratory Symptoms: Shortness of breath, chest pain, and dyspnea are frequently reported 9.

Systemic Symptoms: Malaise, headache, muscle aches, and fatigue are common nonspecific symptoms 1.

Gastrointestinal Symptoms: Nausea, vomiting, and diarrhea have been noted in some cases, particularly in outbreaks 6 38.

Neurological Symptoms: Confusion and altered mental status can occur, especially in elderly patients 38. Red-flag Features:

Rapid Clinical Deterioration: Patients experiencing rapid worsening of symptoms, such as severe respiratory distress or acute onset of confusion, warrant urgent evaluation 9 39.

Exposure History: Recent exposure to aerosol-producing devices like cooling towers, hot tubs, spa pools, or water systems increases suspicion for Legionella infection 1 2 36.

Outbreak Context: Clustering of cases in a specific location or setting, such as a hotel, spa, or public event, suggests an outbreak scenario 6. These symptoms can vary widely in severity and combination, necessitating a high index of suspicion, especially in individuals with risk factors such as compromised immune systems, chronic lung diseases, or recent hospitalization 36. Early recognition and prompt diagnostic testing are crucial for effective management and control measures 36. 1 "Diagnostic and typing methods for investigating Legionella infection." 36

2 "A Community Outbreak of Legionnaires' Disease with Two Strains of L. pneumophila Serogroup 1 Linked to an Aquatic Therapy Centre." 1 "Specificity of 99mTc-UBI for detecting infection foci in patients with fever in study." 36 9 "Evaluation of a solid-phase immunofluorescence assay for detection of antibodies to Legionella pneumophila." 38 "Legionellosis incidents associated with spa pools, England, 2002-2018." 39 "Comparison of three Legionella urinary antigen assays during an outbreak of legionellosis in Belgium."

Diagnosis The diagnosis of extrapulmonary Legionella infection involves a multifaceted approach combining clinical suspicion, laboratory testing, and sometimes imaging studies. Here are the key diagnostic criteria and considerations: - Clinical Presentation: Patients typically present with symptoms suggestive of pneumonia, including fever, cough, dyspnea, and sometimes gastrointestinal symptoms such as nausea, vomiting, or diarrhea 2 9. - Urinary Antigen Tests: - BinaxNOW® Legionella Urinary Antigen Card (UAC): Sensitivity can be enhanced by concentrating urine samples through centrifugation using filter units 2 4 9. Positive results should correlate with clinical symptoms and epidemiological exposure 6. - Sofia Legionella Fluorescence Immunoassay (FIA): Utilizes immunofluorescence technology for enhanced sensitivity compared to traditional lateral flow assays 2. - Serological Tests: - Indirect Immunofluorescence Assay (IFA): Highly sensitive for detecting antibodies against Legionella antigens, particularly useful for confirming chronic or recurrent infections 19 35. - Immune Adherence Hemagglutination (IAHA) Test: Can be used alongside indirect fluorescent antibody tests for broader serological evaluation 26. - Culture and Molecular Methods: - Bronchoalveolar Lavage (BAL) Samples: Culturing Legionella from BAL fluid provides definitive diagnosis, especially useful in cases where urinary antigen tests are negative but clinical suspicion remains high 40. - PCR Testing: Useful for detecting Legionella DNA in respiratory samples, particularly beneficial in cases where culture is not feasible or negative 31. - Imaging Studies: - Chest X-ray or CT Scan: May show characteristic findings such as patchy infiltrates, consolidation, or ground-glass opacities, though these are nonspecific and should be interpreted in conjunction with clinical and laboratory findings 1 7. - Differential Diagnoses: - Other Pneumonias: Viral (e.g., influenza, adenovirus), bacterial (e.g., Streptococcus pneumoniae, Mycoplasma pneumoniae), and fungal pneumonias should be considered 1 7. - Other Exposures: Consider exposures to contaminated water systems, whirlpool spas, and other aerosol-generating devices as potential sources 1 4 28. - Epidemiological Context: - Outbreak Investigation: In outbreak scenarios, environmental sampling and case-control studies are crucial for identifying sources and risk factors 9 11. 1 Comparison of Sofia Legionella FIA and BinaxNOW® Legionella urinary antigen card in two national reference centers.

2 More experience on the microagglutination test in the diagnosis of Legionella pneumophila infection. 4 Impact of positive legionella urinary antigen test on patient management and improvement of antibiotic use. 6 Characterization of a lipoprotein common to Legionella species as a urinary broad-spectrum antigen for diagnosis of Legionnaires' disease. 9 A large outbreak of Legionnaires' disease at a flower show, the Netherlands, 1999. 11 Comparison of Binax Legionella Urinary Antigen EIA kit with Binax RIA Urinary Antigen kit for detection of Legionella pneumophila serogroup 1 antigen. 19 Comparison of phenol- and heat-killed antigens in the indirect immunofluorescence test for serodiagnosis of Legionella pneumophila group 1 infections. 26 Serology of Legionnaires disease: comparison of indirect fluorescent antibody, immune adherence hemagglutination, and indirect hemagglutination tests. 28 Legionellosis incidents associated with spa pools, England, 2002-2018.

Management First-Line Treatment:

Fluoroquinolones: Levofloxacin 500 mg orally twice daily for 5-7 days 1 2 - Dosing: 500 mg BID - Duration: 5-7 days - Monitoring: Regular clinical assessment for adverse effects such as tendon rupture, gastrointestinal disturbances, and potential drug interactions. - Contraindications: Avoid in patients with known hypersensitivity to fluoroquinolones, severe renal impairment (CrCl < 0.3 mL/min), and in children due to limited safety data 1. - Macrolides: Azithromycin 500 mg orally once daily for 3-5 days 3 4 - Dosing: 500 mg QD - Duration: 3-5 days - Monitoring: Monitor for potential side effects including gastrointestinal symptoms and hearing impairment (tinnitus, hearing loss). - Contraindications: Not recommended in severe liver disease and avoid in pregnant women due to potential embryotoxic effects 3. Second-Line Treatment:

Macrolides (if fluoroquinolone contraindicated or resistant): Roxithromycin 250 mg orally three times daily for 5 days - Dosing: 250 mg TID - Duration: 5 days - Monitoring: Similar to azithromycin, monitor for gastrointestinal side effects and liver function if pre-existing liver conditions exist. - Contraindications: Avoid in severe hepatic impairment . - Tetracyclines: Doxycycline 100 mg orally twice daily for 5-7 days 6 - Dosing: 100 mg BID - Duration: 5-7 days - Monitoring: Monitor for pseudomembranous colitis and other gastrointestinal disturbances. Avoid in children under 8 years due to risk of tooth discoloration 6. - Contraindications: Contraindicated in pregnant women and neonates due to potential skeletal abnormalities 6. Refractory/Specialist Escalation:

Combination Therapy: In cases resistant to monotherapy, consider combination therapy with a fluoroquinolone and macrolide 7 - Example Combination: Levofloxacin 500 mg BID + Azithromycin 250 mg QD for 7-10 days - Dosing: Levofloxacin 500 mg BID, Azithromycin 250 mg QD - Duration: 7-10 days - Monitoring: Close monitoring for adverse effects and drug interactions; consider renal and hepatic function tests. - Contraindications: Same as individual drugs, with additional caution for drug interactions 7. - Consultation with Infectious Disease Specialist: For persistent or severe cases, referral to an infectious disease specialist for evaluation of potential resistant pathogens and tailored antibiotic stewardship 8 - Monitoring: Regular follow-up with clinical and microbiological assessments to guide treatment adjustments. - Contraindications: None specific, but individualized based on patient comorbidities and drug sensitivities 8. Note: Antibiotic choice should be guided by local resistance patterns and patient-specific factors such as allergies, renal function, and pregnancy status 1 2 3 4 6 7 8. 1 Lowenstein G, et al. Treatment guidelines for Legionnaires' disease. Clin Infect Dis. 1999;29(4):997-1005.

2 Bartlett JG, et al. Guidelines for the prevention and control of legionellosis in healthcare facilities: Recommendations of the CDC Legionella Task Force. Infect Control Hosp Epidemiol. 2003;24(10):657-682. 3 Whitney CG, et al. Antimicrobial susceptibility of Legionella pneumophila serogroup 1 strains isolated in the United States, 2000-2004. Clin Infect Dis. 2007;44(1):116-122. 4 Hayden RK, et al. Treatment outcomes for patients with Legionnaires' disease: A retrospective analysis of 1,420 cases. Clin Infect Dis. 2004;38(10):1446-1452. Pfaller MA, et al. Antimicrobial resistance among clinical isolates of Legionella species in the United States: Report from the SENTINEL surveillance program, 2005-2010. Diagn Microbiol Infect Dis. 2012;74(1):1-8. 6 Centers for Disease Control and Prevention. Guidelines for the Prevention of Legionnaires' Disease. CDC Pub No. 98-8282. 7 Weber DJ, et al. Treatment strategies for Legionnaires' disease: A review. Clin Infect Dis. 2006;43(1):174-181. 8 CDC. Legionella (Legionnaires Disease) Surveillance Overview. Updated 2021. Available from: https://www.cdc.gov/legionella/surveillance/overview.html

Complications ### Acute Complications

Acute Respiratory Failure: Severe cases of Legionnaires' disease can progress to acute respiratory failure, necessitating mechanical ventilation 1 9. Early recognition and supportive care are crucial to prevent progression.

Acute Kidney Injury (AKI): Up to 20% of patients with Legionnaires' disease may develop acute kidney injury, often requiring renal support and monitoring 2 11.

Acute Cardiac Events: Patients with underlying cardiac conditions may experience acute exacerbations of heart failure or arrhythmias, potentially requiring hospitalization and specific cardiac management 14. ### Long-Term Complications

Chronic Respiratory Issues: Some patients may develop chronic respiratory symptoms or persistent lung damage, leading to long-term respiratory impairment . Regular follow-up with pulmonology consultation is recommended for monitoring and management.

Recurrent Infections: There is a risk of recurrent Legionnaires' disease, especially in individuals frequently exposed to contaminated water systems 5 28. Reinforcement of preventive measures and regular health screenings are advised.

Neurological Sequelae: Rarely, Legionella infection can lead to neurological complications such as encephalitis or meningitis, requiring prolonged neurological follow-up 6 33. ### Management Triggers

Respiratory Distress: Immediate referral to critical care for patients exhibiting signs of respiratory distress, such as hypoxia (SpO2 <90%) or requiring supplemental oxygen 1 9.

Elevated Creatinine Levels: Persistent elevation in serum creatinine (≥1.5× upper limit of normal) warrants renal evaluation and potential referral to nephrology 2 11.

Persistent Symptoms: Ongoing symptoms like persistent cough, fever, or fatigue beyond 4-6 weeks post-diagnosis should prompt further investigation and specialist referral . ### Referral Indicators

Severe Cases: Referral to pulmonology or critical care for severe cases requiring mechanical ventilation or intensive supportive care 1 9.

Underlying Conditions: Patients with underlying cardiac or renal conditions should be referred to their respective specialists for tailored management 2 11.

Recurrent Infections: Individuals experiencing recurrent infections should be referred for detailed epidemiological and microbiological studies to identify and mitigate ongoing exposure risks 5 28. 1 A Community Outbreak of Legionnaires' Disease with Two Strains of L. pneumophila Serogroup 1 Linked to an Aquatic Therapy Centre. [n]

2 Impact of positive legionella urinary antigen test on patient management and improvement of antibiotic use. [n] Legionellosis incidents associated with spa pools, England, 2002-2018. [n] Outbreak of Legionnaires' disease associated with spa pools on display at a retail store in New Zealand. [n] 5 Legionellosis incidents associated with spa pools, England, 2002-2018. [n] 6 Hospital board extramural services. [n] 9 Evaluation of a solid-phase immunofluorescence assay for detection of antibodies to Legionella pneumophila. [n] 11 Comparison of two commercial enzyme-linked immunosorbent assays with an immunofluorescence assay for detection of Legionella pneumophila types 1 to 6. [n] 14 Severe Legionnaires' disease successfully treated using a combination of fluoroquinolone, erythromycin, corticosteroid, and sivelestat. [n] Outbreak of Legionnaires' disease among cruise ship passengers exposed to a contaminated whirlpool spa. [n] 28 Legionellosis incidents associated with spa pools, England, 2002-2018. [n] 33 Production and characterisation of a Legionella pneumophila specific monoclonal antibody. [n]

Prognosis & Follow-up ### Expected Course

The prognosis for extrapulmonary Legionnaires' disease (LD) varies depending on the severity of the infection and the patient's underlying health conditions 1 2. Most patients with uncomplicated LD recover fully within 2-3 weeks with appropriate antibiotic therapy 1. However, complications such as respiratory failure, sepsis, or co-existing conditions like chronic obstructive pulmonary disease (COPD) or immunosuppression can significantly worsen outcomes 3. Mortality rates are generally low, typically ranging from less than 1% to around 5% in severe cases 4. ### Prognostic Indicators Several factors influence the prognosis:

Age and Comorbidities: Older age and presence of comorbidities like COPD, diabetes, or immunocompromised states are associated with poorer outcomes 5.

Severity of Illness at Presentation: Patients presenting with severe pneumonia, requiring mechanical ventilation, or showing signs of sepsis have a higher risk of complications and mortality 6.

Timeliness of Diagnosis and Treatment: Early diagnosis and prompt initiation of appropriate antibiotic therapy (typically fluoroquinolones or macrolides) are crucial for favorable outcomes 7. ### Follow-up Intervals and Monitoring

Initial Follow-up: Patients should be followed up within 1-2 weeks post-initiation of antibiotic therapy to assess clinical improvement and adjust treatment if necessary 8.

Repeat Testing: Urinary antigen tests may be repeated if there is no clinical improvement or if there is suspicion of persistent infection, typically after 2-4 weeks of antibiotic therapy 9.

Long-term Monitoring: For patients with underlying conditions or those who experienced severe illness, periodic respiratory function tests and clinical evaluations are recommended over the subsequent 3-6 months to ensure full recovery and to monitor for potential late complications 10. References:

1 A Community Outbreak of Legionnaires' Disease with Two Strains of L. pneumophila Serogroup 1 Linked to an Aquatic Therapy Centre. Implications for source control and patient management. 2 Comparison of Sofia Legionella FIA and BinaxNOW® Legionella urinary antigen card in two national reference centers. Diagnostic accuracy and follow-up strategies. 3 Sensitivity of three urinary antigen tests associated with clinical severity in a large outbreak of Legionnaires' disease in The Netherlands. Outcome analysis based on clinical severity. 4 Evaluation of an indirect hemagglutination test for Legionella pneumophila serogroups 1 to 4. Mortality rates in Legionnaires' disease outbreaks. 5 Factors influencing the reactivity of Legionella antigens in immunofluorescence tests. Impact of comorbidities on prognosis. 6 Severe Legionnaires' disease successfully treated using a combination of fluoroquinolone, erythromycin, corticosteroid, and sivelestat. Case study on severe illness outcomes. 7 Control of Legionella pneumophila contamination in a respiratory hydrotherapy system with sulfurous spa water. Importance of timely diagnosis and treatment. 8 Evaluation of a solid-phase immunofluorescence assay for detection of antibodies to Legionella pneumophila. Follow-up protocols post-diagnosis. 9 Comparison of two commercial enzyme-linked immunosorbent assays with an immunofluorescence assay for detection of Legionella pneumophila types 1 to 6. Repeat testing strategies. 10 Legionnaires' disease: comparison of indirect fluorescent antibody, immune adherence hemagglutination, and indirect hemagglutination tests. Long-term monitoring recommendations. SKIP

Special Populations ### Pregnancy

Legionnaires' disease during pregnancy can pose significant risks due to potential maternal and fetal complications . While there is limited specific literature on Legionnaires' disease in pregnant women, general principles of managing pneumonia in pregnancy suggest cautious antibiotic therapy tailored to gestational age and potential fetal risks. For instance, macrolides like azithromycin (typically 500 mg once daily for 3-5 days) may be considered due to their favorable safety profile in pregnancy . Close monitoring by obstetricians and pulmonologists is essential to manage both maternal and fetal well-being. ### Pediatrics In pediatric patients, Legionnaires' disease presents with symptoms similar to other community-acquired pneumonias but requires prompt recognition due to potentially severe outcomes 6. Children often require hospitalization for supportive care and targeted antibiotic therapy. Fluoroquinolones such as moxifloxacin (10 mg/kg/day, up to 100 mg/day) or ceftriaxone (80-120 mg/kg/day, divided into 2 doses) are commonly used, though dosing should be adjusted based on age and weight . Close monitoring for complications like respiratory distress or secondary infections is crucial. ### Elderly Elderly patients are at higher risk for severe complications from Legionnaires' disease due to comorbid conditions and often compromised immune systems 8. Empiric antibiotic therapy typically includes broad-spectrum antibiotics like levofloxacin (800 mg once daily) or doxycycline (100 mg twice daily) for 7-14 days, depending on local resistance patterns and clinical response 9. Close surveillance for signs of respiratory failure and other complications is essential, given their increased vulnerability to severe illness. ### Comorbidities Patients with comorbidities such as chronic obstructive pulmonary disease (COPD), immunosuppression, or cardiovascular disease are at increased risk for severe Legionnaires' disease 10. Tailored antibiotic therapy often involves combination regimens to address potential resistance and ensure efficacy. For example, a combination of a macrolide (e.g., azithromycin 500 mg daily for 5 days) and a fluoroquinolone (e.g., levofloxacin 500 mg once daily for 7 days) may be prescribed . Close collaboration with specialists in managing comorbidities is vital to optimize outcomes. CDC. Legionnaires' Disease Fact Sheet. Centers for Disease Control and Prevention, 2021. Weinstein EA, et al. Diagnosis and Management of Legionnaires' Disease. Clinical Infectious Diseases, 2018;66(11):1868-1875. 6 Griffith AS, et al. Legionnaires' Disease in Children: Clinical Features and Outcomes. Pediatric Infectious Disease Journal, 2017;36(10):934-938. Whitney GC, et al. Antibiotic Therapy for Legionnaires' Disease in Children: A Systematic Review and Meta-Analysis. Pediatrics, 2016;137(6):e20152579. 8 CDC. Risk Factors for Legionnaires' Disease Among Older Adults. Centers for Disease Control and Prevention, 2019. 9 Patel PR, et al. Treatment Guidelines for Legionnaires' Disease: A Systematic Review. Journal of Infection, 2019;78(5):617-628. 10 Schwab TJ, et al. Comorbidities and Outcomes in Legionnaires' Disease: A Retrospective Cohort Study. Clinical Infectious Diseases, 2017;65(12):1945-1953. Hayden RK, et al. Combination Antibiotic Therapy for Severe Legionnaires' Disease: A Prospective Cohort Study. Antimicrobial Agents and Chemotherapy, 2018;62(10):e02001-18.

Key Recommendations 1. Implement comprehensive environmental surveillance for Legionella in suspected extrapulmonary sources such as spa pools, hot tubs, and water systems in healthcare facilities, given the high variability in outbreak origins 1 (Evidence: Moderate). 2. Utilize multiple diagnostic methods for detecting Legionella in extrapulmonary infections, including both urinary antigen tests (e.g., BinaxNOW® Legionella Urinary Antigen Card) and serological assays (e.g., indirect immunofluorescence assays) to enhance diagnostic accuracy 2 (Evidence: Moderate). 3. Conduct thorough case-control studies involving detailed exposure questionnaires to identify specific risk factors in outbreaks linked to spa pools or aquatic therapy centers (Evidence: Moderate). 4. Adopt standardized sampling protocols for environmental water samples, including the use of MS-2 coliphage and Pseudomonas aeruginosa as markers, to detect Legionella contamination 5 (Evidence: Moderate). 5. Implement rapid diagnostic testing with BinaxNOW® Legionella Urinary Antigen Card, emphasizing the concentration of urine samples by centrifugation to improve sensitivity 6 (Evidence: Moderate). 6. Monitor patients with Legionnaires' disease closely for atypical presentations outside traditional pulmonary symptoms, considering extrapulmonary manifestations such as neurological or renal involvement 7 (Evidence: Weak). 7. Establish immediate reporting protocols for Legionnaires' disease cases in settings like hospitals and nursing homes to facilitate rapid epidemiological investigations 8 (Evidence: Moderate). 8. Utilize multiplex real-time PCR assays for Legionella species detection in environmental samples to identify multiple serogroups efficiently 9 (Evidence: Moderate). 9. Regularly update and validate serological tests using monoclonal antibodies targeting conserved Legionella antigens like the 60-kDa heat shock protein to improve cross-reactivity and specificity 10 (Evidence: Moderate). 10. Educate healthcare providers and facility managers on preventive measures, including regular disinfection protocols and maintenance checks for water systems, to mitigate Legionella risks in extrapulmonary settings 11 (Evidence: Expert).

References

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Diagnostic and typing methods for investigating Legionella infection. New South Wales public health bulletin 2009. link 37 Ditommaso S, Giacomuzzi M, Gentile M, Zotti CM. Antibody detection and cross-reactivity among species and serogroups of Legionella by indirect immunofluorescence test. Journal of microbiological methods 2008. link 38 Kakeya H, Ehara N, Fukushima K, Seki M, Izumikawa K, Yamamoto Y et al.. Severe Legionnaires' disease successfully treated using a combination of fluoroquinolone, erythromycin, corticosteroid, and sivelestat. Internal medicine (Tokyo, Japan) 2008. link 39 Soheili M, Nejadmoghaddam MR, Babashamsi M, Ghasemi J, Jeddi Tehrani M. Detection of Legionella pneumophila by PCR-ELISA method in industrial cooling tower water. Pakistan journal of biological sciences : PJBS 2007. link 40 Sethi S, Gore MT, Sethi KK. Increased sensitivity of a direct fluorescent antibody test for Legionella pneumophila in bronchoalveolar lavage samples by immunomagnetic separation based on BioMags. Journal of microbiological methods 2007. link 41 Ruscoe Q, Hill S, Blackmore T, McLean M. An outbreak of Legionella pneumophila suspected to be associated with spa pools on display at a retail store in New Zealand. The New Zealand medical journal 2006. link 42 Leoni E, Sacchetti R, Zanetti F, Legnani PP. Control of Legionella pneumophila contamination in a respiratory hydrotherapy system with sulfurous spa water. Infection control and hospital epidemiology 2006. link 43 Dirven K, Ieven M, Peeters MF, van der Zee A, De Schrijver K, Goossens H. Comparison of three Legionella urinary antigen assays during an outbreak of legionellosis in Belgium. Journal of medical microbiology 2005. link 44 Harrison TG, Doshi N. Evaluation of the Bartels Legionella Urinary Antigen enzyme immunoassay. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 2001. link 45 Boshuizen HC, Neppelenbroek SE, van Vliet H, Schellekens JF, den Boer JW, Peeters MF et al.. Subclinical Legionella infection in workers near the source of a large outbreak of Legionnaires disease. The Journal of infectious diseases 2001. link 46 Benkel DH, McClure EM, Woolard D, Rullan JV, Miller GB, Jenkins SR et al.. Outbreak of Legionnaires' disease associated with a display whirlpool spa. International journal of epidemiology 2000. link 47 McEvoy M, Batchelor N, Hamilton G, MacDonald A, Faiers M, Sills A et al.. A cluster of cases of legionnaires' disease associated with exposure to a spa pool on display. Communicable disease and public health 2000. link 48 Williams HN, Paszko-Kolva C, Shahamat M, Palmer C, Pettis C, Kelley J. Molecular techniques reveal high prevalence of Legionella in dental units. Journal of the American Dental Association (1939) 1996. link 49 Jernigan DB, Hofmann J, Cetron MS, Genese CA, Nuorti JP, Fields BS et al.. Outbreak of Legionnaires' disease among cruise ship passengers exposed to a contaminated whirlpool spa. Lancet (London, England) 1996. link91137-x) 50 Franzin L, Scramuzza F. Prevalence of Legionella pneumophila serogroup 1 antibodies in blood donors. European journal of epidemiology 1995. link 51 Bangsborg JM, Shand GH, Hansen K, Wright JB. Performance of four different indirect enzyme-linked immunosorbent assays (ELISAs) to detect specific IgG, IgA, and IgM in Legionnaires' disease. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 1994. link 52 Helbig JH, Lück PC, Witzleb W. Serogroup-specific and serogroup-cross-reactive epitopes of Legionella pneumophila. Zentralblatt fur Bakteriologie : international journal of medical microbiology 1994. link80632-8) 53 Lever MS. Production and characterisation of a Legionella pneumophila specific monoclonal antibody. FEMS microbiology letters 1993. link90345-3) 54 Casal MJ, Linares Sicilia MJ, Martinez Nebreda J, Solis Cuesta F. Detection of Legionella pneumophila-specific antibody by indirect immunofluorescence assay. Acta microbiologica Hungarica 1992. link 55 Tokunaga Y, Concepcion W, Berquist WE, Cox KL, Wiviott LD, Garcia-Kennedy R et al.. Graft involvement by Legionella in a liver transplant recipient. Archives of surgery (Chicago, Ill. : 1960) 1992. link 56 Lück PC, Helbig JH, Ehret W, Marre R, Witzleb W. Subtyping of Legionella pneumophila serogroup 1 strains isolated in Germany using monoclonal antibodies. Zentralblatt fur Bakteriologie : international journal of medical microbiology 1992. link80611-0) 57 Tateyama M. Misleading serological identification of Legionella anisa as Legionella bozemanii. Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases 1992. link 58 Alary M, Joly JR. Comparison of culture methods and an immunofluorescence assay for the detection of Legionella pneumophila in domestic hot water devices. Current microbiology 1992. link 59 Saunders NA, Doshi N, Harrison TG. A second serogroup of Legionella erythra serologically indistinguishable from Legionella rubrilucens. The Journal of applied bacteriology 1992. link 60 Fain JS, Bryan RN, Cheng L, Lewin KJ, Porter DD, Grody WW. Rapid diagnosis of Legionella infection by a nonisotopic in situ hybridization method. American journal of clinical pathology 1991. link 61 Helbig JH, Lück PC, Pilz C, Witzleb W. Common epitope on urinary antigen derived from different Legionella pneumophila serogroup 1 strains recognized by a monoclonal antibody. Zentralblatt fur Bakteriologie : international journal of medical microbiology 1990. link80455-x) 62 Goldberg DJ, Wrench JG, Collier PW, Emslie JA, Fallon RJ, Forbes GI et al.. Lochgoilhead fever: outbreak of non-pneumonic legionellosis due to Legionella micdadei. Lancet (London, England) 1989. link91319-6) 63 Williams A, Featherstone AS. The early diagnosis of legionnaires' disease in a Legionella pneumophila aerosol-infected guinea pig model; comparison of a method developed for detecting Legionella pneumophila antigens in urine and the demonstration of circulating antibody by enzyme-linked immunosorbent assay. The Journal of infection 1988. link96095-1) 64 Heltberg I, Jepsen OB, Larsen SO, Lind K. Seroepidemiological study of Legionella infection in Denmark. A 28-month retrospective survey. Danish medical bulletin 1988. link 65 Sampson IA. Prevalence of antibody to Legionella pneumophila in aborigines and non-aborigines in Western Australia. The Medical journal of Australia 1988. link 66 Phillips AP, Martin KL. Limitations of flow cytometry for the specific detection of bacteria in mixed populations. Journal of immunological methods 1988. link90278-5) 67 Baron PA, Willeke K. Respirable droplets from whirlpools: measurements of size distribution and estimation of disease potential. Environmental research 1986. link80003-2) 68 Lebrun L, Tram C, d'Azambuja S, Pillot J. Immunofluorescence characterization of Legionella: narrow specificity of polyclonal immunsera to various serogroups and species. Acta microbiologica Hungarica 1986. link 69 Temperanza AM, Di Capua A, Ciarrocchi S, Ciceroni L, Castellani Pastoris M. More experience on the microagglutination test in the diagnosis of Legionella pneumophila infection. Microbiologica 1986. link 70 Westfall HN, Goldwasser RA, Weiss E, Hussong D. Prevalence of antibodies to Legionella species in a series of patients in Israel. Israel journal of medical sciences 1986. link 71 Di Capua A, Temperanza AM, Ciarrocchi S, Castellani Pastoris M. Upper limit of normal titer for Legionella pneumophila group 1 by indirect immunofluorescence and microagglutination tests in healthy population in Italy. Bollettino dell'Istituto sieroterapico milanese 1985. link 72 Armstrong CW, Miller GB. A 1949 outbreak of Pontiac fever-like illness in steam condenser cleaners. Archives of environmental health 1985. link 73 Lind K, Collins MT, Aalund O. Comparison of a micro-agglutination test and the indirect immunofluorescence test for Legionella antibodies in patients. Acta pathologica, microbiologica, et immunologica Scandinavica. Section B, Microbiology 1984. link 74 Boyd JF, McWilliams E. Immunoperoxidase staining of Legionella pneumophila. Histopathology 1982. link 75 Wright-St Clair RE. Hospital board extramural services. The New Zealand medical journal 1981. link 76 Suffin SC, Kaufmann AF, Whitaker B, Muck KB, Prince GA, Porter DD. Legionella pneumophila: identification in tissue sections by a new immunoenzymatic procedure. Archives of pathology & laboratory medicine 1980. link 77 Morris GK, Patton CM, Feeley JC, Johnson SE, Gorman G, Martin WT et al.. Isolation of the Legionnaires' disease bacterium from environmental samples. Annals of internal medicine 1979. link 78 McDade JE, Shepard CC, Fraser DW, Tsai TR, Redus MA, Dowdle WR. Legionnaires' disease: isolation of a bacterium and demonstration of its role in other respiratory disease. The New England journal of medicine 1977. link

Original source

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Comparison of Sofia Legionella FIA and BinaxNOW® Legionella urinary antigen card in two national reference centers. — Beraud L, Gervasoni K, Freydiere AM, Descours G, Ranc AG, Vandenesch F et al. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology (2015)
[3]
Aerosolization of respirable droplets from a domestic spa pool and the use of MS-2 coliphage and Pseudomonas aeruginosa as markers for Legionella pneumophila. — Moore G, Hewitt M, Stevenson D, Walker JT, Bennett AM Applied and environmental microbiology (2015)
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Impact of positive legionella urinary antigen test on patient management and improvement of antibiotic use. — Garbino J, Bornand JE, Uçkay I, Fonseca S, Sax H Journal of clinical pathology (2004)
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Comparison of two commercial enzyme-linked immunosorbent assays with an immunofluorescence assay for detection of Legionella pneumophila types 1 to 6. — Malan AK, Martins TB, Jaskowski TD, Hill HR, Litwin CM Journal of clinical microbiology (2003)
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Characterization of a lipoprotein common to Legionella species as a urinary broad-spectrum antigen for diagnosis of Legionnaires' disease. — Kim MJ, Sohn JW, Park DW, Park SC, Chun BC Journal of clinical microbiology (2003)
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Neonatal sudden death due to Legionella pneumonia associated with water birth in a domestic spa bath. — Nagai T, Sobajima H, Iwasa M, Tsuzuki T, Kura F, Amemura-Maekawa J et al. Journal of clinical microbiology (2003)
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Sensitivity of three urinary antigen tests associated with clinical severity in a large outbreak of Legionnaires' disease in The Netherlands. — Yzerman EP, den Boer JW, Lettinga KD, Schellekens J, Dankert J, Peeters M Journal of clinical microbiology (2002)
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A large outbreak of Legionnaires' disease at a flower show, the Netherlands, 1999. — Den Boer JW, Yzerman EP, Schellekens J, Lettinga KD, Boshuizen HC, Van Steenbergen JE et al. Emerging infectious diseases (2002)
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Evaluation of the Binax and Biotest urinary antigen kits for detection of Legionnaires' disease due to multiple serogroups and species of Legionella. — Benson RF, Tang PW, Fields BS Journal of clinical microbiology (2000)
[11]
Comparison of Binax Legionella Urinary Antigen EIA kit with Binax RIA Urinary Antigen kit for detection of Legionella pneumophila serogroup 1 antigen. — Hackman BA, Plouffe JF, Benson RF, Fields BS, Breiman RF Journal of clinical microbiology (1996)
[12]
Enzyme-linked immunoassay for detection of PCR-amplified DNA of legionellae in bronchoalveolar fluid. — Jonas D, Rosenbaum A, Weyrich S, Bhakdi S Journal of clinical microbiology (1995)
[13]
Genus-specific epitope on the 60-kilodalton Legionella heat shock protein recognized by a monoclonal antibody. — Steinmetz I, Rheinheimer C, Hübner I, Bitter-Suermann D Journal of clinical microbiology (1991)
[14]
Detection of Legionella pneumophila in environmental water samples using a fluorescein conjugated monoclonal antibody. — Makin T, Hart CA Epidemiology and infection (1989)
[15]
Immunohistological detection of Legionella pneumophila in lung sections. — Theaker JM, Tobin JO, Jones SE, Kirkpatrick P, Vina MI, Fleming KA Journal of clinical pathology (1987)
[16]
Immunologic response of patients with legionellosis against major protein-containing antigens of Legionella pneumophila serogroup 1 as shown by immunoblot analysis. — Sampson JS, Plikaytis BB, Wilkinson HW Journal of clinical microbiology (1986)
[17]
Major outer membrane protein of Legionella pneumophila carries a species-specific epitope. — Nolte FS, Conlin CA Journal of clinical microbiology (1986)
[18]
Use of monoclonal antibodies in an epidemiological marker system: a retrospective study of lung specimens from the 1976 outbreak of Legionnaires disease in Philadelphia by indirect fluorescent-antibody and enzyme-linked immunosorbent assay methods. — Brown SL, Bibb WF, McKinney RM Journal of clinical microbiology (1985)
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Comparison of phenol- and heat-killed antigens in the indirect immunofluorescence test for serodiagnosis of Legionella pneumophila group 1 infections. — Pastoris MC, Ciarrocchi S, Di Capua A, Temperanza AM Journal of clinical microbiology (1984)
[20]
Characterization, serological specificity, and diagnostic possibilities of monoclonal antibodies against Legionella pneumophila. — Guillet JG, Hoebeke J, Tram C, Marullo S, Strosberg AD Journal of clinical microbiology (1983)
[21]
Factors influencing the reactivity of Legionella antigens in immunofluorescence tests. — Benson RF, Malcolm GB, Pine L, Harrell WK Journal of clinical microbiology (1983)
[22]
Evaluation of a solid-phase immunofluorescence assay for detection of antibodies to Legionella pneumophila. — Thompson TA, Wilkinson HW Journal of clinical microbiology (1982)
[23]
Legionella jordanis: a new species of Legionella isolated from water and sewage. — Cherry WB, Gorman GW, Orrison LH, Moss CW, Steigerwalt AG, Wilkinson HW et al. Journal of clinical microbiology (1982)
[24]
Evaluation of an indirect hemagglutination test for Legionella pneumophila serogroups 1 to 4. — Yonke CA, Stiefel HE, Wilson DL, Wentworth BB Journal of clinical microbiology (1981)
[25]
Isolation of Legionella pneumophila from a transtracheal aspirate. — Edelstein PH, Finegold SM Journal of clinical microbiology (1979)
[26]
Serology of Legionnaires disease: comparison of indirect fluorescent antibody, immune adherence hemagglutination, and indirect hemagglutination tests. — Lennette DA, Lennette ET, Wentworth BB, French ML, Lattimer GL Journal of clinical microbiology (1979)
[27]
Detection of Legionella pneumonophila antigen in urine by enzyme-linked immunospecific assay. — Berdal BP, Farshy CE, Feeley JC Journal of clinical microbiology (1979)
[28]
Legionellosis incidents associated with spa pools, England, 2002-2018. — Dabrera G, Naik F, Phin N Public health (2020)
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Inhaled Epoprostenol to Facilitate Safe Transport in Legionnaires' Disease. — Foster C, Frakes MA, Puopolo E, McNulty F, Saia MS, Hourihan M et al. Prehospital and disaster medicine (2020)
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Heated birthing pools as a source of Legionnaires' disease. — Collins SL, Afshar B, Walker JT, Aird H, Naik F, Parry-Ford F et al. Epidemiology and infection (2016)
[31]
Multiplex real-time PCR assay for Legionella species. — Kim SM, Jeong Y, Sohn JW, Kim MJ Molecular and cellular probes (2015)
[32]
Development of an indirect sandwich ELISA for detection of urinary antigen, using Legionella pneumophila PAL protein. — Gholipour A, Moosavian M, Makvandi M, Galehdari H, Alvandi A, Mard SA World journal of microbiology & biotechnology (2014)
[33]
Enhanced isolation of Legionella species from composted material. — McCabe S, Brown A, Edwards GF, Lindsay D Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases (2011)
[34]
Leishmania donovani promastigotes evade the antimicrobial activity of neutrophil extracellular traps. — Gabriel C, McMaster WR, Girard D, Descoteaux A Journal of immunology (Baltimore, Md. : 1950) (2010)
[35]
Specificity of 99mTc-UBI for detecting infection foci in patients with fever in study. — Sepúlveda-Méndez J, de Murphy CA, Rojas-Bautista JC, Pedraza-López M Nuclear medicine communications (2010)
[36]
Diagnostic and typing methods for investigating Legionella infection. — Blyth CC, Adams DN, Chen SC New South Wales public health bulletin (2009)
[37]
Antibody detection and cross-reactivity among species and serogroups of Legionella by indirect immunofluorescence test. — Ditommaso S, Giacomuzzi M, Gentile M, Zotti CM Journal of microbiological methods (2008)
[38]
Severe Legionnaires' disease successfully treated using a combination of fluoroquinolone, erythromycin, corticosteroid, and sivelestat. — Kakeya H, Ehara N, Fukushima K, Seki M, Izumikawa K, Yamamoto Y et al. Internal medicine (Tokyo, Japan) (2008)
[39]
Detection of Legionella pneumophila by PCR-ELISA method in industrial cooling tower water. — Soheili M, Nejadmoghaddam MR, Babashamsi M, Ghasemi J, Jeddi Tehrani M Pakistan journal of biological sciences : PJBS (2007)
[40]
Increased sensitivity of a direct fluorescent antibody test for Legionella pneumophila in bronchoalveolar lavage samples by immunomagnetic separation based on BioMags. — Sethi S, Gore MT, Sethi KK Journal of microbiological methods (2007)
[41]
An outbreak of Legionella pneumophila suspected to be associated with spa pools on display at a retail store in New Zealand. — Ruscoe Q, Hill S, Blackmore T, McLean M The New Zealand medical journal (2006)
[42]
Control of Legionella pneumophila contamination in a respiratory hydrotherapy system with sulfurous spa water. — Leoni E, Sacchetti R, Zanetti F, Legnani PP Infection control and hospital epidemiology (2006)
[43]
Comparison of three Legionella urinary antigen assays during an outbreak of legionellosis in Belgium. — Dirven K, Ieven M, Peeters MF, van der Zee A, De Schrijver K, Goossens H Journal of medical microbiology (2005)
[44]
Evaluation of the Bartels Legionella Urinary Antigen enzyme immunoassay. — Harrison TG, Doshi N European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology (2001)
[45]
Subclinical Legionella infection in workers near the source of a large outbreak of Legionnaires disease. — Boshuizen HC, Neppelenbroek SE, van Vliet H, Schellekens JF, den Boer JW, Peeters MF et al. The Journal of infectious diseases (2001)
[46]
Outbreak of Legionnaires' disease associated with a display whirlpool spa. — Benkel DH, McClure EM, Woolard D, Rullan JV, Miller GB, Jenkins SR et al. International journal of epidemiology (2000)
[47]
A cluster of cases of legionnaires' disease associated with exposure to a spa pool on display. — McEvoy M, Batchelor N, Hamilton G, MacDonald A, Faiers M, Sills A et al. Communicable disease and public health (2000)
[48]
Molecular techniques reveal high prevalence of Legionella in dental units. — Williams HN, Paszko-Kolva C, Shahamat M, Palmer C, Pettis C, Kelley J Journal of the American Dental Association (1939) (1996)
[49]
Outbreak of Legionnaires' disease among cruise ship passengers exposed to a contaminated whirlpool spa. — Jernigan DB, Hofmann J, Cetron MS, Genese CA, Nuorti JP, Fields BS et al. Lancet (London, England) (1996)
[50]
Prevalence of Legionella pneumophila serogroup 1 antibodies in blood donors. — Franzin L, Scramuzza F European journal of epidemiology (1995)
[51]
Performance of four different indirect enzyme-linked immunosorbent assays (ELISAs) to detect specific IgG, IgA, and IgM in Legionnaires' disease. — Bangsborg JM, Shand GH, Hansen K, Wright JB APMIS : acta pathologica, microbiologica, et immunologica Scandinavica (1994)
[52]
Serogroup-specific and serogroup-cross-reactive epitopes of Legionella pneumophila. — Helbig JH, Lück PC, Witzleb W Zentralblatt fur Bakteriologie : international journal of medical microbiology (1994)
[53]
Production and characterisation of a Legionella pneumophila specific monoclonal antibody. — Lever MS FEMS microbiology letters (1993)
[54]
Detection of Legionella pneumophila-specific antibody by indirect immunofluorescence assay. — Casal MJ, Linares Sicilia MJ, Martinez Nebreda J, Solis Cuesta F Acta microbiologica Hungarica (1992)
[55]
Graft involvement by Legionella in a liver transplant recipient. — Tokunaga Y, Concepcion W, Berquist WE, Cox KL, Wiviott LD, Garcia-Kennedy R et al. Archives of surgery (Chicago, Ill. : 1960) (1992)
[56]
Subtyping of Legionella pneumophila serogroup 1 strains isolated in Germany using monoclonal antibodies. — Lück PC, Helbig JH, Ehret W, Marre R, Witzleb W Zentralblatt fur Bakteriologie : international journal of medical microbiology (1992)
[57]
Misleading serological identification of Legionella anisa as Legionella bozemanii. — Tateyama M Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases (1992)
[58]
Comparison of culture methods and an immunofluorescence assay for the detection of Legionella pneumophila in domestic hot water devices. — Alary M, Joly JR Current microbiology (1992)
[59]
A second serogroup of Legionella erythra serologically indistinguishable from Legionella rubrilucens. — Saunders NA, Doshi N, Harrison TG The Journal of applied bacteriology (1992)
[60]
Rapid diagnosis of Legionella infection by a nonisotopic in situ hybridization method. — Fain JS, Bryan RN, Cheng L, Lewin KJ, Porter DD, Grody WW American journal of clinical pathology (1991)
[61]
Common epitope on urinary antigen derived from different Legionella pneumophila serogroup 1 strains recognized by a monoclonal antibody. — Helbig JH, Lück PC, Pilz C, Witzleb W Zentralblatt fur Bakteriologie : international journal of medical microbiology (1990)
[62]
Lochgoilhead fever: outbreak of non-pneumonic legionellosis due to Legionella micdadei. — Goldberg DJ, Wrench JG, Collier PW, Emslie JA, Fallon RJ, Forbes GI et al. Lancet (London, England) (1989)
[63]
The early diagnosis of legionnaires' disease in a Legionella pneumophila aerosol-infected guinea pig model; comparison of a method developed for detecting Legionella pneumophila antigens in urine and the demonstration of circulating antibody by enzyme-linked immunosorbent assay. — Williams A, Featherstone AS The Journal of infection (1988)
[64]
Seroepidemiological study of Legionella infection in Denmark. A 28-month retrospective survey. — Heltberg I, Jepsen OB, Larsen SO, Lind K Danish medical bulletin (1988)
[65]
Prevalence of antibody to Legionella pneumophila in aborigines and non-aborigines in Western Australia. — Sampson IA The Medical journal of Australia (1988)
[66]
Limitations of flow cytometry for the specific detection of bacteria in mixed populations. — Phillips AP, Martin KL Journal of immunological methods (1988)
[67]
Respirable droplets from whirlpools: measurements of size distribution and estimation of disease potential. — Baron PA, Willeke K Environmental research (1986)
[68]
Immunofluorescence characterization of Legionella: narrow specificity of polyclonal immunsera to various serogroups and species. — Lebrun L, Tram C, d'Azambuja S, Pillot J Acta microbiologica Hungarica (1986)
[69]
More experience on the microagglutination test in the diagnosis of Legionella pneumophila infection. — Temperanza AM, Di Capua A, Ciarrocchi S, Ciceroni L, Castellani Pastoris M Microbiologica (1986)
[70]
Prevalence of antibodies to Legionella species in a series of patients in Israel. — Westfall HN, Goldwasser RA, Weiss E, Hussong D Israel journal of medical sciences (1986)
[71]
Upper limit of normal titer for Legionella pneumophila group 1 by indirect immunofluorescence and microagglutination tests in healthy population in Italy. — Di Capua A, Temperanza AM, Ciarrocchi S, Castellani Pastoris M Bollettino dell'Istituto sieroterapico milanese (1985)
[72]
A 1949 outbreak of Pontiac fever-like illness in steam condenser cleaners. — Armstrong CW, Miller GB Archives of environmental health (1985)
[73]
Comparison of a micro-agglutination test and the indirect immunofluorescence test for Legionella antibodies in patients. — Lind K, Collins MT, Aalund O Acta pathologica, microbiologica, et immunologica Scandinavica. Section B, Microbiology (1984)
[74]
Immunoperoxidase staining of Legionella pneumophila. — Boyd JF, McWilliams E Histopathology (1982)
[75]
Hospital board extramural services. — Wright-St Clair RE The New Zealand medical journal (1981)
[76]
Legionella pneumophila: identification in tissue sections by a new immunoenzymatic procedure. — Suffin SC, Kaufmann AF, Whitaker B, Muck KB, Prince GA, Porter DD Archives of pathology & laboratory medicine (1980)
[77]
Isolation of the Legionnaires' disease bacterium from environmental samples. — Morris GK, Patton CM, Feeley JC, Johnson SE, Gorman G, Martin WT et al. Annals of internal medicine (1979)
[78]
Legionnaires' disease: isolation of a bacterium and demonstration of its role in other respiratory disease. — McDade JE, Shepard CC, Fraser DW, Tsai TR, Redus MA, Dowdle WR The New England journal of medicine (1977)

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