Legionnaire's disease presenting as bilateral central scotomata: a case report.

BACKGROUND: Legionnaire's disease is one of the major causes of community-acquired pneumonia and is occasionally complicated by neurological symptoms. However, reports of ocular lesions due to Legionnaire's disease are limited. CASE PRESENTATION: We report the case of a patient with Legionnaire's disease presenting as bilateral central scotomata due to retinal lesions. The patient consulted due to fever and bilateral central scotomata, as well as other extrapulmonary symptoms. Optical coherence tomography (OCT) showed bilateral accumulations of fluid under the retina, and the patient was diagnosed with bilateral exudative retinal detachment. Later, Legionnaire's disease was confirmed by pulmonary infiltrates on chest imaging and positive urinary antigen for Legionella pneumophila. After administration of antibiotics, the bilateral central scotomata and bilateral subretinal fluid accumulations completely resolved, as did the other extrapulmonary symptoms and the pulmonary infiltrates. Thus, the bilateral central scotomata due to exudative retinal detachment were thought to be caused by Legionnaire's disease. CONCLUSIONS: This case demonstrates that Legionnaire's disease can present as bilateral central scotomata. We may consider the possibility of extrapulmonary involvement complicating Legionnaire's disease when we encounter bilateral ocular lesions in patients with fever and pneumonia.

Legionnaires' Disease Mortality in Guinea Pigs Involves the p45 Mobile Genomic Element.

BACKGROUND: Legionella can cause Legionnaires' disease, a potentially fatal form of pneumonia that occurs as sporadic epidemics. Not all strains display the same propensity to cause disease in humans. Because Legionella pneumophila serogroup 1 is responsible for >85% of infections, the majority of studies have examined this serogroup, but there are 3 commonly used laboratory strains: L pneumophila serogroup 1 Philadelphia (Phil-1)-derived strains JR32 and Lp01 and 130b-derived strain AA100. METHODS: We evaluated the ability of Phil-1, JR32, Lp01, and AA100 to cause disease in guinea pigs. RESULTS: We found that, although Phil-1, JR32, and AA100 cause an acute pneumonia and death by 4 days postinfection (100%), strain Lp01 does not cause mortality (0%). We also noted that Lp01 lacks a mobile element, designated p45, whose presence correlates with virulence. Transfer of p45 into Lp01 results in recovery of the ability of this strain to cause mortality, leads to more pronounced disease, and correlates with increased interferon-γ levels in the lungs and spleens before death. CONCLUSIONS: These observations suggest a mechanism of Legionnaires' disease pathogenesis due to the presence of type IVA secretion systems that cause higher mortality due to overinduction of a proinflammatory response in the host.

Community Acquired Legionnaire's Disease in a Kidney Transplant Patient.

This case report details the clinical picture of a renal transplant recipient infected with community acquired Legionella pneumonia. While it is more commonly associated as a nosocomial infection due to pathogenic organisms in a hospital's water supply, this case serves as a reminder to consider the patient's impaired cellular immune function when trying to diagnose community acquired pneumonia.

Legionnaires' disease at a medical center in southern Taiwan.

BACKGROUND/PURPOSE: Legionella pneumophila had been recognized as a pathogen for both healthcare-associated and community-acquired pneumonia. We aimed to evaluate clinical features and outcomes of patients with Legionnaires' disease at a tertiary medical center in southern Taiwan. METHODS: From January 2005 to December 2013, a retrospective study of adult cases of Legionnaires' disease was conducted in a 1200-bed tertiary hospital. Their medical records were reviewed for further evaluation and analysis. RESULTS: A total of 61 cases of Legionnaires' disease were identified during the study period. Their mean age was 61.1 years, with male predominance (43, 70.5%). Among them, 30 (49.2%) had healthcare-associated pneumonia (HCAP), 20 (32.8%) had community-acquired pneumonia, and notably 11 (18.0%) were caregivers. Patients with healthcare-associated pneumonia tend to have higher Charlson comorbidity scores than those with community-acquired pneumonia (3.6±2.4 vs. 1.9±1.9, p=0.008) and caregivers (0.5±0.5, p<0.001). Six patients died, resulting in an in-hospital mortality rate of 9.8%. Underlying cancer (66.7% vs. 20.0%, p=0.028) and a higher Charlson comorbidity score (4.7±2.6 vs. 2.2±2.2, p=0.013) were related to a fatal outcome. CONCLUSION: L. pneumophila remains an important pathogen for pneumonia acquired from the community or associated with healthcare facility. Healthy caregivers may potentially be at risk for Legionella infection in certain clinical settings.

Legionella pneumonia due to non-Legionella pneumophila serogroup 1: usefulness of the six-point scoring system.

BACKGROUND: Because of a limited number of reports, we aimed to investigate the clinical characteristics of patients with Legionella pneumonia due to non-Legionella pneumophila serogroup 1 and the diagnostic usefulness of the six-point scoring system for such patients compared with patients with pneumonia caused by L. pneumophila serogroup 1. METHODS: We retrospectively analysed patients diagnosed with Legionella pneumonia due to non-L. pneumophila serogroup 1 between March 2001 and June 2016. We examined the clinical characteristics, including symptoms, laboratory findings, radiologic findings, pneumonia severity, initial treatment and prognosis. We also calculated scores using the six-point scoring system in these patients. Furthermore, we compared the clinical characteristics and six-point scores between non-L. pneumophila serogroup 1 patients and L. pneumophila serogroup 1 patients among hospitalized community-acquired pneumonia patients enrolled prospectively between October 2010 and July 2016. RESULTS: Eleven patients had pneumonia due to non-L. pneumophila serogroup 1; their median age was 66 years and 8 patients (72.7%) were male. The most common pathogen was L. pneumophila serogroup 3 (6/11), followed by L. pneumophila serogroup 9 (3/11), L. pneumophila serogroup 6 (1/11) and L. longbeachae (1/11). Non-specific symptoms, such as fever and cough, were common. Six patients (54.5%) had liver enzyme elevation, but no patient developed hyponatraemia at <130 mEq/L. Nine patients (81.8%) showed lobar pneumonia and 7 patients (63.6%) manifested with consolidation and ground-glass opacity. Patients with mild to moderate severity comprised 10 (90.9%) by CURB-65 and 5 (45.5%) by the Pneumonia Severity Index. Of all patients, 4 were admitted to the intensive care unit and 3 died despite appropriate empiric therapy. The clinical characteristics were not significantly different between non-L. pneumophila serogroup 1 patients and L. pneumophila serogroup 1 patients (n = 23). At a cut-off value of ≥ 2 points, the sensitivity of the six-point scoring system was 54.5% (6/11) for non-L. pneumophila serogroup 1 patients and 95.7% (22/23) for L. pneumophila serogroup 1 patients. CONCLUSIONS: Cases of non-L. pneumophila serogroup 1 pneumonia varied in severity from mild to severe and the clinical characteristics were often non-specific. The six-point scoring system was not useful in predicting such Legionella pneumonia cases.

Legionella pneumophila Modulates Mitochondrial Dynamics to Trigger Metabolic Repurposing of Infected Macrophages.

The intracellular bacteria Legionella pneumophila encodes a type IV secretion system (T4SS) that injects effector proteins into macrophages in order to establish and replicate within the Legionella-containing vacuole (LCV). Once generated, the LCV interacts with mitochondria through unclear mechanisms. We show that Legionella uses both T4SS-independent and T4SS-dependent mechanisms to respectively interact with mitochondria and induce mitochondrial fragmentation that ultimately alters mitochondrial metabolism. The T4SS effector MitF, a Ran GTPase activator, is required for fission of the mitochondrial network. These effects of MitF occur through accumulation of mitochondrial DNM1L, a GTPase critical for fission. Furthermore mitochondrial respiration is abruptly halted in a T4SS-dependent manner, while T4SS-independent upregulation of cellular glycolysis remains elevated. Collectively, these alterations in mitochondrial dynamics promote a Warburg-like phenotype in macrophages that favors bacterial replication. Hence the rewiring of cellular bioenergetics to create a replication permissive niche in host cells is a virulence strategy of L. pneumophila.

Legionnaire's Disease in Compromised Hosts.

Legionnaire's disease (LD) is mainly reported in apparently immunocompetent patients. Among them, risk factors include chronic lung disease and smoking. However, LD is also well reported among immunocompromised patients, particularly those treated with anti-tumor necrosis factor alpha therapy, patients with hematological malignancy, and transplant patients. This article discusses the available data on immunity against Legionella spp, epidemiology, clinical presentation, diagnosis, and treatment of LD in immunocompromised patients.

Legionnaire's Disease: A Clinical Diagnostic Approach.

Legionnaire's disease is a nonzoonotic atypical pneumonia caused by Legionella sp that occurs sporadically or in outbreaks. Legionnaire's disease pneumonia is accompanied by several extrapulmonary clinical and laboratory findings. Rather than testing all pneumonias for Legionnaire's disease, the clinical challenge is to recognize the diagnostic significance of Legionnaire's disease's. The pretest probability of Legionnaire's disease is increased if several characteristic extrapulmonary findings are present. Similarly, if certain key findings are absent, Legionnaire's disease may be eliminated from further diagnostic consideration. If characteristic clinical findings are present, then specific tests should be ordered to confirm or rule out Legionnaire's disease.

Legionnaire's Disease and its Mimics: A Clinical Perspective.

Whenever the cardinal manifestations of a disorder occur in similar disorders, there is potential for a disease mimic. Legionnaire's disease has protean manifestations and has the potential to mimic or be mimicked by other community acquired pneumonias (CAPs). In CAPs caused by other than Legionella species, the more characteristic features in common with legionnaire's disease the more difficult the diagnostic conundrum. In hospitalized adults with CAP, legionnaire's disease may mimic influenza or other viral pneumonias. Of the bacterial causes of CAP, psittacosis and Q fever, but not tularemia, are frequent mimics of legionnaire's disease.

Autophagy Evasion and Endoplasmic Reticulum Subversion: The Yin and Yang of Legionella Intracellular Infection.

The gram-negative bacterial pathogen Legionella pneumophila creates a novel organelle inside of eukaryotic host cells that supports intracellular replication. The L. pneumophila-containing vacuole evades fusion with lysosomes and interacts intimately with the host endoplasmic reticulum (ER). Although the natural hosts for L. pneumophila are free-living protozoa that reside in freshwater environments, the mechanisms that enable this pathogen to replicate intracellularly also function when mammalian macrophages phagocytose aerosolized bacteria, and infection of humans by L. pneumophila can result in a severe pneumonia called Legionnaires' disease. A bacterial type IVB secretion system called Dot/Icm is essential for intracellular replication of L. pneumophila. The Dot/Icm apparatus delivers over 300 different bacterial proteins into host cells during infection. These bacterial proteins have biochemical activities that target evolutionarily conserved host factors that control membrane transport processes, which results in the formation of the ER-derived vacuole that supports L. pneumophila replication. This review highlights research discoveries that have defined interactions between vacuoles containing L. pneumophila and the host ER. These studies reveal how L. pneumophila creates a vacuole that supports intracellular replication by subverting host proteins that control biogenesis and fusion of early secretory vesicles that exit the ER and host proteins that regulate the shape and dynamics of the ER. In addition to recruiting ER-derived membranes for biogenesis of the vacuole in which L. pneumophila replicates, these studies have revealed that this pathogen has a remarkable ability to interfere with the host's cellular process of autophagy, which is an ancient cell autonomous defense pathway that utilizes ER-derived membranes to target intracellular pathogens for destruction. Thus, this intracellular pathogen has evolved multiple mechanisms to control membrane transport processes that center on the involvement of the host ER.

Cytomegalovirus Colitis in a Critically Ill Patient Following Severe Legionella Pneumonia with Multiple Organ Failure.

A 68-year-old man visited an emergency department complaining of dyspnea. He was diagnosed to have Legionella pneumonia with multiple organ failure. Although his multiple organ failure improved, he suffered from persistent abdominal pain and diarrhea with continuous minor bleeding. Colonoscopy revealed a longitudinal ulcer of the rectum, below the peritoneal reflection. He was diagnosed with cytomegalovirus (CMV) colitis. Antiviral therapy with ganciclovir was initiated. He finally underwent a colostomy after a bowel stricture caused an intestinal outlet obstruction, which made oral intake impossible. Based on the present case, we believe that CMV colitis must be considered as one of the differential diagnoses when critically ill patients develop continuous diarrhea and abdominal pain.

Legionella: virulence factors and host response.

PURPOSE OF REVIEW: Legionella pneumophila is a facultative intracellular pathogen and an important cause of community-acquired and nosocomial pneumonia. This review focuses on the latest literature examining Legionella's virulence strategies and the mammalian host response. RECENT FINDINGS: Recent studies identify novel virulence strategies used by L. pneumophila and new aspects of the host immune response to this pathogen. Legionella prevents acidification of the phagosome by recruiting Rab1, a host protein. Legionella also blocks a conserved endoplasmic reticulum stress response. To access iron from host stores, L. pneumophila upregulates more regions allowing vacuolar colocalization N. In response to Legionella, the host cell may activate caspase-1, caspase-11 (mice) or caspase-4 (humans). Caspase-3 and apoptosis are activated by a secreted, bacterial effector. Infected cells send signals to their uninfected neighbors, allowing the elaboration of inflammatory cytokines in trans. Antibody subclasses provide robust protection against Legionella. SUMMARY: L. pneumophila is a significant human pathogen that lives in amoebae in the environment but may opportunistically infect the alveolar macrophage. To maintain its intracellular lifestyle, Legionella extracts essential iron from the cell, blocks inflammatory responses and manipulates trafficking to avoid fusion with the lysosome. The mammalian host has counter strategies, which include the release of proinflammatory cytokines, the activation of caspases and antibody-mediated immunity.

Complex clinical and microbiological effects on Legionnaires' disease outcone; A retrospective cohort study.

BACKGROUND: Legionnaires' disease (LD) is associated with high mortality rates and poses a diagnostic and therapeutic challenge. Use of the rapid urinary antigen test (UAT) has been linked to improved outcome. We examined the association between the method of diagnosis (UAT or culture) and various clinical and microbiological characteristics and outcome of LD. METHODS: Consecutive patients with pneumonia and confirmation of Legionella infection by a positive UAT and/or a positive culture admitted between the years 2006-2012 to a university hospital were retrospectively studied. Isolated L. pneumophila strains were subject to serogrouping, immunological subtyping and sequence-based typing. Variables associated with 30-day all-cause mortality were analyzed using logistic regression as well as cox regression. RESULTS: Seventy-two patients were eligible for mortality analyses (LD study group), of whom 15.5 % have died. Diagnosis based on positive L. pneumophila UAT as compared to positive culture (OR = 0.18, 95 % CI 0.03-0.98, p = 0.05) and administration of appropriate antibiotic therapy within 2 hospitalization days as compared to delayed therapy (OR = 0.16, 95 % CI 0.03-0.90, p = 0.04) were independently associated with reduced mortality. When controlling for intensive care unit (ICU) admissions, the method of diagnosis became non-significant. Survival analyses showed a significantly increased death risk for patients admitted to ICU compared to others (HR 12.90, 95 % CI 2.78-59.86, p = 0.001) and reduced risk for patients receiving appropriate antibiotic therapy within the first two admissions days compared to delayed therapy (HR 0.13, 95 % CI 0.04-0.05, p = 0.001). Legionella cultures were positive in 35 patients (including 29 patients from the LD study group), of whom 65.7 % were intubated and 37.1 % have died. Sequence type (ST) ST1 accounted for 50.0 % of the typed cases and ST1, OLDA/Oxford was the leading phenon (53.8 %). Mortality rate among patients in the LD study group infected with ST1 was 18.2 % compared to 42.9 % for non-ST1 genotypes (OR = 0.30, 95 % CI 0.05-1.91, p = 0.23). CONCLUSIONS: The study confirms the importance of early administration of appropriate antibiotic therapy and at the same time highlights the complex associations of different diagnostic approaches with LD outcome. Infection with ST1 was not associated with increased mortality. Genotype effects on outcome mandate examination in larger cohorts.

Precipitation increases the occurrence of sporadic legionnaires' disease in Taiwan.

Legionnaires' disease (LD) is an acute form of pneumonia, and changing weather is considered a plausible risk factor. Yet, the relationship between weather and LD has rarely been investigated, especially using long-term daily data. In this study, daily data was used to evaluate the impacts of precipitation, temperature, and relative humidity on LD occurrence in Taiwan from 1995-2011. A time-stratified 2:1 matched-period case-crossover design was used to compare each case with self-controlled data using a conditional logistic regression analysis, and odds ratios (ORs) for LD occurrence was estimated. The city, gender and age were defined as a stratum for each matched set to modify the effects. For lag day- 0 to 15, the precipitation at lag day-11 significantly affected LD occurrence (p<0.05), and a 2.5% (95% CIs = 0.3-4.7%) increased risk of LD occurrence was associated with every 5-mm increase in precipitation. In addition, stratified analyses further showed that positive associations of precipitation with LD incidence were only significant in male and elderly groups and during the warm season ORs = 1.023-1.029). However, such an effect was not completely linear. Only precipitations at 21-40 (OR = 1.643 (95% CIs = 1.074-2.513)) and 61-80 mm (OR = 2.572 (1.106-5.978)) significantly increased the risk of LD occurrence. Moreover, a negative correlation between mean temperature at an 11-day lag and LD occurrence was also found (OR = 0.975 (0.953-0.996)). No significant association between relative humidity and LD occurrence was identified (p>0.05). In conclusion, in warm, humid regions, an increase of daily precipitation is likely to be a critical weather factor triggering LD occurrence where the risk is found particularly significant at an 11-day lag. Additionally, precipitation at 21-40 and 61-80 mm might make LD occurrence more likely.

[Clinical manifestations of Legionella pneumonia in hematology patients].

AIM: To detect the most common clinical manifestations of Legionella pneumonia (LP) in immunocompromized patients. SUBJECTS AND METHODS: Clinical manifestations, the results of investigation of bronchoalveolar lavage fluid (BALF) and urine, and the data of lung computed tomography (CT) were studied in patients with blood system diseases and acute respiratory failure (ARF). RESULTS: The diagnosis of LP was verified in 8 (10.5%) of 76 patients with blood system diseases and ARF. The disease manifested as fever, higher concentrations of inflammatory markers (procalcitonin, fibrinogen), ARF, hypoxemia, and infiltrative lung injury. Six of the 8 patients were switched to mechanical ventilation. Lung CT showed no pathognomonic signs. Five of the 8 patients were observed to have renal dysfunction. The diagnosis of LP was made on the basis of the results of BALF examination in 7 patients and urinary antigen detection in 1. The disease was caused by Legionella pneumophila serogroup 1 in 3 patients and by L. pneumophila of other serogroups in the other patients. Therapy with respiratory fluoroquinolones was performed in 5 patients. Three patients died from progressive ARF and hypoxemia. BALF results were obtained after their death and therapy for legionellosis was not initiated. CONCLUSION: The incidence of LP is 10.5% in hematology patients. The clinical manifestations of legionellosis are nonspecific; its diagnosis requires bacteriological and/or serological evidence. Due to the high risk of death, it is reasonable to preuse respiratory fluoroquinolones or macrolides in immunocompromized patients with progressive ARF and suspected Legionella pneumonia before diagnosis.

[A case of Legionnaires' infection with meningeal irritation and abnormal cerebrospinal fluid].

A 60-year-old man was admitted to our hospital because of fever and mental status change. Neurological examination showed meningeal irritation and frontal sign. Cerebrospinal fluid (CSF) examination showed mild pleocytosis and elevated protein. Laboratory findings showed hyponatremia, elevated liver enzymes and creatine phosphokinase, and positive Legionella pneumophila antigen in urine. The chest computed tomographic scans showed consolidation in the left lower lobe lung. We diagnosed Legionnaires' pneumonia and started treatment with levofloxacin. Legionella pneumophila was isolated from culture of the bronchoalveolar lavage fluid, but Legionella culture and polymerase chain reaction in CSF were negative. We hypothesize that Legionella pneumophila could produce nerological symptoms by immune-mediated mechanism associated with elevated IgG index. The neurologist should recognize the presence of the meningo-encephalitis associated with Legionnaires' pneumonia lacking remarkable pulmonary symptoms.

Lethal Legionella infection in an immunocompromised child: first reported case in the Middle East.

Legionnaires disease continues to be underreported in the Middle East--a reflection of underdiagnosis, both clinically and by laboratory investigations. We draw the attention to this unusual cause of occasionally fatal, yet severe, pneumonia by reporting an immunocompromised infant who succumbed to Legionella pneumophila pneumonia. The urinary test for Legionella antigen was positive, and this was then confirmed by a bronchoalveolar fluid culture. Moreover we have reviewed the incidence, pathophysiology, association with immunodeficiency, diagnostic tools, and treatment in this case report.

Severe Legionnaire's disease caused by Legionella longbeachae in a long-term renal transplant patient: the importance of safe living strategies after transplantation.

Legionella species are intracellular gram-negative bacilli that require specific culture media for growth. Transplant recipients with impaired cellular immunity are at particular risk for infection with this pathogen. Most human disease is caused by Legionella pneumophila; disease caused by non-L. pneumophila species is reported mainly in immunosuppressed patients with the exception of Legionella longbeachae. L. longbeachae is a common cause of Legionnaires' disease in Australia and New Zealand, and is associated with exposure to potting soil. We report the case of a patient, 26 years post kidney transplant, who presented with severe and rapidly progressive respiratory illness. L. longbeachae serogroup 1 was isolated from respiratory cultures. Further investigation revealed that she had significant soil exposure before the onset of illness. We highlight the importance of following safe living strategies to prevent exposure-related illness even in long-term transplant recipients.