September Case 2021

Miguel Gonzalez Mancera, MD (Resident), Margie Morgan, PhD (Faculty)

The patient is a male in his 70s with past medical history of myelodysplastic syndrome (MDS), who underwent haplo-peripheral blood stem cell transplant (PBSCT). He presented to the emergency department in three months later, day +81 post-transplant, complaining of excessive fatigue, fever, and lethargy for 2 days. The patient denied chest pain or shortness of breath.

Initial laboratory reports showed a white blood cell count of 1.25x103/UL, hemoglobin of 10.4 g/dL, and platelet count of 13x103/UL. The patient's electrolytes showed a sodium of 123 mmol/L, and a potassium of 5.5 mmol/L. Imaging studies revealed unremarkable head CT scan, and chest x-ray was remarkable for a large opacity in the right middle lung concerning for pneumonia. 

The patient was treated empirically with antibiotics and normal saline to correct his hyponatremia. Legionella pneumophila antigen was subsequently detected in urine, and he was discharged on azithromycin after 3 days of hospital course.

Legionella spp are Gram-negative bacteria, ubiquitous in natural aquatic environments and frequently associated with contaminated man-made water systems. It often causes a severe and potentially fatal form of bacterial pneumonia known as Legionnaires' disease or Legionellosis.

Although there are several species of Legionella, L. pneumophila is the most commonly identified, accounting for 79% of culture-confirmed cases. The organism multiplies within human monocytes and macrophages, and cell-mediated immunity is the primary host defense mechanism against the infection. Several risk factors include advanced age, male sex, smoking, chronic cardiovascular disease, diabetes mellitus, alcohol abuse, and malignancy. 

Legionella colonies grow on various solid-selective and non-selective media, with Buffered Charcoal Yeast Extract (BCYE) agar being most used. Colonies are usually detectable after days 3-5 of incubation, however, urinary antigen detection has become the first-line diagnostic test. This antigen test is limited to the detection of L. pneumophila serogroup 1 (Lp1), which is the most virulent and most common species. Hyponatremia, however, not specific for this infection, it is far more common in Legionellosis.

This disease is rare, accounting for only 2-9% of cases of community acquired pneumonia, but immunocompromised patients, particularly with cancer and transplant recipients, are at significantly increased risk. This might be due to impaired cellular immunity that contributes to reduced clearance of Legionella and to a higher risk of nosocomial transmission due to long term hospital admission. 

In a study done by Mikulska et al, 80 cases of legionellosis after hematopoietic stem cell transplant (HSCT) were reported, revealing a median time from HSCT to legionellosis of 203

days. In that study, predictors of legionellosis were allogeneic HSCT, and recent other infection. In our current report, we are not aware of any predictors of legionellosis; however, the patient falls within the time frame for the development of the disease. 

As far as prevention of nosocomial infections is concerned, routine microbial analyses of tab water and use of point-of-use filtration might protect the vulnerable patients against nosocomial transmission of legionellosis. Additionally, future perspectives should include research into Legionella ecology to further understand its virulence and the disease risks of the different forms of the pathogen’s lifecycle and pathogenesis; the identification and assessment of the threat of Legionella in hot water systems along with adequate disinfection measures; improved water system maintenance; and recognizing the risks of even low counts of Legionella in drinking water for people who are immunocompromised.

1. European Centre for Disease Prevention and Control. Legionnaires’ disease. In ECDC. Annual epidemiological report for 2016. Stockholm: ECDC 2018.
2. Fields BS, Benson RF, Besser RE. Legionella and Legionnaires’ disease: 25 years of investigation. Clin Microbiol Rev. 2002;15: 506–26.
3. Mikulska M, Tridello G, Hoek J, Gil L, Yañez L, Labussière-Wallet H, Passweg J, Xhaard A, Pioltelli P, Caillot D, Michel G, Veelken H, Blaise D, Bruno B, Garcia CB, Itälä-Remes M, Crawley C, Bourhis JH, Kaare A, Arcese W, Parody R, Styczynski J. Legionellosis after hematopoietic stem cell transplantation. Bone Marrow Transplant. 2021 May 22.
4. Horwitz MA. Cell-mediated immunity in Legionnaires’ disease. J Clin Investig. 1983;71:1686–97.
5. Chow JW, Yu VL. Legionella: a major opportunistic pathogen in transplant recipients. Semin Respir Infect. 1998 Jun;13(2):132-9. 
6. Cunha BA, Burillo A, Bouza E. Legionnaires' disease. Lancet. 2016 Jan 23;387(10016):376-385.