How long should I expect Legionella urine antigen test to remain positive after diagnosis of legionnaire’s disease in my patient with pneumonia?

The urine antigen test for detection of Legionnaire’s disease (LD) can remain positive for weeks or months after initial infection. So a positive test in a patient with pneumonia may not just be suggestive of an acute infection but also the diagnosis of LD during recent weeks or months (1,2).

In a study of Legionella urine antigen detection as a function of days after onset of symptoms, 11 of 11 (100%) patients tested remained positive after day 14 (1). In the same study, 10 of 23 (43%) patients excreted antigen for 42 days or longer following initiation of therapy, with some patients remaining positive for more than 200 days!

In another study involving 61 patients with Legionella pneumophila pneumonia, 25% excreted Legionella antigen for 60 or more days (2). Longer duration of antigen excretion was significantly associated with immunosuppressed patients in whom the time to resolution of fever was > 72 h.

The long duration of excretion of Legionella antigen in urine following LD is not surprising. Pneumococcal pneumonia has also been associated with prolonged antigen excretion, some for as long as 6 months after diagnosis of pneumonia (3). It is thought that some microbial polysaccharides may be degraded very slowly or not at all by mammalian tissues which could explain their prolonged appearance in the urine long after active infection has resolved (1).

Bonus pearl: Did you know that the sensitivity of Legionella urinary antigen for LD varies from 94% for travel-associated infections to 76%-87% for community-acquired infection, and to as low as ~45% for nosocomially-acquired infections (4)?

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References

  1. Kohler RB, Winn WC, Wheat J. Onset and duration of urinary antigen excretion in Legionnaires disease. J Clin Microbiol 1984;20:605-7. https://pubmed.ncbi.nlm.nih.gov/6490846/
  2. Sopena N, Sabria M, Pedro-Bolet ML, et al. Factors related to persistence of Legionella urinary antigen excretion in patients with legionnaire’s disease. Eur J Clin Microbiol Infect Dis 2002;21:845-48. https://europepmc.org/article/med/12525918
  3. Andreo F, Prat C, Ruiz-Manzano J, et al. Persistence of Streptococcus pneumoniae urinary antigen excretion after pneumococcal pneumonia. Eur J Clin Microbiol Infect Dis 2009;28:197-201. https://pubmed.ncbi.nlm.nih.gov/18830727/
  4. Helbig JH, Uldum SA, Bernander S, et al. Clinical utility of urinary antigen detection for diagnosis of community-acquired, travel-associated, and nosocomial Legionnaire’s disease. Clin Microbiol 2003;41:838-40. https://pubmed.ncbi.nlm.nih.gov/12574296/

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

How long should I expect Legionella urine antigen test to remain positive after diagnosis of legionnaire’s disease in my patient with pneumonia?

How should I interpret a positive urine pneumococcal antigen when my suspicion for pneumococcal disease is very low?

The popular urine pneumococcal antigen (UPA) (based on the C-polysaccharide of Streptococcus pneumoniae cell wall) has been a valuable diagnostic tool in diagnosing invasive pneumococcal infections, but may be associated with up to nearly 10% rate of false-positivity in hospitalized patients1.  Three factors have often been cited as the  cause of false-positive UPA results: a. Nasopharyngeal carriage; b.Prior invasive pneumococcal infection and;  c. Pneumococcal vaccination.

Among adults with nasopharyngeal carriage of S. pneumoniae, particularly those with HIV infection, 12-17% of positive UPA tests may be false-positive1. In patients with recent invasive pneumococcal disease, UAP may remain positive in over 50% of patient at 1 month and about 5% at 6 months1,2.

Among persons receiving the 23-valent polysaccharide pneumococcal vaccine (PPV), over 20% may have a positive UPA up to 30 hours following immunization, some potentially longer1.  In fact, the manufacturer of UPA assay recommends that UPA not be obtained within 5 days of receiving PPV. There is reason to believe that conjugated pneumococcal vaccine may be associated with the same phenomenon3.

So in a hospitalized patient with low suspicion for pneumococcal disease but a positive UAP, it would be wise to first exclude the possibility of PPV administration earlier during hospitalization before the sample was obtained1,4.

 

References

  1. Ryscavage PA, Noskin GA, Bobb A, et al. Incidence and impact of false-positive urine pneumococcal antigen testing in hospitalized patients. S Med J 2011;104:293-97.
  2. Andre F, Prat C, Ruiz-Manzano J, et al. Persistence of Streptococcus pneumoniae urinary antigen excretion after pneumococcal pneumonia. Eur J Clin Microbiol Infect Dis 2009;28:197-201.
  3. Navarro D, Garcia-Maset Leonor, Gimeno C, et al. Performance of the Binax NOW Streptococcus pneumoniae urinary assay for diagnosis of pneumonia in children with underlying pulmonary diseases in the absence of acute pneumococcal infection. J Clin Microbiol 2004; 42: 4853-55.
  4. Song JY, Eun BW, Nahm MH. Diagnosis of pneumococcal pneumonia: current pitfalls and the way forward. Infect Chemother 2013;45:351-66.

 

How should I interpret a positive urine pneumococcal antigen when my suspicion for pneumococcal disease is very low?