Sunday, October 23, 2011

Life after leptospirosis, a pilot study

The signs and symptoms associated with acute human leptospirosis are well known.  Less is known about how well patients manage after they begin recovering from the illness.  Most who survive the illness, even those who had severe illness, appear to regain full health eventually.  However careful examination may reveal subtle deficiencies in organ function.2  Moreover the spectrum of health problems that could crop up later is not known.  The only late complication of leptospirosis that has been well documented is uveitis, which can lead to eye pain and vision problems.3  Old case studies have also reported recurring headaches, general malaise, and even dementia, aggression, depression, and psychosis in those surviving leptospirosis,4,5 although these observations would need to be confirmed in well-designed clinical studies.

To gain a better understanding of the long-term outcomes of leptospirosis, a large systematic study is needed to monitor the health of leptospirosis patients as they heal from the illness.  Such a study was attempted by Spichler and colleagues.1  Their pilot study targeted patients hospitalized with leptospirosis at any time from December 2008 to May 2009 in São Paulo, Brazil, where leptospirosis is endemic.  There were 180 patients hospitalized with leptospirosis during this period, but for a variety of reasons only 47 of the 180 could be enrolled in the study.  All 47 had been treated for at least seven days with antibiotics (penicillin or ceftriaxone) during their hospitalization, and all had their diagnosis confirmed by serologic testing.  17 of the 47 had severe leptospirosis, defined as those who had experienced jaundice, kidney failure, bleeding (hemorrhage), pulmonary (lung) involvement, or shock while hospitalized.  Fortunately no patient died.

The first outpatient visit was conducted an average of 22 ± 12 days after the patients were discharged from the hospital.  23 of the 47 (49%) continued to experience one or more of the following health problems:  general malaise, headache, muscle pain, dizziness, bronchitis, and abdominal pain.  Three patients still had jaundice.

Only 22 of the 47 patients came back for a second visit, which took place a mean of 40 ± 21 days after they were discharged from the hospital.  Two of the 22 patients continued to suffer from medical problems.

One individual was experiencing general malaise, which wasn't a problem for him before being stricken with leptospirosis.  He did always have high blood pressure, which may or may not have been a contributing factor to his malaise. An ECG showed some abnormalities with his heartbeat.  Leptospira is known to cause myocarditis, an inflammation of the heart muscle.  This patient continued to suffer from profound general malaise when examined one year later.

The second patient started to experience panic attacks between the two clinic visits.  Were the panic attacks related to his earlier bout with leptospirosis?  It's difficult to conclude anything from this single patient.  Although the patient had severe leptospirosis, did not suffer from any of the known neurologic features of leptospirosis during his acute illness6 and had not been diagnosed with any neurologic or psychiatric condition before contracting leptospirosis.  Panic disorder has never been described in leptospirosis patients in the scientific literature.

Since this was a pilot study, the investigators probably lacked the resources to address the problems that cropped up during the study.  As pointed out by the authors, the major limitations of the study were that few of the eligible patients were enrolled in the study and that many dropped out between visits, resulting in a potentially biased sampling of leptospirosis patients. Additionally the follow-up visits did not include any laboratory testing to detect lingering functional deficiencies in the kidney, liver, and other organs.  For these reason it's impossible to make any definitive conclusions about the recovery of these subjects.  Despite the preliminary nature of this pilot study, the possible outcomes of acute leptospirosis identified in this study and earlier case studies beg for a future prospective study with a larger number of individuals living in an area where leptospirosis is endemic.  A longer time frame for follow up is also necessary since uveitis can first appear up to four years after recovery from leptospirosis.3

Any future study should also follow those with mild or asymptomatic Leptospira infections.  The reason is that the long-term outcome of mild disease is unknown.  Since those with mild or asymptomatic infections are unlikely to seek medical attention, identifying such individuals will require investigators to monitor healthy high-risk individuals by serologic testing so that the newly infected could be identified as those with increasing anti-Leptospira antibody titers.

In light of the recent discovery of chronically infected individuals in the Peruvian Amazon,7 it would also be prudent to test the urine of healthy individuals for Leptospira being shed from the kidney tubules so that the findings of the Peruvian study could be confirmed.  The long-term effects of chronic infection, if any, could also be identified.

Where could a future study examining the long-term outcomes of Leptospira infection be conducted?  Brazil and India may be best suited for this type of study.  Leptospirosis is highly endemic in those countries, and multiple research teams are already investigating the epidemiology of leptospirosis in those countries.

10-30-2011, edits for clarity.

Featured paper

1.  Spichler A., Athanazio D, Seguro AC, and Vinetz JM (July 2011).  Outpatient follow-up of patients hospitalized for acute leptospirosis.  International Journal of Infectious Diseases 15(7):e486-e490.  DOI:  10.1016/j.ijid.2011.03.020

References

2.  de Francesco Daher E, Zanetta DMT, and Abdulkader RCRM (September 2004).  Pattern of renal function recovery after leptospirosis acute renal failure.  Nephron, Clinical Practice 98(1):c8-c14.  DOI: 10.1159/000079922

3.  Shukla D, Rathinam SR, and Cunningham ET (Spring 2010).  Leptospiral uveitis in the developing world.  International Ophthalmology Clinics 50(2):113-124.  DOI:

4.  Shpilberg O, Shaked Y, Maier MK, Samra D, and Samra Y (April 1990).  Long-term follow-up after leptospirosis.  Southern Medical Journal 83(4):405-407.  Link

5.  Avery TL (July 27, 1983).  Leptospirosis and mental illness.  New Zealand Medical Journal 96(736):589 (Letter).

6.  Panicker JN, Mammachan R, and Jayakumar RV (September 2001).  Primary neuroleptospirosis.  Postgraduate Medical Journal 77(911):589-590. DOI: 10.1136/pmj.77.911.589

7. Ganoza CA, Matthias MA, Collins-Richards D, Brouwer KC, Cunningham CB, Segura ER, Gilman RH, Gotuzzo E, and Vinetz JM (2006). Determining risk for severe leptospirosis by molecular analysis of environmental surface waters for pathogenic Leptospira. PLoS Medicine 3(8):e308.  DOI: 10.1371/journal.pmed.0030308

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