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Abstract

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Declaration of Interests
  7. References

Background

Leptospirosis belongs to the spectrum of travel-related infections.

Methods

We retrospectively studied all the consecutive cases of travel-related leptospirosis seen in our department between January 2008 and September 2011. Patients were included with a clinical picture compatible with the disease within 21 days after return, the presence of a thermoresistant antigen or IgM antibodies, Elisa ≥ 1 /400, and a positive microagglutination test (MAT) ≥ 1/100.

Results

Fifteen leptospirosis cases were evaluated. Exposure occurred in Asia (47%), Africa (20%), the Caribbean (20%), and Indian Ocean (13%). Fourteen patients were infected during water-related activities. On admission the most frequent symptoms were fever (100%), headache (80%), and digestive disorders (67%). Relevant laboratory findings included impaired liver function tests (100%), lymphocytopenia (80%), thrombocytopenia (67%), and elevated C-reactive protein (CRP) (67%). Our cases were confirmed by MAT that found antibodies against nine different serovars. Seven patients were cured with amoxicillin, four with doxycycline, two with ceftriaxone, one with ceftriaxone, doxycycline, and spiramycin, whereas one recovered spontaneously (retrospective diagnosis). Eight patients were hospitalized. All patients recovered.

Conclusion

Our cases involved nine different serovars. They were related to travel in Asia, Africa, and the Caribbean. Bathing or other fresh-water leisure activities (canoeing, kayaking, rafting) are the most likely at-risk exposure. Any traveler with fever and at-risk exposure should be investigated for leptospirosis.

Leptospirosis is a bacterial zoonosis which is widespread throughout the world. Its main sources are rodents, particularly rats, which excrete the spirochete (Leptospira spp) in urine. Humans are infected by direct contact with urine of infected animals or by contact with an infected environment such as surface water. The disease is increasingly reported in travelers, particularly those travelling to tropical areas, due to the development of fresh-water sports and leisure activities such as fishing, rafting, canoeing, kayaking, scrambling, etc.

However, leptospirosis remains an uncommon cause of illness in travelers. Even when focusing on the causes of fever in travelers returning from a tropical area, only 0% to 1.2% of cases were diagnosed with leptospirosis.[1-3] In these three series, 5.5% to 24% of the febrile travelers were considered as having fever of unknown origin. It is therefore possible that leptospirosis was underdiagnosed.

A few sporadic cases of leptospirosis in returning travelers have been reported.[4, 5] Two case series were found at a national level, reporting leptospirosis in returning travelers.[6, 7] Leshem et al. reviewed 48 cases of travel-related leptospirosis seen in Israel between 2002 and 2008, while Van Crevel et al. reported 32 such cases in the Netherlands between 1987 and 1991. The goals of our study were to better evaluate the epidemiological, clinical, and laboratory characteristics of the patients diagnosed with travel-related leptospirosis.

Patients and Methods

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Declaration of Interests
  7. References

All consecutive travel-related cases of leptospirosis that were diagnosed in the Department of Maladies Infectieuses et Tropicales, Hôpital de la Pitié-Salpêtrière, Paris between January 2008 and September 2011 were included. The diagnosis of leptospirosis relied on the following criteria: (1) a clinical picture compatible with the disease occurring within 21 days after return, (2) the presence of a thermoresistant antigen[8] or IgM antibodies, Elisa ≥ 1/400[9], and (3) a positive microagglutination test (MAT) ≥ 1/100.[10] When possible, serogroups were confirmed by MAT. All serology testing except one (done at Biomnis) was carried out at the Pasteur Institute in Paris, National Reference Centre for Leptospirosis, using MAT (Table 1).

Table 1. Antigens used in MAT
  1. MAT was performed at the National Reference Center for Leptospirosis (Institut Pasteur, Paris, France).

Australis (serovar Australis)
Autumnalis (serovar Autumnalis)
Bataviae (serovar Bataviae)
Canicola (serovar Canicola)
Ballum (serovar Castellonis)
Cynopteri (serovar Cynopteri)
Grippotyphosa (serovar Grippotyphosa)
Sejroe (serovars Hardjo and Sejroe)
Hebdomadis (serovar Hebdomadis)
Icterohaemorrhagiae (serovars Icterohaemorrhagiae and Copenhageni)
Panama (serovar Panama)
Pomona (serovar Pomona)
Pyrogenes (serovar Pyrogenes)
Tarassovi (serovar Tarassovi)
Nonpathogen serogroup Semaranga (serovar Patoc)

Patient files were retrospectively analyzed to collect demographic, epidemiological, clinical, and laboratory characteristics, as well as data concerning the at-risk exposure. At-risk activities included bathing in fresh water; fresh-water sports (canoeing, rafting, kayaking, etc.); contact with animals or their urine; and activities such as gardening, hunting, and fishing. Leukocytosis was defined as white blood cells (WBCs) > 12 × 109/L, lymphocytopenia as lymphocytes < 1,500 × 109/L, and thrombocytopenia by platelet count < 150 × 109/L. Impaired liver function tests (LFTs) were defined by the rise of alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) up to twice the normal values. Cholestasis was defined by rise of alkaline phosphatasis and/or gamma-glutamyl transferase superior to twice the normal values. Patients were treated according to the clinical picture and the treating physician. We followed up patients until the resolution of symptoms.

Results

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Declaration of Interests
  7. References

Fifteen cases of travel-related leptospirosis were included in this study. Nearly all patients (14/15) were men, mean age was 34 years [interquartile range (IQR): 28–52] (Table 2). All travelers except one were tourists. The infection was contracted primarily in Asia (47%). The mean duration of travel was 18 days (IQR: 15–32). The most frequent at-risk exposure was bathing in fresh water (10/15), followed by nautical sporting activities (kayaking, rafting, canoeing) in four cases. We found a history of skin wound in 3 of the 10 patients who had fresh-water exposure. In one patient who had stayed in a rural area, exposure was not established. Four patients, including one expatriate, developed symptoms before their return to France. In the 11 remaining patients, the average lag time between return to country of origin and onset of symptoms was 5 days (IQR: 2–7).

Table 2. Demographic and epidemiological characteristics of 15 cases of travel-related leptospirosis diagnosed at the Pitié-Salpêtrière Hospital (Paris) between January 2008 and September 2011
 Cases of leptospirosis, N = 15 (100%)
  • *

    Interval between return to country of origin and onset of symptoms, days (IQR).

Sex14 males; 1 female
Average age, years (IQR)34 (28–52)
Location where acquired 
Asia7 (47%)
Thailand5
Cambodia1
Indonesia1
Africa3 (20%)
Gabon1
Central African Republic1
Cameroon1
Caribbean3 (20%)
Guadeloupe1
Jamaica1
Martinique1
Indian Ocean2 (13%)
Réunion Island2
Average duration of travel, days (IQR)18 (15–32)
Exposure 
Fresh-water bathing10
Kayaking, rafting, canoeing4
Floods water contact1
Unknown1
History of wound3
Time of appearance*5 (2–7)

Fever (temperature >38°C) was found in all patients. Other signs and symptoms included were headache (80%), digestive disorders (67%) (nausea and/or vomiting, diarrhea), myalgias (53%), and arthralgias (47%). Exanthema, jaundice, and hepatosplenomegaly were observed in 20% of patients. Conjunctival suffusion, macroscopic hematuria, and hemoptysis were rarely observed (7%).

Table 3 shows laboratory results. Elevation of LFTs was present in 100% of patients [average values: ASAT = 93 IU/L (3N), ALAT = 137 IU/L (4N)]. The majority of patients had thrombocytopenia (average thrombocyte levels: 93,809/L), lymphocytopenia (average value: lymphocytes = 694/L) together with moderate renal impairment (average value: creatinine = 193 µmol/L (2N).

Table 3. Laboratory characteristics of 15 cases of travel-related leptospirosis
 Cases of leptospirosis, N = 15
  1. CRP = C-reactive protein; LFTs = liver function tests; CPK = creatinine phosphokinase.

Blood tests 
Elevation of LFTs15 (100%)
Lymphocytopenia12 (80%)
Thrombocytopenia10 (67%)
Elevation of CRP10 (67%)
Renal impairment8 (53%)
Cholestasis6 (40%)
Anemia4 (27%)
Leukocytosis4 (27%)
Elevation of CPK3 (20%)
Leukocytopenia2 (13%)
Urine tests 
Microscopic hematuria8 (53%)
Leukocyturia6 (40%)
Proteinuria3 (20%)
Hemoglobinuria2 (13%)

Antibodies to specific serovars were identified in 13 cases out of 15 (87%): Leptospira sejroe serovar Hardjobovis (n = 3; 1/400, 1/1600, 1/400), Leptospira cynopteri (n = 1; 1/800), Leptospira bataviae (n = 1; 1/1,600), Leptospira grippotyphosa (n = 2; 1/400,1/6,400), Leptospira hebdo (n = 1; 1/200), Leptospira javanica (n = 1; 1/800), Leptospira icterohaemorrhagiae (n = 1; 1/200), Leptospira tarrassovi (n = 2; 1/1,600, 1/6,400), Leptospira canicola (n = 1; 1/800).

Hospitalization was required for eight patients (53%). Seven patients (47%) were treated with amoxicillin (1–2 g, three to four times per day for 7–15 days), including four treated with amoxicillin alone, two with amoxicillin and ceftriaxone (because of meningitis), and one with amoxicillin plus spiramycin (because of pneumonia). The other seven treated patients were given doxycycline (n = 4), 200 mg/day for 10 days, ceftriaxone (n = 2) 1 g/day for 10 days or a combination of ceftriaxone, doxycycline, and spiramycin because of severe disease with acute renal failure and pulmonary involvement. One patient was not treated due to delayed diagnosis (6 months). All patients recovered without sequelae within 10 to 15 days.

Discussion

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Declaration of Interests
  7. References

Whereas most studies have described cases of leptospirosis occurring during an outbreak, this study describes a series of travel-related leptospirosis cases. Our cases were also confirmed by MAT that is not only sensitive and specific but also enables the determination of serogroups as it uses antigens of 17 different Leptospira serovars (Table 1). Nine different serovars were thus identified in this series.

Travel represents the main sources of leptospirosis in nonendemic areas.[6, 11-14] In our experience (data not showed), 84% of the cases of leptospirosis diagnosed in the department in Paris between January 2008 and September 2011 were linked to travel in the tropics. In contrast, in endemic areas travel represents a less frequent but still significant source of leptospirosis. In Israel, a country endemic for leptospirosis, of 48 cases of leptospirosis diagnosed between 2002 and 2008, 42% were travel related.[7] In the Netherlands, of 237 cases of leptospirosis diagnosed between 1987 and 1991, 14% were travel related.[6] In a western part of France also endemic for leptospirosis, of 34 patients seen over a period of 10 years, only 6% were related to travel.[15]

The most striking result was a history of at-risk exposure in Africa in 20% of our cases. Indeed, most travel-related leptospirosis cases have been described after travel to Asia, the Caribbean, and Central and South America.[4-6, 15] The incidence of leptospirosis in Africa is unknown. Travelers as epidemiological sentinel point toward this risk in Africa. An epidemic of leptospirosis in Kenya in 2004 also suggests that the disease is present but underdiagnosed.[16] Moreover, a study found a seroprevalence of 15% for leptospirosis in a population of five villages in the northeastern Gabon (Africa).[17] Overall, these recent studies clearly indicate that leptospirosis is underdiagnosed in Africa.

Our epidemiological results are in agreement with those found in other series, with a predominance of males,[18] at-risk fresh-water exposure such as bathing and practicing sports (canoeing, kayaking, rafting), together with a history of skin lesions[19] and high levels of hospitalization. In contrast with those studies, we did not find a predominance of the icterohemorragic serogroup but a large number of serogroups were involved. This indicates the wide diversity of the serogroups responsible for leptospirosis in travelers.

The clinical picture is in agreement with that described in the literature with, in order of frequency, fever, headache, digestive disorders (vomiting, diarrhea, and nausea) myalgias, and arthralgias.[6, 7, 20] Laboratory results were also concordant with those found in the literature, with increased ASAT/ALAT, lymphocytopenia, thrombocytopenia, and renal impairment.[7, 12] We found a high frequency of lymphocytopenia (80%), a percentage higher than that usually reported in the literature, but similar to that found in another study.[15] Fourteen of the 15 patients received effective treatment, either amoxicillin (the most widely used, 47%), ceftriaxone, or doxycycline. Clinical outcome was good for all patients after 15 days.

The limitations of this study resided in its retrospective nature and the small number of cases. However, it may serve as a reminder to clinicians of epidemiological, clinical, and laboratory data associated with this uncommon but potentially lethal disease. It also shows that the risk would appear to be significant in Africa and that lymphocytopenia is a common feature of leptospirosis.

Declaration of Interests

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Declaration of Interests
  7. References

The authors state that they have no conflicts of interest.

References

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Declaration of Interests
  7. References