Clinical presentation of leptospirosis: a retrospective study of 34 patients admitted to a single institution in metropolitan France
Corresponding author and reprint requests: P. Tattevin, Infectious Diseases and Intensive Care Unit, Pontchaillou University Hospital, 35033 Rennes Cedex, France
Leptospirosis has a highly variable clinical presentation, which may be related to different infecting serovars, host factors, or a combination of these. This study investigated retrospectively 34 consecutive patients with serologically confirmed leptospirosis admitted during the period 1992–2002. On admission, the most frequent symptoms were fever (100%), headache (75%), myalgia (55%), arthralgia (45%) and vomiting (39%). Pertinent laboratory findings included lymphopenia (85%), thrombocytopenia (75%), elevated liver enzymes (87%) and renal abnormalities (proteinuria, 77%; haematuria, 58%; elevated serum creatinine, 53%). The study confirmed the variable clinical and biological symptoms of leptospirosis, and indicated that lymphopenia is a common feature of leptospirosis cases.
Leptospirosis is a worldwide zoonotic disease caused by spirochaetes of the genus Leptospira[1,2]. Human infections are endemic in most tropical and temperate climates. Leptospirosis has a highly variable clinical presentation, which may be related to different infecting serovars, host factors, or a combination of these [1–3]. Between 500 and 1000 cases occur each year in territories administered by France, mostly in tropical climates (West Indies, Polynesia, La Réunion, French Guyana, New Caledonia). However, metropolitan France has one of the lowest reported incidences of leptospirosis in western Europe (0.44 cases/100 000 population in 1998) .
Pontchaillou Hospital is a tertiary-care university-affiliated hospital which serves as a referral centre for Ille et Vilaine, a rural area of 900 000 inhabitants, with an estimated annual incidence of leptospirosis of 0.62/100 000 population . The present report describes a retrospective study of 34 consecutive patients with serologically confirmed leptospirosis admitted to Pontchaillou Hospital between 1992 and 2002.
Patients and methods
Case reports of leptospirosis between 1992 and 2002 were investigated. Cases were identified using the Leptospirosis Registry at the Department of Bacteriology, Hôpital Sud, Rennes. For a case to qualify as a confirmed case of leptospirosis, all three of the following criteria were required: (1) a clinically compatible illness; (2) the presence of thermo-resistant antigen  or an IgM antibody titre (ELISA) of at least 1:400 ; and (3) a positive microscopic agglutination test result, with a titre of at least 1:100 . These criteria are considered to be indicative of recent or current leptospirosis in areas with a low incidence .
Isolation of leptospires is not performed routinely at Pontchaillou University Hospital. As definitive identification is not possible with the microscopic agglutination test because of cross-agglutination or cross-reactivity between serovars or different serogroups, infecting serovars were identified presumptively on the basis of the serovar showing the highest titre at 1 month after the appearance of symptoms, but only for cases that demonstrated a four-fold increase in microscopic agglutination test titre between acute- and convalescent-phase sera [1–3]. If there was more than one serovar with the same high titre, the presumptive infecting serovar was designated as ‘indeterminate’. All serological tests were performed by the National Leptospirosis Reference Centre, Institut Pasteur, Paris, France.
A standardised case investigation form was used to compile demographical, epidemiological, clinical and laboratory data. To assess the possible source of exposure, patients were asked about high-risk activities that had occurred during the 30-day period before the onset of symptoms. These included exposure to rats or potentially contaminated fresh water through occupational activities (e.g., farming), recreational activities (e.g., canoeing, freshwater swimming, fishing, hiking) or home-based activities (e.g., gardening, trapping rats).
Cases of leptospirosis
In total, 34 cases of leptospirosis were confirmed serologically between 1992 and 2002, with males accounting for 28 (82%) cases. The median age of the infected patients was 43 years (SD 5.8 years; range 12–70 years). During the 30 days before the onset of symptoms, 24 (70%) patients reported high-risk activities, mostly recreational, including canoeing (n = 9), hunting or fishing (n = 6), farming or aquaculture (n = 5) and freshwater swimming (n = 4). Two patients probably acquired leptospirosis during travel outside France (Ivory Coast and China, one patient each).
Upon admission, the average body temperature of infected patients was 40°C (SD 0.3°C). The most common symptoms were headache (75%), myalgia (55%), arthralgia (45%) and vomiting (39%) (Table 1). Pertinent initial laboratory results included lymphopenia (85%), thrombocytopenia (75%) and evidence of hepatic abnormalities (87%) or renal abnormalities (proteinuria 77%, haematuria 58%, elevated serum creatinine 53%). All patients were hospitalised, with a median duration of 4 days after the first symptoms, in the infectious diseases unit (n = 17), the intensive care unit (ICU) (n = 5), the nephrology department (n = 4), the internal medicine department (n = 4), the hepatology department (n = 3) or the paediatrics department (n = 1).
Table 1. Characteristics of 34 confirmed cases of leptospirosis
| Fever > 38°C||100.0||31|
| Abdominal pain||34.3||32|
| Respiratory signsb||29.0||31|
|Urine strip test|
| Haemoglobin < 12 g/dL||25.0||32|
| WBC > 10 800/mm3||18.7||32|
| WBC < 4800/mm3||18.7||32|
| Lymphocytes < 1000/mm3||85.1||27|
| Platelet count < 150 000/mm3||75.0||32|
| Fibrinogen > 4 g/L||95.0||20|
| Creatinine > 120 µmol/L||53.3||30|
| ALAT > 40 IU/L||86.6||30|
| ASAT > 40 IU/L||83.3||30|
| Bilirubinaemia > 20 µmol/L||52.0||25|
| Rhabdomyolysis > 195 IU/L||47.1||17|
| WBC > 5/mm3||55.5||18|
| Neutrophils > 70%||22.2||9|
| Lymphocytes > 70%||11.1||9|
| Mixed cellularity||66.6||9|
| Proteinorachy > 1 g/L||22.2||9|
Results of serological testing
Initial serological testing for leptospirosis antibodies (ELISA) was positive for only 16 (47%) cases. Eventual presumptive infecting serovars for the 34 patients were Grippotyphosa (n = 10), Icterohaemorrhagiae (n = 5), Copenhageni (n = 4), Australis (n = 3), Cynopteri (n = 1) and indeterminate (n = 11).
Five (15%) patients were admitted to the ICU following acute renal failure that required dialysis (n = 2), diffuse alveolar haemorrhage and pulmonary artery hypertension (n = 1), congestive heart failure (n = 1) or encephalitis (n = 1). The median stay in the ICU was 6 days (range 3–10 days). Among these five patients, two were infected presumptively with Leptospira serovar Copenhageni. Thus, of the four patients infected presumptively with this serovar, 50% were admitted to the ICU, compared with three (10%) of the 30 patients infected presumptively with other serovars or an indeterminate serovar (not significant).
Treatment and outcome
Twenty-five (80%) patients received antibiotics, including 20 (60%) patients who received a β-lactam agent as first-line treatment. Three (15%) of these 20 patients had symptoms suggestive of a Jarish Herxeimer reaction following the first administration of the β-lactam agent. Other antibiotics prescribed included fluoroquinolones (n = 2), cyclines (n = 1), co-trimoxazole (n = 1) and macrolides (n = 1). Seven (22%) patients did not receive antibiotics. Data regarding antibiotic treatment were not available for two patients. All 34 patients made a full recovery.
Few studies have used consistent laboratory criteria that allow valid comparisons between the clinical and epidemiological patterns of leptospirosis in different populations. Most case series published to date have included patients without laboratory confirmation , or with less specific case definitions for the purpose of confirmation [10–17]. Such studies have been performed in the USA [3,9], Brazil , The Seychelles , New Caledonia , India , Israel  and Denmark . The present series comprised most patients admitted for leptospirosis within the catchment area of Pontchaillou Hospital between 1992 and 2002.
The symptoms reported in the present study were consistent with those reported in other series, with fever, headache, myalgia, arthralgia and vomiting being the most common presentations [1,9,10,14,15,18]. Rash was more frequent in this series (37.5%) than is usually reported. This could suggest that the clinical presentation of leptospirosis is somewhat different in the Pontchaillou area of France, but may also be related to differences in physicians' evaluations. The laboratory findings in the study were also similar to descriptions published elsewhere, with thrombocytopenia and elevated liver enzymes being common [1,3,11,13,19]. Urinalysis findings were frequently abnormal, with proteinuria and haematuria being observed in more than half of the patients. An elevated serum creatinine level appears to be one of the best diagnostic signs, as this is rather uncommon for most of the differential diagnoses (influenza-like illness, viral hepatitis, gastroenteritis or meningitis). In the present study, hyperleukocytosis was less frequent (18.7%) than reported previously [1,3,11,13,19]. The high frequency of lymphopenia (85.1%) is not a classical finding and does not appear to have been reported previously as a common feature of leptospirosis. It remains to be determined whether this finding is specific to leptospirosis in the Pontchaillou area, or whether previous series did not address this issue specifically.
With the numerous different manifestations of leptospirosis, clinicians must maintain a high index of suspicion in order to make the correct diagnosis. Moreover, initial serological testing is often negative (53% in this study), which is sometimes misinterpreted as an indication that a patient does not have leptospirosis.
Although leptospirosis has been categorised historically as an occupational illness of farmers, ranch hands and military personnel, there has been a temporal shift since the 1970s, with a decreasing incidence of occupational exposure and a concurrent increase in exposure linked to recreational activities [1,3]. In the present study, canoeing was the most frequent risk factor, reported for nine patients with leptospirosis during an 11-year period. However, the risk linked to this activity remained low in the context of the 1098 individuals registered as members of canoeing clubs in the Pontchaillou area in 2001.
Infection with serovars belonging to the Icterohaemorrhagiae serogroup has been reported to be associated with an increased severity of disease [3,14], and this was reflected in the present study by the relatively high proportion of patients infected presumptively with the serovar Copenhageni (belonging to the serogroup Icterohaemorrhagiae) who were admitted to the ICU. During an outbreak in Brazil with a high (15%) case fatality rate, Leptospira serovar Copenhageni was isolated from 87% of the cases with positive blood cultures . The retrospective design of the present study, the limited sample size, and the spontaneous recovery of the few patients who did not receive antibiotics, allowed no conclusions regarding the benefit of antibiotic treatment for leptospirosis. However, this study, conducted in a rural area of France, confirmed previous data regarding the protean clinical and biological manifestations of leptospirosis. The high frequency of lymphopenia (85% of patients in this series) has not been reported previously and could be a useful diagnostic sign.
Our special thanks go to G. Baranton from the National Reference Centre of Leptospirosis, Institut Pasteur, Paris.