Summary auto-generated
This case study describes leptospirosis in a 39-year-old HIV-positive patient who presented with fever, myalgia, arthralgia, and jaundice consistent with Weil's disease. Liver biopsy confirmed leptospirosis through histological findings of spiral bacteria. PCR analysis of blood detected Leptospira one day after admission, before antibodies appeared. Serological testing using microagglutination identified Leptospira interrogans serogroup Icterohaemorrhagiae as the causative agent. Investigation identified pet white domestic rats as the infection source; all four of the patient's rats tested positive for Leptospira by both PCR and bacterial culture. Molecular typing (MLVA) and serological analysis with monoclonal antibodies confirmed the rat isolates matched serovar Icterohaemorrhagiae or Copenhageni. The patient's HIV immunosuppression did not alter the clinical course or antibody response compared to non-immunosuppressed patients. This case represents the first documented severe leptospirosis from pet rats in an HIV-positive individual, highlighting a potential public health concern as pet rat ownership becomes increasingly popular.
Key findings
- Pet white domestic rats were confirmed as the source of leptospirosis infection in an HIV-positive patient through PCR, bacterial culture, and molecular typing of isolates
- PCR detection methods provided early diagnosis before seroconversion, with positive results on day one, while traditional serology took 5-7 days
- The causative agent was identified as Leptospira interrogans serovar Icterohaemorrhagiae, with isolates from all four pet rats showing identical molecular profiles
- The patient's severe HIV immunosuppression did not significantly alter the clinical presentation or immune response compared to immunocompetent patients with leptospirosis
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Abstract
1 Federal Institute for Risk Assessment (BfR), Department of Biological Safety, Unit for Molecular Diagnostic and Genetic, Diedersdorfer Weg 1, D-12277 Berlin, Germany
2 Charité, Campus Benjamin Franklin, Department for Infectious Diseases, Hindenburgdamm 30, 12203 Berlin, Germany
3 Charité, Campus Benjamin Franklin, Department for Pathology, Hindenburgdamm 30, 12203 Berlin, Germany
4 Robert Koch Institute (RKI), Department of Infectious Diseases Epidemiology, Seestraße. 10, 13353 Berlin, Germany
Correspondence
Beatriz Guerra
(beatriz.guerra{at}bfr.bund.de )
Leptospirosis is a re-emerging zoonotic disease that can be transmitted to humans by direct or indirect contact with the contaminated urine of infected animals (Levett, 2001). Rodents are an important reservoir of Leptospira (Faine et al., 1999; Levett, 2001). In Germany, leptospirosis is a notifiable disease with a low but increasing incidence (0.06 per 100 000 population, from 1998 to 2003) with 30–50 laboratory confirmed cases per year (Jansen et al., 2005). The microagglutination test (MAT) is the standard method for serological diagnosis (Levett, 2001; WHO, 2003), but antibodies are not detectable in blood until 5 to 7 days after the onset of symptoms (Levett, 2003).
Since leptospires are difficult to culture, several PCR methods have been used to facilitate early diagnosis (Gravekamp et al. 1993; Bal et al., 1994; Levett et al., 2005; Merien et al., 2005). In this study, white fancy rats (domestic albino Rattus norvegicus) were identified as the potential infection source for acute leptospirosis in a human immunodeficiency virus (HIV)-positive patient by using a combination of bacteriological, serological, histological and molecular methods.
A 39-year-old male patient was hospitalised due to a fever of sudden onset, myalgia, arthralgia and icterus, and Weil's disease was suspected. The patient was immunosuppressed due to an HIV-infection (824 CD3 cells µl–1, 250 CD4 cells µl–1 and 316 CD8 cells µl–1). Histological examination of a needle biopsy of the liver showed canalicular cholestasis and ballooning of hepatocytes by haematoxylin and eosin staining, and spiral-like bacteria by Warthin–Starry silver staining. These results confirmed the putative diagnosis of leptospirosis and helped to exclude HIV-related cholestasis (e.g. drug-induced hepatic injury or viral infection).
Blood samples taken 1 day after admission of the patient were analysed by Leptospira-specific PCR and bacterial culture. The sample gave positive results in a multiplex PCR with the G1/G2-B64I/II primers (Gravekamp et al., 1993; Bal et al., 1994) and classic PCR with the LipL32 F/B primers (Levett et al., 2005), generating amplicons of 285 and 423 bp, respectively. However, bacterial culture (Faine et al., 1999) was negative after 12 weeks, probably due to antibiotic treatment immediately after admission to the hospital. In a 9 month follow-up study, 6 sera were examined by MAT (Faine et al., 1999; WHO, 2003) performed with Leptospira strains belonging to 10 serogroups and 15 serovars (Table 1). The first antibodies in serum were demonstrated 1 week after admission of the patient, and the highest titre (1 : 3200 serovar Icterohaemorrhagiae) was found at day 21. Cross-reactions with the serovars Copenhageni (1 : 200) and Sejroe (1 : 100) were detected, especially in the acute phase of the illness. Such cross-agglutinations with M84 Sejroe after serovar Icterohaemorrhagiae, Canicola or Pomona infections have been described by others as well (Brem et al., 1995). These unspecific reactions disappear during infection, when antibodies against the real causative agent become more predominant (Levett, 2001, 2003). Consequently, the presumptive causal agent of the infection belonged to Leptospira interrogans serogroup Icterohaemorrhagiae, since only serovars Copenhageni and Icterohaemorrhagiae (both with titres of 1 : 400) reacted in the last samples taken 9 months after admission.