Background Renal carriage and shedding of leptospires is characteristic of carrier or maintenance animal hosts. Sporadic reports indicate that after infection, humans may excrete leptospires for extended periods. We hypothesized that, like mammalian reservoir hosts, humans develop asymptomatic leptospiruria in settings of high disease transmission such as the Peruvian Amazon. Methodology/Principal Findings Using a cross-sectional study design, we used a combination of epidemiological data, serology and molecular detection of the leptospiral 16S rRNA gene to identify asymptomatic urinary shedders of Leptospira. Approximately one-third of the 314 asymptomatic participants had circulating anti-leptospiral antibodies. Among enrolled participants, 189/314 (59%) had evidence of recent infection (microscopic agglutination test (MAT0 ≥1:800 or ELISA IgM-positive or both). The proportion of MAT-positive and high MAT-titer (≥1:800) persons was higher in men than women (p = 0.006). Among these people, 13/314 (4.1%) had Leptospira DNA-positive urine samples. Of these, the 16S rRNA gene from 10 samples was able to be sequenced. The urine-derived species clustered within both pathogenic (n = 6) and intermediate clades of Leptospira (n = 4). All of the thirteen participants with leptospiral DNA in urine were women. The median age of the DNA-positive group was older compared to the negative group (p≤0.05). A group of asymptomatic participants (“long-term asymptomatic individuals,” 102/341 (32.5%) of enrolled individuals) without serological evidence of recent infection was identified; within this group, 6/102 (5.9%) excreted pathogenic and intermediate-pathogenic Leptospira (75–229 bacteria/mL of urine). Conclusions/Significance Asymptomatic renal colonization of leptospires in a region of high disease transmission is common, including among people without serological or clinical evidence of recent infection. Both pathogenic and intermediate Leptospira can persist as renal colonization in humans. The pathogenic significance of this finding remains to be explored but is of fundamental biological significance.
Bharti AR, Nally JE, Ricaldi JN, Matthias MA, Diaz MM, et al. (2003) Leptospirosis: A zoonotic disease of global importance. Lancet Infect Dis 3: 757–771. doi: 10.1016/S1473-3099(03)00830-2
[3]
McBride AJ, Athanazio DA, Reis MG, Ko AI (2005) Leptospirosis. Curr Opin Infect Dis 18: 376–386. doi: 10.1097/01.qco.0000178824.05715.2c
[4]
Segura E, Ganoza C, Campos K, Ricaldi JN, Torres S, et al. (2005) Clinical spectrum of pulmonary involvement in leptospirosis in an endemic region, with quantification of leptospiral burden. Clin Infect Dis 40: 343–351. doi: 10.1086/427110
[5]
Ganoza CA, Matthias MA, Collins-Richards D, Brouwer KC, Cunningham CB, et al. (2006) Determining Risk for Severe Leptospirosis by Molecular Analysis of Environmental Surface Waters for Pathogenic Leptospira. PLoS Med 3: doi: 10.1371/journal.pmed.0030308
[6]
Johnson RC, Walby J, Henry RA, Auran NE (1973) Cultivation of parasitic leptospires: effect of pyruvate. Appl Microbiol 26: 118–119.
[7]
Matthias MA, Ricaldi JN, Cespedes M, Diaz MM, Galloway RL, et al. (2008) Human leptospirosis caused by a new, antigenically unique leptospira associated with a rattus species reservoir in the peruvian Amazon. PLoS Negl Trop Dis 2: e213. doi: 10.1371/journal.pntd.0000213
[8]
Johnson MA, Smith H, Joeph P, Gilman RH, Bautista CT, et al. (2004) Environmental exposure and leptospirosis, Peru. Emerg Infect Dis 10: 1016–1022. doi: 10.3201/eid1006.030660
[9]
Gale DA, Everard CO, Carrington DG, Everard JD (1990) Leptospiral antibodies in patients from a Barbadian general practice. Eur J Epidemiol 6: 150–155. doi: 10.1007/BF00145787
[10]
Bovet P, Yersin C, Merien F, Davis CE, Perolat P (1999) Factors associated with clinical leptospirosis: a population-based case-control study in the Seychelles (Indian Ocean). Int J Epidemiol 28: 583–590. doi: 10.1093/ije/28.3.583
[11]
Ashford DA, Kaiser RM, Spiegel RA, Perkins BA, Weyant RS, et al. (2000) Asymptomatic infection and risk factors for leptospirosis in Nicaragua. Am J Trop Med Hyg 63: 249–254.
[12]
Thai KT, Binh TQ, Giao PT, Phuong HL, Hung le Q, et al. (2006) Seroepidemiology of leptospirosis in southern Vietnamese children. Trop Med Int Health 11: 738–745. doi: 10.1111/j.1365-3156.2006.01619.x
[13]
Babudieri B (1958) Animal reservoirs of leptospires. Ann NY Acad Sci 70: 393–413. doi: 10.1111/j.1749-6632.1958.tb35398.x
[14]
Twigg GI, Cuerden CM, Hughes DM, Medhurst P (1969) The leptospirosis reservoir in British wild mammals. Vet Rec 84: 424–426. doi: 10.1136/vr.84.17.424
[15]
Hathaway SC, Blackmore DK (1981) Ecological aspects of the epidemiology of infection with leptospires of the ballum serogroup in the black rate (Rattus rattus) and the brown rat (Rattus norvegicus) in New Zealand. J Hyg Camb 87: 427. doi: 10.1017/S0022172400069679
[16]
Turner LH (1967) Leptospirosis I. The Royal Society of Tropical Medicine and Hygiene 61: 842–855. doi: 10.1016/0035-9203(67)90045-4
[17]
Cole JR Jr, Sulzer CR, Pursell AR (1973) Improved microtechnique for the leptospiral microscopic agglutination test. Appl Microbiol 25: 976–980.
[18]
Smythe LD, Smith IL, Smith GA, Dohnt MF, Symonds ML, et al. (2002) A quantitative PCR (TaqMan) assay for pathogenic Leptospira spp. BMC Infectious Diseases 2: 13–19. doi: 10.1186/1471-2334-2-13
[19]
Weisburg WG, Barns SM, Pelletier DA, Lane DJ (1991) 16S ribosomal DNA amplification for phylogenetic study. J Bacteriol 173: 697–703.
[20]
Bradshaw CS, Tabrizi SN, Fairley CK, Morton AN, Rudland E, et al. (2006) The association of Atopobium vaginae and Gardnerella vaginalis with bacterial vaginosis and recurrence after oral metronidazole therapy. J Infect Dis 194: 828–836. doi: 10.1086/506621
[21]
Wolfe ND, Dunavan CP, Diamond J (2007) Origins of major human infectious diseases. Nature 447: 279–283. doi: 10.1038/nature05775
[22]
Cumberland P, Everard CO, Wheeler JG, Levett PN (2001) Persistence of anti-leptospiral IgM, IgG and agglutinating antibodies in patients presenting with acute febrile illness in Barbados 1979-1989. Eur J Epidemiol 17: 601–608. doi: 10.1023/A:1015509105668
[23]
Bal AE, Gravekamp C, Hartskeerl RA, De Meza-brewster J, et al. (1994) Detection of leptospires in urine by PCR for early diagnosis of leptospirosis. Journal of Clinical Microbiology 32: 1894–1898.
[24]
Inada R, Ido Y, Hoki R, Kaneko R, Ito H (1916) The etiology, mode of infection, and specific therapy of Weil's disease (Spirochaetosis icterohaemorrhagica). Journal of Experimental Medicine 23: 377-U322. doi: 10.1084/jem.23.3.377
[25]
Ido Y, Hoki R, Ito H, Wani H (1917) The rat as a carrier of spirochaeta ictero-haemorrhagiae, the causative agent of Weils disease (Spirochaetosis icterohaemorrhagica). Journal of Experimental Medicine 26: 341–353. doi: 10.1084/jem.26.3.341
[26]
Audy JR (1958) The localization of disease with special reference to the zoonoses. Trans R Soc Trop Med Hyg 52: 308–328; discussion 329-334. doi: 10.1016/0035-9203(58)90045-2
[27]
Faine S (1962) Factors Affecting Development of Carrier State in Leptospirosis. Journal of Hygiene 60: 427–434. doi: 10.1017/s0022172400020556
[28]
Blackmore DK, Hathaway SCThe nidality of zoonoses 1979; New Zeland.207–213.
[29]
Bolin CA, Koellner P (1988) Human-to-human transmission of Leptospira interrogans by milk. J Infect Dis 158: 246–247. doi: 10.1093/infdis/158.1.246
[30]
Faine S (1998) Leptospira. In: Collier L, Balows A, Sussman M, editors. Topley & Wilson's Microbiology and Microbial Infections. 9 ed. London: Arnold. pp. 1287–1303.
[31]
Maciel EA, de Carvalho AL, Nascimento SF, de Matos RB, Gouveia EL, et al. (2008) Household transmission of leptospira infection in urban slum communities. PLoS Negl Trop Dis 2: e154. doi: 10.1371/journal.pntd.0000154
[32]
Levett PN, Morey RE, Galloway RL, Turner DE, Steigerwalt AG, et al. (2005) Detection of pathogenic leptospires by real-time quantitative PCR. J Med Microbiol 54: 45–49. doi: 10.1099/jmm.0.45860-0
[33]
Lucchesi PM, Arroyo GH, Etcheverria AI, Parma AE, Seijo AC (2004) Recommendations for the detection of Leptospira in urine by PCR. Rev Soc Bras Med Trop 37: 131–134. doi: 10.1590/S0037-86822004000200003
[34]
Klimpel GR, Matthias MA, Vinetz JM (2003) Leptospira interrogans activation of human peripheral blood mononuclear cells: Preferential expansion of TCRγδ+ T cells versus TCRβαβ+ T cells. J Immunol 171: 1447–1455.
