Asymptomatic Renal Colonization of Humans in the Peruvian Amazon by Leptospira

Abstract

BackgroundRenal 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 FindingsUsing 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/SignificanceAsymptomatic 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.

Redefining Gold Standard Testing for Diagnosing Leptospirosis: Further Evidence from a Well-Characterized, Flood-Related Outbreak in Sri Lanka

“…Leptospiral infection may be clinically inapparent, 24 or may result in undifferentiated fever, fulminant disease, and mimics other tropical diseases such as malaria, 25 dengue, [26][27][28][29] hantaviral syndromes, 18,30-32 scrub typhus, 33,34 and others. During the acute phase of leptospirosis, timely confirmation is an important clinical priority to optimize both specific treatment and supportive management.…”

Myelodysplastic syndrome (MDS) as a late stage of subclinical hemophagocytic lymphohistiocytosis (HLH): A putative role forLeptospirainfection. A hypothesis

“…Accordingly, IgG antibodies against Leptospira are, at a low prevalence, common among different, mainly rural populations [27][28][29][30]. Furthermore, while renal carriage and leptospiruria is a well-known phenomenon in rats [31], asymptomatic renal colonization has only recently been described in humans [32]. A significant proportion of individuals who asymptomatically shed the DNA of pathogenic or intermediate-pathogenic Leptospira strains have not developed antibody titers [32].…”

“…Furthermore, while renal carriage and leptospiruria is a well-known phenomenon in rats [31], asymptomatic renal colonization has only recently been described in humans [32]. A significant proportion of individuals who asymptomatically shed the DNA of pathogenic or intermediate-pathogenic Leptospira strains have not developed antibody titers [32]. In general, a negative IgG titer after bacterial contact may be due to the insufficient sensitivity or quality of the respective serological test, the decline of the antibody titer over time, or a functionally insufficient immune response to the infectious agent.…”

The Paradox of the Chicken and the Egg: Lack of Actionable Diagnostics Prevents Global Burden of Disease Assessment and Deployment of Public Health Preventive Measures

“…In the developing world, reference laboratories are generally based at government-supported entities; in the industrialized world, reference laboratories are far removed from the field setting where the burden of disease is highest. Leptospirosis has sporadic,(2,3,4) highly endemic (5,6,7,8) and explosively epidemic patterns of disease, (9,10,11) which are related to how humans interact with the environment around them and the diversity of Leptospiradue to the presence of mammalian reservoir hosts such as rodents, dogs and livestock. Sporadic leptospirosis occurs dramatically in the context of intermittent activities in which people come into contact with Leptospira-contaminated environmental surface waters and wet soils, for example during the EcoChallenge Sabah in 2000 (12) or other adventure traveler events such as triathlons.…”