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      Asymptomatic Renal Colonization of Humans in the Peruvian Amazon by Leptospira

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Author Summary

          Leptospirosis is a bacterial disease commonly transmitted from animals to humans. The more than 200 types of spiral-shaped bacteria (spirochetes) in the genus Leptospira are classified as pathogenic, intermediately pathogenic, or saprophytic (meaning not causing infection in any mammal) based on their ability to cause disease and on genetic information. Unique among the spirochetes that infect humans, Leptospira live both in the environment (in surface waters and moist soils), and in mammals, where they cause chronic infection by colonizing kidney tubules. Infected animals are the source of human infection, but humans have not been systematically studied as chronic Leptospira carriers. In our study, we found that more than 5% of people (in fact, only women) in a rural Amazonian village, without clinical evidence of infection by Leptospira, were chronically colonized by the bacteria. Chronic infection was not associated with a detectable immune response against the spirochete. Pathogenic and intermediately pathogenic Leptospira caused asymptomatic, chronic kidney infections. Future work is needed to determine whether such chronic infection can lead to human-to-human transmission of leptospirosis, and whether subtle measures of kidney disease are associated with asymptomatic, long-term leptospiral infection.

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          Most cited references 27

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          16S ribosomal DNA amplification for phylogenetic study.

          A set of oligonucleotide primers capable of initiating enzymatic amplification (polymerase chain reaction) on a phylogenetically and taxonomically wide range of bacteria is described along with methods for their use and examples. One pair of primers is capable of amplifying nearly full-length 16S ribosomal DNA (rDNA) from many bacterial genera; the additional primers are useful for various exceptional sequences. Methods for purification of amplified material, direct sequencing, cloning, sequencing, and transcription are outlined. An obligate intracellular parasite of bovine erythrocytes, Anaplasma marginale, is used as an example; its 16S rDNA was amplified, cloned, sequenced, and phylogenetically placed. Anaplasmas are related to the genera Rickettsia and Ehrlichia. In addition, 16S rDNAs from several species were readily amplified from material found in lyophilized ampoules from the American Type Culture Collection. By use of this method, the phylogenetic study of extremely fastidious or highly pathogenic bacterial species can be carried out without the need to culture them. In theory, any gene segment for which polymerase chain reaction primer design is possible can be derived from a readily obtainable lyophilized bacterial culture.
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            Leptospirosis: a zoonotic disease of global importance.

            In the past decade, leptospirosis has emerged as a globally important infectious disease. It occurs in urban environments of industrialised and developing countries, as well as in rural regions worldwide. Mortality remains significant, related both to delays in diagnosis due to lack of infrastructure and adequate clinical suspicion, and to other poorly understood reasons that may include inherent pathogenicity of some leptospiral strains or genetically determined host immunopathological responses. Pulmonary haemorrhage is recognised increasingly as a major, often lethal, manifestation of leptospirosis, the pathogenesis of which remains unclear. The completion of the genome sequence of Leptospira interrogans serovar lai, and other continuing leptospiral genome sequencing projects, promise to guide future work on the disease. Mainstays of treatment are still tetracyclines and beta-lactam/cephalosporins. No vaccine is available. Prevention is largely dependent on sanitation measures that may be difficult to implement, especially in developing countries.
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              Leptospirosis.

              Leptospirosis, a spirochaetal zoonotic disease, has been recognized as an important emerging infectious disease in the last 10 years. This review addresses the issues in the epidemiology, diagnosis and clinical management which confront public health responses, and highlights the progress made towards understanding the Leptospira genome, biology and pathogenesis. Leptospirosis has spread from its traditional rural base to become the cause of epidemics in poor urban slum communities in developing countries. Mortality from severe disease forms, Weil's disease and severe pulmonary haemorrhage syndrome, is high (>10% and >50%, respectively) even when optimal treatment is provided. Moreover, the overall disease burden is underestimated, since leptospirosis is a significant cause of undifferentiated fever and frequently not recognized. Barriers to addressing this problem have been the lack of an adequate diagnostic test and effective control measures. China and Brazil, countries in which leptospirosis is a major health problem, have completed the sequence of the Leptospira interrogans genome. Together with new genetic tools and proteomics, new insights have been made into the biology of Leptospira and the mechanisms used to adapt to host and external environments. Surface-exposed proteins and putative virulence determinants have been identified which may serve as sub-unit vaccine candidates. Major progress has been made in the basic research of leptospirosis. Future challenges will be to translate these advances into public health measures for developing countries. Yet the most effective responses may be interventions that directly address the determinants of poverty, such as poor sanitation, which are often responsible for transmission.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, USA )
                1935-2727
                1935-2735
                February 2010
                23 February 2010
                : 4
                : 2
                Affiliations
                [1 ]Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru
                [2 ]Division of Infectious Diseases, Department of Medicine, University of California San Diego School of Medicine, La Jolla, California, United States of America
                [3 ]Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
                [4 ]Department of Microbiology, Universidad Peruana Cayetano Heredia, Lima, Peru
                [5 ]Asociacion Benefica PRISMA, Lima, Peru
                [6 ]Instituto Nacional de Salud, Lima, Peru
                Cambridge University, United Kingdom
                Author notes
                [¤]

                Current address: Department of Immunology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany

                Conceived and designed the experiments: CAG MAM EG JMV. Performed the experiments: CAG MAM. Analyzed the data: CAG MAM MS MC EG JMV. Contributed reagents/materials/analysis tools: CAG MAM MS MC EG JMV. Wrote the paper: CAG MAM MS EG JMV.

                Article
                09-PNTD-RA-0606R2
                10.1371/journal.pntd.0000612
                2826405
                20186328
                Ganoza et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                Page count
                Pages: 10
                Categories
                Research Article
                Infectious Diseases/Bacterial Infections
                Microbiology
                Microbiology/Applied Microbiology
                Microbiology/Environmental Microbiology

                Infectious disease & Microbiology

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