ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
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1.
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-
8.
Spanakos G, Piperaki E-T, Menounos PG, Tegos N, Flemetakis A, Vakalis NC, 2008. Detection and species identification of Old World Leishmania in clinical samples using a PCR-based method. Trans R Soc Trop Med Hyg 102: 46–53.
-
9.
Vergel C, Palacios R, Cadena H, Posso CJ, Valderrama L, Perez M, Walker J, Travi BL, Saravia NG, 2006. Evidence for Leishmania (Viannia) parasites in the skin and blood of patients before and after treatment. J Infect Dis 194: 503–511.
-
10.
Venazzi EA, Roberto AC, Barbosa-Tessmann IP, Zanarini PD, Lonardoni MV, Silveira TG, 2007. Detection of Leishmania (Viannia) DNA in blood from patients with American cutaneous leishmaniasis. Exp Parasitol 115: 399–402.
-
11.
Schubach A, Haddad F, Oliveira-Neto MP, Degrave W, Pirmez C, Grimaldi G Jr, Fernandes O, 1998. Detection of Leishmania DNA by polymerase chain reaction in scars of treated human patients. J Infect Dis 178: 911–914.
-
12.
de Oliveira Camera P, Junger J, do Espirito Santo Silva Pires F, Mattos M, Oliveira-Neto MP, Fernandes O, Pirmez C, 2006. Hematogenous dissemination of Leishmania (Viannia) braziliensis in human American tegumentary leishmaniasis. Trans R Soc Trop Med Hyg 100: 1112–1117.
-
13.
Botezatu I, Serdyuk O, Potapova G, Shelepov V, Alechina R, Molyaka Y, Ananév V, Bazin I, Garin A, Narimanov M, Knysh V, Melkonyan H, Umansky S, Lichtenstein A, 2000. Genetic analysis of DNA excreted in urine: a new approach for detecting specific genomic DNA sequences from cells dying in an organism. Clin Chem 46: 1078–1084.
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14.
Su YH, Wang M, Brenner D, Ng A, Melkonyan H, Umansky S, Syngal S, Block TM, 2004. Human urine contains small 150 to 250 nucleotide-size, soluble DNA derived from the circulation and may be useful in the detection of colorectal cancer. J Mol Diagn 6: 101–107.
-
15.
Boggild AK, Valencia BM, Espinosa D, Veland N, Ramos AP, Arevalo J, Llanos-Cuentas A, Low DE, 2010. Detection and species identification of Leishmania DNA from filter paper lesion impressions for patients with American cutaneous leishmaniasis. Clin Infect Dis 50: e1–e6.
-
16.
Boggild AK, Miranda-Verastegui C, Espinosa D, Arevalo J, Adaui V, Tulliano G, Llanos-Cuentas A, Low DE, 2007. Evaluation of a microculture method for the isolation of Leishmania parasites from cutaneous lesions in Peru. J Clin Microbiol 45: 3680–3684.
-
17.
Boggild AK, Miranda-Verastegui C, Espinosa D, Arevalo J, Martinez-Medina D, Llanos-Cuentas A, Low DE, 2008. Optimization of microculture and evaluation of miniculture for the isolation of Leishmania parasites from cutaneous lesions in Peru. Am J Trop Med Hyg 79: 847–852.
-
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-
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Lopez M, Orrego C, Cangalaya M, Inga R, Arevalo J, 1993. Diagnosis of Leishmania via the polymerase chain reaction: a simplified procedure for field work. Am J Trop Med Hyg 49: 348–356.
-
20.
Arevalo J, Ramirez L, Adaui V, Zimic M, Tulliano G, Miranda-Verstegui C, Lazo M, Loayza-Muro R, De Doncker S, Mauer A, Chappuis F, Dujardin JC, Llanos-Cuentas A, 2007. Influence of Leishmania (Viannia) species on the response to antimonial treatment in patients with American tegumentary leishmaniasis. J Infect Dis 195: 1846–1851.
-
21.
Lucas CM, Franke ED, Cachay MI, Tejada A, Cruz ME, Kreutzer RD, Barker DC, McCann SH, Watts DM, 1998. Geographic distribution and clinical description of leishmaniasis cases in Peru. Am J Trop Med Hyg 59: 312–317.
-
22.
Zhang W-W, Miranda-Verastegui C, Arevalo J, Ndao M, Ward B, Llanos-Cuentas A, Matlashewski G, 2006. Development of a genetic assay to distinguish between Leishmania viannia species on the basis of isoenzyme differences. Clin Infect Dis 42: 801–809.
-
23.
Garcia AL, Kindt A, Quispe-Tintaya KW, Bermudez H, Llanos A, Arevalo J, Bañuls AL, De Doncker S, Le Ray D, Dujardin JC, 2005. American tegumentary leishmaniasis: antigen-gene polymorphism, taxonomy and clinical pleomorphism. Infect Genet Evol 5: 109–116.
-
24.
Garcia L, Kindt A, Bermudez H, Llanos-Cuentas A, De Doncker S, Arevalo J, Wilber Quispe Tintaya K, Dujardin JC, 2004. Culture-independent species typing of neotropical Leishmania for clinical validation of a PCR-based assay targeting heat shock protein 70 genes. J Clin Microbiol 42: 2294–2297.
-
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Polymerase Chain Reaction Detection of Leishmania kDNA from the Urine of Peruvian Patients with Cutaneous and Mucocutaneous Leishmaniasis
Nicolas Veland
Nicolas Veland
Instituto de Medicina Tropical “Alexander von Humboldt,” Universidad Peruana Cayetano Heredia (UPCH), Lima, Peru; Departamento de Bioquimica, Biologia Molecular y Farmacologia, Facultad de Ciencias, Universidad Peruana Cayetano Heredia; Laboratories Branch, Ontario Agency for Health Protection and Promotion, Etobicoke, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Hospital Nacional Cayetano Heredia, Lima, Peru; Tropical Disease Unit, Division of Infectious Diseases, Toronto General Hospital, Toronto, Canada
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Diego Espinosa
Diego Espinosa
Instituto de Medicina Tropical “Alexander von Humboldt,” Universidad Peruana Cayetano Heredia (UPCH), Lima, Peru; Departamento de Bioquimica, Biologia Molecular y Farmacologia, Facultad de Ciencias, Universidad Peruana Cayetano Heredia; Laboratories Branch, Ontario Agency for Health Protection and Promotion, Etobicoke, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Hospital Nacional Cayetano Heredia, Lima, Peru; Tropical Disease Unit, Division of Infectious Diseases, Toronto General Hospital, Toronto, Canada
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Braulio Mark Valencia
Braulio Mark Valencia
Instituto de Medicina Tropical “Alexander von Humboldt,” Universidad Peruana Cayetano Heredia (UPCH), Lima, Peru; Departamento de Bioquimica, Biologia Molecular y Farmacologia, Facultad de Ciencias, Universidad Peruana Cayetano Heredia; Laboratories Branch, Ontario Agency for Health Protection and Promotion, Etobicoke, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Hospital Nacional Cayetano Heredia, Lima, Peru; Tropical Disease Unit, Division of Infectious Diseases, Toronto General Hospital, Toronto, Canada
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Ana Pilar Ramos
Ana Pilar Ramos
Instituto de Medicina Tropical “Alexander von Humboldt,” Universidad Peruana Cayetano Heredia (UPCH), Lima, Peru; Departamento de Bioquimica, Biologia Molecular y Farmacologia, Facultad de Ciencias, Universidad Peruana Cayetano Heredia; Laboratories Branch, Ontario Agency for Health Protection and Promotion, Etobicoke, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Hospital Nacional Cayetano Heredia, Lima, Peru; Tropical Disease Unit, Division of Infectious Diseases, Toronto General Hospital, Toronto, Canada
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Flor Calderon
Flor Calderon
Instituto de Medicina Tropical “Alexander von Humboldt,” Universidad Peruana Cayetano Heredia (UPCH), Lima, Peru; Departamento de Bioquimica, Biologia Molecular y Farmacologia, Facultad de Ciencias, Universidad Peruana Cayetano Heredia; Laboratories Branch, Ontario Agency for Health Protection and Promotion, Etobicoke, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Hospital Nacional Cayetano Heredia, Lima, Peru; Tropical Disease Unit, Division of Infectious Diseases, Toronto General Hospital, Toronto, Canada
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Jorge Arevalo
Jorge Arevalo
Instituto de Medicina Tropical “Alexander von Humboldt,” Universidad Peruana Cayetano Heredia (UPCH), Lima, Peru; Departamento de Bioquimica, Biologia Molecular y Farmacologia, Facultad de Ciencias, Universidad Peruana Cayetano Heredia; Laboratories Branch, Ontario Agency for Health Protection and Promotion, Etobicoke, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Hospital Nacional Cayetano Heredia, Lima, Peru; Tropical Disease Unit, Division of Infectious Diseases, Toronto General Hospital, Toronto, Canada
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Donald E. Low
Donald E. Low
Instituto de Medicina Tropical “Alexander von Humboldt,” Universidad Peruana Cayetano Heredia (UPCH), Lima, Peru; Departamento de Bioquimica, Biologia Molecular y Farmacologia, Facultad de Ciencias, Universidad Peruana Cayetano Heredia; Laboratories Branch, Ontario Agency for Health Protection and Promotion, Etobicoke, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Hospital Nacional Cayetano Heredia, Lima, Peru; Tropical Disease Unit, Division of Infectious Diseases, Toronto General Hospital, Toronto, Canada
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Alejandro Llanos-Cuentas
Alejandro Llanos-Cuentas
Instituto de Medicina Tropical “Alexander von Humboldt,” Universidad Peruana Cayetano Heredia (UPCH), Lima, Peru; Departamento de Bioquimica, Biologia Molecular y Farmacologia, Facultad de Ciencias, Universidad Peruana Cayetano Heredia; Laboratories Branch, Ontario Agency for Health Protection and Promotion, Etobicoke, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Hospital Nacional Cayetano Heredia, Lima, Peru; Tropical Disease Unit, Division of Infectious Diseases, Toronto General Hospital, Toronto, Canada
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Andrea K. Boggild
Andrea K. Boggild
Instituto de Medicina Tropical “Alexander von Humboldt,” Universidad Peruana Cayetano Heredia (UPCH), Lima, Peru; Departamento de Bioquimica, Biologia Molecular y Farmacologia, Facultad de Ciencias, Universidad Peruana Cayetano Heredia; Laboratories Branch, Ontario Agency for Health Protection and Promotion, Etobicoke, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Hospital Nacional Cayetano Heredia, Lima, Peru; Tropical Disease Unit, Division of Infectious Diseases, Toronto General Hospital, Toronto, Canada
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We hypothesized that Leishmania kDNA may be present in urine of patients with cutaneous leishmaniasis (CL). Urine samples and standard diagnostic specimens were collected from patients with skin lesions. kDNA polymerase chain reaction (PCR) was performed on samples from patients and 10 healthy volunteers from non-endemic areas. Eighty-six of 108 patients were diagnosed with CL and 18 (21%) had detectable Leishmania Viannia kDNA in the urine. Sensitivity and specificity were 20.9% (95% confidence interval [CI] 12.3–29.5%) and 100%. Six of 8 patients with mucocutaneous involvement had detectable kDNA in urine versus 12 of 78 patients with isolated cutaneous disease (P < 0.001). L. (V.) braziliensis (N = 3), L. (V.) guyanensis (N = 6), and L. (V.) peruviana (N = 3) were identified from urine. No healthy volunteer or patient with an alternate diagnosis had detectable kDNA in urine. Sensitivity of urine PCR is sub-optimal for diagnosis. On the basis of these preliminary data in a small number of patients, detectable kDNA in urine may identify less localized forms of infection and inform treatment decisions.
Author Notes
Financial support: AKB was supported by a professional development grant (2009) and a Detweiler traveling fellowship (2010) through the Royal College of Physicians and Surgeons of Canada. This study was partially funded by the Ontario Association of Medical Laboratories. Personnel support for members of the Arevalo molecular laboratory (NV, DE, and JA) was provided by the Institutional Collaboration Framework Agreement 3 from the Belgian Development Cooperation.
Authors' addresses: Nicolas Veland, Braulio Mark Valencia, Ana Pilar Ramos, Flor Calderon, and Alejandro Llanos-Cuentas, Instituto de Medicina Tropical “Alexander von Humboldt,” Universidad Peruana Cayetano Heredia, Lima, Peru, E-mails: nicolasveland@yahoo.com, 18406@upch.edu.pe, anapilarupch@hotmail.com, calderon.flor@gmail.com, and elmer.llanos@upch.pe. Diego Espinosa, John Hopkins School of Public Health, Baltimore, MD, E-mail: despinos@jhsph.edu. Jorge Arevalo, Departmento de Bioquimica, Biologia Molecular y Farmacologia, Facultad de Ciencias, Universidad Peruana Cayetano Heredia, Lima, Peru, E-mail: biomoljazz@gmail.com. Donald E. Low, Department of Microbiology, Mount Sinai Hospital, Toronto, ON and Laboratories Branch, Ontario Agency for Health Protection and Promotion, Etobicoke, ON, E-mail: Don.Low@oahpp.ca. Andrea K. Boggild, Tropical Disease Unit, UHN-Toronto General Hospital, Toronto, ON, E-mail: andrea.boggild@utoronto.ca.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Reithinger R, Dujardin JC, Louzir H, Pirmez C, Alexander B, Brooker S, 2007. Cutaneous leishmaniasis. Lancet Infect Dis 7: 581–596.
-
2.
Reithinger R, Dujardin JC, 2007. Molecular diagnosis of leishmaniasis: current status and future applications. J Clin Microbiol 45: 21–25.
-
3.
Tavares CA, Fernandes AP, Melo MN, 2003. Molecular diagnosis of leishmaniasis. Expert Rev Mol Diagn 3: 657–667.
-
4.
Singh S, 2006. New developments in diagnosis of leishmaniasis. Indian J Med Res 123: 311–330.
-
5.
Murray HW, Berman JD, Davies CR, Saravia NG, 2005. Advances in leishmaniasis. Lancet 366: 1561–1577.
-
6.
Barral A, Guerreiro J, Bomfim G, Correia D, Barral-Netto M, Carvalho EM, 1995. Lymphadenopathy as the first sign of human cutaneous infection by Leishmania braziliensis. Am J Trop Med Hyg 53: 256–259.
-
7.
Fagundes A, Marzochi MC, Fernandes O, Perez MA, Schubach AO, Schubach TM, Amendoeira MR, Mouta-Confort E, Marzochi KB, 2007. First encounter of subclinical human Leishmania (Viannia) infection in the state of Rio Grande do Sul, Brazil. Mem Inst Oswaldo Cruz 102: 1003–1006.
-
8.
Spanakos G, Piperaki E-T, Menounos PG, Tegos N, Flemetakis A, Vakalis NC, 2008. Detection and species identification of Old World Leishmania in clinical samples using a PCR-based method. Trans R Soc Trop Med Hyg 102: 46–53.
-
9.
Vergel C, Palacios R, Cadena H, Posso CJ, Valderrama L, Perez M, Walker J, Travi BL, Saravia NG, 2006. Evidence for Leishmania (Viannia) parasites in the skin and blood of patients before and after treatment. J Infect Dis 194: 503–511.
-
10.
Venazzi EA, Roberto AC, Barbosa-Tessmann IP, Zanarini PD, Lonardoni MV, Silveira TG, 2007. Detection of Leishmania (Viannia) DNA in blood from patients with American cutaneous leishmaniasis. Exp Parasitol 115: 399–402.
-
11.
Schubach A, Haddad F, Oliveira-Neto MP, Degrave W, Pirmez C, Grimaldi G Jr, Fernandes O, 1998. Detection of Leishmania DNA by polymerase chain reaction in scars of treated human patients. J Infect Dis 178: 911–914.
-
12.
de Oliveira Camera P, Junger J, do Espirito Santo Silva Pires F, Mattos M, Oliveira-Neto MP, Fernandes O, Pirmez C, 2006. Hematogenous dissemination of Leishmania (Viannia) braziliensis in human American tegumentary leishmaniasis. Trans R Soc Trop Med Hyg 100: 1112–1117.
-
13.
Botezatu I, Serdyuk O, Potapova G, Shelepov V, Alechina R, Molyaka Y, Ananév V, Bazin I, Garin A, Narimanov M, Knysh V, Melkonyan H, Umansky S, Lichtenstein A, 2000. Genetic analysis of DNA excreted in urine: a new approach for detecting specific genomic DNA sequences from cells dying in an organism. Clin Chem 46: 1078–1084.
-
14.
Su YH, Wang M, Brenner D, Ng A, Melkonyan H, Umansky S, Syngal S, Block TM, 2004. Human urine contains small 150 to 250 nucleotide-size, soluble DNA derived from the circulation and may be useful in the detection of colorectal cancer. J Mol Diagn 6: 101–107.
-
15.
Boggild AK, Valencia BM, Espinosa D, Veland N, Ramos AP, Arevalo J, Llanos-Cuentas A, Low DE, 2010. Detection and species identification of Leishmania DNA from filter paper lesion impressions for patients with American cutaneous leishmaniasis. Clin Infect Dis 50: e1–e6.
-
16.
Boggild AK, Miranda-Verastegui C, Espinosa D, Arevalo J, Adaui V, Tulliano G, Llanos-Cuentas A, Low DE, 2007. Evaluation of a microculture method for the isolation of Leishmania parasites from cutaneous lesions in Peru. J Clin Microbiol 45: 3680–3684.
-
17.
Boggild AK, Miranda-Verastegui C, Espinosa D, Arevalo J, Martinez-Medina D, Llanos-Cuentas A, Low DE, 2008. Optimization of microculture and evaluation of miniculture for the isolation of Leishmania parasites from cutaneous lesions in Peru. Am J Trop Med Hyg 79: 847–852.
-
18.
Sambrook J, Fritsch EF, Maniatis T, 1989. Molecular Cloning: A Laboratory Manual. Second edition. New York: Cold Spring Harbor Laboratory Press.
-
19.
Lopez M, Orrego C, Cangalaya M, Inga R, Arevalo J, 1993. Diagnosis of Leishmania via the polymerase chain reaction: a simplified procedure for field work. Am J Trop Med Hyg 49: 348–356.
-
20.
Arevalo J, Ramirez L, Adaui V, Zimic M, Tulliano G, Miranda-Verstegui C, Lazo M, Loayza-Muro R, De Doncker S, Mauer A, Chappuis F, Dujardin JC, Llanos-Cuentas A, 2007. Influence of Leishmania (Viannia) species on the response to antimonial treatment in patients with American tegumentary leishmaniasis. J Infect Dis 195: 1846–1851.
-
21.
Lucas CM, Franke ED, Cachay MI, Tejada A, Cruz ME, Kreutzer RD, Barker DC, McCann SH, Watts DM, 1998. Geographic distribution and clinical description of leishmaniasis cases in Peru. Am J Trop Med Hyg 59: 312–317.
-
22.
Zhang W-W, Miranda-Verastegui C, Arevalo J, Ndao M, Ward B, Llanos-Cuentas A, Matlashewski G, 2006. Development of a genetic assay to distinguish between Leishmania viannia species on the basis of isoenzyme differences. Clin Infect Dis 42: 801–809.
-
23.
Garcia AL, Kindt A, Quispe-Tintaya KW, Bermudez H, Llanos A, Arevalo J, Bañuls AL, De Doncker S, Le Ray D, Dujardin JC, 2005. American tegumentary leishmaniasis: antigen-gene polymorphism, taxonomy and clinical pleomorphism. Infect Genet Evol 5: 109–116.
-
24.
Garcia L, Kindt A, Bermudez H, Llanos-Cuentas A, De Doncker S, Arevalo J, Wilber Quispe Tintaya K, Dujardin JC, 2004. Culture-independent species typing of neotropical Leishmania for clinical validation of a PCR-based assay targeting heat shock protein 70 genes. J Clin Microbiol 42: 2294–2297.
-
25.
Croft SL, Sundar S, Fairlamb AH, 2006. Drug resistance in leishmaniasis. Clin Microbiol Rev 19: 111–126.
-
26.
Weinrauch L, Carvich F, Craig P, Sosa JX, el-On J, 1993. Topical treatment of New World cutaneous leishmaniasis in Belize: a clinical study. J Am Acad Dermatol 29: 443–446.
-
27.
Arana BA, Mendoza CE, Rizzo NR, Kroeger A, 2001. Randomized, controlled, double-blind trial of topical treatment of cutaneous leishmaniasis with paromomycin plus methylbenzethonium chloride ointment in Guatemala. Am J Trop Med Hyg 65: 466–470.
-
28.
Armijos RX, Weigel MM, Calvopina M, Mancheno M, Rodriguez R, 2004. Comparison of the effectiveness of two topical paromomycin treatments versus meglumine antimoniate for New World cutaneous leishmaniasis. Acta Trop 91: 153–160.
-
29.
Neva FA, Ponce C, Ponce E, Kreutzer R, Modabber F, Olliaro P, 1997. Non-ulcerative cutaneous leishmaniasis in Honduras fails to respond to topical paromomycin. Trans R Soc Trop Med Hyg 91: 473–475.
-
30.
Hyun Kim D, Jin Chung H, Bleys J, Ghohestani RF, 2009. Is paromomycin an effective and safe treatment against cutaneous leishmaniasis? A meta-analysis of 14 randomized controlled trials. PLoS Negl Trop Dis 3: e381.
-
31.
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