Alvar J, Velez ID, Bern C, Herrero M, Desjeux P, Cano J, Jannin J, den Boer M; the WHO Leishmaniasis Control Team, 2012. Leishmaniasis worldwide and global estimates of its incidence. PLoS One 7: e35671.
Sundar S, Chakravarty J, Agarwal D, Rai M, Murray HW, 2010. Single-dose liposomal amphotericin B for visceral leishmaniasis in India. N Engl J Med 362: 504ā512.
Harhay MO, Olliaro PL, Costa DL, Costa CH, 2011. Urban parasitology: visceral leishmaniasis in Brazil. Trends Parasitol 27: 403ā409.
Solano-Gallego L, Koutinas A, Miro G, Cardoso L, Pennisi MG, Ferrer L, Bourdeau P, Oliva G, Baneth G, 2009. Directions for the diagnosis, clinical staging, treatment and prevention of canine leishmaniasis. Vet Parasitol 165: 1ā18.
Nunes CM, Pires MM, da Silva KM, Assis FD, Goncalves Filho J, Perri SH, 2010. Relationship between dog culling and incidence of human visceral leishmaniasis in an endemic area. Vet Parasitol 170: 131ā133.
Costa CH, Gomes RB, Silva MR, Garcez LM, Ramos PK, Santos RS, Shaw JJ, David JR, Maguire JH, 2000. Competence of the human host as a reservoir for Leishmania chagasi. J Infect Dis 182: 997ā1000.
Ready PD, 2014. Epidemiology of visceral leishmaniasis. Clin Epidemiol 6: 147ā154.
Dantas-Torres F, Brandao-Filho SP, 2006. Visceral leishmaniasis in Brazil: revisiting paradigms of epidemiology and control. Rev Inst Med Trop Sao Paulo 48: 151ā156.
Mahmoudi MR, Kazemi B, Mohammadiha A, Mirzaei A, Karanis P, 2013. Detection of Cryptosporidium and Giardia (oo)cysts by IFA, PCR and LAMP in surface water from Rasht, Iran. Trans R Soc Trop Med Hyg 107: 511ā517.
Antinori S, Calattini S, Longhi E, Bestetti G, Piolini R, Magni C, Orlando G, Gramiccia M, Acquaviva V, Foschi A, 2007. Clinical use of polymerase chain reaction performed on peripheral blood and bone marrow samples for the diagnosis and monitoring of visceral leishmaniasis in HIV-infected and HIV-uninfected patients: a single-center, 8-year experience in Italy and review of the literature. Clin Infect Dis 44: 1602ā1610.
Ozerdem D, Eroglu F, Genc A, Demirkazik M, Koltas IS, 2009. Comparison of microscopic examination, rK39, and PCR for visceral leishmaniasis diagnosis in Turkey. Parasitol Res 106: 197ā200.
Boggild AK, Ramos AP, Espinosa D, Valencia BM, Veland N, Miranda-Verastegui C, Arevalo J, Low DE, Llanos-Cuentas A, 2010. Clinical and demographic stratification of test performance: a pooled analysis of five laboratory diagnostic methods for American cutaneous leishmaniasis. Am J Trop Med Hyg 83: 345ā350.
Crannell ZA, Rohrman B, Richards-Kortum R, 2014. Equipment-free incubation of recombinase polymerase amplification reactions using body heat. PLoS One 9: e112146.
Piepenburg O, Williams CH, Stemple DL, Armes NA, 2006. DNA detection using recombination proteins. PLoS Biol 4: e204.
Euler M, Wang Y, Heidenreich D, Patel P, Strohmeier O, Hakenberg S, Niedrig M, Hufert FT, Weidmann M, 2013. Development of a panel of recombinase polymerase amplification assays for detection of biothreat agents. J Clin Microbiol 51: 1110ā1117.
Euler M, Wang Y, Nentwich O, Piepenburg O, Hufert FT, Weidmann M, 2012. Recombinase polymerase amplification assay for rapid detection of Rift Valley fever virus. J Clin Virol 54: 308ā312.
Euler M, Wang Y, Otto P, Tomaso H, Escudero R, Anda P, Hufert FT, Weidmann M, 2012. Recombinase polymerase amplification assay for rapid detection of Francisella tularensis. J Clin Microbiol 50: 2234ā2238.
Crannell ZA, Castellanos-Gonzalez A, Irani A, Rohrman B, White AC, Richards-Kortum R, 2014. A nucleic acid test to diagnose cryptosporidiosis: lab assessment in animal and patient specimens. Anal Chem 86: 2565ā2571.
Rohrman BA, Richards-Kortum RR, 2012. A paper and plastic device for performing recombinase polymerase amplification of HIV DNA. Lab Chip 12: 3082ā3088.
Salomon O, Sinagra A, Nevot M, Barberian G, Paulin P, Estevez J, Riarte A, 2008. First visceral leishmaniasis focus in Argentina. Mem Inst Oswaldo Cruz 103: 109ā111.
Yurchenko VY, Merzlyak EM, Kolesnikov AA, Martinkina LP, Vengerov YY, 1999. Structure of Leishmania minicircle kinetoplast DNA classes. J Clin Microbiol 37: 1656ā1657.
Pita-Pereira D, Lins R, Oliveira MP, Lima RB, Pereira BA, Moreira OC, Brazil RP, Britto C, 2012. SYBR Green-based real-time PCR targeting kinetoplast DNA can be used to discriminate between the main etiologic agents of Brazilian cutaneous and visceral leishmaniasis. Parasit Vectors 5: 15.
Barao SC, de Fonseca Camargo-Neves VL, Resende MR, da Silva LJ, 2007. Human asymptomatic infection in visceral leishmaniasis: a seroprevalence study in an urban area of low endemicity. Preliminary results. Am J Trop Med Hyg 77: 1051ā1053.
Lemos EM, Laurenti MD, Moreira MA, Reis AB, Giunchetti RC, Raychaudhuri S, Dietze R, 2008. Canine visceral leishmaniasis: performance of a rapid diagnostic test (Kalazar Detect) in dogs with and without signs of the disease. Acta Trop 107: 205ā207.
Mary C, Faraut F, Drogoul MP, Xeridat B, Schleinitz N, Cuisenier B, Dumon H, 2006. Reference values for Leishmania infantum parasitemia in different clinical presentations: quantitative polymerase chain reaction for therapeutic monitoring and patient follow-up. Am J Trop Med Hyg 75: 858ā863.
Vaish M, Mehrotra S, Chakravarty J, Sundar S, 2011. Noninvasive molecular diagnosis of human visceral leishmaniasis. J Clin Microbiol 49: 2003ā2005.
Lombardo G, Pennisi MG, Lupo T, Migliazzo A, Capri A, Solano-Gallego L, 2012. Detection of Leishmania infantum DNA by real-time PCR in canine oral and conjunctival swabs and comparison with other diagnostic techniques. Vet Parasitol 184: 10ā17.
Campos-Ponce M, Ponce C, Ponce E, Maingon RD, 2005. Leishmania chagasi/infantum: further investigations on Leishmania tropisms in atypical cutaneous and visceral leishmaniasis foci in Central America. Exp Parasitol 109: 209ā219.
Quinnell RJ, Carson C, Reithinger R, Garcez LM, Courtenay O, 2013. Evaluation of rK39 rapid diagnostic tests for canine visceral leishmaniasis: longitudinal study and meta-analysis. PLoS Negl Trop Dis 7: e1992.
Carson C, Quinnell RJ, Holden J, Garcez LM, Deborggraeve S, Courtenay O, 2010. Comparison of Leishmania OligoC-TesT PCR with conventional and real-time PCR for diagnosis of canine Leishmania infection. J Clin Microbiol 48: 3325ā3330.
David JR, Stamm LM, Bezerra HS, Souza RN, Killick-Kendrick R, Lima JWO, 2001. Deltamethrin-impregnated dog collars have a potent anti-feeding and insecticidal effect on Lutzomyia longipalpis and Lutzomyia migonei. Mem Inst Oswaldo Cruz 96: 839ā847.
Sinha PK, Bhattacharya S, 2014. Single-dose liposomal amphotericin B: an effective treatment for visceral leishmaniasis. Lancet Glob Health 2: e7āe8.
Chappuis F, Sundar S, Hailu A, Ghalib H, Rijal S, Peeling RW, Alvar J, Boelaert M, 2007. Visceral leishmaniasis: what are the needs for diagnosis, treatment and control? Nat Rev Microbiol 5: 873ā882.
De Almeida Silva L, Romero HD, Prata A, Costa RT, Nascimento E, Carvalho SF, Rodrigues V, 2006. Immunologic tests in patients after clinical cure of visceral leishmaniasis. Am J Trop Med Hyg 75: 739ā743.
Silveira FT, Lainson R, Crescente JA, de Souza AA, Campos MB, Gomes CM, Laurenti MD, Corbett CE, 2010. A prospective study on the dynamics of the clinical and immunological evolution of human Leishmania (L.) infantum chagasi infection in the Brazilian Amazon region. Trans R Soc Trop Med Hyg 104: 529ā535.
Bern C, Courtenay O, Alvar J, 2010. Of cattle, sand flies and men: a systematic review of risk factor analyses for south Asian visceral leishmaniasis and implications for elimination. PLoS Negl Trop Dis 4: e599.
Fakiola M, Miller EN, Fadl M, Mohamed HS, Jamieson SE, Francis RW, Cordell HJ, Peacock CS, Raju M, Khalil EA, Elhassan A, Musa AM, Silveira F, Shaw JJ, Sundar S, Jeronimo SM, Ibrahim ME, Blackwell JM, 2011. Genetic and functional evidence implicating DLL1 as the gene that influences susceptibility to visceral leishmaniasis at chromosome 6q27. J Infect Dis 204: 467ā477.
Bhunia GS, Kesari S, Chatterjee N, Kumar V, Das P, 2013. Spatial and temporal variation and hotspot detection of kala-azar disease in Vaishali District (Bihar), India. BMC Infect Dis 13: 64.
Perry DDK, Garlapati R, Gendernalik A, PochĆ© D, PochĆ© R, 2013. Visceral leishmaniasis prevalence and associated risk factors in the saran district of Bihar, India, from 2009 to July of 2011. ASTMH 88: 778ā784.
Clemente WT, Rabello A, Faria LC, Peruhype-Magalhaes V, Gomes LI, da Silva TA, Nunes RV, Iodith JB, Protil KZ, Fernandes HR, Cortes JR, Lima SS, Lima AS, Romanelli RM, 2014. High prevalence of asymptomatic Leishmania spp. infection among liver transplant recipients and donors from an endemic area of Brazil. Am J Transplant 14: 96ā101.
Singh S, Kumari V, Singh N, 2002. Predicting kala-azar disease manifestations in asymptomatic patients with latent Leishmania donovani infection by detection of antibody against recombinant K39 antigen. Clin Diagn Lab Immunol 9: 568ā572.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 26 | 26 | 9 |
Full Text Views | 401 | 120 | 0 |
PDF Downloads | 119 | 20 | 0 |
Dogs are the principal reservoir hosts of zoonotic visceral leishmaniasis (VL) but current serological methods are not sensitive enough to detect all subclinically infected animals, which is crucial to VL control programs. Polymerase chain reaction (PCR) methods have greater sensitivity but require expensive equipment and trained personnel, impairing its implementation in endemic areas. We developed a diagnostic test that uses isothermal recombinase polymerase amplification (RPA) to detect Leishmania infantum. This method was coupled with lateral flow (LF) reading with the naked eye to be adapted as a point-of-care test. The L. infantum RPA-LF had an analytical sensitivity similar to real time-PCR, detecting DNA of 0.1 parasites spiked in dog blood, which was equivalent to 40 parasites/mL. There was no cross amplification with dog or human DNA or with Leishmania braziliensis, Leishmania amazonensis, or Trypanosoma cruzi. The test also amplified Leishmania donovani strains (N = 7). In a group of clinically normal dogs (N = 30), RPA-LF detected more subclinical infections than rK39 strip test, a standard serological method (50% versus 13.3% positivity, respectively; P = 0.005). Also, RPA-LF detected L. infantum in noninvasive mucosal samples of dogs with a sensitivity comparable to blood samples. This novel molecular test may have a positive impact in leishmaniasis control programs.
Financial support: This study was conducted with the support of the Institute for Translational Sciences at the University of Texas Medical Branch, supported in part by a Clinical and Translational Science Award (UL1TR000071) from the National Center for Advancing Translational Sciences, National Institutes of Health. Elissa Temple was the recipient of a Summer Undergraduate Internship in Tropical Diseases Research awarded by the UTMB Center for Tropical Diseases. The work also received support from the Secretaria de Calidad de Vida and Instituto Municipal de Sanidad Animal of the Municipality of Posadas, Misiones, Argentina.
Authors' addresses: Alejandro Castellanos-Gonzalez, Omar A. Saldarriaga, Elissa Temple, Hayley Sparks, and Bruno L. Travi, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, E-mails: alcastel@utmb.edu, omsaldar@utmb.edu, elissa_temple@baylor.edu, hnsparks@utmb.edu, and brltravi@utmb.edu. Lilian Tartaglino, Secretaria de Calidad de Vida, Municipalidad Ciudad de Posadas, Misiones, Argentina, E-mail: lilitartaglino@gmail.com. Rosana Gacek, Instituto Municipal de Sanidad Animal, Municipalidad de Posadas, Misiones, Argentina, E-mail: pelulia@hotmail.com. Peter C. Melby, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, E-mail: pcmelby@utmb.edu.
Alvar J, Velez ID, Bern C, Herrero M, Desjeux P, Cano J, Jannin J, den Boer M; the WHO Leishmaniasis Control Team, 2012. Leishmaniasis worldwide and global estimates of its incidence. PLoS One 7: e35671.
Sundar S, Chakravarty J, Agarwal D, Rai M, Murray HW, 2010. Single-dose liposomal amphotericin B for visceral leishmaniasis in India. N Engl J Med 362: 504ā512.
Harhay MO, Olliaro PL, Costa DL, Costa CH, 2011. Urban parasitology: visceral leishmaniasis in Brazil. Trends Parasitol 27: 403ā409.
Solano-Gallego L, Koutinas A, Miro G, Cardoso L, Pennisi MG, Ferrer L, Bourdeau P, Oliva G, Baneth G, 2009. Directions for the diagnosis, clinical staging, treatment and prevention of canine leishmaniasis. Vet Parasitol 165: 1ā18.
Nunes CM, Pires MM, da Silva KM, Assis FD, Goncalves Filho J, Perri SH, 2010. Relationship between dog culling and incidence of human visceral leishmaniasis in an endemic area. Vet Parasitol 170: 131ā133.
Costa CH, Gomes RB, Silva MR, Garcez LM, Ramos PK, Santos RS, Shaw JJ, David JR, Maguire JH, 2000. Competence of the human host as a reservoir for Leishmania chagasi. J Infect Dis 182: 997ā1000.
Ready PD, 2014. Epidemiology of visceral leishmaniasis. Clin Epidemiol 6: 147ā154.
Dantas-Torres F, Brandao-Filho SP, 2006. Visceral leishmaniasis in Brazil: revisiting paradigms of epidemiology and control. Rev Inst Med Trop Sao Paulo 48: 151ā156.
Mahmoudi MR, Kazemi B, Mohammadiha A, Mirzaei A, Karanis P, 2013. Detection of Cryptosporidium and Giardia (oo)cysts by IFA, PCR and LAMP in surface water from Rasht, Iran. Trans R Soc Trop Med Hyg 107: 511ā517.
Antinori S, Calattini S, Longhi E, Bestetti G, Piolini R, Magni C, Orlando G, Gramiccia M, Acquaviva V, Foschi A, 2007. Clinical use of polymerase chain reaction performed on peripheral blood and bone marrow samples for the diagnosis and monitoring of visceral leishmaniasis in HIV-infected and HIV-uninfected patients: a single-center, 8-year experience in Italy and review of the literature. Clin Infect Dis 44: 1602ā1610.
Ozerdem D, Eroglu F, Genc A, Demirkazik M, Koltas IS, 2009. Comparison of microscopic examination, rK39, and PCR for visceral leishmaniasis diagnosis in Turkey. Parasitol Res 106: 197ā200.
Boggild AK, Ramos AP, Espinosa D, Valencia BM, Veland N, Miranda-Verastegui C, Arevalo J, Low DE, Llanos-Cuentas A, 2010. Clinical and demographic stratification of test performance: a pooled analysis of five laboratory diagnostic methods for American cutaneous leishmaniasis. Am J Trop Med Hyg 83: 345ā350.
Crannell ZA, Rohrman B, Richards-Kortum R, 2014. Equipment-free incubation of recombinase polymerase amplification reactions using body heat. PLoS One 9: e112146.
Piepenburg O, Williams CH, Stemple DL, Armes NA, 2006. DNA detection using recombination proteins. PLoS Biol 4: e204.
Euler M, Wang Y, Heidenreich D, Patel P, Strohmeier O, Hakenberg S, Niedrig M, Hufert FT, Weidmann M, 2013. Development of a panel of recombinase polymerase amplification assays for detection of biothreat agents. J Clin Microbiol 51: 1110ā1117.
Euler M, Wang Y, Nentwich O, Piepenburg O, Hufert FT, Weidmann M, 2012. Recombinase polymerase amplification assay for rapid detection of Rift Valley fever virus. J Clin Virol 54: 308ā312.
Euler M, Wang Y, Otto P, Tomaso H, Escudero R, Anda P, Hufert FT, Weidmann M, 2012. Recombinase polymerase amplification assay for rapid detection of Francisella tularensis. J Clin Microbiol 50: 2234ā2238.
Crannell ZA, Castellanos-Gonzalez A, Irani A, Rohrman B, White AC, Richards-Kortum R, 2014. A nucleic acid test to diagnose cryptosporidiosis: lab assessment in animal and patient specimens. Anal Chem 86: 2565ā2571.
Rohrman BA, Richards-Kortum RR, 2012. A paper and plastic device for performing recombinase polymerase amplification of HIV DNA. Lab Chip 12: 3082ā3088.
Salomon O, Sinagra A, Nevot M, Barberian G, Paulin P, Estevez J, Riarte A, 2008. First visceral leishmaniasis focus in Argentina. Mem Inst Oswaldo Cruz 103: 109ā111.
Yurchenko VY, Merzlyak EM, Kolesnikov AA, Martinkina LP, Vengerov YY, 1999. Structure of Leishmania minicircle kinetoplast DNA classes. J Clin Microbiol 37: 1656ā1657.
Pita-Pereira D, Lins R, Oliveira MP, Lima RB, Pereira BA, Moreira OC, Brazil RP, Britto C, 2012. SYBR Green-based real-time PCR targeting kinetoplast DNA can be used to discriminate between the main etiologic agents of Brazilian cutaneous and visceral leishmaniasis. Parasit Vectors 5: 15.
Barao SC, de Fonseca Camargo-Neves VL, Resende MR, da Silva LJ, 2007. Human asymptomatic infection in visceral leishmaniasis: a seroprevalence study in an urban area of low endemicity. Preliminary results. Am J Trop Med Hyg 77: 1051ā1053.
Lemos EM, Laurenti MD, Moreira MA, Reis AB, Giunchetti RC, Raychaudhuri S, Dietze R, 2008. Canine visceral leishmaniasis: performance of a rapid diagnostic test (Kalazar Detect) in dogs with and without signs of the disease. Acta Trop 107: 205ā207.
Mary C, Faraut F, Drogoul MP, Xeridat B, Schleinitz N, Cuisenier B, Dumon H, 2006. Reference values for Leishmania infantum parasitemia in different clinical presentations: quantitative polymerase chain reaction for therapeutic monitoring and patient follow-up. Am J Trop Med Hyg 75: 858ā863.
Vaish M, Mehrotra S, Chakravarty J, Sundar S, 2011. Noninvasive molecular diagnosis of human visceral leishmaniasis. J Clin Microbiol 49: 2003ā2005.
Lombardo G, Pennisi MG, Lupo T, Migliazzo A, Capri A, Solano-Gallego L, 2012. Detection of Leishmania infantum DNA by real-time PCR in canine oral and conjunctival swabs and comparison with other diagnostic techniques. Vet Parasitol 184: 10ā17.
Campos-Ponce M, Ponce C, Ponce E, Maingon RD, 2005. Leishmania chagasi/infantum: further investigations on Leishmania tropisms in atypical cutaneous and visceral leishmaniasis foci in Central America. Exp Parasitol 109: 209ā219.
Quinnell RJ, Carson C, Reithinger R, Garcez LM, Courtenay O, 2013. Evaluation of rK39 rapid diagnostic tests for canine visceral leishmaniasis: longitudinal study and meta-analysis. PLoS Negl Trop Dis 7: e1992.
Carson C, Quinnell RJ, Holden J, Garcez LM, Deborggraeve S, Courtenay O, 2010. Comparison of Leishmania OligoC-TesT PCR with conventional and real-time PCR for diagnosis of canine Leishmania infection. J Clin Microbiol 48: 3325ā3330.
David JR, Stamm LM, Bezerra HS, Souza RN, Killick-Kendrick R, Lima JWO, 2001. Deltamethrin-impregnated dog collars have a potent anti-feeding and insecticidal effect on Lutzomyia longipalpis and Lutzomyia migonei. Mem Inst Oswaldo Cruz 96: 839ā847.
Sinha PK, Bhattacharya S, 2014. Single-dose liposomal amphotericin B: an effective treatment for visceral leishmaniasis. Lancet Glob Health 2: e7āe8.
Chappuis F, Sundar S, Hailu A, Ghalib H, Rijal S, Peeling RW, Alvar J, Boelaert M, 2007. Visceral leishmaniasis: what are the needs for diagnosis, treatment and control? Nat Rev Microbiol 5: 873ā882.
De Almeida Silva L, Romero HD, Prata A, Costa RT, Nascimento E, Carvalho SF, Rodrigues V, 2006. Immunologic tests in patients after clinical cure of visceral leishmaniasis. Am J Trop Med Hyg 75: 739ā743.
Silveira FT, Lainson R, Crescente JA, de Souza AA, Campos MB, Gomes CM, Laurenti MD, Corbett CE, 2010. A prospective study on the dynamics of the clinical and immunological evolution of human Leishmania (L.) infantum chagasi infection in the Brazilian Amazon region. Trans R Soc Trop Med Hyg 104: 529ā535.
Bern C, Courtenay O, Alvar J, 2010. Of cattle, sand flies and men: a systematic review of risk factor analyses for south Asian visceral leishmaniasis and implications for elimination. PLoS Negl Trop Dis 4: e599.
Fakiola M, Miller EN, Fadl M, Mohamed HS, Jamieson SE, Francis RW, Cordell HJ, Peacock CS, Raju M, Khalil EA, Elhassan A, Musa AM, Silveira F, Shaw JJ, Sundar S, Jeronimo SM, Ibrahim ME, Blackwell JM, 2011. Genetic and functional evidence implicating DLL1 as the gene that influences susceptibility to visceral leishmaniasis at chromosome 6q27. J Infect Dis 204: 467ā477.
Bhunia GS, Kesari S, Chatterjee N, Kumar V, Das P, 2013. Spatial and temporal variation and hotspot detection of kala-azar disease in Vaishali District (Bihar), India. BMC Infect Dis 13: 64.
Perry DDK, Garlapati R, Gendernalik A, PochĆ© D, PochĆ© R, 2013. Visceral leishmaniasis prevalence and associated risk factors in the saran district of Bihar, India, from 2009 to July of 2011. ASTMH 88: 778ā784.
Clemente WT, Rabello A, Faria LC, Peruhype-Magalhaes V, Gomes LI, da Silva TA, Nunes RV, Iodith JB, Protil KZ, Fernandes HR, Cortes JR, Lima SS, Lima AS, Romanelli RM, 2014. High prevalence of asymptomatic Leishmania spp. infection among liver transplant recipients and donors from an endemic area of Brazil. Am J Transplant 14: 96ā101.
Singh S, Kumari V, Singh N, 2002. Predicting kala-azar disease manifestations in asymptomatic patients with latent Leishmania donovani infection by detection of antibody against recombinant K39 antigen. Clin Diagn Lab Immunol 9: 568ā572.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 26 | 26 | 9 |
Full Text Views | 401 | 120 | 0 |
PDF Downloads | 119 | 20 | 0 |