Evaluation of Genetic Polymorphism of Leishmania (V.) Braziliensis Isolates Obtained from the Same Patient Before and After Therapeutic Failure or Reactivation of Cutaneous Lesions

Overview

Journal J Trop Med

Publisher Wiley

Specialty Tropical Medicine

Date 2013 Jan 11

PMID 23304168

Authors

Cibele Baptista

Armando de Oliveira Schubach

Maria de Fatima Madeira

Luciana de Freitas Campos Miranda

Andressa Guimaraes de Souza Pinto

Juliana Helena da Silva Barros

Fatima Conceicao-Silva

Maria Ines Fernandes Pimentel

Raquel da Silva Pacheco

Affiliations

Soon will be listed here.

Abstract

The aim of this study was to investigate genetic polymorphism in Leishmania braziliensis population previously typed through isoenzyme electrophoresis, isolated from the same patient in two different moments: (A) before the beginning of treatment and (B) after treatment failure to meglumine antimoniate or reactivation after successful initial treatment. Fifteen pairs of isolates were assessed using the polymorphic molecular marker LSSP-PCR and following the phenetic analysis. The genetic profiles of the 30 samples were grouped in four clusters. Only two patients presented total identity in the A and B isolates. Most isolates presented similarity coefficients varying from 0.63 to 0.91. In this group of patients genetic polymorphisms could be observed indicating low similarity between the pairs of isolates. The results demonstrate the existence of genetic polymorphism between the samples isolated before treatment and after reactivation or treatment failure, suggesting a possible differentiation of the structure of the original parasite population which could be involved in the mechanisms of resistance to treatment or reactivation of lesions in the ATL. This phenomenon is important, although other factors also could be involved in this context and are discussed in this paper.

References

Vergel C, Palacios R, Cadena H, Posso C, Valderrama L, Perez M . Evidence for leishmania (viannia) parasites in the skin and blood of patients before and after treatment. J Infect Dis. 2006; 194(4):503-11. DOI: 10.1086/505583. View

Brown W, George Jr M, Wilson A . Rapid evolution of animal mitochondrial DNA. Proc Natl Acad Sci U S A. 1979; 76(4):1967-71. PMC: 383514. DOI: 10.1073/pnas.76.4.1967. View

Pacheco R, Martinez J, Valderrama L, Momen H, Saravia N . Genotypic polymorphisms in experimental metastatic dermal leishmaniasis. Mol Biochem Parasitol. 1995; 69(2):197-209. DOI: 10.1016/0166-6851(94)00212-6. View

Laurent T, Rijal S, Yardley V, Croft S, De Doncker S, Decuypere S . Epidemiological dynamics of antimonial resistance in Leishmania donovani: genotyping reveals a polyclonal population structure among naturally-resistant clinical isolates from Nepal. Infect Genet Evol. 2006; 7(2):206-12. DOI: 10.1016/j.meegid.2006.08.005. View

Schubach A, Marzochi K, Moreira J, Schubach T, Araujo M, do Vale A . Retrospective study of 151 patients with cutaneous leishmaniasis treated with meglumine antimoniate. Rev Soc Bras Med Trop. 2005; 38(3):213-7. DOI: 10.1590/s0037-86822005000300001. View

Schubach A, Marzochi M, Cuzzi-Maya T, Oliveira A, Araujo M, Oliveira A . Cutaneous scars in American tegumentary leishmaniasis patients: a site of Leishmania (Viannia) braziliensis persistence and viability eleven years after antimonial therapy and clinical cure. Am J Trop Med Hyg. 1998; 58(6):824-7. DOI: 10.4269/ajtmh.1998.58.824. View

Rodrigues A, Hueb M, Santos T, Fontes C . [Factors associated with treatment failure of cutaneous leishmaniasis with meglumine antimoniate]. Rev Soc Bras Med Trop. 2006; 39(2):139-45. DOI: 10.1590/s0037-86822006000200001. View

Cupolillo E, Grimaldi Jr G, Momen H . A general classification of New World Leishmania using numerical zymotaxonomy. Am J Trop Med Hyg. 1994; 50(3):296-311. DOI: 10.4269/ajtmh.1994.50.296. View

Guerin P, Olliaro P, Sundar S, Boelaert M, Croft S, Desjeux P . Visceral leishmaniasis: current status of control, diagnosis, and treatment, and a proposed research and development agenda. Lancet Infect Dis. 2002; 2(8):494-501. DOI: 10.1016/s1473-3099(02)00347-x. View

10.

Santos de Oliveira F, Valete-Rosalino C, Schubach A, da Silva Pacheco R . kDNA minicircle signatures of Leishmania (Viannia) braziliensis in oral and nasal mucosa from mucosal leishmaniasis patients. Diagn Microbiol Infect Dis. 2010; 66(4):361-5. DOI: 10.1016/j.diagmicrobio.2009.11.004. View

11.

Unger A, ONeal S, Machado P, Guimaraes L, Morgan D, Schriefer A . Association of treatment of American cutaneous leishmaniasis prior to ulcer development with high rate of failure in northeastern Brazil. Am J Trop Med Hyg. 2009; 80(4):574-9. PMC: 3557504. View

12.

Simpson L . The mitochondrial genome of kinetoplastid protozoa: genomic organization, transcription, replication, and evolution. Annu Rev Microbiol. 1987; 41:363-82. DOI: 10.1146/annurev.mi.41.100187.002051. View

13.

Sundar S, More D, Singh M, Singh V, Sharma S, Makharia A . Failure of pentavalent antimony in visceral leishmaniasis in India: report from the center of the Indian epidemic. Clin Infect Dis. 2000; 31(4):1104-7. DOI: 10.1086/318121. View

14.

Santos de Oliveira F, Valete-Rosalino C, Schubach A, Madeira M, da Silva Pacheco R . Genetic polymorphism in Leishmania (Viannia) braziliensis detected in mucosal leishmaniasis of HIV-infected and non-HIV-infected patients. Trans R Soc Trop Med Hyg. 2012; 106(11):683-7. DOI: 10.1016/j.trstmh.2012.07.007. View

15.

Marzochi M, Marzochi K . Tegumentary and visceral leishmaniases in Brazil: emerging anthropozoonosis and possibilities for their control. Cad Saude Publica. 1994; 10 Suppl 2:359-75. DOI: 10.1590/s0102-311x1994000800014. View

16.

Baptista C, Schubach A, Madeira M, Leal C, Pires M, Oliveira F . Leishmania (Viannia) braziliensis genotypes identified in lesions of patients with atypical or typical manifestations of tegumentary leishmaniasis: evaluation by two molecular markers. Exp Parasitol. 2009; 121(4):317-22. DOI: 10.1016/j.exppara.2008.12.006. View

17.

Ponte-Sucre A . Physiological consequences of drug resistance in Leishmania and their relevance for chemotherapy. Kinetoplastid Biol Dis. 2003; 2(1):14. PMC: 272938. DOI: 10.1186/1475-9292-2-14. View

18.

Oliveira-Neto M, Schubach A, Mattos M, Pirmez C . A low-dose antimony treatment in 159 patients with American cutaneous leishmaniasis: extensive follow-up studies (up to 10 years). Am J Trop Med Hyg. 1998; 57(6):651-5. DOI: 10.4269/ajtmh.1997.57.651. View

19.

Sereno D, Cordeiro da Silva A, Mathieu-Daude F, Ouaissi A . Advances and perspectives in Leishmania cell based drug-screening procedures. Parasitol Int. 2006; 56(1):3-7. DOI: 10.1016/j.parint.2006.09.001. View

20.

Alvarenga J, Ligeiro C, Gontijo C, Cortes S, Campino L, Vago A . KDNA genetic signatures obtained by LSSP-PCR analysis of Leishmania (Leishmania) infantum isolated from the new and the old world. PLoS One. 2012; 7(8):e43363. PMC: 3422226. DOI: 10.1371/journal.pone.0043363. View