ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
World Health Organization , 2023. Leishmaniasis. Available at: https://www.who.int/news-room/fact-sheets/detail/leishmaniasis. Accessed May 21, 2023.
-
2.
Mansueto P , Seidita A , Vitale G , Cascio A , 2014. Leishmaniasis in travelers: A literature review. Travel Med Infect Dis 12: 563–581.
-
3.
Clarke CF , Bradley KK , Wright JH , Glowicz J , 2013. Case report: Emergence of autochthonous cutaneous leishmaniasis in northeastern Texas and southeastern Oklahoma. Am J Trop Med Hyg 88: 157–161.
-
4.
McIlwee BE , Weis SE , Hosler GA , 2018. Incidence of endemic human cutaneous leishmaniasis in the United States. JAMA Dermatol 154: 1032–1039.
-
5.
Sereno D , 2019. Leishmania (Mundinia) spp.: From description to emergence as new human and animal Leishmania pathogens. New Microbes New Infect 30: 100540.
-
6.
Espinosa OA , Serrano MG , Camargo EP , Teixeira MMG , Shaw JJ , 2018. An appraisal of the taxonomy and nomenclature of trypanosomatids presently classified as Leishmania and Endotrypanum. Parasitology 145: 430–442.
-
7.
Kipp EJ , de Almeida M , Marcet PL , Bradbury RS , Benedict T , Lin W , Dotson EM , Hergert M , 2020. An atypical case of autochthonous cutaneous leishmaniasis associated with naturally infected phlebotomine sand flies in Texas, United States. Am J Trop Med Hyg 103: 1496–1501.
-
8.
Douvoyiannis M , Khromachou T , Byers N , Hargreaves J , Murray HW , 2014. Cutaneous leishmaniasis in North Dakota. Clin Infect Dis 59: e73–e75.
-
9.
Evans DA , Lanham SM , Baldwin CI , Peters W , 1984. The isolation and isoenzyme characterization of Leishmania braziliensis subsp. from patients with cutaneous leishmaniasis acquired in Belize. Trans R Soc Trop Med Hyg 78: 35–42.
-
10.
Bourdoiseau G , Marchal T , Magnol JP , 1997. Immunohistochemical detection of Leishmania infantum in formalin-fixed, paraffin-embedded sections of canine skin and lymph nodes. J Vet Diagn Invest 9: 439–440.
-
11.
Tafuri WL , de Oliveira MR , Melo MN , Tafuri WL , 2001. Canine visceral leishmaniosis: A remarkable histopathological picture of one case reported from Brazil. Vet Parasitol 96: 203–212.
-
12.
Dias-Polak D , Geffen Y , Ben-Izhak O , Bergman E , 2017. The role of histopathology and immunohistochemistry in the diagnosis of cutaneous leishmaniasis without “discernible” Leishman-Donovan bodies. Am J Dermatopathol 12: 890–895.
-
13.
Dos Santos IB , Tortelly R , Quintella LP , de Fatima Madeira M , Monteiro de Miranda LH , Borges Figueredo F , Carvalhaes de Oliveira Rde V , Pacheco Schubach TM , 2015. Higher sensitivity of immunohistochemistry for bone fide diagnosis of dog Leishmania (Viannia) braziliensis‒driven American tegumentary leishmaniasis: Description of an optimized immunohistochemistry method. Trans R Soc Trop Med Hyg 7: 469–476.
-
14.
Al-Jawabreh A , Schoenian G , Hamarsheh O , Presber W , 2006. Clinical diagnosis of cutaneous leishmaniasis: A comparison study between standardized graded direct microscopy and ITS1-PCR of Giemsa-stained smears. Acta Trop 99: 55–61.
-
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.
de Almeida ME , Koru O , Steurer F , Herwaldt BL , da Silva AJ , 2017. Detection and differentiation of Leishmania spp. in clinical specimens by use of a SYBR green-based real-time PCR assay. J Clin Microbiol 55: 281–290.
-
17.
de Almeida ME , Steurer FJ , Koru O , Herwaldt BL , Pieniazek NJ , da Silva AJ , 2011. Identification of Leishmania spp. by molecular amplification and DNA sequencing analysis of a fragment of rRNA internal transcribed spacer 2. J Clin Microbiol 49: 3143–3149.
-
18.
Specht K , Richter T , Muller U , Walch A , Werner M , Hofler H , 2001. Quantitative gene expression analysis in microdissected archival formalin-fixed and paraffin-embedded tumor tissue. Am J Pathol 158: 419–429.
-
19.
Cronin M , Pho M , Dutta D , Stephans JC , Shak S , Kiefer MC , Esteban JM , Baker JB , 2004. Measurement of gene expression in archival paraffin-embedded tissues: Development and performance of a 92-gene reverse transcriptase-polymerase chain reaction assay. Am J Pathol 164: 35–42.
-
20.
Kreutzer RD , Christensen HA , 1980. Characterization of Leishmania spp. by isozyme electrophoresis. Am J Trop Med Hyg 29: 199–208.
-
21.
Kreutzer RD , Semko ME , Hendricks LD , Wright N , 1983. Identification of Leishmania spp. by multiple isozyme analysis. Am J Trop Med Hyg 32: 703–715.
-
22.
Tordini G , Giaccherini R , Pacenti L , Miracco C , Zazzi M , Zanelli G , 2007. Cutaneous leishmaniasis: Usefulness of PCR on paraffin-embedded skin biopsies as part of routine investigation. Ann Trop Med Parasitol 101: 745–749.
-
23.
de Lima ACS , Zampieri R , Tomokane T , Laurenti M , Silveira F , Corbett C , Floeter-Winter L , Gomes C , 2011. Leishmania sp. identification by PCR associated with sequencing of target SSU rDNA in paraffin-embedded skin samples stored for more than 30 years. Parasitol Res 108: 1525–1531.
-
24.
Moreira OC , Yadon ZE , Cupolillo E , 2018. The applicability of real-time PCR in the diagnostic of cutaneous leishmaniasis and parasite quantification for clinical management: Current status and perspectives. Acta Trop 184: 29–37.
-
25.
Anders G , Eisenberger CL , Jonas F , Greenblatt CL , 2002. Distinguishing Leishmania tropica and Leishmania major in the Middle East using the polymerase chain reaction with kinetoplast DNA-specific primers. Trans R Soc Trop Med Hyg 96: S87–S92.
-
26.
Parvizi P , Mauricio I , Aransay AM , Miles MA , Ready PD , 2005. First detection of Leishmania major in peridomestic Phlebotomus papatasi from Isfahan province, Iran: Comparison of nested PCR of nuclear ITS ribosomal DNA and semi-nested PCR of minicircle kinetoplast DNA. Acta Trop 93: 75–83.
-
27.
Reithinger R , Dujardin JC , 2007. Molecular diagnosis of leishmaniasis: Current status and future applications. J Clin Microbiol 45: 21–25.
-
28.
Disch J , Pedras MJ , Orsini M , Pirmez C , de Oliveria MC , Castro M , Rabello A , 2005. Leishmania (Viannia) subgenus kDNA amplification for the diagnosis of mucosal leishmaniasis. Diagn Microbiol Infect Dis 51: 185–190.
-
29.
Bensoussan E , Nasereddin A , Jonas F , Schnur LF , Jaffe CL , 2006. Comparison of PCR assays for diagnosis of cutaneous leishmaniasis. J Clin Microbiol 44: 1435–1439.
-
30.
van Eys GJ , Schoone GJ , Kroon NC , Ebeling SB , 1992. Sequence analysis of small subunit rRNA genes and its use for detection and identification of Leishmania parasites. Mol Biochem Parasitol 51: 133–142.
-
31.
Dietrich D , Uhl B , Sailer V , Holmes EE , Jung M , Meller S , Kristiansen G , 2013. Improved PCR performance using template DNA from formalin-fixed and paraffin-embedded tissues by overcoming PCR inhibition. PLoS One 8: e77771.
-
32.
Srinivasan M , Sedmak D , Jewell S , 2002. Effect of fixatives and tissue processing on the content and integrity of nucleic acids. Am J Pathol 161: 1961–1971.
-
33.
Bacich DJ , Sobek KM , Cummings JL , Atwood AA , O’Keefe DS , 2011. False negative results from using common PCR reagents. BMC Res Notes 4: 457.
-
34.
Sunderkötter C et al., 2018. Molecular diagnosis of skin infectious using paraffin-embedded tissue – Review and interdisciplinary consensus. J Dtsch Dermatol Ges 16: 139–147.
-
35.
Alves CF , Alves CF , Figueiredo MM , Souza CC , Machado-Coelho GL , Melo MN , Tafuri WL , Raso P , Soares RP , Tafuri WL , 2013. American tegumentary leishmaniasis: Effectiveness of an immunohistochemical protocol for the detection of Leishmania in skin. PLoS One 8: e63343.
-
36.
Pena HP et al., 2020. Accuracy of diagnostic tests for American tegumentary leishmaniasis: A systematic literature review with meta-analyses. Trop Med Int Health 10: 1168–1181.
-
37.
Schubach A , Cuzzi-Maya T , Oliveira AV , Sartori A , 2001. Leishmanial antigens in the diagnosis of active lesions and ancient scars of American tegumentary leishmaniasis patients. Mem Inst Oswaldo Cruz 96: 987–996.
-
38.
Marques FA et al., 2017. Effectiveness of an immunohistochemical protocol for Leishmania detection in different clinical forms of American tegumentary leishmaniasis. Parasitol Int 66: 884–888.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 1386 | 1386 | 84 |
| Full Text Views | 79 | 79 | 5 |
| PDF Downloads | 96 | 96 | 5 |
A Diagnostic Algorithm for Detection of Leishmania spp. in Human Fresh and Fixed Tissue Samples
Luciana M. Silva-Flannery
Luciana M. Silva-Flannery
Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia;
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Marcos E. de Almeida
Marcos E. de Almeida
Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia
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Alexandre J. da Silva
Alexandre J. da Silva
Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia
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Brigid C. Bollweg
Brigid C. Bollweg
Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia;
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Pamela S. Fair
Pamela S. Fair
Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia;
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Jana M. Ritter
Jana M. Ritter
Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia;
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Christopher D. Paddock
Christopher D. Paddock
Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia;
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Roosecelis B. Martines
Roosecelis B. Martines
Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia;
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Sherif R. Zaki
Sherif R. Zaki
Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia;
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ABSTRACT.
Leishmaniasis is an important travel-related parasitic infection in the United States. Treatment regimens vary by Leishmania species and require an accurate diagnosis. The sensitivity and specificity of diagnostic methods depend on the type and condition of specimen analyzed. To identify the best algorithm for detection of parasites in fresh and fixed tissue samples, we evaluated parasite cultures, two PCR methods, and Leishmania immunohistochemistry (IHC) in samples received by the CDC from 2012 through 2019. The sensitivity and specificity of IHC assays were evaluated in fresh specimens tested. Diagnostic accuracy for formalin-fixed tissue was evaluated by using PCR-based methods and IHC. Of 100 suspected cases with fresh tissue available, Leishmania spp. infection was identified by PCR in 56% (56/100) of specimens; from these, 80% (45/56) were positive by parasite culture and 59% (33/56) by IHC. Of 420 possible cases where only fixed specimens were available, 58% (244/420) were positive by IHC and/or PCR. Of these, 96% (235/420) were positive by IHC and 84% (204/420) by PCR-based methods. Overall parasite detection using all methodologies was similar for fresh and formalin-fixed tissue specimens (56% versus 58%, respectively). Although PCR-based methods were superior for diagnosis of leishmaniasis and species identification in fresh samples, IHC in combination with PCR increased the accuracy for Leishmania spp. detection in fixed samples. In conclusion, PCR is the most effective method for detecting Leishmania infection in fresh tissue samples, whereas for formalin-fixed samples, IHC and PCR-based methods should be used in combination.
Author Notes
Disclosures: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC. This activity was reviewed by the CDC, deemed nonresearch, and conducted consistent with applicable federal law and CDC policy.
Authors’ addresses: Luciana M. Silva-Flannery, Brigid C. Bollweg, Roosecelis B. Martines, Jana M. Ritter, Christopher D. Paddock, and Pamela S. Fair, Division of High-Consequence Pathogens and Pathology, Infectious Diseases Pathology Branch, Centers for Diseases Control and Prevention, Atlanta, GA: E-mails: vva3@cdc.gov, brigid.caroline@gmail.com, xgn7@cdc.gov, vtr0@cdc.gov, cdp9@cdc.gov, and hia9@cdc.gov. Marcos E. de Almeida, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Diseases Control and Prevention, Atlanta, GA, E-mail: bnz0@cdc.gov. Alexandre J. da Silva, Center for Food Safety and Applied Nutrition, Office of Food Safety, Food and Drug Administration, Silver Spring, MD, E-mail: alexandre.dasilva@fda.hhs.gov.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
World Health Organization , 2023. Leishmaniasis. Available at: https://www.who.int/news-room/fact-sheets/detail/leishmaniasis. Accessed May 21, 2023.
-
2.
Mansueto P , Seidita A , Vitale G , Cascio A , 2014. Leishmaniasis in travelers: A literature review. Travel Med Infect Dis 12: 563–581.
-
3.
Clarke CF , Bradley KK , Wright JH , Glowicz J , 2013. Case report: Emergence of autochthonous cutaneous leishmaniasis in northeastern Texas and southeastern Oklahoma. Am J Trop Med Hyg 88: 157–161.
-
4.
McIlwee BE , Weis SE , Hosler GA , 2018. Incidence of endemic human cutaneous leishmaniasis in the United States. JAMA Dermatol 154: 1032–1039.
-
5.
Sereno D , 2019. Leishmania (Mundinia) spp.: From description to emergence as new human and animal Leishmania pathogens. New Microbes New Infect 30: 100540.
-
6.
Espinosa OA , Serrano MG , Camargo EP , Teixeira MMG , Shaw JJ , 2018. An appraisal of the taxonomy and nomenclature of trypanosomatids presently classified as Leishmania and Endotrypanum. Parasitology 145: 430–442.
-
7.
Kipp EJ , de Almeida M , Marcet PL , Bradbury RS , Benedict T , Lin W , Dotson EM , Hergert M , 2020. An atypical case of autochthonous cutaneous leishmaniasis associated with naturally infected phlebotomine sand flies in Texas, United States. Am J Trop Med Hyg 103: 1496–1501.
-
8.
Douvoyiannis M , Khromachou T , Byers N , Hargreaves J , Murray HW , 2014. Cutaneous leishmaniasis in North Dakota. Clin Infect Dis 59: e73–e75.
-
9.
Evans DA , Lanham SM , Baldwin CI , Peters W , 1984. The isolation and isoenzyme characterization of Leishmania braziliensis subsp. from patients with cutaneous leishmaniasis acquired in Belize. Trans R Soc Trop Med Hyg 78: 35–42.
-
10.
Bourdoiseau G , Marchal T , Magnol JP , 1997. Immunohistochemical detection of Leishmania infantum in formalin-fixed, paraffin-embedded sections of canine skin and lymph nodes. J Vet Diagn Invest 9: 439–440.
-
11.
Tafuri WL , de Oliveira MR , Melo MN , Tafuri WL , 2001. Canine visceral leishmaniosis: A remarkable histopathological picture of one case reported from Brazil. Vet Parasitol 96: 203–212.
-
12.
Dias-Polak D , Geffen Y , Ben-Izhak O , Bergman E , 2017. The role of histopathology and immunohistochemistry in the diagnosis of cutaneous leishmaniasis without “discernible” Leishman-Donovan bodies. Am J Dermatopathol 12: 890–895.
-
13.
Dos Santos IB , Tortelly R , Quintella LP , de Fatima Madeira M , Monteiro de Miranda LH , Borges Figueredo F , Carvalhaes de Oliveira Rde V , Pacheco Schubach TM , 2015. Higher sensitivity of immunohistochemistry for bone fide diagnosis of dog Leishmania (Viannia) braziliensis‒driven American tegumentary leishmaniasis: Description of an optimized immunohistochemistry method. Trans R Soc Trop Med Hyg 7: 469–476.
-
14.
Al-Jawabreh A , Schoenian G , Hamarsheh O , Presber W , 2006. Clinical diagnosis of cutaneous leishmaniasis: A comparison study between standardized graded direct microscopy and ITS1-PCR of Giemsa-stained smears. Acta Trop 99: 55–61.
-
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.
de Almeida ME , Koru O , Steurer F , Herwaldt BL , da Silva AJ , 2017. Detection and differentiation of Leishmania spp. in clinical specimens by use of a SYBR green-based real-time PCR assay. J Clin Microbiol 55: 281–290.
-
17.
de Almeida ME , Steurer FJ , Koru O , Herwaldt BL , Pieniazek NJ , da Silva AJ , 2011. Identification of Leishmania spp. by molecular amplification and DNA sequencing analysis of a fragment of rRNA internal transcribed spacer 2. J Clin Microbiol 49: 3143–3149.
-
18.
Specht K , Richter T , Muller U , Walch A , Werner M , Hofler H , 2001. Quantitative gene expression analysis in microdissected archival formalin-fixed and paraffin-embedded tumor tissue. Am J Pathol 158: 419–429.
-
19.
Cronin M , Pho M , Dutta D , Stephans JC , Shak S , Kiefer MC , Esteban JM , Baker JB , 2004. Measurement of gene expression in archival paraffin-embedded tissues: Development and performance of a 92-gene reverse transcriptase-polymerase chain reaction assay. Am J Pathol 164: 35–42.
-
20.
Kreutzer RD , Christensen HA , 1980. Characterization of Leishmania spp. by isozyme electrophoresis. Am J Trop Med Hyg 29: 199–208.
-
21.
Kreutzer RD , Semko ME , Hendricks LD , Wright N , 1983. Identification of Leishmania spp. by multiple isozyme analysis. Am J Trop Med Hyg 32: 703–715.
-
22.
Tordini G , Giaccherini R , Pacenti L , Miracco C , Zazzi M , Zanelli G , 2007. Cutaneous leishmaniasis: Usefulness of PCR on paraffin-embedded skin biopsies as part of routine investigation. Ann Trop Med Parasitol 101: 745–749.
-
23.
de Lima ACS , Zampieri R , Tomokane T , Laurenti M , Silveira F , Corbett C , Floeter-Winter L , Gomes C , 2011. Leishmania sp. identification by PCR associated with sequencing of target SSU rDNA in paraffin-embedded skin samples stored for more than 30 years. Parasitol Res 108: 1525–1531.
-
24.
Moreira OC , Yadon ZE , Cupolillo E , 2018. The applicability of real-time PCR in the diagnostic of cutaneous leishmaniasis and parasite quantification for clinical management: Current status and perspectives. Acta Trop 184: 29–37.
-
25.
Anders G , Eisenberger CL , Jonas F , Greenblatt CL , 2002. Distinguishing Leishmania tropica and Leishmania major in the Middle East using the polymerase chain reaction with kinetoplast DNA-specific primers. Trans R Soc Trop Med Hyg 96: S87–S92.
-
26.
Parvizi P , Mauricio I , Aransay AM , Miles MA , Ready PD , 2005. First detection of Leishmania major in peridomestic Phlebotomus papatasi from Isfahan province, Iran: Comparison of nested PCR of nuclear ITS ribosomal DNA and semi-nested PCR of minicircle kinetoplast DNA. Acta Trop 93: 75–83.
-
27.
Reithinger R , Dujardin JC , 2007. Molecular diagnosis of leishmaniasis: Current status and future applications. J Clin Microbiol 45: 21–25.
-
28.
Disch J , Pedras MJ , Orsini M , Pirmez C , de Oliveria MC , Castro M , Rabello A , 2005. Leishmania (Viannia) subgenus kDNA amplification for the diagnosis of mucosal leishmaniasis. Diagn Microbiol Infect Dis 51: 185–190.
-
29.
Bensoussan E , Nasereddin A , Jonas F , Schnur LF , Jaffe CL , 2006. Comparison of PCR assays for diagnosis of cutaneous leishmaniasis. J Clin Microbiol 44: 1435–1439.
-
30.
van Eys GJ , Schoone GJ , Kroon NC , Ebeling SB , 1992. Sequence analysis of small subunit rRNA genes and its use for detection and identification of Leishmania parasites. Mol Biochem Parasitol 51: 133–142.
-
31.
Dietrich D , Uhl B , Sailer V , Holmes EE , Jung M , Meller S , Kristiansen G , 2013. Improved PCR performance using template DNA from formalin-fixed and paraffin-embedded tissues by overcoming PCR inhibition. PLoS One 8: e77771.
-
32.
Srinivasan M , Sedmak D , Jewell S , 2002. Effect of fixatives and tissue processing on the content and integrity of nucleic acids. Am J Pathol 161: 1961–1971.
-
33.
Bacich DJ , Sobek KM , Cummings JL , Atwood AA , O’Keefe DS , 2011. False negative results from using common PCR reagents. BMC Res Notes 4: 457.
-
34.
Sunderkötter C et al., 2018. Molecular diagnosis of skin infectious using paraffin-embedded tissue – Review and interdisciplinary consensus. J Dtsch Dermatol Ges 16: 139–147.
-
35.
Alves CF , Alves CF , Figueiredo MM , Souza CC , Machado-Coelho GL , Melo MN , Tafuri WL , Raso P , Soares RP , Tafuri WL , 2013. American tegumentary leishmaniasis: Effectiveness of an immunohistochemical protocol for the detection of Leishmania in skin. PLoS One 8: e63343.
-
36.
Pena HP et al., 2020. Accuracy of diagnostic tests for American tegumentary leishmaniasis: A systematic literature review with meta-analyses. Trop Med Int Health 10: 1168–1181.
-
37.
Schubach A , Cuzzi-Maya T , Oliveira AV , Sartori A , 2001. Leishmanial antigens in the diagnosis of active lesions and ancient scars of American tegumentary leishmaniasis patients. Mem Inst Oswaldo Cruz 96: 987–996.
-
38.
Marques FA et al., 2017. Effectiveness of an immunohistochemical protocol for Leishmania detection in different clinical forms of American tegumentary leishmaniasis. Parasitol Int 66: 884–888.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 1386 | 1386 | 84 |
| Full Text Views | 79 | 79 | 5 |
| PDF Downloads | 96 | 96 | 5 |