Quantitative Kinetoplast DNA Assessment During Treatment of Mucosal Leishmaniasis as a Potential Biomarker of Outcome: A Pilot Study.
Mucosal leishmaniasis (ML) is a disfiguring manifestation of Leishmania (Viannia) infection. We evaluated parasite load (PL) over time as a potential biomarker of treatment outcome in ML. PL was assessed with kinetoplast DNA quantitative real-time polymerase chain reaction (kDNA-qPCR) at enrollment, days 14 and 21-28 of therapy and 3, 6, 12-18, and 18-24 months after treatment of ML and correlated to demographic, clinical, and parasitologic factors. Forty-four patients were enrolled: 30 men and 14 women. Enrollment PL differed significantly by causative species (P < 0.001), and was higher in patients with severe ML (nasal and laryngeal involvement) compared with those with only isolated nasal involvement (median = 1,285 versus 51.5 parasites/μg tissue DNA; P = 0.005). Two patterns of PL emerged: pattern 1 (N = 23) was characterized by a sequential decline in PL during and after therapy until kDNA was undetectable. Pattern 2 (N = 18) was characterized by clearance of detectable kDNA during treatment, followed by an increased PL thereafter. All patients who failed treatment (N = 4) demonstrated pattern 1. Leishmania (Viannia) braziliensis was overrepresented among those with pattern 2 (P = 0.019). PL can be quantified by cytology brush qPCR during and after treatment in ML. We demonstrate that treatment failure was associated with undetectable PL, and L. (V.) braziliensis infection was overrepresented in those with rebounding PL.
Instituto de Medicina Tropical "Alexander von Humboldt," Universidad Peruana Cayetano Heredia, Lima, Peru; Public Health Ontario Laboratories, Public Health Ontario, Toronto, Canada; Department of Medicine, University of Toronto, Canada; Tropical Disease Unit, University Health Network Toronto General Hospital, Toronto, Canada.
Marlene
M
Jara
Instituto de Medicina Tropical "Alexander von Humboldt," Universidad Peruana Cayetano Heredia, Lima, Peru; Public Health Ontario Laboratories, Public Health Ontario, Toronto, Canada; Department of Medicine, University of Toronto, Canada; Tropical Disease Unit, University Health Network Toronto General Hospital, Toronto, Canada.
Braulio Mark
BM
Valencia
Instituto de Medicina Tropical "Alexander von Humboldt," Universidad Peruana Cayetano Heredia, Lima, Peru; Public Health Ontario Laboratories, Public Health Ontario, Toronto, Canada; Department of Medicine, University of Toronto, Canada; Tropical Disease Unit, University Health Network Toronto General Hospital, Toronto, Canada.
Vanessa
V
Adaui
Instituto de Medicina Tropical "Alexander von Humboldt," Universidad Peruana Cayetano Heredia, Lima, Peru; Public Health Ontario Laboratories, Public Health Ontario, Toronto, Canada; Department of Medicine, University of Toronto, Canada; Tropical Disease Unit, University Health Network Toronto General Hospital, Toronto, Canada.
Milena
M
Alba
Instituto de Medicina Tropical "Alexander von Humboldt," Universidad Peruana Cayetano Heredia, Lima, Peru; Public Health Ontario Laboratories, Public Health Ontario, Toronto, Canada; Department of Medicine, University of Toronto, Canada; Tropical Disease Unit, University Health Network Toronto General Hospital, Toronto, Canada.
Rachel
R
Lau
Instituto de Medicina Tropical "Alexander von Humboldt," Universidad Peruana Cayetano Heredia, Lima, Peru; Public Health Ontario Laboratories, Public Health Ontario, Toronto, Canada; Department of Medicine, University of Toronto, Canada; Tropical Disease Unit, University Health Network Toronto General Hospital, Toronto, Canada.
Jorge
J
Arevalo
Instituto de Medicina Tropical "Alexander von Humboldt," Universidad Peruana Cayetano Heredia, Lima, Peru; Public Health Ontario Laboratories, Public Health Ontario, Toronto, Canada; Department of Medicine, University of Toronto, Canada; Tropical Disease Unit, University Health Network Toronto General Hospital, Toronto, Canada.
Alejandro
A
Llanos-Cuentas
Instituto de Medicina Tropical "Alexander von Humboldt," Universidad Peruana Cayetano Heredia, Lima, Peru; Public Health Ontario Laboratories, Public Health Ontario, Toronto, Canada; Department of Medicine, University of Toronto, Canada; Tropical Disease Unit, University Health Network Toronto General Hospital, Toronto, Canada andrea.boggild@utoronto.ca.
Andrea K
AK
Boggild
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000666:Amphotericin B / Q000008:administration & dosage / Q000627:therapeutic use*; D000967:Antimony Sodium Gluconate / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers; D002648:Child; D018105:DNA, Kinetoplast / Q000235:genetics*; D016054:DNA, Protozoan / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D006801:Humans; D007897:Leishmaniasis, Mucocutaneous / Q000469:parasitology*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D060888:Real-Time Polymerase Chain Reaction; D016896:Treatment Outcome; D055815:Young Adult
D015415:Biomarkers; D018105:DNA, Kinetoplast; D016054:DNA, Protozoan; D000666:Amphotericin B; D000967:Antimony Sodium Gluconate