The Relationship of Leishmania braziliensis Subspecies and Immune Response to Disease Expression in New World Leishmaniasis

Saravia, Nancy Gore; Valderrama, Liliana; Labrada, Maricel; Holguín, A F; Navas, Claudia; Palma, Gloria; Weigle, Kristen A.

doi:10.1093/infdis/159.4.725

Cited by 75 publications

(61 citation statements)

References 37 publications

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“…In contrast, in Manaus only 42.5% of the patients were cured with this drug similar to other results already published (OLIVEIRA- NETO et al, 1997;ROMERO et al, 2001). These data support the high variability in cure rate of this disease depending on Leishmania spp., the clinical picture and the geographical region (SARAVIA et al, 1989;ROMERO et al, 2001;SOTO & TOLEDO, 2007). Besides, drug resistance that would be a naturally acquired condition in leishmania, has been partially associated with poor response (GROGL et al, 1992).…”

Section: Resultsmentioning

confidence: 99%

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Failure of both azithromycin and antimony to treat cutaneous leishmaniasis in Manaus, AM, Brazil

Teixeira

Paes

Guerra

et al. 2008

Rev. Inst. Med. trop. S. Paulo

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SUMMARYA non-randomized controlled clinical trial was carried out in order to evaluate both azithromycin and antimony efficacy in cutaneous leishmaniasis in Manaus, AM, Brazil. Forty nine patients from both genders, aged 14 to 70, with cutaneous ulcers for less than three months and a positive imprint for Leishmania spp. amastigotes were recruited into two groups. Group I (26 patients) received a daily-single oral dose of 500 mg of azithromycin for 20 days and Group II (23 patients) received a daily-single intramuscular dose of 20 mg/kg of meglumine antimony, also for 20 days. Azithromycin cured three of 24 (12.5%) patients on days 60, 90 and 120 respectively whereas therapeutic failure was considered in 21 of 24 (87.5%) cases. In group II, antimony cured eight of 19 (42.1%) cases as follows: three on day 30, one each on day 60 and day 90, and three on day 120. Therapeutic failure occurred in 11 of 19 (57.9%) individuals. The efficacy of antimony for leishmaniasis was better than azithromycin but analysis for the intention-to-treat response rate did not show statistical difference between them. Although azithromycin was better tolerated, it showed a very low efficacy to treat cutaneous leishmaniasis in Manaus.

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Section: Resultsmentioning

confidence: 99%

“…Leishmaniasis has been treated for decades with pentavalent antimony, pentamidine or amphotericin B but patients cure rate presents high variability depending on Leishmania spp., clinical picture and geographical location (SARAVIA et al, 1989;ROMERO et al, 2001). …”

Section: Introductionmentioning

confidence: 99%

Failure of both azithromycin and antimony to treat cutaneous leishmaniasis in Manaus, AM, Brazil

Teixeira

Paes

Guerra

et al. 2008

Rev. Inst. Med. trop. S. Paulo

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“…Thus, most of the knowledge on the immune responses in CL and ML caused by L. braziliensis has originated from studies of patients (5,11,12,17,27,28). Therefore, human tegumentary leishmaniasis does not present a clearly polarized Th1 or Th2 immune response as observed in the mouse-L. major experimental model (11).…”

Section: American Tegumentary Leishmaniasis (Atl) Is Produced Inmentioning

confidence: 99%

T-Cell-Mediated Immune Responses in Patients with Cutaneous or Mucosal Leishmaniasis: Long-Term Evaluation after Therapy

Da‐Cruz¹,

Bittar²,

Mattos

et al. 2002

Clin Vaccine Immunol

100

153

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T-cell immune responses in patients with cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML)were studied during the active disease, at the end of therapy, and 1 to 17 years posttherapy (long-term follow-up). Lymphocyte proliferative responses, phenotypic characterization of CD4 ؉ and CD8 ؉ Leishmaniareactive T cells, and cytokine production were assayed. Patients with active ML and CL showed higher proportions of CD4 ؉ than CD8 ؉ T cells. In CL, the healing process was associated with a decrease of CD4؉ and an increase of CD8 ؉ , leading to similar CD4 ؉ and CD8 ؉ proportions. This pattern was only seen in ML after long-term therapy. Long-term follow-up of patients with CL showed a positive CD4؉ /CD8 ؉ ratio as observed during the active disease, although the percentages of these T cell subsets were significantly lower. Patients with CL did not show significant differences between gamma interferon (IFN-␥) and interleukin-5 (IL-5) production during the period of study. Patients with active ML presented higher IFN-␥ and IL-5 levels compared to patients with active CL. IL-4 was only detected during active disease. Patients long term after cure from ML showed increasing production of IFN-␥, significant decrease of IL-5, and no IL-4 production. Two apparently beneficial immunological parameters were detected in tegumentary leishmaniasis: (i) decreasing proportions of CD4 ؉ Leishmania-reactive T cells in the absence of IL-4 production associated with cure of CL and ML and (ii) decreasing levels of IL-5 long after cure, better detected in patients with ML. The observed T-cell responses maintained for a long period in healed patients could be relevant for immunoprotection against reinfection and used as a parameter for determining the prognosis of patients and selecting future vaccine preparations.

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“…However, protection amongst M+L-people ( [38], and positively correlated with fibrinoid necrosis and severity of disease [39]. In contrast, Saravia [40] found no correlation between MST response and lesion size, although there was an association between MST response and Leishmania species.…”

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confidence: 96%

Cutaneous leishmaniasis in the Peruvian Andes: an epidemiological study of infection and immunity

et al. 1995

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SUMMARYA prospective longitudinal survey of cutaneous leishmaniasis (Leishmania peruviana) was carried out in Peru on a study population of 4716 persons living in 38 villages (Departments of Lima, Ancash and Piura). Demographic and clinical data were collected from all individuals, and a Montenegro skin test (MST) was carried out on 72 % (3418) of the study population. Each household was revisited at 3-monthly intervals for up to 2 years to detect new leishmaniasis cases; 497 people received a second MST at the end of the study. Analysis of the epidemiological data indicated that (i) 17 % (16/94) of all infections were subclinical, (ii) this percentage increased significantly with age, (iii) clinical infections led to 73-9 % protective immunity (95 % C.I. 53-0-85-5 %) and relatively permanent MST responsiveness (recovery rate = 0-0098/year; 95% C.I. 0000-00020/year), (iv) sub-clinical infections led to protective immunity, which was positively correlated with their MST induration size (increasing by 17-9% per mm; P < 0-0001), and a mean MST recovery rate of 0-414/year (4/421 manmonths), and (v) recurrent leishmaniasis was dominated by reactivations, not by reinfections.

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The Relationship of Leishmania braziliensis Subspecies and Immune Response to Disease Expression in New World Leishmaniasis

Cited by 75 publications

References 37 publications

Failure of both azithromycin and antimony to treat cutaneous leishmaniasis in Manaus, AM, Brazil

Failure of both azithromycin and antimony to treat cutaneous leishmaniasis in Manaus, AM, Brazil

T-Cell-Mediated Immune Responses in Patients with Cutaneous or Mucosal Leishmaniasis: Long-Term Evaluation after Therapy

Cutaneous leishmaniasis in the Peruvian Andes: an epidemiological study of infection and immunity

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