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. 2015 Oct 22;9(10):e0004093.
doi: 10.1371/journal.pntd.0004093. eCollection 2015.

Decline in Clinical Efficacy of Oral Miltefosine in Treatment of Post Kala-azar Dermal Leishmaniasis (PKDL) in India

Affiliations

Decline in Clinical Efficacy of Oral Miltefosine in Treatment of Post Kala-azar Dermal Leishmaniasis (PKDL) in India

V Ramesh et al. PLoS Negl Trop Dis. .

Erratum in

Abstract

Background: Recent studies have shown significant decline in the final cure rate after miltefosine treatment in visceral leishmaniasis. This study evaluates the efficacy of miltefosine in the treatment of post kala-azar dermal leishmaniasis (PKDL) patients recruited over a period of 5 years with 18 months of follow-up.

Methodology: In this study 86 confirmed cases of PKDL were treated with two different dosage regimens of miltefosine (Regimen I- 50mg twice daily for 90 days and Regimen II- 50 mg thrice for 60 days) and the clinical outcome assessed monthly. Cure/relapse was ascertained by clinical and histopathological examination, and measuring parasite burden by quantitative real-time PCR. In vitro susceptibility of parasites towards miltefosine was estimated at both promastigote and amastigote stages.

Results: Seventy three of eighty six patients completed the treatment and achieved clinical cure. Approximately 4% (3/73) patients relapsed by the end of 12 months follow-up, while a total of 15% (11/73) relapsed by the end of 18 months. Relapse rate was significantly higher in regimen II (31%) compared to regimen I (10.5%)(P<0.005). Parasite load at the pre-treatment stage was significantly higher (P<0.005) in cases that relapsed compared to the cases that remained cured. In vitro susceptibility towards miltefosine of parasites isolated after relapse was significantly lower (>2 fold) in comparison with the pre-treatment isolates (P<0.005).

Conclusion: Relapse rate in PKDL following miltefosine treatment has increased substantially, indicating the need of introducing alternate drugs/ combination therapy with miltefosine.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Recruitment, treatment and follow-up of PKDL patients.
Fig 2
Fig 2. A PKDL patient (Case 11, table no. 3) that relapsed after MIL treatment and was subsequently cured with AmB.
Papulo-nodules present on face before treatment (A), and complete regression after 3 months of MIL treatment (B), relapse at 13 months after completion of MIL treatment with papules on the root of nose (C), and cured after treatment with AmB (D).
Fig 3
Fig 3. Scatter plot showing parasite load at the pre-treatment stage in the cases that eventually relapsed vs those that remained cured.
Parasite load was determined by Q-PCR in slit aspirate sample at the time of diagnosis of PKDL and expressed as the number of Leishmania parasite/μl slit aspirate. P value was calculated using Mann-Whitney test. Horizontal bars indicate mean± SEM.
Fig 4
Fig 4. In vitro MIL susceptibility of parasite isolates from cured (n = 7) and relapsed (n = 6) PKDL patients.
MIL susceptibility at (A) promastigote stage (B) amastigote stage. Each individual value represents mean IC50± SD of the results from two separate assays. P value was calculated using Mann-Whitney test. Horizontal bars indicate mean ±SEM.

References

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