Acute uveitis: A rare adverse effect of miltefosine in the treatment of post-kala-azar dermal leishmaniasis

Abstract Post-kala-azar dermal leishmaniasis is a skin disorder occurring in 5-10% of visceral leishmaniasis patients after treatment with miltefosine,the first-line drug for this skin disorder. We reported a case of acute anterior uveitis,a rare adverse effect, experienced by a patient treated with miltefosine for post-kala-azar dermal leishmaniasis. This adverse effect developed after 15 days of miltefosine consumption, and the patient himself discontinued the treatment. The ophthalmic complication was completely resolved with antibiotics and steroid eye drops. After recovery from the ophthalmic complication, the patient was successfully treated with liposomal amphotericin B for the skin lesions.

Evaluation of anti-gal enzyme-linked immunosorbent assay for the diagnosis of Indian post-kala-azar dermal leishmaniasis

Background: Elimination of kala azar from India is challenging as there are potential reservoirs of Leishmania donovani in patients with post-kala-azar dermal leishmaniasis (PKDL). The vast repertoire of carbohydrate moieties on L. donovani is known to elicit specific and strong humoral responses in patients with kala azar. Aim: The present study was undertaken to evaluate the diagnostic performances of anti-gal antibodies using enzyme-linked immunosorbent assay for successful serological diagnosis of PKDL in Indian patients and to differentiate cases of past cured visceral leishmaniasis infections. Methods: We developed Gal enzyme-linked immunosorbent assay to measure specific anti-gal IgG isotype in the sera of 71 Indian patients with PKDL. The diagnostic efficacy of the newly developed assay was evaluated for precision, sensitivity and accuracy. Results: Gal2 enzyme-linked immunosorbent assay revealed three-fold increased anti-gal titers in 71 patients with active PKDL compared to controls. Subclass enzyme-linked immunosorbent assay analysis further revealed enhanced IgG2 and IgG3 anti-gal titers in patients with PKDL compared to control subjects. The rank order for specificity and sensitivity for IgG subclasses was IgG3>IgG2>IgG4>IgG1. The area under the curve values of 0.98 and 0.99 were obtained for IgG and IgG3 Gal2 enzyme-linked immunosorbent assays respectively. Overall sensitivity and specificity were 95.7% (95% CI: 88.1–99.1) and 98.1% (95% confidence interval: 90.1–99.9), and 98.5% (95% CI: 92.4–99.9) and 98.1% (95% CI: 90.1–99.9), respectively. Intra-assay coefficient of variation was 1.5% and inter-assay coefficient of variation was 11.7%. Limitations: The Gal2 enzyme-linked immunosorbent assay needs to be further investigated in mass surveys. Conclusion: Taken together, anti-gal titers detected through Gal2 enzyme-linked immunosorbent assay can serve as an effective diagnostic tool in disease elimination setting and help in better case management in endemic districts.

Assessment of Treatment Outcome in Post-Kala-Azar Dermal Leishmaniasis (PKDL) Patients– A Record-Based Observational study in a Speciality Public Hospital, Kolkata

In the absence of effective vector control measures and vaccines against leishmaniasis, effective chemotherapy remains the mainstay of treatment. Identification of post-kala-azar dermal leishmaniasis (PKDL) is important due to the long and toxic treatment and the fact that PKDL patients may serve as a reservoir for visceral leishmaniasis (VL). This retrospective study was done to assess the outcome of pharmacotherapy in post-kala-azar dermal leishmaniasis (PKDL) patients in a specialty public hospital in Kolkata. Methods: The hospital records of all consecutive PKDL patients admitted at Calcutta School of Tropical Medicine (CSTM), Kolkata during the last five years - 2010-2014, were reviewed and the relevant information inputs as documented studied to realize the noted objectives. Clinical presentation on admission including presence of co-infections (particularly HIV), trends and patterns of treatment regimens and rationale thereof, if available; treatment (anti-leishmaniasis) outcomes in reference to efficacy, safety and tolerability, fatality like serious complications and mortality and adverse drug reactions (for anti-leishmaninal drugs primarily), if any was noted. Results: PKDL cases presented with insidious onset skin lesions of different types without much systemic illness. 2 out of 19 cases presented with fever and 2 other cases had mild anemia. PKDL cases presented with 4 types of skin lesions. Multiple macular or hyppigmented macular lesions were commonest, 8 out of 19 cases (42.10%). In PKDL cases treatment outcome was difficult to say unless parasitologically declared negative, though clinically regression of the lesions were visible in all cases. Tolerability was least with AmB followed by SSG and best with miltefosine. Conclusion: So, it can be concluded from this study that in this institute PKDL were treated with conventional and liposomal AmB as well as with SSG, miltefosine and combination therapy. Among the regimens short course L-AmB was found to be the most efficacious and tolerable in respect to ADRs and hospital stay.

A Hospital Based Retrospective Study of Post Kala-Azar Dermal Leishmaniasis (PKDL) Cases

Post Kala-azar dermal leishmaniasis (PKDL) is a cutaneous form of leishmaniasis and usually occurs one to several years after apparent cure of visceral leishmaniasis (VL). Methods: The present work was designed as a retrospective tertiary urban hospital based, observational, clinico-epidemiological study during the period from February 2018 to January 2019. Results: A total of 24 PKDL patients, 16 males (66.66%) and 8 females (33.34%) were included in the study. The age of the patients ranged from 8 years to 56 years (mean age 30.6 years). Lesions in most of our patients (n=21, 87.50%) were located on the face, including the lip and nose. Most of our patients (n=20, 83.33%) were nodular (non-ulcerative), while two (08.33%) had nodulo ulcerative lesions and one (04.16%) had macular lesions. In the present study, 91.66.47 % (n = 22) of PKDL patients reported history of VL. The median time of manifestation of PKDL after VL treatment were 32 months (range = 5–286 months). Majority (n=20) of cases with history of VL had been treated with amphotericin B while the remaining (n=4,) had been treated with sodium stibogluconate. Conclusion: The present study highlights occurrence of PKDL in endemic area.Further epidemiological studies are required for identification of vector and strain of Leishmania involved.

Cure of post Kala-azar dermal leishmaniasis with paromomycin/sodium stibogluconate combination: a proof of concept.

Background: Post kala-azar dermal leishmaniasis (PKDL) is a recognized dermatologic complication of successfully treated visceral leishmaniasis (VL). PKDL lesions are suspected to be important reservoirs for VL transmission in Sudan. Prolonged treatment schedules, feeling of general well-being and the social stigmata of PKDL prevent most patients seeking treatment. The mainstay of treatment is cardiotoxic sodium stibogluconate (SSG) for 60-120 days. Recently, liposomal amphotericin B (Ambisome®) and immunochemotherapy gave promising results. Ambisome® is expensive and difficult to prepare under field conditions. Paromomycin/SSG combination has been shown to be safe, efficacious and can save time in VL treatment. This study aims to prove that Paromomycin/SSG combination can cure and reduce PKDL treatment duration. Methods: We are reporting nine cases of patients with PKDL lesions of ≥6 months duration who were diagnosed by clinical signs, histopathological/immunohistochemical and PCR. Results: Patients’ mean age was 11.7 ± 4.3 years. A third of the patients (3/9; 33.3%) who failed previous SSG treatment of 2-3 months duration responded completely to 40 days of paromomycin/SSG combination. The majority of patients (5/9; 55.6%) responded completely to 30 days of the combination. One patient (1/9; 11.1%) relapsed following 30 days paromomycin/SSG combination. Conclusion: It was concluded that paromomycin/SSG combination for 30 days is time-saving, safe and efficacious for PKDL treatment.