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13 result(s)
Journal Article > ReviewFull Text

Cutaneous leishmaniasis in Afghanistan

Trans R Soc Trop Med Hyg. 7 May 2025; Online ahead of print; DOI:10.1093/trstmh/traf028
Rahimi BA, Ghatee MA, Habib MN, Farooqi K, Ritmeijer K,  et al.
Trans R Soc Trop Med Hyg. 7 May 2025; Online ahead of print; DOI:10.1093/trstmh/traf028

Old World cutaneous leishmaniasis (OWCL) is a sand fly-transmitted skin infection caused by Leishmania species that extends from West Africa to China. Afghanistan probably has the highest burden of OWCL and is home chiefly to Leishmania tropica and Leishmania major, which cause anthroponotic and zoonotic CL, respectively. Although data on the species distribution in Afghanistan are patchy, L. tropica predominates over L. major, reflecting its concentration in large cities. CL prevalence in Afghanistan increases with increasing age to peak at 5–10 y, depending on the local epidemiology. Clinically, there is a spectrum of lesions common to both main species with nodules, ulcerated nodules and papules accounting for the majority (50–80%) of lesions at presentation. When healed, CL lesions leave pale scars that often have deleterious psychosocial effects. Leishmania control involves vector control and treating patients, but these are severely challenged by decades of war and disruption to the health system. In the public sector, only injectable antimonials, sodium stibogluconate or meglumine antimoniate, are available and, anecdotally, efficacy remains high. Few clinical trials have been conducted in Afghanistan and data support antimonial efficacy; small clinical series suggest good efficacy of oral miltefosine against the two main species. Herein, we focus our review on the epidemiological and clinical aspects of CL in Afghanistan and suggest avenues of future research.

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Journal Article > CommentaryFull Text

Disease-specific differences in pharmacokinetics of paromomycin and miltefosine between post-kala-azar dermal leishmaniasis and visceral leishmaniasis patients in eastern Africa

J Infect Dis. 16 December 2024; Volume 230 (Issue 6); e1375-1384.; DOI:10.1093/infdis/jiae413
Chu WY, Verrest L, Younis BM, Musa AM, Mbui J,  et al.
J Infect Dis. 16 December 2024; Volume 230 (Issue 6); e1375-1384.; DOI:10.1093/infdis/jiae413

Treatment regimens for post-kala-azar dermal leishmaniasis (PKDL) are usually extrapolated from those for visceral leishmaniasis (VL), but drug pharmacokinetics (PK) can differ due to disease-specific variations in absorption, distribution, and elimination. This study characterized PK differences in paromomycin and miltefosine between 109 PKDL and 264 VL patients from eastern Africa. VL patients showed 0.55-fold (95%CI: 0.41-0.74) lower capacity for paromomycin saturable reabsorption in renal tubules, and required a 1.44-fold (1.23-1.71) adjustment when relating renal clearance to creatinine-based eGFR. Miltefosine bioavailability in VL patients was lowered by 69% (62-76) at treatment start. Comparing PKDL to VL patients on the same regimen, paromomycin plasma exposures were 0.74-0.87-fold, while miltefosine exposure until the end of treatment day was 1.4-fold. These pronounced PK differences between PKDL and VL patients in eastern Africa highlight the challenges of directly extrapolating dosing regimens from one leishmaniasis presentation to another.

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Journal Article > ResearchFull Text

A phase II, non-comparative randomised trial of two treatments involving liposomal amphotericin B and miltefosine for post-kala-azar dermal leishmaniasis in India and Bangladesh

PLoS Negl Trop Dis. 20 June 2024; Volume 18 (Issue 6); e0012242.; DOI:10.1371/journal.pntd.0012242
Sundar S, Pandey K, Mondal D, Madhukar M, Kamal Topno R,  et al.
PLoS Negl Trop Dis. 20 June 2024; Volume 18 (Issue 6); e0012242.; DOI:10.1371/journal.pntd.0012242
BACKGROUND
In Southeast Asia, treatment is recommended for all patients with post-kala-azar dermal leishmaniasis (PKDL). Adherence to the first-line regimen, twelve weeks of miltefosine (MF), is low and ocular toxicity has been observed with this exposure period. We assessed the safety and efficacy of two shorter-course treatments: liposomal amphotericin B (LAmB) alone and combined with MF.

METHODOLOGY/PRINCIPAL FINDINGS
An open-label, phase II, randomized, parallel-arm, non-comparative trial was conducted in patients with parasitologically confirmed PKDL, 6 to ≤60 years. Patients were assigned to 20 mg/kg LAmB (total dose, in five injections over 15 days) alone or combined with allometric MF (3 weeks). The primary endpoint was definitive cure at 12 months, defined as complete resolution of papular and nodular lesions and >80% re-pigmentation of macular lesions. Definitive cure at 24 months was a secondary efficacy endpoint. 118/126 patients completed the trial. Definitive cure at 12 months was observed in 29% (18/63) patients receiving LAmB and 30% (19/63) receiving LAmB/MF (mITT), increasing to 58% and 66%, respectively, at 24 months. Most lesions had resolved/improved at 12 and 24 months for patients receiving LAmB (90%, 83%) and LAmB/MF (85%, 88%) by qualitative assessment. One death, unrelated to study drugs, was reported; no study drug-related serious adverse events were observed. The most frequent adverse drug reactions were MF-related vomiting and nausea, and LAmB-related hypokalaemia and infusion reactions. Most adverse events were mild; no ocular adverse events occurred.

CONCLUSIONS/SIGNIFICANCE
Both regimens are suitably safe and efficacious alternatives to long-course MF for PKDL in South Asia.
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Conference Material > Poster

Improving the patient journey and reducing stigma for people with cutaneous leishmaniasis in Brazil, Ethiopia, and Sri Lanka: findings from the ECLIPSE programme

Price H, Agampodi S, Dikomitis L, Machado P, Mulugeta A,  et al.
MSF Scientific Day International 2024. 16 May 2024; DOI:10.57740/utMmyg3dt
Journal Article > EditorialFull Text

Therapeutic strategies against leishmania and trypanosoma

Pathogens. 19 October 2023; Volume 12 (Issue 10); 1263.; DOI:10.3390/pathogens12101263
Santos ALS, Rodrigues IA, d’Avila-Levy CM, Sodré CL, Ritmeijer KKD,  et al.
Pathogens. 19 October 2023; Volume 12 (Issue 10); 1263.; DOI:10.3390/pathogens12101263
Human African trypanosomiasis (also known as sleeping sickness, with Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense as etiological agents), American trypanosomiasis (also known as Chagas disease, with Trypanosoma cruzi as the etiological agent), and leishmaniasis (including cutaneous, mucocutaneous, and visceral forms, with multiple species belonging to the Leishmania genus as etiological agents) are recognized as neglected tropical diseases (NTDs). These diseases affect marginalized populations and pose a high-impact health problem, primarily in low- or low-to-middle-income countries in Africa, Asia, Latin America, and the Caribbean. Leishmania and Trypanosoma not only infect humans, but they also infect wild and domesticated animals, which serve as reservoirs for these diseases. Relevantly, the movement of people and animals across borders and within countries has become increasingly common in our interconnected world, and this mobility can both facilitate the transmission of diseases and challenge efforts to control outbreaks. Furthermore, climate changes can contribute to the spread of NTDs to areas that were previously unaffected.More
Journal Article > ResearchFull Text

Prevalence and determinants of asymptomatic Leishmania infection in HIV-infected individuals living within visceral leishmaniasis endemic areas of Bihar, India

PLoS Negl Trop Dis. 30 August 2022; Volume 16 (Issue 8); e0010718.; DOI:10.1371/journal.pntd.0010718
Mahajan R, Owen SI, Kumar S, Pandey K, Kazmi S,  et al.
PLoS Negl Trop Dis. 30 August 2022; Volume 16 (Issue 8); e0010718.; DOI:10.1371/journal.pntd.0010718
People living with HIV (PLHIV) have an increased risk of developing visceral leishmaniasis (VL) and poor outcomes compared to HIV negative individuals. Here, we aim to establish the prevalence and determinants of asymptomatic Leishmania infection (ALI) in a cohort of PLHIV in Bihar, India. We hoped to evaluate optimal diagnostic algorithms to detect ALI in PLHIV. We conducted a cross-sectional survey of PLHIV ≥18 years of age with no history or current diagnosis of VL or post kala-azar dermal leishmaniasis (PKDL) at anti-retroviral therapy centres within VL endemic districts of Bihar. ALI was defined as a positive rK39 enzyme-linked immunosorbent assay (ELISA), rK39 rapid diagnostic test (RDT) and/or quantitative polymerase chain reaction (qPCR). Additionally, the urinary Leishmania antigen ELISA was evaluated. Determinants for ALI were established using logistic regression and agreement between diagnostic tests calculated using Cohen’s Kappa. A total of 1,296 PLHIV enrolled in HIV care, 694 (53.6%) of whom were female and a median age of 39 years (interquartile range 33–46), were included in the analysis. Baseline prevalence of ALI was 7.4% (n = 96). All 96 individuals were positive by rK39 ELISA, while 0.5% (n = 6) and 0.4% (n = 5) were positive by qPCR and rK39 RDT, respectively. Negligible or weak agreement was seen between assays. Independent risk factors for ALI were CD4 counts <100 (OR 3.1; 95% CI 1.2–7.6) and CD4 counts 100–199 (OR = 2.1;95% CI:1.1–4.0) compared to CD4 counts ≥300, and a household size ≥5 (OR = 1.9;95% CI:1.1–3.1). A total of 2.2% (n = 28) participants were positive by Leishmania antigen ELISA, detecting 20 additional participants to the asymptomatic cohort. Prevalence of ALI in PLHIV in VL endemic villages in Bihar was relatively high. Using the Leishmania antigen ELISA, prevalence increased to 9.0%. Patients with low CD4 counts and larger household size were found to have significantly higher risk of ALI.More
Journal Article > ResearchFull Text

A comparison of the effectiveness of sodium stibogluconate monotherapy to sodium stibogluconate and paromomycin combination for the treatment of severe post kala azar dermal leishmaniasis in South Sudan - A retrospective cohort study

PLOS One. 22 September 2016; Volume 11 (Issue 9); e0163047.; DOI:10.1371/journal.pone.0163047
Abongomera C, Gatluak F, Buyze J, Ritmeijer KKD
PLOS One. 22 September 2016; Volume 11 (Issue 9); e0163047.; DOI:10.1371/journal.pone.0163047
BACKGROUND
Post-kala-azar dermal leishmaniasis (PKDL) is a common dermatological complication following successful treatment of Visceral Leishmaniasis (VL) caused by Leishmania donovani. PKDL presents as macular, papular, nodular or mixed skin rash on sun-exposed body parts. Patients are not ill unless there are complications due to mucosal involvement or ulceration. As PKDL in East Africa is typically self-healing, and treatment is long and with significant adverse events, only severe and complicated cases are treated. Studies to determine optimal treatment of PKDL are rare and based on small cohorts. Since 1989, Médecins Sans Frontières is treating severe PKDL within VL treatment programmes in South Sudan. Treatment was initially with sodium stibogluconate (SSG) monotherapy and since 2002 with a combination of SSG and paromomycin (PM). SSG monotherapy (20 mg/kg/day for a minimum of 30 days) was provided in primary health units, and the combination of PM (15 mg sulphate/kg/day for 17 days) plus SSG (30 mg/kg/day for a minimum of 17 days) was provided in secondary health facilities.

METHODOLOGY/PRINCIPAL FINDINGS
By retrospective analysis of routinely collected programme data we compared the effectiveness (outcome and treatment duration) of both regimens. Between 2002 and 2008, 422 patients with severe PKDL were treated; 343 received SSG and 79 SSG/PM combination. The cure rate was significantly better with combination treatment when compared to monotherapy (97% vs. 90%; odds ratio [OR], 7.6; p = 0.02), treatment duration was shorter (mean 34 days vs. 42 days; p = 0.005), and defaulter rate was lower (3% vs. 9%; OR, 0.3; p = 0.03). There was no significant difference in death rate (0% vs. 1%; p = 0.5).

CONCLUSION/SIGNIFICANCE
We found that SSG/PM combination therapy resulted in more favourable outcomes than SSG monotherapy. An additional advantage is the lower cost of the combination therapy, due to the shorter treatment duration. A combination of SSG and PM is therefore a suitable option for the treatment of PKDL in East Africa.
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Conference Material > Video

Safety and efficacy data from a phase 2 randomized trial of a miltefosine/thermotherapy combination in uncomplicated New World cutaneous leishmaniasis

Arana B
MSF Scientific Days International 2020: Research. 13 May 2020
Conference Material > Abstract

Safety and efficacy data from a phase 2 randomized trial of a miltefosine/thermotherapy combination in uncomplicated New World cutaneous leishmaniasis

Arana B, Lopez L, Velez ID, Llanos-Cuentas A, Boni MF,  et al.
MSF Scientific Days International 2020: Research. 13 May 2020
Conference Material > Poster

Patient characteristics and treatment outcomes from MSF's cutaneous leishmaniasis programme in Pakistan: a retrospective cohort

Kamink SS, Masih B, Saleem A, Khan J, Masih S,  et al.
MSF Scientific Days International 2021: Research. 18 May 2021