Journal Article > ResearchFull Text
PLOS One. 2016 September 22; Volume 11 (Issue 9); e0163047.; DOI:10.1371/journal.pone.0163047
Abongomera C, Gatluak F, Buyze J, Ritmeijer KKD
PLOS One. 2016 September 22; 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.
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.
Journal Article > EditorialFull Text
Pathogens. 2023 October 19; Volume 12 (Issue 10); 1263.; DOI:10.3390/pathogens12101263
Santos ALS, Rodrigues IA, d’Avila-Levy CM, Sodré CL, Ritmeijer KKD, et al.
Pathogens. 2023 October 19; 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.
Conference Material > Video (talk)
Arana B
MSF Scientific Days International 2020: Research. 2020 May 13
Conference Material > Poster
Kamink SS, Masih B, Saleem A, Khan J, Masih S, et al.
MSF Scientific Days International 2021: Research. 2021 May 18
Conference Material > Abstract
Arana B, Lopez L, Velez ID, Llanos-Cuentas A, Boni MF, et al.
MSF Scientific Days International 2020: Research. 2020 May 13
Conference Material > Poster
Kamink SS, Masih B, Saleem A, Khan J, Masih S, et al.
MSF Scientific Days International 2021: Research. 2021 May 18
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2022 August 30; 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. 2022 August 30; 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.
Conference Material > Poster
Price H, Agampodi S, Dikomitis L, Machado P, Mulugeta A, et al.
MSF Scientific Day International 2024. 2024 May 16; DOI:10.57740/utMmyg3dt
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2015 March 10; Volume 9 (Issue 3); e0003594.; DOI:10.1371/journal.pntd.0003594
Herrador Z, Gherasim A, Jimenez BC, Granados M, San Martin JV, et al.
PLoS Negl Trop Dis. 2015 March 10; Volume 9 (Issue 3); e0003594.; DOI:10.1371/journal.pntd.0003594
In Spain, Leishmania infantum is endemic, human visceral and cutaneous leishmaniasis cases occurring both in the Peninsula, as well as in the Balearic Islands. We aimed to describe the clinical characteristics of leishmaniasis patients and the changes in the disease evolution after the introduction of antiretroviral therapy in 1997. In this descriptive study, we used Spanish Centralized Hospital Discharge Database for the hospitalized leishmaniasis cases between 1997 and 2011. We included in the analysis only the records having leishmaniasis as the first registered diagnosis and calculated the hospitalization rates. Disease trend was described taking into account the HIV status. Adjusted odds-ratio was used to estimate the association between clinical and socio-demographic factors and HIV co-infection. Of the total 8010 Leishmaniasis hospitalizations records, 3442 had leishmaniasis as first diagnosis; 2545/3442 (75.6%) were males and 2240/3442 (65.1%) aged between 14-65 years. Regarding disease forms, 2844/3442 (82.6%) of hospitalizations were due to visceral leishmaniasis (VL), while 118/3442 (3.4%) hospitalizations were cutaneous leishmaniasis (CL). Overall, 1737/2844 of VL (61.1%) were HIV negatives. An overall increasing trend was observed for the records with leishmaniasis as first diagnosis (p=0.113). Non-HIV leishmaniasis increased during this time period (p=0.021) while leishmaniasis-HIV co-infection hospitalization revealed a slight descending trend (p=0.717). Leishmaniasis-HIV co-infection was significantly associated with male sex (aOR=1.6; 95% CI: 1.25-2.04), 16-64 years age group (aOR=17.4; 95%CI: 2.1-143.3), visceral leishmaniasis aOR=6.1 (95%CI: 3.27-11.28) and solid neoplasms 4.5 (95% CI: 1.65-12.04). The absence of HIV co-infection was associated with lymph/hematopoietic neoplasms (aOR=0.3; 95%CI:0.14-0.57), other immunodeficiency (aOR=0.04; 95% CI:0.01-0.32) and transplant (aOR=0.01; 95%CI:0.00-0.07). Our findings suggest a significant increase of hospitalization in the absence of HIV co-infection, with a predomination of VL. We consider that clinicians in Spain should be aware of leishmaniasis not only in the HIV population but also in non HIV patients, especially for those having immunosuppression as an associate condition.
Journal Article > CommentaryFull Text
J Infect Dis. 2024 August 21; Online ahead of print; DOI:10.1093/infdis/jiae413
Chu WY, Verrest L, Younis BM, Musa AM, Mbui J, et al.
J Infect Dis. 2024 August 21; Online ahead of print; 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.