• Developments in the treatment of visceral leishmaniasis

      den Boer, Margriet Leontine; Alvar, Jorge; Davidson, Robert N; Ritmeijer, Koert; Balasegaram, Manica; Medecins Sans Frontieres, Amsterdam, The Netherlands (2009-09-01)
      BACKGROUND: Visceral leishmaniasis (VL) is one of the most neglected parasitic diseases causing large scale mortality and morbidity among the poorest of the poor in the Indian subcontinent and Africa. OBJECTIVE: This review aims to describe the potential and the (lack of) current impact of newly developed treatments on the control of VL. It describes how the problem of an empty research pipeline is addressed, and discusses the emerging threat of incurable HIV/VL coinfection. METHODS: The literature was searched for drugs used in VL. CONCLUSION: Research and development of VL drugs has received a financial boost but no new drugs are expected in the next 5 years. Only three new and highly effective treatments have been licensed in the past 10 years. These remain, however, largely inaccessible as VL control programs in the developing world are lacking. This is deserving of immediate and urgent attention, especially in the context of the rapidly expanding HIV/VL coinfection.
    • Field evaluation of rK39 test and direct agglutination test for diagnosis of visceral leishmaniasis in a population with high prevalence of human immunodeficiency virus in Ethiopia

      ter Horst, Rachel; Tefera, Tewodros; Assefa, Gessesse; Ebrahim, Abdurazik Z; Davidson, Robert N; Ritmeijer, Koert; Médecins Sans Frontières, Humera, Ethiopia; Kahsay Abera Hospital, Humera, Ethiopia; Ethiopian Health and Nutrition Research Institute, Addis Ababa, Ethiopia; Department of Infection and Tropical Medicine, Northwick Park Hospital, Harrow, United Kingdom; Médecins Sans Frontières, Amsterdam, The Netherlands (2009-06-01)
      Accuracy of an rK39 rapid diagnostic test (DiaMed-IT-Leish ) for visceral leishmaniasis (VL) was compared with splenic aspiration and the direct agglutination test (DAT) in a population with a high prevalence of infection with human immunodeficiency virus (HIV) in Ethiopia. There were 699 patients clinically suspected of having VL (153 parasitologically confirmed, 482 DAT confirmed, and 130 DAT negative), and 97 DAT-negative controls. A total of 84% were tested for HIV and 34% were HIV positive. Sensitivity of the rK39 test in parasitologically confirmed VL patients was 84% (77% in HIV positive and 87% in HIV negative; P = 0.25). Sensitivity of the DAT was higher (94%; P = 0.01), 89% in HIV-positive patients and 95% in HIV-negative patients; P = 0.27). Specificity of the rK39 test was 99% in DAT-negative controls and 92% in DAT-negative patients clinically suspected of having VL. A diagnostic algorithm combining DAT and the rK39 test had a sensitivity of 98% in HIV-positive VL patients and 99% in HIV-negative VL patients. Despite the lower sensitivity in a population with a high prevalence of HIV, the DiaMed-IT-Leish rK39 test enables decentralization of diagnosis. Patients clinically suspected of having VL who show negative results on the rK39 antigen test should undergo follow-up DAT testing, especially if they are HIV positive.
    • Hypokalaemia-Induced Rhabdomyolysis after Treatment of Post-Kala-azar Dermal Leishmaniasis (PKDL) with High-Dose AmBisome in Bangladesh-A Case Report

      Marking, Ulrika; den Boer, Margriet; Das, Asish Kumar; Ahmed, Elshafie Mohamed; Rollason, Victoria; Ahmed, Be-Nazir; Davidson, Robert N; Ritmeijer, Koert (Public Library of Science, 2014-06-12)
    • Visceral leishmaniasis relapse in Southern Sudan (1999-2007): a retrospective study of risk factors and trends

      Gorski, Stanislaw; Collin, Simon M; Ritmeijer, Koert; Keus, Kees; Gatluak, Francis; Mueller, Marius; Davidson, Robert N; Médecins Sans Frontières, Amsterdam, The Netherlands; Department of Social Medicine, University of Bristol, Bristol, United Kingdom; Department of Infection and Tropical Medicine, Northwick Park Hospital, Harrow, United Kingdom (2010-06-08)
      BACKGROUND: Risk factors associated with L. donovani visceral leishmaniasis (VL; kala azar) relapse are poorly characterized. METHODS: We investigated patient characteristics and drug regimens associated with VL relapse using data from Médecins Sans Frontières - Holland (MSF) treatment centres in Southern Sudan. We used MSF operational data to investigate trends in VL relapse and associated risk factors. RESULTS: We obtained data for 8,800 primary VL and 621 relapse VL patients treated between 1999 and 2007. Records of previous treatment for 166 VL relapse patients (26.7%) were compared with 7,924 primary VL patients who had no record of subsequent relapse. Primary VL patients who relapsed had larger spleens on admission (Hackett grade >or=3 vs 0, odds ratio (OR) for relapse = 3.62 (95% CI 1.08, 12.12)) and on discharge (Hackett grade >or=3 vs 0, OR = 5.50 (1.84, 16.49)). Age, sex, malnutrition, mobility, and complications of treatment were not associated with risk of relapse, nor was there any trend over time. Treatment with 17-day sodium stibogluconate/paromomycin (SSG/PM) combination therapy vs 30-day SSG monotherapy was associated with increased risk of relapse (OR = 2.08 (1.21, 3.58)) but reduced risk of death (OR = 0.27 (0.20, 0.37)), although these estimates are likely to be residually confounded. MSF operational data showed a crude upward trend in the proportion of VL relapse patients (annual percentage change (APC) = 11.4% (-3.4%, 28.5%)) and a downward trend in deaths (APC = -18.1% (-22.5%, -13.4%)). CONCLUSIONS: Splenomegaly and 17-day SSG/PM vs 30-day SSG were associated with increased risk of VL relapse. The crude upward trend in VL relapses in Southern Sudan may be attributable to improved access to treatment and reduced mortality due to SSG/PM combination therapy.