• Accounting for False Positive HIV Tests: Is Visceral Leishmaniasis Responsible?

      Shanks, Leslie; Ritmeijer, Koert; Piriou, Erwan; Siddiqui, M Ruby; Kliescikova, Jarmila; Pearce, Neil; Ariti, Cono; Muluneh, Libsework; Masiga, Johnson; Abebe, Almaz (Public Library of Science, 2015-07-10)
      Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL) infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals.
    • Burden of visceral leishmaniasis in villages of eastern gedaref state, Sudan: an exhaustive cross-sectional survey.

      Mueller, Yolanda Kathrin; Nackers, Fabienne; Ahmed, Khalid A; Boelaert, Marleen; Djoumessi, Jean-Claude; Eltigani, Rahma; Gorashi, Himida Ali; Hammam, Omer; Ritmeijer, Koert; Salih, Niven; et al. (2012-11)
      Since December 2009, Médecins Sans Frontières has diagnosed and treated patients with visceral leishmaniasis (VL) in Tabarak Allah Hospital, eastern Gedaref State, one of the main endemic foci of VL in Sudan. A survey was conducted to estimate the VL incidence in villages around Tabarak Allah.
    • 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.
    • Effectiveness and Safety of Short Course Liposomal Amphotericin B (AmBisome) as First Line Treatment for Visceral Leishmaniasis in Bangladesh

      Lucero, Emiliano; Collin, Simon M; Gomes, Sujit; Akter, Fatima; Asad, Asaduzzam; Kumar Das, Asish; Ritmeijer, Koert (Public Library of Science, 2015-04-02)
      Bangladesh is one of the endemic countries for Visceral Leishmaniasis (VL). Médecins Sans Frontières (MSF) ran a VL treatment clinic in the most endemic district (Fulbaria) between 2010 and 2013 using a semi-ambulatory regimen for primary VL of 15mg/kg Liposomal Amphotericin-B (AmBisome) in three equal doses of 5mg/kg. The main objective of this study was to analyze the effectiveness and safety of this regimen after a 12 month follow-up period by retrospective analysis of routinely collected program data. A secondary objective was to explore risk factors for relapse.
    • 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.
    • High mortality among older patients treated with pentavalent antimonials for visceral leishmaniasis in East Africa and rationale for switch to liposomal amphotericin B

      Chappuis, François; Alirol, Emilie; Worku, Dagemlidet T; Mueller, Yolanda; Ritmeijer, Koert; Médecins Sans Frontières, Geneva, Switzerland; Médecins Sans Frontières, Amsterdam, The Netherlands (2010-11-15)
      Visceral leishmaniasis (VL; kala azar), a fatal disease if left untreated, is one of the most neglected tropical diseases....
    • 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)
    • Liposomal amphotericin B as a treatment for human leishmaniasis

      Balasegaram, Manica; Ritmeijer, Koert; Lima, Maria Angeles; Burza, Sakib; Ortiz Genovese, Gemma; Milani, Barbara; Gaspani, Sara; Potet, Julien; Chappuis, François; Drugs for Neglected Diseases Initiative, Geneva, Switzerland;2 Médecins Sans Frontières, Operational Centre Amsterdam, Amsterdam, The Netherlands; Médecins Sans Frontières, Operational Centre Barcelona Athens, Barcelona, Spain; Médecins Sans Frontières, Access Campaign, Paris, France; Médecins Sans Frontières, Operational Centre Geneva, Geneva, Switzerland;Médecins Sans Frontières, Access Campaign, Geneva, Switzerland; University of Geneva, andGeneva University Hospitals, Division of International and Humanitarian Medicine, 6, rue Gabrielle-Perret-Gentil, 1211 Geneva 14, Switzerland. (Informa, 2012-12-11)
    • A Screen-and-Treat Strategy Targeting Visceral Leishmaniasis in HIV-Infected Individuals in Endemic East African Countries: The Way Forward?

      van Griensven, Johan; Diro, Ermias; Lopez-Velez, Rogelio; Ritmeijer, Koert; Boelaert, Marleen; Zijlstra, Ed E; Hailu, Asrat; Lynen, Lutgarde (Public Library of Science, 2014-08-07)
      In the wake of the HIV epidemic, visceral leishmaniasis (VL), a disseminated protozoan infection caused by the Leishmania donovani complex, has been re-emerging, particularly in North Ethiopia where up to 40% of patients with VL are co-infected with HIV. Management of VL in HIV co-infection is complicated by increased drug toxicity, and high treatment failure and relapse rates with all currently available drugs, despite initiation of antiretroviral treatment. Tackling L. donovani infection before disease onset would thus be a logical approach. A screen-and-treat approach targeting latent or the early stage of infection has successfully been implemented in other HIV-associated opportunistic infections. While conceptually attractive in the context of VL-HIV, the basic understanding and evidence underpinning such an approach is currently lacking. Prospective cohort studies will have to be conducted to quantify the risk of VL in different risk groups and across CD4 cell count levels. This will allow developing clinical prognostic tools, integrating clinical, HIV and Leishmania infection markers. Interventional studies will be needed to evaluate prophylactic or pre-emptive treatment strategies for those at risk, ideally relying on an oral (combination) regimen. Issues like tolerability, emergence of resistance and drug interactions will require due attention. The need for maintenance therapy will have to be assessed. Based on the risk-benefit data, VL risk cut-offs will have to be identified to target treatment to those most likely to benefit. Such a strategy should be complemented with early initiation of antiretroviral treatment and other strategies to prevent HIV and Leishmania infection.
    • Visceral Leishmaniasis and HIV Coinfection in East Africa

      Diro, Ermias; Lynen, Lutgarde; Ritmeijer, Koert; Boelaert, Marleen; Hailu, Asrat; van Griensven, Johan (2014-06-26)
      Visceral Leishmaniasis (VL) is an important protozoan opportunistic disease in HIV patients in endemic areas. East Africa is second to the Indian subcontinent in the global VL caseload and first in VL-HIV coinfection rate. Because of the alteration in the disease course, the diagnostic challenges, and the poor treatment responses, VL with HIV coinfection has become a very serious challenge in East Africa today. Field experience with the use of liposomal amphotericin B in combination with miltefosine, followed by secondary prophylaxis and antiretroviral drugs, looks promising. However, this needs to be confirmed through clinical trials. Better diagnostic and follow-up methods for relapse and prediction of relapse should also be looked for. Basic research to understand the immunological interaction of the two infections may ultimately help to improve the management of the coinfection.
    • Visceral Leishmaniasis as an AIDS Defining Condition: Towards Consistency across WHO Guidelines

      van Griensven, Johan; Ritmeijer, Koert; Lynen, Lutgarde; Diro, Ermias (2014-07-17)
    • 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.
    • Who Is a Typical Patient with Visceral Leishmaniasis? Characterizing the Demographic and Nutritional Profile of Patients in Brazil, East Africa, and South Asia

      Harhay, Michael O; Olliaro, Piero L; Vaillant, Michel; Chappuis, François; Lima, María Angeles; Ritmeijer, Koert; Costa, Carlos Henrique; Costa, Dorcas Lamounier; Rijal, Suman; Sundar, Shyam; et al. (2011-04-01)
      Abstract. Drug-dosing recommendations for visceral leishmaniasis (VL) treatment are based on the patients' weight or age. A current lack of demographic and anthropometric data on patients hinders (1) the ability of health providers to properly prepare for patient management, (2) an informed drug procurement for disease control, and (3) the design of clinical trials and development of new drug therapies in the different endemic areas. We present information about the age, gender, weight, and height of 29,570 consecutive VL patients presenting to 20 locations in six geographic endemic regions of Brazil, East Africa, Nepal, and India between 1997 and 2009. Our compilation shows substantial heterogeneity in the types of patients seeking care for VL at the clinics within the different locations. This suggests that drug development, procurement, and perhaps even treatment protocols, such as the use of the potentially teratogenic drug miltefosine, may require distinct strategies in these geographic settings.