• Accessibility of diagnostic and treatment centres for visceral leishmaniasis in Gedaref State, northern Sudan.

      Gerstl, S; Amsalu, R; Ritmeijer, K; Médecins Sans Frontières Holland, Amsterdam, The Netherlands. sgerstl@aol.com (Wiley-Blackwell, 2006-02)
      OBJECTIVE: To evaluate the accessibility of visceral leishmaniasis (VL) treatment. METHOD: Community-based study using in-depth qualitative interviews and focus group discussions with key informants, as well as quantitative questionnaires with 448 randomly selected heads of households in nine representative villages in three geographical sub-regions. RESULTS: Despite the high incidence of the disease, most people in Gedaref State know little about VL, and help at a treatment centre is usually sought only after traditional remedies and basic allopathic drugs have failed. Factors barring access to treatment are: lack of money for treatment and transport, impassability of roads, work priorities, severe cultural restrictions of women's decision-making power and distance to the next health center. CONCLUSIONS: To provide more VL patients with access to treatment in this highly endemic area, diagnostic and treatment services should be decentralized. Health education would be a useful tool to rationalise people's health-seeking behaviour.
    • 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.
    • Active and passive case detection strategies for the control of leishmaniasis in Bangladesh

      Das, A. K.; Harries, A. D.; Hinderaker, S. G.; Zachariah, R; Ahmad, B; Shah, G. N.; Khogali, M. A.; Das, G. I.; Ahmed, E. M.; Ritmeijer, K (The Union, 2014-03-21)
    • Barriers to access to visceral leishmaniasis diagnosis and care among seasonal mobile workers in Western Tigray, Northern Ethiopia: A qualitative study

      Coulborn, RM; Gebrehiwot, TG; Schneider, M; Gerstl, S; Adera, C; Herrero, M; Porten, K; den Boer, M; Ritmeijer, K; Alvar, J; Hassen, A; Mulugeta, A (PLoS, 2018-11-08)
      Ethiopia bears a high burden of visceral leishmaniasis (VL). Early access to VL diagnosis and care improves clinical prognosis and reduces transmission from infected humans; however, significant obstacles exist. The approximate 250,000 seasonal mobile workers (MW) employed annually in northwestern Ethiopia may be particularly disadvantaged and at risk of VL acquisition and death. Our study aimed to assess barriers, and recommend interventions to increase access, to VL diagnosis and care among MWs.
    • 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; Worku, Dagemlidet; Etard, Jean-François; Chappuis, François; Epicentre, Paris, France; Médecins Sans Frontières - Operational Centre Geneva, Geneva, Switzerland; Institute of Tropical Medicine, Antwerp, Belgium; Federal Ministry of Health, Khartoum, Sudan;Community Medicine Department, University of Gedaref, Gedaref, Sudan; Médecins Sans Frontières - Operational Centre Amsterdam, Amsterdam, Holland; Institut de Recherche pour le Développement (IRD), Montpellier, France; Médecins Sans Frontières - Operational Centre Amsterdam, Amsterdam, Holland. (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.
    • Clinical Epidemiology, Diagnosis and Treatment of Visceral Leishmaniasis in the Pokot Endemic Area of Uganda and Kenya

      Mueller, Yolanda K; Kolaczinski, Jan H; Koech, Timothy; Lokwang, Peter; Riongoita, Mark; Velilla, Elena; Brooker, Simon J; Chappuis, François; Epicentre, Paris, France; Faculty of Infectious and Tropical Disease, London School of Hygiene and Tropical Medicine, Keppel Street, London, United Kingdom; Médecins Sans Frontières, Operational Centre, Geneva, Switzerland; Geneva University Hospitals and University of Geneva, Geneva, Switzerland. (2013-11-11)
      Between 2000 and 2010, Médecins Sans Frontières diagnosed and treated 4,831 patients with visceral leishmaniasis (VL) in the Pokot region straddling the border between Uganda and Kenya. A retrospective analysis of routinely collected clinical data showed no marked seasonal or annual fluctuations. Males between 5 and 14 years of age were the most affected group. Marked splenomegaly and anemia were striking features. An Rk39 antigen-based rapid diagnostic test was evaluated and found sufficiently accurate to replace the direct agglutination test and spleen aspiration as the first-line diagnostic procedure. The case-fatality rate with sodium stibogluconate as first-line treatment was low. The VL relapses were rare and often diagnosed more than 6 months post-treatment. Post-kala-azar dermal leishmaniasis was rare but likely to be underdiagnosed. The epidemiological and clinical features of VL in the Pokot area differed markedly from VL in Sudan, the main endemic focus in Africa.
    • A Clinical Severity Scoring System for Visceral Leishmaniasis in Immunocompetent Patients in South Sudan

      Kämink, SS; Collin, SM; Harrison, T; Gatluak, F; Mullahzada, AW; Ritmeijer, K (Public Library of Science, 2017-10-02)
      South Sudan is one of the most endemic countries for visceral leishmaniasis (VL), and is frequently affected by large epidemics. In resource-limited settings, clinicians require a simple clinical tool to identify VL patients who are at increased risk of dying, and who need specialised treatment with liposomal amphotericin B and other supportive care. The aim of this study was to develop and validate a clinical severity scoring system based on risk factors for death in VL patients in South Sudan.
    • Combination Treatment for Visceral Leishmaniasis Patients Co-infected with Human Immunodeficiency Virus in India

      Mahajan, Raman; Das, Pradeep; Isaakidis, Petros; Sunyoto, Temmy; Sagili, Karuna D; Lima, Marıa Angeles; Mitra, Gaurab; Kumar, Deepak; Pandey, Krishna; Van Geertruyden, Jean-Pierre; Boelaert, Marleen; Burza, Sakib (Oxford University Press, 2015-06-30)
      There are considerable numbers of patients co-infected with Human Immunodeficiency Virus (HIV) and Visceral Leishmaniasis (VL) in the VL-endemic areas of Bihar, India. These patients are at higher risk of relapse and death, but there are still no evidence-based guidelines on how to treat them. In this study, we report on treatment outcomes of co-infected patients up to 18 months following treatment with a combination regimen.
    • Comparison of an rK39 dipstick rapid test with direct agglutination test and splenic aspiration for the diagnosis of kala-azar in Sudan.

      Veeken, H; Ritmeijer, K; Seaman, J; Davidson, R N; Médecins sans Frontières-Holland, Amsterdam, The Netherlands. hans_veeken@amsterdam.msf.org (Wiley-Blackwell, 2003-02)
      We compared an rK39 dipstick rapid test (Amrad ICT, Australia) with a direct agglutination test (DAT) and splenic aspirate for the diagnosis of kala-azar in 77 patients. The study was carried out under field conditions in an endemic area of north-east Sudan. The sensitivity of the rK39 test compared with splenic aspiration was 92% (46/50), the specificity 59% (16/27), and the positive predictive value 81% (46/57). Compared with the diagnostic protocol used by Médecins sans Frontières, the sensitivity of the rK39 test was 93% (50/54), the specificity 70% (16/23), and the positive predictive value 88% (50/57). Compared with splenic aspirates, the sensitivity of a DAT with a titre > or =1:400 was 100% (50/50), but its specificity only 55% (15/27) and the positive predictive value was 80% (50/62). Using a DAT titre > or =1:6400, the sensitivity was 84% (42/50), the specificity 85% (23/27) and the positive predictive value 91% (42/46). All four patients with DAT titre > or =1:6400 but negative splenic aspirate were also rK39 positive; we consider these are probably 'true' cases of kala-azar, i.e. false negative aspirates, rather than false DAT and rK39 seropositives. There were no false negative DATs (DAT titre < or =1:400 and aspirate positive), but there were four false negative rK39 tests (rK39 negative and aspirate positive). The rK39 dipstick is a good screening test for kala-azar; but further development is required before it can replace the DAT as a diagnostic test in endemic areas of the Sudan.
    • Comparison of Generic and Proprietary Sodium Stibogluconate for the Treatment of Visceral Leishmaniasis in Kenya.

      Moore, E; O'Flaherty, D; Heuvelmans, H; Seaman, J; Veeken, H; de Wit, S; Davidson, R N; Médecins Sans Frontières-Holland (MSF-H) Kala-azar Programme, South Sudan/Kenya. (Published by WHO, 2001)
      OBJECTIVE: To compare the use of generic and proprietary sodium stibogluconate for the treatment of visceral leishmaniasis (kala-azar). METHODS: A total of 102 patients with confirmed kala-azar were treated in a mission hospital in West Pokot region, Kenya, with sodium stibogluconate (20 mg/kg/day for 30 days)--either as Pentostam (PSM) or generic sodium stibogluconate (SSG); 51 patients were allocated alternately to each treatment group. FINDINGS: There were no significant differences in baseline demographic characteristics or disease severity, or in events during treatment. There were 3 deaths in the PSM group and 1 in the SSG group; 2 patients defaulted in each group. Only 1 out of 80 test-of-cure splenic aspirates was positive for Leishmania spp.; this patient was in the SSG group. Follow-up after > or = 6 months showed that 6 out of 58 patients had relapsed, 5 in the SSG group and 1 in the PSM group. No outcome variable was significantly different between the two groups. CONCLUSION: The availability of cheaper generic sodium stibogluconate, subject to rigid quality controls, now makes it possible for the health authorities in kala-azar endemic areas to provide treatment to many more patients in Africa.
    • A Comparison of Miltefosine and Sodium Stibogluconate for Treatment of Visceral Leishmaniasis in an Ethiopian Population with High Prevalence of HIV Infection.

      Ritmeijer, K; Dejenie, A; Assefa, Y; Hundie, T B; Mesure, J; Boots, G; den Boer, M; Davidson, R N; Médecins Sans Frontières-Holland, Amsterdam, The Netherlands. koert.ritmeijer@amsterdam.msf.org (Published by: Infectious Diseases Society of America, 2006-08-01)
      BACKGROUND: Antimonials are the mainstay of visceral leishmaniasis (VL) treatment in Africa. The increasing incidence of human immunodeficiency virus (HIV) coinfection requires alternative safe and effective drug regimens. Oral miltefosine has been proven to be safe and effective in the treatment of Indian VL but has not been studied in Africa or in persons with HIV and VL coinfection. METHODS: We compared the efficacy of miltefosine and sodium stibogluconate (SSG) in the treatment of VL in persons in Ethiopia. A total of 580 men with parasitologically and/or serologically confirmed VL were randomized to receive either oral miltefosine (100 mg per day for 28 days) or intramuscular SSG (20 mg/kg per day for 30 days). RESULTS: The initial cure rate was 88% in both treatment groups. Mortality during treatment was 2% in the miltefosine group, compared with 10% in the SSG group. Initial treatment failure was 8% in the miltefosine group, compared with 1% in the SSG group. Among the 375 patients (65%) who agreed to HIV testing, HIV seroprevalence was 29%. Among patients not infected with HIV, initial cure, mortality, and initial treatment failure rates were not significantly different (94% vs. 95%, 1% vs. 3%, and 5% vs. 1% for the miltefosine and SSG groups, respectively). Initial treatment failure with miltefosine occurred in 18% of HIV-coinfected patients, compared with treatment failure in 5% of non-HIV-infected patients. At 6 months after treatment, 174 (60%) of the 290 miltefosine recipients and 189 (65%) of the 290 SSG recipients experienced cure; 30 (10%) of 290 in the miltefosine group and 7 (2%) of 290 in the SSG group experienced relapse, and the mortality rate was 6% in the miltefosine group, compared with 12% in the SSG group. HIV-infected patients had higher rates of relapse (16 [25%] of 63 patients), compared with non-HIV-infected patients (5 [5%] of 131). CONCLUSIONS: Treatment with miltefosine is equally effective as standard SSG treatment in non-HIV-infected men with VL. Among HIV-coinfected patients, miltefosine is safer but less effective than SSG.
    • 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

      Abongomera, C; Gatluak, F; Buyze, J; Ritmeijer, K (Public Library of Science (PLoS), 2016-09-22)
      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.
    • Concordant HIV Infection and Visceral Leishmaniasis in Ethiopia: The Influence of Antiretroviral Treatment and Other Factors on Outcome

      ter Horst, R; Collin, S; Ritmeijer, K; Bogale, A; Davidson, R N (Infectious Disease Society of America, 2008-06-04)
    • Control of mucocutaneous leishmaniasis, a neglected disease: results of a control programme in Satipo Province, Peru.

      Guthmann, J P; Arlt, D; Garcia, L M L; Rosales, M; de Jesus Sanchez, J; Alvarez, E; Lonlas, S; Conte, M; Bertoletti, G; Fournier, C; Huari, R; Torreele, E; Llanos-Cuentas, A; Epicentre, Paris, France. jguthmann@epicentre.msf.org (Wiley-Blackwell, 2005-09)
      Mucocutaneous leishmaniasis (MCL) is an important health problem in many rural areas of Latin America, but there are few data on the results of programmatic approaches to control the disease. We report the results of a control programme in San Martin de Pangoa District, which reports one of the highest prevalences of MCL in Peru. For 2 years (2001--2002), the technicians at the health post were trained in patient case management, received medical support and were supplied with antimonials. An evaluation after 2 years showed the following main achievements: better diagnosis of patients, who were confirmed by microscopy in 34% (82/240) of the cases in 2001 and 60% of the cases (153/254) in 2002; improved follow-up during treatment: 237 of 263 (90%) patients who initiated an antimonial therapy ended the full treatment course; improved follow-up after treatment: 143 of 237 (60%) patients who ended their full treatment were correctly monitored during the required period of 6 (cutaneous cases) or 12 (mucosal cases) months after the end of treatment. These achievements were largely due to the human and logistical resources made available, the constant availability of medications and the close collaboration between the Ministry of Health, a national research institute and an international non-governmental organization. At the end of this period, the health authorities decided to register a generic brand of sodium stibogluconate, which is now in use. This should allow the treatment of a significant number of additional patients, while saving money to invest in other facets of the case management.
    • Cost-Effectiveness Analysis of Humanitarian Relief Interventions: Visceral Leishmaniasis Treatment in the Sudan.

      Griekspoor, A; Sondorp, H; Vos, T; Médecins Sans Frontières, Amsterdam, The Netherlands. (Published by Oxford University Press, 1999-03)
      Spending by aid agencies on emergencies has quadrupled over the last decade, to over US$6 billion. To date, cost-effectiveness has seldom been considered in the prioritization and evaluation of emergency interventions. The sheer volume of resources spent on humanitarian aid and the chronicity of many humanitarian interventions call for more attention to be paid to the issue of 'value for money'. In this paper we present data from a major humanitarian crisis, an epidemic of visceral leishmaniasis (VL) in war-torn Sudan. The special circumstances provided us, in retrospect, with unusually accurate data on excess mortality, costs of the intervention and its effects, thus allowing us to express cost-effectiveness as the cost per Disability Adjusted Life Year (DALY) averted. The cost-effectiveness ratio, of US$18.40 per DALY (uncertainty range between US$13.53 and US$27.63), places the treatment of VL in Sudan among health interventions considered 'very good value for money' (interventions of less than US$25 per DALY). We discuss the usefulness of this analysis to the internal management of the VL programme, the procurement of funds for the programme, and more generally, to priority setting in humanitarian relief interventions. We feel that in evaluations of emergency interventions attempts could be made more often to perform cost-effectiveness analyses, including the use of DALYs, provided that the outcomes of these analyses are seen in the broad context of the emergency situation and its consequences on the affected population. This paper provides a first contribution to what is hoped to become an international database of cost-effectiveness studies of health interventions during relief operations, which use a comparable measure of health outcome such as the DALY.
    • Development and External Validation of a Clinical Prognostic Score for Death in Visceral Leishmaniasis Patients in a High HIV Co-Infection Burden Area in Ethiopia

      Abongomera, C; Ritmeijer, K; Vogt, F; Buyze, J; Mekonnen, Z; Admassu, H; Colebunders, R; Mohammed, R; Lynen, L; Diro, E; van Griensven, J (Public Library of Science, 2017-06-05)
      In Ethiopia, case fatality rates among subgroups of visceral leishmaniasis (VL) patients are high. A clinical prognostic score for death in VL patients could contribute to optimal management and reduction of these case fatality rates. We aimed to identify predictors of death from VL, and to develop and externally validate a clinical prognostic score for death in VL patients, in a high HIV co-infection burden area in Ethiopia.
    • 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.
    • Diagnostic accuracy of two rK39 antigen-based dipsticks and the formol gel test for rapid diagnosis of visceral leishmaniasis in northeastern Uganda.

      Chappuis, F; Mueller, Y; Nguimfack, A; Rwakimari, J; Couffignal, S; Boelaert, M; Cavailler, P; Loutan, L; Piola, P; Travel and Migration Medicine Unit, Geneva University Hospital, Rue Micheli-du-Crest 24, 1211 Geneva 14, Switzerland. francois.chappuis@hcuge.ch (American Society for Microbiology, 2005-12)
      The development of an accurate, practical, and affordable diagnostic test is essential to improve the management of visceral leishmaniasis (VL) in remote health centers. We evaluated the Formol Gel test (FGT) and two rK39 antigen-based dipsticks, the DUAL-IT L/M, and the Kalazar Detect for VL diagnosis in Amudat Hospital in Uganda. The DUAL-IT L/M was also evaluated for the diagnosis of malaria. All patients clinically suspect of VL were prospectively included in the study between October 2003 and March 2004. The gold standard used to define a VL case was a positive spleen aspirate or a direct agglutination test titer of >1:12,800 with an appropriate clinical response to antileishmanial therapy. A total of 131 VL and 112 non-VL patients were included in the analysis. The DUAL IT L/M was found to be more sensitive than the Kalazar Detect: 97% (95% confidence interval [95%CI] = 92 to 99%) versus 82% (95%CI = 74 to 87%). The Kalazar Detect and the DUAL IT L/M were highly specific (99% [95%CI = 95 to 100%] and 97% [95%CI = 92 to 99%], respectively). The FGT lacked both sensitivity (66% [95%CI = 57 to 73%]) and specificity (90% [95%CI = 83 to 94%]). The sensitivity of the DUAL IT L/M for malaria was only 57% (95%CI = 37 to 76%). The two rK39 dipsticks can be used for diagnostic confirmation of VL in this region. The DUAL-IT L/M without its malaria diagnostic component (DiaMed-IT LEISH) will be adopted as first-line test for VL in Uganda.
    • Does Timing of Antiretroviral Treatment Influence Treatment Outcomes of Visceral Leishmaniasis in Northwest Ethiopia?

      Aderie, E; Diro, E; Zachariah, R; da Fonseca, M; Abongomera, C; Dolamo, B; Ritmeijer, K (Oxford University Press, 2017-03-01)
      Visceral leishmaniasis (VL) patients with HIV co-infection should receive antiretroviral treatment (ART). However, the best timing for initiation of ART is not known. Among such individuals, we assessed the influence of ART timing on VL outcomes.