• 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.
    • 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; et al. (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.
    • 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.
    • 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.
    • 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)
    • 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; et al. (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.
    • 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.
    • Emergence or re-emergence of visceral leishmaniasis in areas of Somalia, north-eastern Kenya, and south-eastern Ethiopia in 2000-01.

      Marlet, M V L; Sang, D K; Ritmeijer, K; Muga, R O; Onsongo, J; Davidson, R N; Medecins Sans Frontieres-Holland, Max Euweplein, EA Amsterdam, The Netherlands. mvlmarlet@hetnet.nl (Elsevier, 2008-01-31)
      Visceral leishmaniasis (VL) was known to be endemic in Somalia along the basins of the (Middle) Shebelle and (Lower) Juba rivers, and in Kenya in parts of the Rift Valley, on the border with Uganda and the Eastern Provinces. From May 2000 to August 2001, we diagnosed 904 patients with VL. The patients came from an area which spanned the Wajir and Mandera districts of north-eastern Kenya, southern Somalia, and south-eastern Ethiopia. Small numbers of patients were also seen in northern Somalia. These areas were either previously non-endemic for VL, or had only sporadic cases prior to the epidemic. We describe the features of the outbreak and review the history of VL in the region. Unusual rainfall patterns, malnutrition, and migration of a Leishmania-infected population seeking food and security may have contributed to this outbreak.
    • Ethiopian visceral leishmaniasis: generic and proprietary sodium stibogluconate are equivalent; HIV co-infected patients have a poor outcome.

      Ritmeijer, K; Veeken, H; Melaku, Y; Leal, G; Amsalu, R; Seaman, J; Davidson, R N; Médecins sans Frontières-Holland, P.O. Box 10014, 1001 EA Amsterdam, The Netherlands. koert_ritmeijer@amsterdam.msf.org (Elsevier, 2008-01-31)
      We evaluated generic sodium stibogluconate (SSG) (International Dispensary Association, Amsterdam) versus Pentostam (sodium stibogluconate, GlaxoWellcome, London) under field conditions in Ethiopian patients with visceral leishmaniasis (VL; kala-azar). The 199 patients were randomly assigned to Pentostam (n = 104) or SSG (n = 95) in 1998/99; both drugs were given at 20 mg/kg intra-muscularly for 30 days. A clinical cure after 30-days treatment was achieved in 70.2% (Pentostam) and 81.1% (SSG). There were no significant differences between the 2 drugs for the following parameters: frequency of intercurrent events (vomiting, diarrhoea, bleeding or pneumonia) or main outcome (death during treatment and death after 6-month follow-up; relapse or post kala-azar dermal leishmaniasis at 6-months follow-up). Twenty-seven patients had confirmed co-infection with HIV. On admission, HIV co-infected VL patients were clinically indistinguishable from HIV-negative VL patients. The HIV co-infected VL patients had a higher mortality during treatment (33.3% vs 3.6%). At 6-month follow-up, HIV-positive patients had a higher relapse rate (16.7% vs 1.2%), a higher death rate during the follow-up period (14.3% vs 2.4%), and more frequent moderate or severe post kala-azar dermal leishmaniasis (27.3% vs 13.3%). Only 43.5% of the HIV-positive patients were considered cured at 6-months follow-up vs 92.1% of the HIV-negative patients. HIV-positive patients relapsing with VL could become a reservoir of antimonial-resistant Leishmania donovani.
    • Evaluation of a mass distribution programme for fine-mesh impregnated bednets against visceral leishmaniasis in eastern Sudan.

      Ritmeijer, K; Davies, C; van Zorge, R; Wang, S J; Schorscher, J; Dongu'du, S I; Davidson, R N; Médecins Sans Frontières-Holland, Amsterdam, The Netherlands. koert_ritmeijer@amsterdam.msf.org (Wiley-Blackwell, 2007-03)
      During an epidemic of visceral leishmaniasis (VL) in eastern Sudan, Médecins Sans Frontières distributed 357,000 insecticide-treated bednets (ITN) to 155 affected villages between May 1999 and March 2001. To estimate the protective effect of the ITN, we evaluated coverage and use of ITN, and analysed VL incidence by village from March 1996 to June 2002. We provided ITN to 94% of the individuals >5 years old. Two years later, 44% (95% CI 39-48%) of nets were reasonably intact. Because ITN were mainly used as protection against nuisance mosquitoes, bednet use during the VL transmission season ranged from <10% during the hot dry months to 55% during the beginning of the rainy season. ITN were put up from 9 to 11 p.m., leaving children unprotected during a significant period of sandfly-biting hours after sunset. Regression analysis of incidence data from 114 villages demonstrated a significant reduction of VL by village and month following ITN provision. The greatest effect was 17-20 months post-intervention, with VL cases reduced by 59% (95% CI: 25-78%). An estimated 1060 VL cases were prevented between June 1999 and January 2001, a mean protective effect of 27%. Although results need to be interpreted with caution, this analysis indicates a potentially strong reduction in VL incidence following a community distribution of ITN. The effectiveness of ITN depends on behavioural factors, which differ between communities.
    • Evaluation of a New Recombinant K39 Rapid Diagnostic Test for Sudanese Visceral Leishmaniasis.

      Ritmeijer, K; Melaku, Y; Mueller, M; Kipngetich, S; O'keeffe, C; Davidson, R N; Médecins sans Frontières-Holland, Amsterdam, The Netherlands. koert.ritmeijer@amsterdam.msf.org (Published by: American Society of Tropical Medicine and Hygiene, 2006-01)
      A new rK39 rapid diagnostic dipstick test (DiaMed-IT-Leish) was compared with aspiration and a direct agglutination test (DAT) for diagnosis of visceral leishmaniasis (VL) in 201 parasitologically confirmed cases, 133 endemic controls, and in 356 clinical suspects in disease-endemic and -epidemic areas in Sudan. The sensitivity of the rK39 test in parasitologically confirmed VL cases was 90%, whereas the specificity in disease-endemic controls was 99%. The sensitivity of the DAT was 98%. In clinically suspected cases, the sensitivity of the rK39 test was 81% and the specificity was 97%. When compared with the diagnostic protocol based on the DAT and aspiration used by Médecins sans Frontières in epidemic situations, the positive predictive value was 98%, and the negative predictive value was 71%. This rK39 rapid diagnostic test is suitable for screening as well as diagnosis of VL. Further diagnostic work-up of dipstick-negative patients with clinically suspected VL is important. The ease and convenience of the dipstick test will allow decentralization and improved access to care in disease-endemic areas in Sudan.
    • Exploring global and country-level barriers to an effective supply of leishmaniasis medicines and diagnostics in eastern Africa: a qualitative study.

      Sunyoto, T; Potet, J; den Boer, M; Ritmeijer, K; Postigo, JAR; Ravinetto, R; Alves, F; Picado, A; Boelaert, M (BMJ Publishing Group, 2019-05-30)
      OBJECTIVES: To understand stakeholders' perceptions of the access barriers to quality-assured diagnostics and medicines for leishmaniasis in the high-burden region of eastern Africa, and to identify key bottlenecks to improve the supply of commodities for neglected tropical diseases. DESIGN: Desk reviews and qualitative in-depth interview study with purposive sampling. METHODS: A landscape analysis through literature and desk review was performed. Next, 29 representatives from international organisations, non-governmental agencies, national control programmes from six countries (Ethiopia, Kenya, Somalia, South Sudan, Sudan and Uganda) and manufacturers were interviewed between May and July 2018. Participants were selected purposively and expanded through a snowballing technique.Data analysis was aided by NVivo, applying the framework method as a part of the thematic content analysis approach. RESULTS: The barriers along the visceral leishmaniasis (VL) supply chain were identified as emerging themes, grouped across supply chain activities and health systems component(s). Stakeholders expressed the perception of progress, but bottlenecks persist. VL medicines, in general, lack multisource production capacity and with small market volume, expansion of suppliers is difficult. Procurement is plagued by forecasting difficulties, complex regulatory policies and procedures, and distribution challenges. Weak communication and coordination across different levels resulted in shortages and loss of trust among different actors. Cross-cutting issues spanned from limited political and resource commitment due to low awareness and limited in-country capacity. However, study respondents were optimistic to pursue several remedies, most importantly to build bridges between supply and demand sides through continued dialogue and collaborations. Diagnostics supply has mostly been overlooked; thus, improved investment in this area is needed. CONCLUSIONS: Addressing supply barriers in eastern Africa requires consistent, specific efforts at the global and national levels, progressing from current partnerships and agreements. Priority actions include pooled procurement, improved forecast, and increased commitment and resources. Sustainability remains an elusive goal, yet to be integrated into discussions moving forward.
    • Failure of an Innovative Low-Cost, Noninvasive Thermotherapy Device for Treating Cutaneous Leishmaniasis Caused by in Pakistan.

      Kamink, S; Abdi, A; Kamau, C; Ashraf, S; Ansari, MA; Qureshi, NA; Schallig, H; Grobusch, MB; Fernhout, J; Ritmeijer, K (The American Society of Tropical Medicine and Hygiene, 2019-10-07)
      Cutaneous leishmaniasis (CL), a neglected parasitic skin disease, is endemic in Pakistan, where Leishmania tropica and Leishmania major are the causative protozoan species. Standard treatment with antimonial injections is long, painful, and costly; has toxic side effects; and is not always available in public hospitals. Small pilot studies have previously evaluated a low-cost and noninvasive hand-held exothermic crystallization thermotherapy (HECT-CL) device. We aimed to further establish the effectiveness, safety, and feasibility of HECT-CL in L. tropica. In a prospective observational study, patients with parasitological confirmation of CL were treated using the HECT-CL heat pack for 3 minutes with an initial temperature of 52-53°C for 7 consecutive days. Dried blood spot samples were taken for species identification by PCR. Effectiveness was assessed by using medical photographs and measurements of the lesion size at baseline and subsequent follow-up visits, for up to 180 days. We intended to enroll 317 patients. The HECT-CL treatment was easy to apply and well tolerated. Species identification demonstrated the presence of L. tropica. Interim analysis of 56 patients showed a failure rate of 91% at follow-up (median 45 days after treatment, interquartile range 30-60 days). Enrollment of patients was prematurely suspended because of futility. This study showed a high failure rate for HECT-CL thermotherapy in this setting. Leishmania tropica is known to be less sensitive to antileishmanial drugs, more temperature-resistant, and spontaneous healing is slower than that in L. major. More research is needed to identify low-cost, effective, and more patient-friendly treatment for L. tropica.
    • "Kala-Azar is a Dishonest Disease": Community Perspectives on Access Barriers to Visceral Leishmaniasis (Kala-Azar) Diagnosis and Care in Southern Gadarif, Sudan

      Sunyoto, T; Adam, GK; Atia, AM; Hamid, Y; Babiker, RA; Abdelrahman, N; Vander Kelen, C; Ritmeijer, K; Alcoba, G; den Boer, M; et al. (American Society of Tropical Medicine and Hygiene, 2018-04-13)
      Early diagnosis and treatment is the principal strategy to control visceral leishmaniasis (VL), or kala-azar in East Africa. As VL strikes remote rural, sparsely populated areas, kala-azar care might not be accessed optimally or timely. We conducted a qualitative study to explore access barriers in a longstanding kala-azar endemic area in southern Gadarif, Sudan. Former kala-azar patients or caretakers, community leaders, and health-care providers were purposively sampled and thematic data analysis was used. Our study participants revealed the multitude of difficulties faced when seeking care. The disease is well known in the area, yet misconceptions about causes and transmission persist. The care-seeking itineraries were not always straightforward: "shopping around" for treatments are common, partly linked to difficulties in diagnosing kala-azar. Kala-azar is perceived to be "hiding," requiring multiple tests and other diseases must be treated first. Negative perceptions on quality of care in the public hospitals prevail, with the unavailability of drugs or staff as the main concern. Delay to seek care remains predominantly linked to economic constraint: albeit treatment is for free, patients have to pay out of pocket for everything else, pushing families further into poverty. Despite increased efforts to tackle the disease over the years, access to quality kala-azar care in this rural Sudanese context remains problematic. The barriers explored in this study are a compelling reminder of the need to boost efforts to address these barriers.
    • Leishmania Antigenuria to Predict Initial Treatment Failure and Relapse in Visceral Leishmaniasis/HIV Coinfected Patients: An Exploratory Study Nested Within a Clinical Trial in Ethiopia

      van Griensven, J; Mengesha, B; Mekonnen, T; Fikre, H; Takele, Y; Adem, E; Mohammed, R; Ritmeijer, K; Vogt, F; Adriaensen, W; et al. (Frontiers Media, 2018-03-29)
      Background: Biomarkers predicting the risk of VL treatment failure and relapse in VL/HIV coinfected patients are needed. Nested within a two-site clinical trial in Ethiopia (2011-2015), we conducted an exploratory study to assess whether (1) levels of Leishmania antigenuria measured at VL diagnosis were associated with initial treatment failure and (2) levels of Leishmania antigenuria at the end of treatment (parasitologically-confirmed cure) were associated with subsequent relapse. Methods:Leishmania antigenuria at VL diagnosis and cure was determined using KAtex urine antigen test and graded as negative (0), weak/moderate (grade 1+/2+) or strongly-positive (3+). Logistic regression and Kaplan-Meier methods were used to assess the association between antigenuria and (1) initial treatment failure, and (2) relapse over the 12 months after cure, respectively. Results: The analysis to predict initial treatment failure included sixty-three coinfected adults [median age: 30 years interquartile range (IQR) 27-35], median CD4 count: 56 cells/μL (IQR 38-113). KAtex results at VL diagnosis were negative in 11 (17%), weak/moderate in 17 (27%) and strongly-positive in 35 (36%). Twenty (32%) patients had parasitologically-confirmed treatment failure, with a risk of failure of 9% (1/11) with KAtex-negative results, 0% (0/17) for KAtex 1+/2+ and 54% (19/35) for KAtex 3+ results. Compared to KAtex-negative patients, KAtex 3+ patients were at increased risk of treatment failure [odds ratio 11.9 (95% CI 1.4-103.0); P: 0.025]. Forty-four patients were included in the analysis to predict relapse [median age: 31 years (IQR 28-35), median CD4 count: 116 cells/μL (IQR 95-181)]. When achieving VL cure, KAtex results were negative in 19 (43%), weak/moderate (1+/2+) in 10 (23%), and strongly positive (3+) in 15 patients (34%). Over the subsequent 12 months, eight out of 44 patients (18%) relapsed. The predicted 1-year relapse risk was 6% for KAtex-negative results, 14% for KAtex 1+/2+ and 42% for KAtex 3+ results [hazard ratio of 2.2 (95% CI 0.1-34.9) for KAtex 1+/2+ and 9.8 (95% CI 1.8-82.1) for KAtex 3+, compared to KAtex negative patients; P: 0.03]. Conclusion: A simple field-deployable Leishmania urine antigen test can be used for risk stratification of initial treatment failure and VL relapse in HIV-patients. A dipstick-format would facilitate field implementation.
    • Long term outcomes and prognostics of visceral leishmaniasis in HIV infected patients with use of pentamidine as secondary prophylaxis based on CD4 level: a prospective cohort study in Ethiopia

      Diro, E; Edwards, T; Ritmeijer, K; Fikre, H; Abongomera, c; Kibret, A; Bardonneau, C; Soipei, P; Mutinda, B; Omollo, R; et al. (Public Library of Science, 2019-02-21)
      BACKGROUND: The long-term treatment outcome of visceral leishmaniasis (VL) patients with HIV co-infection is complicated by a high rate of relapse, especially when the CD4 count is low. Although use of secondary prophylaxis is recommended, it is not routinely practiced and data on its effectiveness and safety are limited. METHODS: A prospective cohort study was conducted in Northwest Ethiopia from August 2014 to August 2017 (NCT02011958). HIV-VL patients were followed for up to 12 months. Patients with CD4 cell counts below 200/μL at the end of VL treatment received pentamidine prophylaxis starting one month after parasitological cure, while those with CD4 count ≥200 cells/μL were followed without secondary prophylaxis. Compliance, safety and relapse-free survival, using Kaplan-Meier analysis methods to account for variable time at risk, were summarised. Risk factors for relapse or death were analysed. RESULTS: Fifty-four HIV patients were followed. The probability of relapse-free survival at one year was 50% (95% confidence interval [CI]: 35-63%): 53% (30-71%) in 22 patients with CD4 ≥200 cells/μL without pentamidine prophylaxis and 46% (26-63%) in 29 with CD4 <200 cells/μL who started pentamidine. Three patients with CD4 <200 cells/μL did not start pentamidine. Amongst those with CD4 ≥200 cells/μL, VL relapse was an independent risk factor for subsequent relapse or death (adjusted rate ratio: 5.42, 95% CI: 1.1-25.8). Except for one case of renal failure which was considered possibly related to pentamidine, there were no drug-related safety concerns. CONCLUSION: The relapse-free survival rate for VL patients with HIV was low. Relapse-free survival of patients with CD4 count <200cells/μL given pentamidine secondary prophylaxis appeared to be comparable to patients with a CD4 count ≥200 cells/μL not given prophylaxis. Patients with relapsed VL are at higher risk for subsequent relapse and should be considered a priority for secondary prophylaxis, irrespective of their CD4 count.
    • Long-term Clinical Outcomes in Visceral Leishmaniasis-HIV Co-infected Patients during and after Pentamidine Secondary Prophylaxis in Ethiopia: a single-arm clinical trial

      Diro, E; Ritmeijer, K; Boelaert, M; Alves, F; Mohammed, R; Abongomera, C; Ravinetto, R; De Crop, M; Fikre, H; Adera, C; et al. (Oxford University Press, 2017-09-13)
      We have conducted a single-arm trial evaluating monthly pentamidine secondary prophylaxis (PSP) to prevent visceral leishmaniasis (VL) relapse in Ethiopian HIV-patients. Outcomes at 12 months of PSP have been previously reported, supporting PSP effectiveness and safety. However, remaining relapse-free after PSP discontinuation is vital. We now report outcomes and associated factors for a period of upto 2.5 years after initiating PSP, including one year follow-up after PSP discontinuation.