• 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.
    • 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)
    • 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.
    • Epidemic Visceral Leishmaniasis in Sudan: A Randomized Trial of Aminosidine Plus Sodium Stibogluconate Versus Sodium Stibogluconate Alone.

      Seaman, J; Pryce, D; Sondorp, H; Moody, A; Bryceson, A; Davidson, R N; Medecins Sans Frontieres-Holland, Amsterdam. (Published by Infectious Diseases Society of America, 1993-09)
      In a comparative trial of treatment in southern Sudan, visceral leishmaniasis was diagnosed by the following symptoms: fever for > 1 month, splenomegaly, and antileishmanial direct agglutination test (DAT) titer of > or = 1:25,600. Patients (200) were randomized to receive sodium stibogluconate (Sbv) at 20 mg/kg/day for 30 days (groups S, n = 99) or Sbv at 20 mg/kg/day plus aminosidine at 15 mg/kg/day for 17 days (group AS, n = 101). Of 192 patients who had spleens or lymph nodes aspirated at entry, 134 (70%) were positive for parasites. During treatment, 7% in group S and 4% in group AS died. All 184 patients who completed treatment were clinically cured. At days 15-17, microscopy of aspirates showed that 57 (95%) of 60 in group AS were negative for parasites compared with 47 (81%) of 58 in group S (P = .018). At day 30, 57 (93.4%) of 61 group S aspirates were negative.
    • 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.
    • Liposomal Amphotericin B (AmBisome) in the Treatment of Complicated Kala-Azar Under Field Conditions.

      Seaman, J; Boer, C; Wilkinson, R; de Jong, J; de Wilde, E; Sondorp, H; Davidson, R N; Medecins Sans Frontieres Holland, The Netherlands. (Published by: Infectious Diseases Society of America, 1995-07)
      An open trial of liposomal amphotericin B (AmBisome [L-AmB]; Vestar, San Dimas, CA) for treatment of complicated visceral leishmaniasis was performed in Sudan. Forty-nine patients were treated, and there were six deaths (12% mortality); these were not attributed to therapy. Thirty-seven patients were selected for the trial because of (1) relapse after treatment with a combination of pentavalent antimony (Sbv) and aminosidine, (2) incomplete parasitological response to Sbv and aminosidine, or (3) severe illness. Drug regimen 1 (3 doses of 3-5 mg/kg, on days 0, 3, and 10) cured 8 (50%) of 16 patients; regimen 2 (6 doses of 3-5 mg/kg, on days 0, 3, 6, 8, 10, and 13) cured 14 (88%) of 16. For four of 10 partial responders, "rescue" therapy with L-AmB alone (3 mg/kg daily for 10 days) resulted in cure. Twelve less-unwell patients received regimen 3 (4 doses of 4-5 mg/kg, on days 0, 2, 5, and 7); seven of 11 patients evaluated (64%) were cured. The optimal regimen of L-AmB in these circumstances is administration of 4 mg/kg on days 0, 3, 6, 8, 10, and 13.
    • A randomized comparison of branded sodium stibogluconate and generic sodium stibogluconate for the treatment of visceral leishmaniasis under field conditions 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, 2000-05)
      OBJECTIVE: To compare the outcome of treatment of Sudanese kala-azar patients treated under field conditions with either branded sodium stibogluconate (SSG) (Pentostam GlaxoWellcome) or generic SSG (Albert David Ltd, Calcutta, supplied by International Dispensary Association, Amsterdam). METHOD: Randomised comparison. 271 patients were treated with Pentostam and 245 with generic SSG. RESULTS: No statistically significant differences in cure rate or mortality were detected between Pentostam and generic SSG. No differences in side-effects between the two drugs were noted. The initial cure rate at the time of discharge was 93.7 and 97.6%, respectively; the death rate during treatment 5.9 and 2.4%. Six months follow up was achieved in 88.5% of the discharged patients. Two patients had died in the Pentostam group and two had died in the generic SSG group, giving a final death rate of 7.5 and 3.7%. The number of relapses in the Pentostam and generic SSG groups were 3 and 1, respectively. The final cure rates, calculated at 6 months after discharge, were 91.3% and 95.9%. CONCLUSION: No difference was observed in the performance of generic SSG compared to Pentostam for the treatment of visceral leishmaniasis in Sudan. Generic SSG can be routinely and safely used for the treatment of kala-azar. Generic SSG costs only 1/14 of the price of Pentostam. The use of generic SSG may make treatment of kala-azar affordable for national governments in Africa.
    • Treatment of Kala-azar in Southern Sudan Using a 17-day Regimen of Sodium Stibogluconate Combined with Paromomycin: A Retrospective Comparison with 30-day Sodium Stibogluconate Monotherapy.

      Melaku, Y; Collin, S; Keus, K; Gatluak, F; Ritmeijer, K; Davidson, R N; Médecins sans Frontières-Holland, Amsterdam, The Netherlands. (American Society of Tropical Medicine and Hygiene, 2007-07)
      Médecins sans Frontières-Holland has treated > 67,000 patients with kala-azar (KA) in southern Sudan since 1989. In 2002, we replaced the standard regimen of 30 days of daily sodium stibogluconate (SSG) with a 17-day regimen of daily SSG combined with paromomycin (PM). We analyzed data for 4,263 primary KA patients treated between 2002 and 2005 in southern Sudan to determine the relative efficacy of the combination therapy regimen (PM/SSG). The initial cure rate among patients treated with PM/SSG was 97.0% compared with 92.4% among patients treated with SSG monotherapy. Relative efficacy of PM/SSG compared with SSG increased over the study period: odds of death in the PM/SSG group were 44% lower (odds ratio [OR] = 0.56, 95% confidence interval [CI] = 0.37-0.84) in 2002, 78% lower (OR = 0.22, 95% CI = 0.10-0.50) in 2003, and 86% lower (OR = 0.14, 95% CI = 0.07-0.27) in 2004-2005. In remote field settings, 17 days of SSG combined with PM gives better survival and initial cure rates than 30 days of SSG monotherapy.