• 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.
    • The epidemic of visceral leishmaniasis in western Upper Nile, southern Sudan: course and impact from 1984 to 1994.

      Seaman, J; Mercer, A; Sondorp, H; MSF (Médecins sans Frontières)-Holland, Amsterdam, The Netherlands. (Oxford University Press, 1996-08)
      BACKGROUND: Although endemic in parts of southern Sudan, visceral leishmaniasis (VL) had not been reported in Western Upper Nile (WUN) until an epidemic was confirmed in 1989. A combination of circumstances created conditions for transmission among a population of mainly Nuer and Dinka people who had no immunity. The civil war which restarted in 1983 has been a major contributing cause and continues to hinder provision of treatment, data collection and control measures. METHODS: Since the first of three clinics to treat VL was established in WUN in 1989, data on the epidemic and mortality have been collected in seven retrospective surveys of villages and among patients. Adults were interviewed about surviving family members and those who had died since the epidemic came. Survey death rates are used here to estimate mortality from VL and 'excess mortality' above expected levels. RESULTS: The surveys found high mortality at all ages and suggest an overall death rate of 38-57% since the epidemic started in 1984, and up to 70% in the most affected areas. Both methods of estimation suggest that around 100,000 deaths, among about 280,000 people in the epidemic area, might be attributable to VL. CONCLUSIONS: This continuing epidemic has shown that VL can cause high mortality in an outbreak with astonishingly high infection rates. Population movement has been a major factor in transmission and poor nutritional status has probably contributed to the risk of clinical infection. Although over 17,000 people have been successfully treated for VL at the clinics in WUN, the disease is likely to become endemic there.
    • Epidemic Visceral Leishmaniasis in Southern Sudan: Treatment of Severely Debilitated Patients Under Wartime Conditions and with Limited Resources.

      Seaman, J; Mercer, A; Sondorp, H; Herwaldt, B L; Médecins sans Frontières-Holland, Amsterdam, The Netherlands. (1996-04-01)
      OBJECTIVES: 1) To determine the proportions of patients with visceral leishmaniasis who had various treatment outcomes when cared for under wartime conditions and with limited resources and 2) to identify patient characteristics associated with the outcomes. DESIGN: Cohort study. SETTING: Médecins sans Frontières-Holland's treatment center in Duar, Western Upper Nile Province, an area in southern Sudan that has been severely affected by Sudan's civil war and a massive epidemic of visceral leishmaniasis. PATIENTS: 3076 consecutive patients who had visceral leishmaniasis, were admitted to the treatment center the first year the center was operational (August 1990 to July 1991), and were treated with the pentavalent antimonial compound sodium stibogluconate. MEASUREMENTS: Patient characteristics on admission and four mutually exclusive treatment outcomes (default during first admission, death during first admission, discharge and readmission for retreatment [relapse], and discharge and no readmission for retreatment [successful treatment]). RESULTS: The patients had a median age of 15 years and were notably anemic (median hemoglobin level, 77g/L) and malnourished (median body mass index of adults [> or = 18 years of age], 15.2 kg/m2); most (91.0%) had been sick less than 5 months. Although patients could not be monitored after treatment to document cure, most (2562 [83.3%]) were successfully treated; 336 (10.9%) died during their first admission, and 79 are known to have relapsed (3.0% of those discharged alive [that is, those whose final treatment outcome was successful treatment or relapse]). In univariable analysis, young and older age (<5 or > or = 45 years of age), long duration of illness (> or = 5 months), markedly low hemoglobin level or body mass index, large spleen, high parasite density, and vomiting at least once during the treatment course were associated with death. In multiple logistic regression analysis of data for a subgroup of 1207 adults (those who did not default or relapse and for whom data were recorded on age, sex, duration of illness, hemoglobin level, body mass index, and spleen size), the approximate risk ratios for death were 2.2 (95% Cl, 1.4 to 3.6) for those with a long duration of illness, 3.6 (Cl, 2.1 to 5.9) for those 45 years of age or older, 4.6 (Cl, 2.2 to 9.4) for those with a hemoglobin level less than 60 g/L, and 12.2 (Cl, 3.2 to 47.2) for those with a body mass index less than 12.2 kg/m2. CONCLUSION; Despite the severe debility of the patients and the exceptionally difficult circumstances under which they were treated, most fared remarkably well.
    • Epidemic visceral leishmaniasis in southern Sudan: treatment of severely debilitated patients under wartime conditions with limited resources

      Mercer, A; Herwaldt, B; Seaman, J; Sondorp, H; Medecins Sans Fronteres - Amsterdam (American College of Physicians, 2008-03-06)
    • 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.
    • 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.
    • Visceral Leishmaniasis in Southern Sudan: Status of Healthy Villagers in Epidemic Conditions.

      Seaman, J; Ashford, R W; Schorscher, J; Dereure, J; MSF Holland (Artsen Zonder Grenzen), Nairobi, Kenya. (Published by: Maney Publishing, 1992-10)
      A combination of interview, serology and skin testing was used to investigate the status of apparently healthy villagers during a visceral leishmaniasis epidemic in southern Sudan. The number of people who had died equalled the number who were alive at the time of the survey. The direct agglutination test (DAT) identified 10% of the people as being serologically positive. Most young children (36/39) and 34% (22/64) of adults had neither positive serology nor skin test. About 64% (42/66) of adults had positive skin tests. In two villages, 54% and 76% of those over four years of age showed evidence of having been infected. The mortality associated with infection was estimated as at least 69%; 25% of those infected appeared to have cured spontaneously. The outcome for the remaining 6% was still doubtful. Even in this devastating epidemic there is, therefore, evidence of a considerable amount of infection without severe disease. Serological tests, while useful clinically, are apparently not useful for detecting early cases. Combined skin testing and serology produces a comprehensive though partially hypothetical picture.