Journal Article > ResearchFull Text
Am J Trop Med Hyg. 1 June 2009; Volume 80 (Issue 6); 929-34.
ter Horst R, Tefera T, Assefa G, Ebrahim AZ, Davidson RN, et al.
Am J Trop Med Hyg. 1 June 2009; Volume 80 (Issue 6); 929-34.
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.
Journal Article > ResearchFull Text
Trans R Soc Trop Med Hyg. 1 January 2007; Volume 101 (Issue 1); DOI:10.1016/j.trstmh.2006.02.005
Mueller M, Ritmeijer KKD, Balasegaram M, Koummuki Y, Santana MR, et al.
Trans R Soc Trop Med Hyg. 1 January 2007; Volume 101 (Issue 1); DOI:10.1016/j.trstmh.2006.02.005
In Sudan, two treatments are currently registered for visceral leishmaniasis: sodium stibogluconate (SSG) as first line and liposomal amphotericin B (AmBisome) as second line. We present 64 patients (52 relapse cases to SSG, 12 new but complicated cases) treated with AmBisome in eastern Sudan. AmBisome was administered at 2.5-8.2mg/kg (15-49mg/kg in total) per dose six times (days 1, 2, 3, 5, 10, 15) as an intravenous infusion. We measured outcome according to clinical response and parasitological clearance (lymph node aspiration). Patient outcomes fell into three groups: group 1, clinical responders (cured) with a negative test of cure (n=35); group 2, clinical responders with a positive test of cure (n=19); group 3, clinical non-responders (failures) with a positive test of cure (n=10). Of the 10 failures, six were already relapse cases. All of group 3, and 15 from group 2, were also treated with additional SSG (20mg/kg intramuscularly daily for 30-50 d) with resulting clinical and parasitological improvement. Parasite persistence and clinical failure were associated with a higher parasite density on admission (P<0.002) and underlying immunosuppressive disease: tuberculosis (three cases) or HIV (two cases). Because AmBisome monotherapy may fail in Sudan, a combination of AmBisome and SSG is recommended for relapse cases.
Journal Article > ResearchFull Text
Trop Med Int Health. 1 February 2003; Volume 8 (Issue 2); 164-167.; DOI:10.1046/j.1365-3156.2003.00996.x
Veeken H, Ritmeijer KKD, Seaman J, Davidson RN
Trop Med Int Health. 1 February 2003; Volume 8 (Issue 2); 164-167.; DOI:10.1046/j.1365-3156.2003.00996.x
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.
Journal Article > ResearchFull Text
Ann Trop Med Parasitol. 1 April 2006; Volume 100 (Issue 3); DOI:10.1179/136485906X91440
Belay AD, Asafa Y, Mesure J, Davidson RN
Ann Trop Med Parasitol. 1 April 2006; Volume 100 (Issue 3); DOI:10.1179/136485906X91440
The first two patients to be treated with miltefosine for post-kala-azar dermal leishmaniasis (PKDL) are reported. One was a 26-year-old Ethiopian man who had been treated with sodium stibogluconate, for relapsing visceral leishmaniasis (VL), four times between August 2002 and March 2004. In January 2004 this patient was found to be seropositive for HIV and began antiretroviral treatment with stavudine, lamivudine and nevirapine. Five months later he developed clinical PKDL, with extensive cutaneous, conjunctival and oral mucosal involvement. The second patient was a 42-year-old Ethiopian man who was treated for relapsing VL in November 2003. He too was subsequently found to be seropositive for HIV and was treated with stavudine, lamivudine and nevirapine from May 2004. He developed a nodular rash of PKDL over his face and upper body 2 weeks after starting the antiretroviral therapy. Treatment of both patients with oral miltefosine, at 100 mg/day for 28 days, led to the complete regression of their PKDL lesions. When checked 3-6 months after the end of the miltesofine treatment, neither patient showed any signs of VL, PKDL or other HIV-associated disease.
Journal Article > ResearchFull Text
Trop Med Int Health. 1 May 2000; Volume 5 (Issue 5); 312-317.; DOI:10.1046/j.1365-3156.2000.00555.x
Veeken H, Ritmeijer KKD, Seaman J, Davidson RN
Trop Med Int Health. 1 May 2000; Volume 5 (Issue 5); 312-317.; DOI:10.1046/j.1365-3156.2000.00555.x
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.
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.
Protocol > Research Protocol
Diro EGJ, Griensven JV, Woldegebreal T, Belew Z, Taye M, et al.
1 July 2018
2.1 OBJECTIVES
2.1.1 General objective:
To document the effectiveness, safety and feasibility of monthly PM secondary prophylaxis (PSP) in VL/HIV co-infected patients that have documented parasite clearance after VL treatment when used for prevention of VL relapse.
2.1.2 Specific objectives of the primary study period
2.1.2.1 Primary objectives
In VL/HIV co-infected patients that have documented parasite clearance after VL treatment:
- to assess the effectiveness of PSP in terms of preventing relapse and death;
- to assess the safety of PSP in terms of drug-related serious adverse events or permanent drug discontinuations due to adverse events;
- to assess the feasibility of PSP in terms of number of patients compliant to therapy
during the first year of monthly PM secondary prophylaxis.
2.1.2.2 Secondary objectives;
In VL/HIV co-infected patients that have documented parasite clearance after VL treatment:
- to assess the safety of PSP in terms of:
- drug-related non-serious adverse events
- serious adverse events (drug-related or not)
- to assess the feasibility of PSP in terms of:
- number of treatment interruptions/discontinuations,
- number of therapeutic interventions needed to treat adverse drug reactions
2.1.1 General objective:
To document the effectiveness, safety and feasibility of monthly PM secondary prophylaxis (PSP) in VL/HIV co-infected patients that have documented parasite clearance after VL treatment when used for prevention of VL relapse.
2.1.2 Specific objectives of the primary study period
2.1.2.1 Primary objectives
In VL/HIV co-infected patients that have documented parasite clearance after VL treatment:
- to assess the effectiveness of PSP in terms of preventing relapse and death;
- to assess the safety of PSP in terms of drug-related serious adverse events or permanent drug discontinuations due to adverse events;
- to assess the feasibility of PSP in terms of number of patients compliant to therapy
during the first year of monthly PM secondary prophylaxis.
2.1.2.2 Secondary objectives;
In VL/HIV co-infected patients that have documented parasite clearance after VL treatment:
- to assess the safety of PSP in terms of:
- drug-related non-serious adverse events
- serious adverse events (drug-related or not)
- to assess the feasibility of PSP in terms of:
- number of treatment interruptions/discontinuations,
- number of therapeutic interventions needed to treat adverse drug reactions
Journal Article > ResearchFull Text
Am J Trop Med Hyg. 1 January 2006; Volume 74 (Issue 1); 76-80.
Ritmeijer KKD, Melaku Y, Mueller M, Kipngetich S, O'keeffe C, et al.
Am J Trop Med Hyg. 1 January 2006; Volume 74 (Issue 1); 76-80.
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.
Journal Article > ResearchFull Text
Trans R Soc Trop Med Hyg. 31 January 2008
Ritmeijer KKD, Veeken H, Melaku Y, Leal G, Amsalu R, et al.
Trans R Soc Trop Med Hyg. 31 January 2008
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.
Journal Article > ResearchFull Text
Trans R Soc Trop Med Hyg. 1 April 2006; Volume 100 (Issue 4); DOI:10.1016/j.trstmh.2005.08.010
Balasegaram M, Dejene S, Tinnemann P, Perkins S, Davidson RN
Trans R Soc Trop Med Hyg. 1 April 2006; Volume 100 (Issue 4); DOI:10.1016/j.trstmh.2005.08.010
Humanitarian medical programmes in the tropics have the opportunity to provide beacons of good practice. The use of modern drugs and diagnostics, a lack of bureaucracy, adequate budgets, motivated staff and well-functioning supply lines all contribute to the success of this approach. At a joint meeting of the Royal Society of Tropical Medicine, the London School of Hygiene and Tropical Medicine, Médecins Sans Frontières and Merlin, new data were presented on the outcomes of recent humanitarian programmes to control malaria (Ethiopia), human African trypanosomiasis (south Sudan), Lassa fever (Sierra Leone) and tuberculosis (Tomsk, former USSR).
Journal Article > ResearchFull Text
Clin Infect Dis. 19 October 2011; Volume 53 (Issue 12); DOI:10.1093/cid/cir674
Ritmeijer KKD, ter Horst R, Chane S, Aderie EM, Piening T, et al.
Clin Infect Dis. 19 October 2011; Volume 53 (Issue 12); DOI:10.1093/cid/cir674
Due to unacceptably high mortality with pentavalent antimonials, Médecins Sans Frontières in 2006 began using liposomal amphotericin B (AmBisome) for visceral leishmaniasis (VL) patients in Ethiopia who were severely ill or positive for human immunodeficiency virus (HIV).