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.

OBJECTIVE: To identify risk factors for in-hospital mortality in patients treated for visceral leishmaniasis (VL) in Uganda. METHODS: Retrospective analysis of VL patients' clinical data collected for project monitoring by Médecins Sans Frontières in Amudat, eastern Uganda. RESULTS: Between 2000 and 2005, of 3483 clinically suspect patients, 53% were confirmed with primary VL. Sixty-two per cent were children <16 years of age with a male/female ratio of 2.2. The overall case-fatality rate during pentavalent antimonial (n = 1641) or conventional amphotericin B treatment (n = 217) was 3.7%. There was no difference in the case-fatality rate between treatment groups (P > 0.20). The main risk factors for in-hospital death identified by a multivariate analysis were age <6 years and >15 years, concomitant tuberculosis or hepatopathy, and drug-related adverse events. The case-fatality rate among patients >45 years of age was strikingly high (29.0%). CONCLUSION: Subgroups of VL patients at higher risk of death during treatment with drugs currently available in Uganda were identified. Less toxic drugs should be evaluated and used in these patients.

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.

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.

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.

Since 1989, Médecins Sans Frontières (MSF) has provided medical humanitarian assistance during outbreaks of visceral leishmaniasis (VL; kala-azar) in Sudan. First, in western Upper Nile in southern Sudan, where a VL epidemic occurred after the resumption of the civil war in Sudan in 1983, with an estimated 100,000 deaths. Later, MSF started interventions in eastern Upper Nile and Gedaref State. In these two endemic regions VL incidence has risen markedly since 2001, which could be the start of a new epidemic cycle. Outbreaks of VL in Sudan remain unpredictable, and access to affected populations in war-torn southern Sudan is often hampered by insecurity. Therefore, MSF takes a flexible approach, establishing treatment centres where patients can be accessed. From 1989 to 2002, MSF treated >51,000 VL cases in Sudan. Despite very basic field conditions, high cure rates of 95% are being achieved. Lack of diagnostics is a major obstacle to treatment, especially during epidemic situations. Therefore, development of simple and rapid technologies is required, allowing reliable diagnosis under field conditions. For treatment of VL there is a limited choice of effective, affordable drugs. There are strong indications of an emerging resistance to antimonials in Malakal. Introduction of combination therapies is urgently needed to prevent the further emergence and spread of resistance to antimonials, which are still the mainstay of VL treatment in eastern Africa. Experience with combination therapy with sodium stibogluconate (SSG) and paromomycin is promising, and combinations of SSg with liposomal amphotericin B and miltefosine are currently being explored.

We conducted a case-control study to evaluate risk factors for visceral leishmaniasis during an epidemic in a previously unaffected district of Ethiopia. We also collected blood and bone marrow specimens from dogs in the outbreak villages. In multivariable analyses of 171 matched case-control pairs, dog ownership, sleeping under an acacia tree during the day, and habitually sleeping outside at night were associated with significantly increased risk. Specimens from 7 (3.8%) dogs were positive by immunofluorescent antibody test (IFAT) and both enzyme-linked immunosorbent assays (ELISAs), whereas Leishmania DNA was detected in 5 (2.8%) bone marrow aspirates (from 3 seropositive and 2 seronegative dogs). Insecticide-treated nets may only protect a portion of those at risk. Further research on the vectors, the role of the dog in the transmission cycle, and the effect of candidate interventions are needed to design the best strategy for control.

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.

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.