[Leishmaniasis: progress in diagnosis, treatment and prevention]. / Leishmaniasis: vorderingen in diagnostiek, behandeling en preventie.

Visceral leishmaniasis ranks second after malaria in the top 10 fatal parasitic diseases worldwide. Treatment is effective, but most patients live in developing countries where even basic health care is unavailable. Economic factors hamper a targeted approach, which should include the following: preventing transmission by distributing bednets; developing diagnostic tools that can be used in the field without a laboratory; developing new and affordable drugs; and evaluating different drug combinations and treatment schedules that may prevent the development of resistance, as has been done in tuberculosis, HIV and malaria.

Royal Society of Tropical Medicine and Hygiene joint meeting with Médecins Sans Frontières at Manson House, London, 20 March 2003: field research in humanitarian medical programmes. Médecins Sans Frontières interventions against kala-azar in the Sudan, 1989-2003.

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.

Ethiopian visceral leishmaniasis: generic and proprietary sodium stibogluconate are equivalent; HIV co-infected patients have a poor outcome.

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.

Emergence or re-emergence of visceral leishmaniasis in areas of Somalia, north-eastern Kenya, and south-eastern Ethiopia in 2000-01.

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.

Active and passive case detection strategies for the control of leishmaniasis in Bangladesh.

SETTING: Two subdistricts in Bangladesh, Fulbaria and Trishal, which are hyperendemic for leishmaniasis. OBJECTIVE: To determine 1) the numbers of patients diagnosed with visceral leishmaniasis (VL) and post-kala azar dermal leishmaniasis (PKDL) using an active case detection (ACD) strategy in Fulbaria and a passive case detection (PCD) strategy in Trishal, and 2) the time taken from symptoms to diagnosis in the ACD subdistrict. DESIGN: A cross-sectional descriptive study of patients diagnosed from May 2010 to December 2011. The ACD strategy involved community education and outreach workers targeting households of index patients using symptom-based screening and rK-39 tests for suspected cases. RESULTS: In the ACD subdistrict (Fulbaria) and PCD sub-district (Trishal), respectively 1088 and 756 residents were diagnosed with VL and 1145 and 37 with PKDL. In the ACD subdistrict, the median time to diagnosis for patients directly referred by outreach workers or self-referred was similar, at 60 days for VL and respectively 345 and 360 days for PKDL. CONCLUSION: An ACD strategy at the subdistrict level resulted in an increased yield of VL and a much higher yield of PKDL. As PKDL acts as a reservoir for infection, a strategy of ACD and treatment can contribute to the regional elimination of leishmaniasis in the Indian sub-continent.

Contexte : Deux sous-districts du Bangladesh, Fulbaria et Trishai, où la leishmaniose est hyper-endémique.Objectif : Déterminer 1) le nombre de patients ayant eu un diagnostic de leishmaniose viscérale (VL) et de leishmaniose dermique post-kala azar (PKDL) grâce à une stratégie de détection active des cas (ACD) à Fulbaria et à une stratégie de détection passive (PCD) à Trishai, et 2) le temps écoulé entre les symptômes et le diagnostic dans le sous-district à ACD.Schéma : Etude descriptive transversale des patients diagnostiqués entre mai 2010 et décembre 2011. La stratégie ACD comportait une éducation des communautés et des stratégies avancées ciblant les foyers des patients index grâce à un dépistage basé sur les symptômes et au test rK-39 pour les patients suspects.Résultats : Dans les districts de stratégie ACD (Fulbaria) et le sous-district de stratégie PCD (Trishai), 1088 et 756 patients respectivement ont eu un diagnostic de VL et 1145 et 37 respectivement ont eu un diagnostic de PKDL. Dans ce sous-district, le délai médian de diagnostic était de 60 jours pour tous les patients atteints de VL, qu'ils soient référés par du personnel des stratégies avancées ou viennent d'eux-mêmes. Il était respectivement de 345 et 360 jours pour la PKDL.Conclusion : Une stratégie ACD au niveau d'un sous-district permet de dépister un nombre accru de VL et encore plus de PKDL. Comme la PKDL constitue un réservoir d'infection, la stratégie d'ACD et le traitement des cas dépistés peuvent contribuer à l'élimination régionale de la leishmaniose du sous-continent indien.

Marco de referencia: Los subdistritos de Fulbaria y Trishal en Bangladesh, donde es hiper-endémica la leishmaniasis.Objetivo: Determinar: 1) el número de pacientes con diagnóstico de leishmaniasis visceral (VL) y de leishmaniasis cutánea pos kala azar (PKDL) mediante una estrategia de detección activa de casos (ACD) en Fulbaria y una detección pasiva (PCD) en Trishal; y 2) y el lapso entre la aparición de los síntomas y el diagnóstico en el subdistrito que aplicó la estrategia ACD.Método: Se llevó a cabo un estudio transversal descriptivo de los pacientes en quienes se estableció el diagnóstico de leishmaniasis entre mayo del 2010 y diciembre del 2011. Como parte de la estrategia ACD se impartió educación a la comunidad y participaron trabajadores extrainstitucionales que contactaban a los hogares de los casos iniciales y practicaban una detección basada en los síntomas y la prueba rK-39 de diagnóstico rápido en los casos de presunción diagnóstica.Resultados: En el subdistrito de Fulbaria la estrategia ACD permitió el reconocimiento de 1088 residentes con VL y 1145 con PKDL; en el subdistrito de Trishal se detectaron mediante la estrategia PCD 756 y 37 casos, respectivamente. La mediana del lapso necesario hasta establecer el diagnóstico de VL en los pacientes remitidos directamente por los trabajadores periféricos fue análoga a la mediana del lapso en los que se presentaron por su propia iniciativa y correspondió a 60 días en casos de VL; en los pacientes con PKDL la mediana del lapso fue 360 días en los pacientes remitidos por los trabajadores periféricos y 360 en los pacientes que acudieron por su propia cuenta.Conclusión: Una estrategia ACD a escala del subdistrito ofrece un mayor rendimiento diagnóstico de la VL y un incremento aun mayor del diagnóstico de PKDL. Dado que la PKDL representa un reservorio de la infección, una estrategia ACD y tratamiento puede contribuir a la eliminación regional de la leishmaniasis en el subcontinente indio.

Implementation of liquid culture for tuberculosis diagnosis in a remote setting: lessons learned.

Although sputum smear microscopy is the primary method for tuberculosis (TB) diagnosis in low-resource settings, it has low sensitivity. The World Health Organization recommends the use of liquid culture techniques for TB diagnosis and drug susceptibility testing in low- and middle-income countries. An evaluation of samples from southern Sudan found that culture was able to detect cases of active pulmonary TB and extra-pulmonary TB missed by conventional smear microscopy. However, the long delays involved in obtaining culture results meant that they were usually not clinically useful, and high rates of non-tuberculous mycobacteria isolation made interpretation of results difficult. Improvements in diagnostic capacity and rapid speciation facilities, either on-site or through a local reference laboratory, are crucial.

Accessibility of diagnostic and treatment centres for visceral leishmaniasis in Gedaref State, northern Sudan.

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.

Priority during a meningitis epidemic: vaccination or treatment?

From November 1995 to May 1996, a meningitis epidemic occurred in northern Nigeria. More than 75,000 cases and 8440 deaths (case fatality rate (CFR), 11%) were recorded. Médecins sans Frontières, in cooperation with the Nigerian government, carried out an assistance programme (support to case management, surveillance and mass vaccination) in three states (Bauchi, Kano, Katsina) where 75% of cases occurred. Cost analysis of this assistance in Katsina State reveals that case management and mass vaccination were efficient: US$ 35 per case treated and US$ 0.64 per vaccination. There was, however, a remarkable difference in cost-effectiveness between the two strategies. The cost per death averted by improved case treatment was estimated to be US$ 396, while the cost per death averted by vaccination was estimated to be US$ 6000. In large part this difference is attributed to the late start of vaccination: more than 6 weeks after the epidemic threshold had been passed. During meningitis epidemics in countries where surveillance systems are inadequate, such as in most of sub-Saharan Africa, curative programmes should have priority.

A randomized comparison of branded sodium stibogluconate and generic sodium stibogluconate for the treatment of visceral leishmaniasis under field conditions in Sudan.

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.