High Mortality among Older Patients Treated with Pentavalent Antimonials for Visceral Leishmaniasis in East Africa and Rationale for Switch to Liposomal Amphotericin B

Chappuis, François; Alirol, Emilie; Worku, Dagemlidet Tesfaye; Müeller, Yolanda; Ritmeijer, Koert

doi:10.1128/aac.01298-10

Cited by 25 publications

(18 citation statements)

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“…Therefore in our dataset, AmBisome may have mediated the effect of older age on VL mortality. This seems to confirm the recommendation that treatment with AmBisome may be lifesaving for the elderly VL patients [9]. …”

Section: Discussionsupporting

confidence: 85%

A clinical severity scoring system for visceral leishmaniasis in immunocompetent patients in South Sudan

et al. 2017

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BackgroundSouth Sudan is one of the most endemic countries for visceral leishmaniasis (VL), and is frequently affected by large epidemics. In resource-limited settings, clinicians require a simple clinical tool to identify VL patients who are at increased risk of dying, and who need specialised treatment with liposomal amphotericin B and other supportive care. The aim of this study was to develop and validate a clinical severity scoring system based on risk factors for death in VL patients in South Sudan.MethodsA retrospective analysis was conducted of data from a cohort of 6,633 VL patients who were treated in the Médecins Sans Frontières (MSF) hospital in Lankien between July 2013 and June 2015. Risk factors for death during treatment were identified using multivariable logistic regression models, and the regression coefficients were used to develop a severity scoring system. Sensitivity and specificity of score cut-offs were assessed by receiver operating characteristic (ROC) analysis.ResultsIn multivariable models, risk factors for death in adult VL patients were: anaemia (odds ratio (OR) 4.46 (95% CI 1.58–12.6) for Hb <6g/dL compared with ≥9g/dL), nutritional status (OR 4.84 (2.09–11.2) for BMI <13 kg/m2 compared with ≥16 kg/m2), weakness (OR 4.20 (1.82–9.73) for collapsed compared with normal weakness), jaundice (OR 3.41 (1.17–9.95)), and oedema/ascites (OR 4.86 (1.67–14.1)). For children and adolescents the risk factors were: age (OR 10.7 (6.3–18.3) for age <2 years compared with 6–18 years), anaemia (OR 7.76 (4.15–14.5) for Hb <6g/dL compared with ≥9g/dL), weakness (OR 3.13 (22.8–105.2) for collapsed compared with normal weakness), and jaundice (OR 12.8 (4.06–40.2)). Severity scoring predictive ability was 74.4% in adults and 83.4% in children and adolescents.ConclusionOur evidenced-based severity scoring system demonstrated sufficient predictive ability to be operationalised as a clinical tool for rational allocation of treatment to VL patients at MSF centres in South Sudan.

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Section: Discussionsupporting

confidence: 85%

A clinical severity scoring system for visceral leishmaniasis in immunocompetent patients in South Sudan

et al. 2017

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“…Patients with severe or complicated VL have a poor tolerability for antimonials, resulting in a significantly increased mortality risk [62]. Because of its more favorable safety profile, LAMB is the first-line treatment in pregnancy, due to the high risk of spontaneous abortion with antimonials [21], as well as in elderly VL patients, because of high antimonial toxicity-related mortality in patients over 45 years of age [63]. Because of the poor tolerability and high mortality associated with pentavalent antimonials in HIV co-infected VL patients, LAMB is the recommended drug of choice in this patient group, even though its efficacy is limited [24].…”

Section: Expert Opinionmentioning

confidence: 99%

Liposomal amphotericin B as a treatment for human leishmaniasis

Balasegaram

Ritmeijer

Lima

et al. 2012

Expert Opinion on Emerging Drugs

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Introduction:Leishmaniasis is a parasitic disease transmitted by phlebotomine sandflies. Between 700,000 and 1.2 million cases of cutaneous leishmaniasis and between 200,000 and 400,000 cases of visceral leishmaniasis (VL), which is fatal if left untreated, occur annually worldwide. Liposomal amphotericin B (LAMB), alone or in combination with other drugs, has been extensively studied as VL treatment, but data on routine field use are limited, and several challenges to patients' access to this life-saving drug remain.Areas covered:This article provides a review of clinical studies on LAMB for VL and other forms of leishmaniasis. The current development of generic versions of LAMB and related challenges are also discussed.Expert opinion:LAMB proved to be highly efficacious and safe in over 8000 VL patients treated by MÉdecins Sans Frontières in South Asia, and its use was feasible even at primary healthcare level. Despite requiring higher doses, LAMB is the drug of choice to treat vulnerable groups (e.g., pregnant or HIV positive) and relapsing VL patients in East Africa. LAMB should be included in national VL guidelines and registered in all VL endemic countries. Its cost should be further reduced and regulatory pathways to prove bioequivalence for generic LAMB products should be implemented.

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“…Yet older people are rarely identified as an at-risk group for communicable diseases or their specific needs considered by infection control programmes [28].…”

Section: How Are Older People Neglected?mentioning

confidence: 99%