“…Despite the fact that the difficult context of civil war, violence and displacement, the weak and unstable health care system was similar between this study and the earlier studies in South Sudan [30, 31]. This may be partially explained by earlier presentation at the Lankien hospital: more than 92% of the patients were able to present early, i.e.…”
Section: Discussionsupporting
confidence: 60%
“…As there were only 13 deaths in 527 patients presenting more than 1 month after onset of symptoms, duration of illness could not be identified as a risk factor. This seems to support the interpretation that specific joint efforts led since 2009 by the World Health Organisation in collaboration with Ministry of Health and nongovernmental organisations (NGOs), have been successful in achieving improved access to VL care in South Sudan (by decentralising VL treatment services and ensuring supply of tests and drugs) [3, 30]. …”
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.
“…Despite the fact that the difficult context of civil war, violence and displacement, the weak and unstable health care system was similar between this study and the earlier studies in South Sudan [30, 31]. This may be partially explained by earlier presentation at the Lankien hospital: more than 92% of the patients were able to present early, i.e.…”
Section: Discussionsupporting
confidence: 60%
“…As there were only 13 deaths in 527 patients presenting more than 1 month after onset of symptoms, duration of illness could not be identified as a risk factor. This seems to support the interpretation that specific joint efforts led since 2009 by the World Health Organisation in collaboration with Ministry of Health and nongovernmental organisations (NGOs), have been successful in achieving improved access to VL care in South Sudan (by decentralising VL treatment services and ensuring supply of tests and drugs) [3, 30]. …”
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.
“…With tensions reduced in South Sudan, VL cases declined sharply to fewer than 5,000 cases in 2012 and to the lowest level in 2013 when only 2,714 cases were reported [45, 46]. Serological diagnoses using the rK39 rapid immunochromatographic and direct agglutination tests have been applied to diagnose VL cases in South Sudan [45], however, there is a lack of information regarding specific etiologic agents identified through molecular methods.Fig. 2Timeline of political unrest and number of VL deaths and cases in South Sudan [15, 38–41].…”
Section: Methodsmentioning
confidence: 99%
“…This current level of food insecurity is exacerbated by the current conflict.Fig. 3The “perfect storm” of conditions leading to VL Epidemics [35, 45–47]. The overarching problem in South Sudan since 2013 has two major factors.…”
Background: Visceral leishmaniasis (VL), caused predominantly by Leishmania donovani and transmitted by both Phlebotomus orientalis and Phlebotomus martini, is highly endemic in East Africa where approximately 30 thousands VL cases are reported annually. The largest numbers of cases are found in Sudan -where Phlebotomus orientalis proliferate in Acacia forests especially on Sudan's eastern border with Ethiopia, followed by South Sudan, Ethiopia, Somalia, Kenya and Uganda. Long-standing civil war and unrest is a dominant determinant of VL in East African countries. Here we attempt to identify the correlation between VL epidemics and civil unrest. Objective and methodology: In this review, literature published between 1955 and 2016 have been gathered from MSF, UNICEF, OCHA, UNHCR, PubMed and Google Scholar to analyse the correlation between conflict and human suffering from VL, which is especially apparent in South Sudan.
“…2 Paromomycin, liposomal amphotericin B, and miltefosine are also used for VL treatment. A combination of paromomycin and sodium stibogluconate recently replaced sodium stibogluconate monotherapy as the recommended treatment for VL in South Sudan, 5 and paromomycin monotherapy has been approved for use against VL in India. 6 Liposomal amphotericin B is highly effective against VL on the Indian subcontinent, even when given in a single dose, 7 …”
Visceral leishmaniasis is a neglected parasitic disease that has a high fatality rate in the absence of treatment. New drugs that are inexpensive, orally active, and effective could be useful tools in the fight against this disease. We previously showed that N2,N4-disubstituted quinazoline-2,4-diamines displayed low- to sub-micromolar potency against intracellular Leishmania, and lead compound N4-(furan-2-ylmethyl)-N2-isopropyl-7-methylquinazoline-2,4-diamine (4) exhibited modest efficacy in an acute murine model of visceral leishmaniasis. In the present work, thirty-one N2,N4-disubstituted quinazoline-2,4-diamines that had not previously been examined for their antileishmanial activity were evaluated for their potency and selectivity against Leishmania donovani, the causative parasite of visceral leishmaniasis. Quinazoline-2,4-diamines with aromatic substituents at both N2 and N4 exhibited potent in vitro antileishmanial activity but relatively low selectivity, while compounds substituted with small alkyl groups at either N2 or N4 generally showed lower antileishmanial potency but were less toxic to a murine macrophage cell line. Based on their in vitro antileishmanial potency, N4-benzyl-N2-(4-chlorobenzyl)quinazoline-2,4-diamine (15) and N2-benzyl-N4-isopropylquinazoline-2,4-diamine (40) were selected for in vivo evaluation of their pharmacokinetic and antileishmanial properties. While 15 displayed a longer plasma half-life and a greater area under the curve than 40, both compounds showed low efficacy in an acute murine visceral leishmaniasis model. Although the present study did not identify new quinazoline-2,4-diamines with promising in vivo efficacy, the reduced in vitro toxicity of derivatives bearing small alkyl groups at either N2 or N4 may provide clues for the design of safe and effective antileishmanial quinazolines.
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