Development and external validation of a clinical prognostic score for death in visceral leishmaniasis patients in a high HIV co-infection burden area in Ethiopia

Abstract

BackgroundIn Ethiopia, case fatality rates among subgroups of visceral leishmaniasis (VL) patients are high. A clinical prognostic score for death in VL patients could contribute to optimal management and reduction of these case fatality rates. We aimed to identify predictors of death from VL, and to develop and externally validate a clinical prognostic score for death in VL patients, in a high HIV co-infection burden area in Ethiopia.Methodology/Principal findingsWe conducted a retrospective cohort study in north west Ethiopia. Predictors with an adjusted likelihood ratio ≥1.5 or ≤0.67 were retained to calculate the predictor score. The derivation cohort consisted of 1686 VL patients treated at an upgraded health center and the external validation cohort consisted of 404 VL patients treated in hospital. There were 99 deaths in the derivation cohort and 53 deaths in the external validation cohort. The predictors of death were: age >40 years (score +1); HIV seropositive (score +1); HIV seronegative (score -1); hemoglobin ≤6.5 g/dl (score +1); bleeding (score +1); jaundice (score +1); edema (score +1); ascites (score +2) and tuberculosis (score +1). The total predictor score per patient ranged from -1 to +5. A score of -1, indicated a low risk of death (1.0%), a score of 0 an intermediate risk of death (3.8%) and a score of +1 to +5, a high risk of death (10.4–85.7%). The area under the receiver operating characteristic curve was 0.83 (95% confidence interval: 0.79–0.87) in derivation, and 0.78 (95% confidence interval: 0.72–0.83) in external validation.Conclusions/SignificanceThe overall performance of the score was good. The score can enable the early detection of VL cases at high risk of death, which can inform operational, clinical management guidelines, and VL program management. Implementation of focused strategies could contribute to optimal management and reduction of the case fatality rates.

The initial effectiveness of liposomal amphotericin B (AmBisome) and miltefosine combination for treatment of visceral leishmaniasis in HIV co-infected patients in Ethiopia: A retrospective cohort study

“…The predictors of death identified—age >40 years and hemoglobin level ≤6.5 g/dL—are similar to those reported from other studies [ 35 , 48 , 49 ]. Patients aged >40 years, may have underlying co-morbidities (e.g.…”

“…In the present study, we had a higher admission rate of late stage VL patients that were referred from other hospitals as compared to the previous AmBisome monotherapy study. We have recently shown that besides HIV serostatus, other important predictors of death were: age >40 years, hemoglobin ≤6.5 g/dL, bleeding, jaundice, edema, ascites and tuberculosis [ 35 ]. We also found that in the presence of major predictors of death, the predictive effect of treatment on outcome may be minimal [ 35 , 36 ].…”

“…We have recently shown that besides HIV serostatus, other important predictors of death were: age >40 years, hemoglobin ≤6.5 g/dL, bleeding, jaundice, edema, ascites and tuberculosis [ 35 ]. We also found that in the presence of major predictors of death, the predictive effect of treatment on outcome may be minimal [ 35 , 36 ]. If we are to consider initial parasitological failure and death as overall initial failure (assuming that patients who died also had parasitological failure), then the overall initial failure rate with the combination regimen were also significantly lower than with AmBisome monotherapy (16.2% vs .…”

“…Working in a remote area with relatively limited capacity, we did not have the capacity to perform autopsies. However, basing on clinical experience, some of the underlying causes of death include: severe anemia, severe pneumonia, tuberculosis, hepatic failure and sepsis [ 35 , 57 , 58 ]. Also, as a retrospective study, we could only study predictors from the collected variables.…”

“…To overcome the problem of substantial missing baseline CD4 count results, we created a composite marker for advanced HIV disease, defined as having either additional WHO stage IV disease [ 33 ] or a CD4 count <50 cells/μL at VL diagnosis [ 34 ]. Continuous variables were categorized based on information from literature and a recent study on predictors of death [ 35 ]. The association between predictors and parasitological failure or death were first assessed with Chi-squared or Fisher’s exact test.…”