Visceral leishmaniasis (VL) is one of the most neglected tropical diseases caused by protozoa of the genus
In Ethiopia, VL is caused by
Visceral leishmaniasis is highly fatal if left untreated in over 95% of cases [
In Ethiopia, the first-line drugs for the management of VL are a combination of antimonials with aminoglycosides and Liposomal Amphotericin B (LAMB) for special situations (for HIV-positive and severely ill immunocompetent VL patients) [
Thus, determination of local data about treatment outcome and the risk factors of poor treatment outcome is very crucial for national control, prevention, and elimination of VL. A better understanding of treatment outcomes helps policymakers, clinicians, and funding organizations to develop strategies for improving outcomes. Studies that determine VL treatment outcome at some interval are vital to prevent the occurrence of drug resistance in our region even though resistance is not a common problem in East Africa at the present time. However, limited data are available in Ethiopia in general and there is no study on treatment outcome of VL patients in our setting. The present study aimed to assess the treatment outcome and associated factors among VL patients at Ayder Comprehensive Specialized Hospital (ACSH), northern Ethiopia.
The study was conducted at ACSH, Tigray region, Northern Ethiopia. ACSH is a teaching and referral hospital with 500 beds. The hospital serves for more than 9 million people in the catchment area. It provides both outpatient and in-patient services.
We conducted an institutional based cross-sectional study. The study was conducted using retrospectively collected data. All adult patients (age >18 years) with a well-established diagnosis of VL who were admitted to ACSH from June 01/2016 to April 30/2018 were included consecutively. Diagnosis of VL was performed according to Ethiopian Ministry of Health guidelines using a positive recombinant kinesin antigen (rK39) rapid diagnostic test (DiaMed-IT-Leish, DiaMed, Cressier, Switzerland) and the microscopic examination of aspirates from the spleen and/or bone marrow in a patient presented with sign and symptoms suggestive of VL [
The ethical approval and clearance were obtained from Ethics Review Committee of the School of Pharmacy, College of Health Sciences, Mekelle University (reference number: CHS/158/pharm-10). Permission was obtained from the hospital's medical director to access the patient's medical records. The privacy of personal information was strictly conserved.
VL case definition is the following: “A person who presents with fever for more than two weeks and an enlarged spleen (splenomegaly) and/or enlarged lymph nodes (lymphadenopathy), or either loss of weight, anemia or leucopenia while living in a known VL endemic area or having travelled to an endemic area” [
The treatment in the present study was done using either the combination of SSG and paromomycin (PM) or LAMB. SSG (20mg/kg /day) and
Demographic, clinical, laboratory, and treatment related factors were collected using a data extraction tool. These variables were collected from the patients’ medical record by trained health professionals.
Data were entered into an Epi data management (version 4.2.0) and analyzed using the Statistical Package (IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp). Descriptive analysis was computed using mean and median for quantitative variables and frequency (percentage) for categorical variables. Multicollinearity test was performed to determine correlation among independent variables using variance inflation factor (VIF) and there was no collinearity (VIF<2 for all the variables). A univariate logistic regression analysis was performed to determine the association of each independent variable with the outcome. Subsequently, variables with a p-value<0.25 in the multivariable analysis were included in the multivariable logistic regression model to identify predictors of poor treatment outcome. A p-value of <0.05 (
A total of 148 VL patients were included in this study. Of these, 94.6% were males. The mean (SD) age of the patients was 32.86 ± 11.9 years. Majorities (91.6%) were from rural areas. Fever, weight loss, and loss of appetite were present in all patients. The majority (76.4%) of the participants were newly diagnosed VL patients. The median duration of the illness was 28 days with interquartile range (IQR) from 14 to 56 days. All patients were rK39 positive and majorities (74%) of the patients were splenic aspirate positive. Majorities (95.9%) of the patients had anemia, leucopenia (93.9%), and thrombocytopenia (84.5%). TB coinfection was presented in 24.3% of the patients. Multiple coinfection with HIV-TB-VL coinfection was present in 10.1% of patients and malaria in 27% of patients (Table
Demographic and disease related characteristics of VL patients in ACSH, Tigray Region, Northern Ethiopia, June 2016–April 2018.
Variable | Category | Frequency (%) |
---|---|---|
Gender | Female | 8 (5.4) |
Male | 140 (94.6) | |
Age in years | 18-35 | 94 (63.5) |
36-50 | 42 (28.4) | |
>50 | 12 (8.1) | |
Mean ± SD | | |
Residence | Rural | 136 (91.9) |
Urban | 12 (8.1) | |
Treatment History | New case | 113 (76.4) |
Previously treated | 35 (23.6) | |
Duration prior to diagnosis | < 2 | 42 (28.4) |
2-4 | 52 (35.1) | |
> 4 | 54 (36.5) | |
Presence of signs and symptoms | ||
Fever | Yes | 100 (100) |
Body weakness | Yes | 124 (83.8) |
No | 24 (16.2) | |
Epistaxis | Yes | 23 (15.5) |
No | 125 (84.5) | |
Weight loss | Yes | 148 (100) |
Loss of appetite | Yes | 148 (100) |
Diarrhea | Yes | 15 (10.1) |
No | 132 (89.2) | |
Splenomegaly | Yes | 145 (98) |
Lymphadenopathy | No | 03 (2.0) |
Yes | 06 (4.1) | |
Anemia | Yes | 142 (95.9) |
No | 06 (4.1) | |
Leucopenia | Yes | 139 (93.9) |
No | 09 (6.1) | |
Thrombocytopenia | Yes | 125 (84.5) |
No | 23 (15.5) | |
Method of diagnosis | ||
| Positive | 148 (100) |
| Positive | 110 (74.3) |
Negative | 01 (0.7) | |
Not done | 37 (25) | |
Concomitant infection | ||
| Yes | 36 (24.3) |
No | 112 (75.7) | |
| Positive | 31 (20.9) |
Negative | 117 (79.1) | |
| Yes | 15 (10.1) |
No | 133 (89.9) | |
| Yes | 40 (27) |
No | 108 (73) |
Majorities (71.6%) of the patients were treated using a combination of SSG & PM. A blood transfusion was administered to 24.3% of the patients. Anti-TB drugs were administered to 24.3% of the patients and 16.9% of the patients were on ART. Our finding revealed that majorities (87.9%) of the patients had good treatment outcome/cured and 12.1% had poor treatment outcome (6.7% of the patients had treatment failure and 5.4% died) (Table
Medication related characteristics of VL patients at ACSH, Tigray Region, Northern Ethiopia, June 2016–April 2018.
Characteristics | Category | Frequency (%) |
---|---|---|
VL Treatment | SSG + PM | 106 (71.6) |
LAMB | 42 (28.4) | |
Concomitant treatment | Blood transfusion | 36 (24.3) |
Antibiotics | 15 (10.3) | |
Anti-TB | 36 (24.3) | |
ART | 25 (16.9) | |
Treatment outcome | Cured | 130(87.9) |
Treatment failure | 10 (6.7) | |
Death | 08 (5.4) |
ART: antiretroviral therapy, LAMB: liposomal amphotericin B, PM: paromomycin, and SSG: sodium stibogluconate.
A univariate logistic regression analysis was performed to determine the association of each independent variable with the outcome (Table
The model contained seven independent variables and the full model containing all predictors was statistically significant (X2 = 28.96; df = 10; N= 148; p-value=0.001). The results of the multivariate logistic regression indicated that patients who were hospitalized lately after the clinical manifestation (long duration of illness > four weeks) were more likely to have poor treatment outcome (adjusted odds ratio (AOR):
Multivariable logistic regression analysis of predictors of poor treatment outcome among VL patients at ACSH, Tigray Region, Northern Ethiopia, June 2016–April 2018.
Variables | Category | Treatment outcome | COR (95% CI) | P- value | AOR (95% CI) | P -Value | |
---|---|---|---|---|---|---|---|
Good, n (%) | Poor, n (%) | ||||||
Age in years | 18-35 | 84(64.6) | 10(55.6) | 1 | 1 | ||
36-50 | 37(28.5) | 5(27.8) | 1.14(0.36, 3.55) | 0.83 | 0.83(0.22, 3.20) | 0.78 | |
>50 | 9(6.9) | 3(16.7) | 2.8(0.65,12.08) | 0.17 | 4.80(0.87, 26.46) | 0.07 | |
Duration prior to diagnosis (weeks) | <2 | 39(30) | 3(16.7) | 1 | 1 | ||
2-4 | 50(38.5) | 2(11.1) | 0.52(0.83, 3.23) | 0.48 | 0.56(0.07, 4.25) | 0.58 | |
>4 | 41(31.5) | 13(72.2) | | | | | |
Body weakness | No | 19(14.6) | 5(27.8) | 1 | 1 | ||
Yes | 111(85.4) | 13(72.2) | 0.44(0.14, 1.39) | 0.164 | 0.69(0.18, 2.68) | 0.59 | |
Epistaxis | No | 112(86.2) | 14(77.8) | 1 | 1 | ||
Yes | 18(13.8) | 4(22.2) | 2.39(0.76, 7.52) | 0.135 | 3.22(0.73, 14. 31) | 0.12 | |
TB | No | 104(80) | 8(44.4) | 1 | 1 | ||
Yes | 26(20) | 10(55.6) | | | | | |
HIV Status | No | 105(80.8) | 12(66.7) | 1 | 1 | ||
Yes | 25(19.2) | 6(33.3) | 2.10(0.72, 6.12) | 0.17 | 1.29(0.12, 14.56) | 0.83 | |
Malaria | No | 97(74.6) | 11(61.1) | 1 | 1 | ||
Yes | 33(25.4) | 7(38.9) | 1.87(0.67, 5.22) | 0.23 | 2.30(0.63, 8.43) | 0.21 | |
TB/HIV coinfection | No | 120 (92.3) | 13 (72.2) | 1 | 1 | ||
Yes | 10 (7.7) | 5 (27.8) | | | 2.68(0.14, 50.64) | 0.51 |
AOR: adjusted odds ratio, CI: confidence interval, and HIV: human immune deficiency virus.
We found that 12.1% of patients had poor treatment outcomes, similar to the rate seen in East Africa [
The study also determined the predictive factors of poor VL treatment outcomes. Long duration of illness and coinfection with TB were associated with poor treatment outcome. We found that patients with long duration of illness (> four weeks) were six times more likely to have poor treatment outcome (AOR: 6.08 [95% CI: 1.29-28.55], p=0.02). Poor treatment outcome related to the delay in diagnosis was reported in other similar studies [
Patients with concomitant TB infection were more likely to have a poor outcome (AOR 4.55 [95% CI: 1.08-19.13], p=0.04). In a study conducted in Bangladesh, about 8% of the deceased patients had TB, indicating the existence of VL/TB coinfection [
In our study, around 20% of the patients were coinfected with HIV. Despite the many studies which reported a significant association between HIV and VL [
The results of this study have important implications. The poor treatment outcomes seen in a significant proportion of patients require special attention. Policy makers and health care providers should be involved in improving treatment outcomes. Since this study shows that longer pretreatment duration is an important predictor, attention should be paid to early diagnosis of VL patients. Diagnosis can be made early through active case finding, which was an effective component for eliminating leishmaniasis in the Indian subcontinent [
Finally, a number of important limitations need to be considered. The data were extracted retrospectively from the patients’ medical chart and some important information was not consistently available (e.g., bone marrow aspiration result). The safety data for antileishmanial drugs were incomplete and were not presented in this study. The cross-sectional nature of our study may not provide adequate evidence of causality regarding the risk factor for the poor treatment outcome. We were also unable to assess the long-term treatment outcome (treatment outcome at 6 months), since most of the VL patients were from rural areas and did not have follow-up data after the initial discharge. Long-term outcomes of the disease in our setting remain to be investigated.
Poor treatment outcome was observed in a considerable proportion of VL patients. Long duration of illness and coinfection with TB were associated with poor VL treatment outcome. Hence, early diagnosis and effective prompt treatment are important to improve treatment outcomes among VL patients. Special attention should also be given in the treatment of VL/TB coinfected patients in our setting.
The dataset of this study is available from the corresponding author upon request.
The authors have declared that there are no conflicts of interest with respect to the authorship and/or publication of this study.
The authors would like to thank the College of Health Science, Mekelle University, for their cooperation and material support. The authors would also like to thank all Ayder Comprehensive Specialized Hospital staff members for their support during this study.
Table S1: univariable logistic regression analysis of predictors of poor treatment outcome among VL patients at ACSH, Tigray Region, Northern Ethiopia, June 2016–April 2018.