Blood Parasite Load as an Early Marker to Predict Treatment Response in Visceral Leishmaniasis in Eastern Africa (original) (raw)
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Predictors of relapse of visceral leishmaniasis in inner São Paulo State, Brazil
International Journal of Infectious Diseases
Objectives: Visceral leishmaniasis (VL) is a public health threat for several tropical countries, including Brazil. Therapy failures and relapses aggravate VL morbidity and mortality. Our study aimed at identifying predictors of relapse and thus contributes to directing therapeutic options and patient followup. Methods: A nonconcurrent cohort of 571 subjects who completed successful therapy for VL in the city of Bauru, São Paulo State, Brazil, was followed for 24 months in order to identify the incidence and predictors of relapse. Extensive review of medical charts and laboratory files was conducted. Univariate and multivariable Cox regression models were used to identify predictors for the outcome of interest. A hierarchical strategy was used for variable selection in multivariable models. Results: Relapses occurred in 6.8% of treated subjects, after a median of 6 months (interquartile range, 4-9). In a comprehensive multivariable model, relapse was associated with: HIV-coinfection (hazard ratio [HR], 7.47; 95% confidence interval [CI], 2.58-21.55); the presence of lower limb edema (HR, 6.06; 95%CI, 1.38-26.77) and low platelet count upon admission (HR for platelet count  1000, 0.99; 95%CI, 0.98-0.99) ; and secondary pneumonia (HR, 5.49; 95%CI, 1.49-20.18). On the other hand, therapy with Liposomal Amphotericin (as opposed to Antimoniate) was not independently associated with relapse (HR, 5.97; 95% CI, 0.63-56.29). Conclusion: Besides reinforcing the impact of HIV coinfection on the outcome of VL, our study points to clinical and laboratory findings that characterize patients who were more likely to relapse. Those groups should be more closely followed, and possibly could benefit from novel therapeutic options.
Journal of Antimicrobial Chemotherapy, 2011
This study describes parasite kinetics in the blood of visceral leishmaniasis patients treated with liposomal amphotericin B (L-AmB) or a preformed fat emulsion of amphotericin B (ApL) using real-time quantitative PCR (qPCR). Methods: Forty-six patients were treated with a single dose (15 mg/kg of body weight) of either LAmB (n¼ 13) or ApL (n ¼33). qPCR was used to estimate parasite kinetics by detection of Leishmania donovani DNA using kinetoplast DNA-specific primers in peripheral blood samples using an absolute quantification method. Results: The mean parasite load decreased from baseline (day 0) values of 894.07 and 980.48 to 71.72 and 211.52 parasite genomes/mL at day 7 in LAmB and ApL groups, respectively, and at day 30 these further declined to 8.30 and 133.98 parasite genomes/mL, respectively. At day 30 post-treatment evaluation, the decline in parasite load was significantly greater (P ¼ 0.024) with LAmB compared with ApL. Four of 33 patients in the ApL group failed treatment (1 primary failure and 3 relapses) with the presence of parasites, whereas all patients in the LAmB group were cured at 6 month follow-up. Conclusions: qPCR can be a tool to measure parasite dynamics accurately and provide a marker to measure the efficacy of various drugs. It can be used as a test of cure, allowing us to do away with invasive and risky methods such as splenic or bone marrow aspiration.
Systematic Review of Biomarkers To Monitor Therapeutic Response in Leishmaniasis
Antimicrobial Agents and Chemotherapy, 2014
Recently, there has been a renewed interest in the development of new drugs for the treatment of leishmaniasis. This has spurred the need for pharmacodynamic markers to monitor and compare therapies specifically for visceral leishmaniasis, in which the primary recrudescence of parasites is a particularly long-term event that remains difficult to predict. We performed a systematic review of studies evaluating biomarkers in human patients with visceral, cutaneous, and post-kala-azar dermal leishmaniasis, which yielded a total of 170 studies in which 53 potential pharmacodynamic biomarkers were identified. In conclusion, the large majority of these biomarkers constituted universal indirect markers of activation and subsequent waning of cellular immunity and therefore lacked specificity. Macrophage-related markers demonstrate favorable sensitivity and times to normalcy, but more evidence is required to establish a link between these markers and clinical outcome. Most promising are the markers directly related to the parasite burden, but future effort should be focused on optimization of molecular or antigenic targets to increase the sensitivity of these markers. In general, future research should focus on the longitudinal evaluation of the pharmacodynamic biomarkers during treatment, with an emphasis on the correlation of studied biomarkers and clinical parameters.
2019
BackgroundVisceral leishmaniasis (VL) is a neglected tropical disease resulting in a huge burden of mortality and impact on development of a country. Even though anti-leishmanial drugs reduce the incidence of mortality among VL patients, still there is a death of VL patients while on treatment. However, study on incidence of mortality and its predictors among these patients while on treatment is scarce in Ethiopia.ObjectiveThe aim of this study was to determine incidence of mortality and its predictors among adult VL patients at University of Gondar Hospital.MethodsInstitution based retrospective follow up study was conducted from 2013 to 2018 at University of Gondar Hospital. Data were collected from patients’ chart and analyzed using Stata 14. Kaplan Meier failure curve and Log Rank test was used to compare survival probability of patients with categorical variables. Multivariable stratified Cox model was used to identify predictors of mortality among VL patients. P≤ 0.05 was empl...
Memórias do Instituto Oswaldo Cruz, 2014
Clinical and laboratory risk factors for death from visceral leishmaniasis (VL) are relatively known, but quantitative real-time polymerase chain reaction (qPCR) might assess the role of parasite load in determining clinical outcome. The aim of this study was to identify risk factors, including parasite load in peripheral blood, for VL poor outcome among children. This prospective cohort study evaluated children aged ≤ 12 years old with VL diagnosis at three times: pre-treatment (T0), during treatment (T1) and post-treatment (T2). Forty-eight patients were included and 16 (33.3%) met the criteria for poor outcome. Age ≤ 12 months [relative risk (RR) 3.51; 95% confidence interval (CI) 1.89-6.52], tachydyspnoea (RR 3.46; 95% CI 2.19-5.47), bacterial infection (RR 3.08; 95% CI 1.27-7.48), liver enlargement (RR 3.00; 95% CI 1.44-6.23) and low serum albumin (RR 7.00; 95% CI 1.80-27.24) were identified as risk factors. qPCR was positive in all patients at T0 and the parasite DNA was undetectable in 76.1% of them at T1 and in 90.7% at T2. There was no statistical association between parasite load at T0 and poor outcome.
BMC Infectious Diseases, 2021
Background Visceral leshimaniasis is a parasitic disease characterized by systemic infection of phagocytic cells and an intense inflammatory response. The progression of the disease or treatment may have an effect on hematological parameters of these patients'. Thus, the current study sought to compare the hematological profiles of visceral leishmaniasis patients before and after treatment with anti-leishmaniasis drugs. Method An institutional-based retrospective cohort study was conducted among visceral leishmaniasis patients admitted to the University of Gondar comprehensive specialized referral hospital leishmaniasis research and treatment centre between September 2013 and August 2018. Hematological profiles were extracted from the laboratory registration book before and after treatment. Data were entered to Epi-info and exported to SPSS for analysis. Descriptive statistics were summarized using frequency and percentage to present with the table. The mean, standard deviation,...
Visceral Leishmaniasis Treatment Outcome and Associated Factors in Northern Ethiopia
BioMed Research International, 2019
Background. Visceral leishmaniasis (VL), one of the most neglected tropical diseases, is placing a huge burden on Ethiopia. Despite the introduction of antileishmanial drugs, treatment outcomes across regions are variable due to drug resistance and other factors. Thus, understanding of VL treatment outcomes and its contributing factors helps decisions on treatment. However, the magnitude and the risk factors of poor treatment outcome are not well studied in our setting. Therefore, our study was designed to assess treatment outcomes and associated factors in patients with VL. Materials and Methods. A cross-sectional study was conducted in VL patients admitted between June 2016 and April 2018 to Ayder Comprehensive Specialized Hospital, Tigray, Northern Ethiopia. Data was collected through chart review of patient records. Logistic regression analysis was used to identify factors associated with poor treatment outcome. Results. A total of 148 VL patients were included in the study. The...
Trials, 2011
Background Treatment options for Visceral Leishmaniasis (VL) in East Africa are far from satisfactory due to cost, toxicity, prolonged treatment duration or emergence of parasite resistance. Hence there is a need to explore alternative treatment protocols such as miltefosine alone or in combinations including miltefosine, sodium stibogluconate (SSG) or liposomal amphotericin B. The aim of this trial is to identify regimen(s) which are sufficiently promising for future trials in East Africa. Methods/Design A phase II randomized, parallel arm, open-labelled trial is being conducted to assess the efficacy of each of the three regimens: liposomal amphotericin B with SSG, Liposomal amphotericin B with miltefosine and miltefosine alone. The primary endpoint is cure at day 28 with secondary endpoint at day 210 (6 months). Initial cure is a single composite measure based on parasitologic evaluation (bone marrow, spleen or lymph node aspirate) and clinical assessment. Repeated interim analys...
The American Journal of Tropical Medicine and Hygiene, 2009
Forty-two patients with visceral leishmaniasis in Tunisia were treated with meglumine antimoniate and followed-up for clinical improvement and blood parasite load determined by quantitative real-time polymerase chain reaction (PCR). Parasite loads before treatment ranged from 27 to 5.3 × 10 7 parasites/mL. At the end of treatment, parasite load decreased significantly in 39 cured patients (P < 0.001). The decrease in parasite load after treatment was greater than 99% for 34 patients and PCR results became negative in 23 of them. Two patients without clinical improvement showed no or slight decreases in parasite load (209 versus 202 parasites/mL and 1,765 versus 146 parasites/mL). One patient showed had a relapse seven months after showing a good response to treatment. His parasitemia remained high despite a sharp decrease (5.2 × 10 5 versus 5.9 × 10 3 parasites/mL).
Evidence for a relationship between Leishmania load and clinical manifestations
Research in Veterinary Science, 2009
Visceral leishmaniasis (VL) is a life-threatening disease of medical, social and economic importance in endemic areas. Dogs are the main reservoir of Leishmania infantum. In this study, the authors investigated a group of 56 natural infected dogs to establish the relationship between parasite load and various clinical forms of leishmaniasis.