scholarly journals Blood parasite load as an early marker to predict treatment response in visceral leishmaniasis in Eastern Africa

2021 ◽  
Author(s):  
Luka Verrest ◽  
Anke E Kip ◽  
Ahmed Musa ◽  
Gerard J Schoone ◽  
Henk D F H Schallig ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Visceral Leishmaniasis ◽  
Treatment Response ◽  
Oral Treatment ◽  
Parasite Load ◽  
Blood Parasite ◽  
Eastern Africa ◽  
Clinical Relapse ◽  
Treatment Regimens ◽  
Clinical Trial Simulations

Abstract Background In order to expedite the development of new oral treatment regimens for visceral leishmaniasis (VL), there is a need for early markers to evaluate treatment response and predict long-term outcomes. Methods Data from three clinical trials were combined in this study, where Eastern African VL patients received various antileishmanial therapies. Leishmania kinetoplast DNA was quantified in whole blood with real-time quantitative PCR (qPCR) before, during and up to six months after treatment. The predictive performance of pharmacodynamic parameters for clinical relapse was evaluated using receiver-operating characteristic curves. Clinical trial simulations were performed to determine the power associated with the use of blood parasite load as a surrogate endpoint to predict clinical outcome at six months. Results The absolute parasite density on day 56 after start of treatment was found to be a highly sensitive predictor of relapse within six months of follow-up at a cut-off of 20 parasites/mL (AUC 0.92, specificity 0.91, sensitivity 0.89). Blood parasite loads correlated well with tissue parasite loads (ρ= 0.80) and with microscopy gradings of bone marrow and spleen aspirate smears. Clinical trial simulations indicated a >80% power to detect a difference in cure rate between treatment regimens if this difference was high (>50%) and when minimally 30 patients were included per regimen. Conclusion Blood Leishmania parasite load determined by qPCR is a promising early biomarker to predict relapse in VL patients. Once optimized, it might be useful in dose finding studies of new chemical entities.

scholarly journals Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis

2016 ◽  
Vol 60 (6) ◽  
pp. 3794-3801 ◽  
Author(s):  
Edézio Ferreira Cunha-Júnior ◽  
Thiago Martino Martins ◽  
Marilene Marcuzzo Canto-Cavalheiro ◽  
Paulo Roberto Marques ◽  
Elyzabeth Avvad Portari ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Oral Treatment ◽  
Hematological Parameters ◽  
Leukemic Cell ◽  
Parasite Load ◽  
Severe Form ◽  
Drug Candidates ◽  
Leukocytic Infiltration ◽  
Therapeutic Doses

Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is the second major cause of death by parasites, after malaria. The arsenal of drugs against leishmaniasis is small, and each has a disadvantage in terms of toxicity, efficacy, price, or treatment regimen. Our group has focused on studying new drug candidates as alternatives to current treatments. The pterocarpanquinone LQB-118 was designed and synthesized based on molecular hybridization, and it exhibited antiprotozoal and anti-leukemic cell line activities. Our previous work demonstrated that LQB-118 was an effective treatment for experimental cutaneous leishmaniasis. In this study, we observed that treatment with 10 mg/kg of body weight/day LQB-118 orally inhibited the development of hepatosplenomegaly with a 99% reduction in parasite load. Anin vivotoxicological analysis showed no change in the clinical, biochemical, or hematological parameters. Histologically, all of the analyzed organs were normal, with the exception of the liver, where focal points of necrosis with leukocytic infiltration were observed at treatment doses 5 times higher than the therapeutic dose; however, these changes were not accompanied by an increase in transaminases. Our findings indicate that LQB-118 is effective at treating different clinical forms of leishmaniasis and presents no relevant signs of toxicity at therapeutic doses; thus, this framework is demonstrated suitable for developing promising drug candidates for the oral treatment of leishmaniasis.

scholarly journals A Correlative Study of Splenic Parasite Score and Peripheral Blood Parasite Load Estimation by Quantitative PCR in Visceral Leishmaniasis: TABLE 1

2015 ◽  
Vol 53 (12) ◽  
pp. 3905-3907 ◽  
Author(s):  
Medhavi Sudarshan ◽  
Toolika Singh ◽  
Jaya Chakravarty ◽  
Shyam Sundar
Keyword(s):  
Visceral Leishmaniasis ◽  
Quantitative Pcr ◽  
Peripheral Blood ◽  
Parasite Load ◽  
Blood Parasite ◽  
Load Estimation ◽  
Invasive Procedures ◽  
Parasitological Diagnosis ◽  
Highly Sensitive ◽  
Severe Hemorrhage

Parasitological diagnosis of visceral leishmaniasis (VL) by splenic smear is highly sensitive, but it is associated with the risk of severe hemorrhage. In this study, the diagnosis of VL using quantitative PCR (qPCR) in peripheral blood was evaluated in 100 patients with VL. Blood parasitemia ranged from 5 to 93,688 leishmania parasite genomes/ml of blood and positively correlated with splenic score (P< 0.0001;r2= 0.58). Therefore, quantification of parasite genomes by qPCR can replace invasive procedures for diagnostic and prognostic evaluations.

scholarly journals Experimental Evaluation of Second-Line Oral Treatments of Visceral Leishmaniasis Caused by Leishmania infantum

1999 ◽  
Vol 43 (1) ◽  
pp. 172-174 ◽  
Author(s):  
Jean-Pierre Gangneux ◽  
Michael Dullin ◽  
Annie Sulahian ◽  
Yves Jean-Francois Garin ◽  
Francis Derouin
Keyword(s):  
Visceral Leishmaniasis ◽  
Murine Model ◽  
Experimental Evaluation ◽  
Leishmania Infantum ◽  
Parasite Load ◽  
Second Line ◽  
Meglumine Antimoniate ◽  
Marked Activity

ABSTRACT In a murine model of Leishmania infantum visceral leishmaniasis, metronidazole, ketoconazole, fluconazole, itraconazole, and terbinafine were less effective than antimonial agents in reducing hepatic parasite load. Ketoconazole potentiated the effect of meglumine antimoniate reference therapy through its marked activity against spleen infection.

Carotenoid-based plumage colouration in red bishops (Euplectes orix) — signalling presence rather than quality?

Behaviour ◽  
2011 ◽  
Vol 148 (11-13) ◽  
pp. 1372-1392 ◽  
Author(s):  
Alice U. Edler ◽  
Thomas W.P. Friedl
Keyword(s):  
Reproductive Success ◽  
Parasite Load ◽  
Blood Parasite ◽  
Male Reproductive Success ◽  
Sexually Dimorphic ◽  
Male Quality ◽  
Plumage Colouration ◽  
Selection For ◽  
Breeding Plumage

AbstractThe role of bright plumage colouration for female choice has been the focus of research in sexual selection for many years, with several studies showing that females prefer the most elaborately ornamented males, which are often also the highest quality individuals. Here, we analysed the associations between reproductive performance and plumage, body condition and blood parasite load in the red bishop (Euplectes orix), a sexually dimorphic and polygynous weaverbird species, where males in a carotenoid-based orange-to-red breeding plumage defend territories and build many nests to which they try to attract females. Male reproductive success in terms of number of nests accepted was mainly determined by the number of nests built, but was also positively related to blood parasite load, while we found no influence of plumage characteristics. Together with previously obtained data, our results indicate that plumage characteristics in the red bishop do not affect male reproductive success and are generally not suitable to reliably indicate male quality. We suggest that the primary function of the brilliant orange-scarlet breeding plumage might be presence signalling in terms of increasing conspicuousness of breeding males to females searching for mates.

scholarly journals T cell suppression in the bone marrow of visceral leishmaniasis patients: impact of parasite load

2017 ◽  
Vol 191 (3) ◽  
pp. 318-327 ◽  
Author(s):  
P. Kumar ◽  
P. Misra ◽  
C. P. Thakur ◽  
A. Saurabh ◽  
N. Rishi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Visceral Leishmaniasis ◽  
Parasite Load ◽  
T Cell Suppression ◽  
Cell Suppression

scholarly journals Integrating multimodal data sets into a mathematical framework to describe and predict therapeutic resistance in cancer

2020 ◽  
Author(s):  
Kaitlyn Johnson ◽  
Grant R. Howard ◽  
Daylin Morgan ◽  
Eric A. Brenner ◽  
Andrea L. Gardner ◽  
...  
Keyword(s):  
Mathematical Models ◽  
Single Cell ◽  
Treatment Response ◽  
Model Parameters ◽  
Data Sets ◽  
Response Dynamics ◽  
Multimodal Data ◽  
Transcriptomic Data ◽  
Treatment Regimens ◽  
New Treatment

SummaryA significant challenge in the field of biomedicine is the development of methods to integrate the multitude of dispersed data sets into comprehensive frameworks to be used to generate optimal clinical decisions. Recent technological advances in single cell analysis allow for high-dimensional molecular characterization of cells and populations, but to date, few mathematical models have attempted to integrate measurements from the single cell scale with other data types. Here, we present a framework that actionizes static outputs from a machine learning model and leverages these as measurements of state variables in a dynamic mechanistic model of treatment response. We apply this framework to breast cancer cells to integrate single cell transcriptomic data with longitudinal population-size data. We demonstrate that the explicit inclusion of the transcriptomic information in the parameter estimation is critical for identification of the model parameters and enables accurate prediction of new treatment regimens. Inclusion of the transcriptomic data improves predictive accuracy in new treatment response dynamics with a concordance correlation coefficient (CCC) of 0.89 compared to a prediction accuracy of CCC = 0.79 without integration of the single cell RNA sequencing (scRNA-seq) data directly into the model calibration. To the best our knowledge, this is the first work that explicitly integrates single cell clonally-resolved transcriptome datasets with longitudinal treatment response data into a mechanistic mathematical model of drug resistance dynamics. We anticipate this approach to be a first step that demonstrates the feasibility of incorporating multimodal data sets into identifiable mathematical models to develop optimized treatment regimens from data.

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