scholarly journals Molecular Surveillance of Drug Resistance of Plasmodium falciparum Isolates Imported from Angola in Henan Province, China

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Ruimin Zhou ◽  
Chengyun Yang ◽  
Suhua Li ◽  
Yuling Zhao ◽  
Ying Liu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Antimalarial Drug ◽  
Henan Province ◽  
Nucleotide Polymorphisms ◽  
Combination Therapies ◽  
Antimalarial Drug Resistance ◽  
Single Nucleotide ◽  
Molecular Surveillance ◽  
Content Type

ABSTRACT Angola was the main origin country for the imported malaria in Henan Province, China. Antimalarial drug resistance has posed a threat to the control and elimination of malaria. Several molecular markers were confirmed to be associated with the antimalarial drug resistance, such as pfcrt, pfmdr1, pfdhfr, pfdhps, and K13. This study evaluated the drug resistance of the 180 imported Plasmodium falciparum isolates from Angola via nested PCR using Sanger sequencing. The prevalences of pfcrt C72V73M74N75K76, pfmdr1 N86Y184S1034N1042D1246, pfdhfr A16N51C59S108D139I164, and pfdhps S436A437A476K540A581 were 69.4%, 59.9%, 1.3% and 6.3%, respectively. Three nonsynonymous (A578S, M579I, and Q613E) and one synonymous (R471R) mutation of K13 were found, the prevalences of which were 2.5% and 1.3%, respectively. The single nucleotide polymorphisms (SNPs) in pfcrt, pfmdr1, pfdhfr, and pfdhps were generally shown as multiple mutations. The mutant prevalence of pfcrt reduced gradually, but pfdhfr and pfdhps still showed high mutant prevalence, while pfmdr1 was relatively low. The mutation of the K13 gene was rare. Molecular surveillance of artemisinin (ART) resistance will be used as a tool to evaluate the real-time efficacy of the artemisinin-based combination therapies (ACTs) and the ART resistance situation.

scholarly journals Community perceptions of a mass administration of an antimalarial drug combination in The Gambia

2001 ◽  
Vol 6 (6) ◽  
pp. 442-448 ◽  
Author(s):  
Sarah De Martin ◽  
Lorenz von Seidlein ◽  
Jacqueline L. Deen ◽  
Margaret Pinder ◽  
Gijs Walraven ◽  
...  
Keyword(s):  
Drug Combination ◽  
Antimalarial Drug ◽  
The Gambia ◽  
Community Perceptions

Antimalarial drug combination policy: a caveat

The Lancet ◽  
2000 ◽  
Vol 355 (9222) ◽  
pp. 2245-2247 ◽  
Author(s):  
Chansuda Wongsrichanalai ◽  
Krongthong Thimasarn ◽  
Jeeraphat Sirichaisinthop
Keyword(s):  
Drug Combination ◽  
Antimalarial Drug ◽  
Combination Policy

scholarly journals Systematic measurement of combination drug landscapes to predict in vivo treatment outcomes for tuberculosis

2021 ◽  
Author(s):  
Jonah Larkins-Ford ◽  
Talia Greenstein ◽  
Nhi Van ◽  
Yonatan N. Degefu ◽  
Michaela C. Olson ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Treatment Outcomes ◽  
Mouse Models ◽  
Drug Combination ◽  
Combination Therapies ◽  
Therapy Outcomes ◽  
Combination Drug ◽  
Shorten Treatment Duration

AbstractA lengthy multidrug chemotherapy is required to achieve a durable cure in tuberculosis. Variation in Mycobacterium tuberculosis drug response is created by the differing microenvironments in lesions, which generate different bacterial drug susceptibilities. To better realize the potential of combination therapy to shorten treatment duration, multidrug therapy design should deliberately explore the vast combination space. We face a significant scaling challenge in making systematic drug combination measurements because it is not practical to use animal models for comprehensive drug combination studies, nor are there well-validated high-throughput in vitro models that predict animal outcomes. We hypothesized that we could both prioritize combination therapies and quantify the predictive power of various in vitro models for drug development using a dataset of drug combination dose responses measured in multiple in vitro models. We systematically measured M. tuberculosis response to all 2- and 3-drug combinations among ten antibiotics in eight conditions that reproduce lesion microenvironments. Applying machine learning to this comprehensive dataset, we developed classifiers predictive of multidrug treatment outcome in a mouse model of disease relapse. We trained classifiers on multiple mouse models and identified ensembles of in vitro models that best describe in vivo treatment outcomes. Furthermore, we found that combination synergies are less important for predicting outcome than metrics of potency. Here, we map a path forward to rationally prioritize combinations for animal and clinical studies using systematic drug combination measurements with validated in vitro models. Our pipeline is generalizable to other difficult-to-treat diseases requiring combination therapies.One Sentence SummarySignatures of in vitro potency and drug interaction measurements predict combination therapy outcomes in mouse models of tuberculosis.

scholarly journals Adherence to Triple-Free-Drug Combination Therapies Among Patients With Cardiovascular Disease

2020 ◽  
Vol 125 (9) ◽  
pp. 1429-1435
Author(s):  
Niccolò Lombardi ◽  
Giada Crescioli ◽  
Monica Simonetti ◽  
Ettore Marconi ◽  
Alfredo Vannacci ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Drug Combination ◽  
Free Drug ◽  
Combination Therapies

scholarly journals Assessment of Malaria In Vitro Drug Combination Screening and Mixed-Strain Infections Using the Malaria Sybr Green I-Based Fluorescence Assay

2009 ◽  
Vol 53 (6) ◽  
pp. 2557-2563 ◽  
Author(s):  
Edgie-Mark A. Co ◽  
Richard A. Dennull ◽  
Drew D. Reinbold ◽  
Norman C. Waters ◽  
Jacob D. Johnson
Keyword(s):  
Drug Combination ◽  
Antimalarial Drug ◽  
Fixed Ratio ◽  
Drug Combinations ◽  
Sybr Green ◽  
Sybr Green I ◽  
The Individual ◽  
Parasite Populations ◽  
Concentration Curves

ABSTRACT Several drug development strategies, including optimization of new antimalarial drug combinations, have been used to counter malaria drug resistance. We evaluated the malaria Sybr green I-based fluorescence (MSF) assay for its use in in vitro drug combination sensitivity assays. Drug combinations of previously published synergistic (atovaquone and proguanil), indifferent (chloroquine and azithromycin), and antagonistic (chloroquine and atovaquone) antimalarial drug interactions were tested against Plasmodium falciparum strains D6 and W2 using the MSF assay. Fifty percent inhibitory concentrations (IC50s) were calculated for individual drugs and in fixed ratio combinations relative to their individual IC50s. Subsequent isobologram analysis and fractional inhibitory concentration determinations demonstrated the expected drug interaction pattern for each combination tested. Furthermore, we explored the ability of the MSF assay to examine mixed parasite population dynamics, which are commonly seen in malaria patient isolates. Specifically, the capacity of the MSF assay to discern between single and mixed parasite populations was determined. To simulate mixed infections in vitro, fixed ratios of D6 and W2 strains were cocultured with antimalarial drugs and IC50s were determined using the MSF assay. Dichotomous concentration curves indicated that the sensitive and resistant parasites composing the genetically heterogeneous population were detectable. Biphasic analysis was performed to obtain subpopulation IC50s for comparison to those obtained for the individual malaria strains alone. In conclusion, the MSF assay allows for reliable antimalarial drug combination screening and provides an important method to discern between homogenous and heterogeneous parasite populations.

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