scholarly journals The genomic architecture of antimalarial drug resistance

2019 ◽  
Vol 18 (5) ◽  
pp. 314-328 ◽  
Author(s):  
Annie N Cowell ◽  
Elizabeth A Winzeler
Keyword(s):  
Parasite Species ◽  
Protozoan Parasite ◽  
Clinical Samples ◽  
Genetic Mutations ◽  
Antimalarial Drug Resistance ◽  
Asexual Blood Stage ◽  
Genomic Architecture ◽  
Antimalarial Resistance ◽  
Antifolate Drugs ◽  
Emergence Of Resistance

Abstract Plasmodium falciparum and Plasmodium vivax, the two protozoan parasite species that cause the majority of cases of human malaria, have developed resistance to nearly all known antimalarials. The ability of malaria parasites to develop resistance is primarily due to the high numbers of parasites in the infected person’s bloodstream during the asexual blood stage of infection in conjunction with the mutability of their genomes. Identifying the genetic mutations that mediate antimalarial resistance has deepened our understanding of how the parasites evade our treatments and reveals molecular markers that can be used to track the emergence of resistance in clinical samples. In this review, we examine known genetic mutations that lead to resistance to the major classes of antimalarial medications: the 4-aminoquinolines (chloroquine, amodiaquine and piperaquine), antifolate drugs, aryl amino-alcohols (quinine, lumefantrine and mefloquine), artemisinin compounds, antibiotics (clindamycin and doxycycline) and a napthoquinone (atovaquone). We discuss how the evolution of antimalarial resistance informs strategies to design the next generation of antimalarial therapies.

scholarly journals Cisplatin Resistance in Testicular Germ Cell Tumors: Current Challenges from Various Perspectives

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1601 ◽  
Author(s):  
João Lobo ◽  
Carmen Jerónimo ◽  
Rui Henrique
Keyword(s):  
Germ Cell ◽  
Cisplatin Resistance ◽  
Germ Cell Tumors ◽  
Poor Quality ◽  
Good Prognosis ◽  
Experimental Models ◽  
Clinical Samples ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Emergence Of Resistance

Testicular germ cell tumors share a marked sensitivity to cisplatin, contributing to their overall good prognosis. However, a subset of patients develop resistance to platinum-based treatments, by still-elusive mechanisms, experiencing poor quality of life due to multiple (often ineffective) interventions and, eventually, dying from disease. Currently, there is a lack of defined treatment opportunities for these patients that tackle the mechanism(s) underlying the emergence of resistance. Herein, we aim to provide a multifaceted overview of cisplatin resistance in testicular germ cell tumors, from the clinical perspective, to the pathobiology (including mechanisms contributing to induction of the resistant phenotype), to experimental models available for studying this occurrence. We provide a systematic summary of pre-target, on-target, post-target, and off-target mechanisms putatively involved in cisplatin resistance, providing data from preclinical studies and from those attempting validation in clinical samples, including those exploring specific alterations as therapeutic targets, some of them included in ongoing clinical trials. We briefly discuss the specificities of resistance related to teratoma (differentiated) phenotype, including the phenomena of growing teratoma syndrome and development of somatic-type malignancy. Cisplatin resistance is most likely multifactorial, and a combination of therapeutic strategies will most likely produce the best clinical benefit.

Toxoplasmosis

2010 ◽  
pp. 1090-1097
Author(s):  
Oliver Liesenfeld ◽  
Eskild Petersen
Keyword(s):  
Polymerase Chain Reaction ◽  
Toxoplasma Gondii ◽  
Direct Detection ◽  
Protozoan Parasite ◽  
Human Infection ◽  
Clinical Samples ◽  
Worldwide Distribution ◽  
Polymerase Chain ◽  
The Brain ◽  
Undercooked Meat

Toxoplasma gondii is a protozoan parasite with worldwide distribution that infects up to one-third of the world’s population. Human infection is acquired through ingestion in water or food of oocysts shed by cats, or by ingestion of bradyzoites released from cysts contained in uncooked or undercooked meat (e.g. sheep, swine, cattle). Following invasion in the intestine, tachyzoites rapidly disseminate throughout the host. Immune mechanisms mediate the formation of cysts, primarily in the brain, eye, and skeletal and heart muscles, where they persist for the life of the host. Presence of infection may be established by direct detection of the parasite in clinical samples (often by polymerase chain reaction, PCR) or by serological techniques....

Toxoplasmosis

2020 ◽  
pp. 1416-1424
Author(s):  
Oliver Liesenfeld ◽  
Eskild Petersen
Keyword(s):  
Polymerase Chain Reaction ◽  
Toxoplasma Gondii ◽  
Direct Detection ◽  
Protozoan Parasite ◽  
Human Infection ◽  
Clinical Samples ◽  
Worldwide Distribution ◽  
Polymerase Chain ◽  
The Brain ◽  
Undercooked Meat

Toxoplasma gondii is a protozoan parasite with worldwide distribution that infects up to one-third of the world’s population. Human infection is acquired through ingestion in water or food of oocysts shed by cats, or by ingestion of bradyzoites released from cysts contained in uncooked or undercooked meat (e.g. sheep, swine, cattle). Following invasion in the intestine, tachyzoites rapidly disseminate throughout the host. Immune mechanisms mediate the formation of cysts, primarily in the brain, eye, and skeletal and heart muscles, where they persist for the life of the host. Presence of infection can be established by direct detection of the parasite in clinical samples (often by polymerase chain reaction) or by serological techniques.

scholarly journals High-Quality Genome Assembly and Annotation for Plasmodium coatneyi , Generated Using Single-Molecule Real-Time PacBio Technology

2016 ◽  
Vol 4 (5) ◽  
Author(s):  
Jung-Ting Chien ◽  
Suman B. Pakala ◽  
Juliana A. Geraldo ◽  
Stacey A. Lapp ◽  
Jay C. Humphrey ◽  
...  
Keyword(s):  
Real Time ◽  
Genome Sequence ◽  
Single Molecule ◽  
Genome Assembly ◽  
Parasite Species ◽  
Protozoan Parasite ◽  
Human Malaria Parasite ◽  
Simian Malaria ◽  
High Quality Genome ◽  
Plasmodium Coatneyi

Plasmodium coatneyi is a protozoan parasite species that causes simian malaria and is an excellent model for studying disease caused by the human malaria parasite, P. falciparum . Here we report the complete (nontelomeric) genome sequence of P. coatneyi Hackeri generated by the application of only Pacific Biosciences RS II (PacBio RS II) single-molecule real-time (SMRT) high-resolution sequence technology and assembly using the Hierarchical Genome Assembly Process (HGAP). This is the first Plasmodium genome sequence reported to use only PacBio technology. This approach has proven to be superior to short-read only approaches for this species.

scholarly journals The Malaria TaqMan Array Card Includes 87 Assays for Plasmodium falciparum Drug Resistance, Identification of Species, and Genotyping in a Single Reaction

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Suporn Pholwat ◽  
Jie Liu ◽  
Suzanne Stroup ◽  
Shevin T. Jacob ◽  
Patrick Banura ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Large Scale ◽  
Limit Of Detection ◽  
Artemisinin Resistance ◽  
Clinical Samples ◽  
Content Type ◽  
Antimalarial Resistance ◽  
Resistance Markers ◽  
Taqman Array

ABSTRACT Antimalarial drug resistance exacerbates the global disease burden and complicates eradication efforts. To facilitate the surveillance of resistance markers in countries of malaria endemicity, we developed a suite of TaqMan assays for known resistance markers and compartmentalized them into a single array card (TaqMan array card, TAC). We included 87 assays for species identification, for the detection of Plasmodium falciparum mutations associated with chloroquine, atovaquone, pyrimethamine, sulfadoxine, and artemisinin resistance, and for neutral single nucleotide polymorphism (SNP) genotyping. Assay performance was first optimized using DNA from common laboratory parasite lines and plasmid controls. The limit of detection was 0.1 to 10 pg of DNA and yielded 100% accuracy compared to sequencing. The tool was then evaluated on 87 clinical blood samples from around the world, and the malaria TAC once again achieved 100% accuracy compared to sequencing and in addition detected the presence of mixed infections in clinical samples. With its streamlined protocol and high accuracy, this malaria TAC should be a useful tool for large-scale antimalarial resistance surveillance.

scholarly journals Drug Resistance in Leishmaniasis

2006 ◽  
Vol 19 (1) ◽  
pp. 111-126 ◽  
Author(s):  
Simon L. Croft ◽  
Shyam Sundar ◽  
Alan H. Fairlamb
Keyword(s):  
Complex Disease ◽  
Therapy Monitoring ◽  
Acquired Resistance ◽  
Protozoan Parasite ◽  
New Drugs ◽  
Cutaneous Manifestations ◽  
The Past ◽  
Bihar State ◽  
Emergence Of Resistance ◽  
Genus Leishmania

SUMMARY Leishmaniasis is a complex disease, with visceral and cutaneous manifestations, and is caused by over 15 different species of the protozoan parasite genus Leishmania. There are significant differences in the sensitivity of these species both to the standard drugs, for example, pentavalent antimonials and miltefosine, and those on clinical trial, for example, paromomycin. Over 60% of patients with visceral leishmaniasis in Bihar State, India, do not respond to treatment with pentavalent antimonials. This is now considered to be due to acquired resistance. Although this class of drugs has been used for over 60 years for leishmaniasis treatment, it is only in the past 2 years that the mechanisms of action and resistance have been identified, related to drug metabolism, thiol metabolism, and drug efflux. With the introduction of new therapies, including miltefosine in 2002 and paromomycin in 2005-2006, it is essential that there be a strategy to prevent the emergence of resistance to new drugs; combination therapy, monitoring of therapy, and improved diagnostics could play an essential role in this strategy.

scholarly journals A novel PCR-based point-of-care method enables rapid, sensitive and reliable diagnosis of Babesia gibsoni infection in dogs

2019 ◽  
Vol 15 (1) ◽  
Author(s):  
I-Li Liu ◽  
Nai-Yu Chi ◽  
Chia-Ling Chang ◽  
Ming-Long Hung ◽  
Chun-Ta Chiu ◽  
...  
Keyword(s):  
Disease Management ◽  
Diagnostic Method ◽  
Point Of Care ◽  
Protozoan Parasite ◽  
Clinical Samples ◽  
Diagnostic Assay ◽  
Babesia Gibsoni ◽  
Point Of Care Test ◽  
Reliable Diagnosis ◽  
Dog Blood

Abstract Background Babesia gibsoni (B. gibsoni) is an intraerythrocytic protozoan parasite of dogs that causes fever and hemolytic illness. A timely diagnosis is essential for the disease management. Results Here, we report a QubeMDx PCR system which enables a rapid, sensitive and reliable diagnosis of B. gibsoni near the dog patient. Within 30 min, this diagnostic assay was able to detect as low as 0.002% parasitemia of the dog blood. Using clinical samples, this new assay was validated to demonstrate 100% agreement with real-time PCR. Conclusions This novel diagnostic method provides a reliable point-of-care test to assist in the identification of B. gibsoni.

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