Parasitic Sensitivity Tests

Publication Title: 
Science (New York, N.Y.)

Recent reports of increased tolerance to artemisinin derivatives--the most recently adopted class of antimalarials--have prompted a need for new treatments. The spirotetrahydro-beta-carbolines, or spiroindolones, are potent drugs that kill the blood stages of Plasmodium falciparum and Plasmodium vivax clinical isolates at low nanomolar concentration. Spiroindolones rapidly inhibit protein synthesis in P. falciparum, an effect that is ablated in parasites bearing nonsynonymous mutations in the gene encoding the P-type cation-transporter ATPase4 (PfATP4).

Author(s): 
Rottmann, Matthias
McNamara, Case
Yeung, Bryan K. S.
Lee, Marcus C. S.
Zou, Bin
Russell, Bruce
Seitz, Patrick
Plouffe, David M.
Dharia, Neekesh V.
Tan, Jocelyn
Cohen, Steven B.
Spencer, Kathryn R.
González-Páez, Gonzalo E.
Lakshminarayana, Suresh B.
Goh, Anne
Suwanarusk, Rossarin
Jegla, Timothy
Schmitt, Esther K.
Beck, Hans-Peter
Brun, Reto
Nosten, François
Renia, Laurent
Dartois, Veronique
Keller, Thomas H.
Fidock, David A.
Winzeler, Elizabeth A.
Diagana, Thierry T.
Publication Title: 
Emerging Infectious Diseases

Plasmodium falciparum malaria developed in an African-born traveler who returned to Canada after visiting Nigeria. While there, she took artesunate prophylactically. Isolates had an elevated 50% inhibitory concentration to artemisinin, artesunate, and artemether, compared with that of other African isolates. Inappropriate use of artemisinin derivatives can reduce P. falciparum susceptibility.

Author(s): 
Shahinas, Dea
Lau, Rachel
Khairnar, Krishna
Hancock, David
Pillai, Dylan R.
Publication Title: 
Malaria Journal

BACKGROUND: Little information is available on resistance to anti-malarial drugs in the Solomon Islands (SI). The analysis of single nucleotide polymorphisms (SNPs) in drug resistance associated parasite genes is a potential alternative to classical time- and resource-consuming in vivo studies to monitor drug resistance. Mutations in pfmdr1 and pfcrt were shown to indicate chloroquine (CQ) resistance, mutations in pfdhfr and pfdhps indicate sulphadoxine-pyrimethamine (SP) resistance, and mutations in pfATPase6 indicate resistance to artemisinin derivatives.

Author(s): 
Ballif, Marie
Hii, Jeffrey
Marfurt, Jutta
Crameri, Andreas
Fafale, Adam
Felger, Ingrid
Beck, Hans-Peter
Genton, Blaise
Publication Title: 
Antimicrobial Agents and Chemotherapy

The emergence of artemisinin-resistant Plasmodium falciparum malaria jeopardizes efforts to control this infectious disease. To identify factors contributing to reduced artemisinin susceptibility, we have employed a classical genetic approach by analyzing artemisinin responses in the F1 progeny of a genetic cross. Our data show that reduced artemisinin susceptibility is a multifactorial trait, with pfmdr1 and two additional loci (on chromosomes 12 and 13) contributing to it.

Author(s): 
Beez, Dorothee
Sanchez, Cecilia P.
Stein, Wilfred D.
Lanzer, Michael
Publication Title: 
Malaria Journal

BACKGROUND: Artemisinin-based combination therapy, currently considered the therapy of choice for uncomplicated Plasmodium falciparum malaria in endemic countries, may be under threat from newly emerging parasite resistance to the artemisinin family of drugs. Studies in Southeast Asia suggest some patients exhibit an extended parasite clearance time in the three days immediately following treatment with artesunate monotherapy.

Author(s): 
Beshir, Khalid B.
Hallett, Rachel L.
Eziefula, Alice C.
Bailey, Robin
Watson, Julie
Wright, Stephen G.
Chiodini, Peter L.
Polley, Spencer D.
Sutherland, Colin J.
Publication Title: 
Malaria Journal

BACKGROUND: The efficacy of anti-malarial drugs is determined by the level of parasite susceptibility, anti-malarial drug bioavailability and pharmacokinetics, and host factors including immunity. Host immunity improves the in vivo therapeutic efficacy of anti-malarial drugs, but the mechanism and magnitude of this effect has not been characterized. This study characterized the effects of 'immune' plasma to Plasmodium falciparumon the in vitro susceptibility of P. falciparum to anti-malarial drugs.

Author(s): 
Monatrakul, Preeyaporn
Mungthin, Mathirut
Dondorp, Arjen M.
Krudsood, Srivicha
Udomsangpetch, Rachanee
Wilairatana, Polrat
White, Nicholas J.
Chotivanich, Kesinee
Publication Title: 
Malaria Journal

BACKGROUND: Anti-malarial drug resistance in Kenya prompted two drug policy changes within a decade: sulphadoxine-pyrimethamine (SP) replaced chloroquine (CQ) as the first-line anti-malarial in 1998 and artemether-lumefantrine (AL) replaced SP in 2004. Two cross-sectional studies were conducted to monitor changes in the prevalence of molecular markers of drug resistance over the period in which SP was used as the first-line anti-malarial.

Author(s): 
Spalding, Maroya D.
Eyase, Fredrick L.
Akala, Hoseah M.
Bedno, Sheryl A.
Prigge, Sean T.
Coldren, Rodney L.
Moss, William J.
Waters, Norman C.
Publication Title: 
Antimicrobial Agents and Chemotherapy

Plasmodium species ex vivo sensitivity assay protocols differ in the requirement for leukocyte removal before culturing. This study shows that the presence of leukocytes significantly increases the 50% inhibitory concentration (IC??) of P. vivax and P. falciparum to artesunate and chloroquine relative to results with the paired leukocyte-free treatment. Although leukocyte removal is not an essential requirement for the conduct of ex vivo assays, its use has important implications for the interpretation of temporal and spatial antimalarial sensitivity data.

Author(s): 
Kaewpongsri, S.
Sriprawat, K.
Suwanarusk, R.
Kyle, D. E.
Lek-Uthai, U.
Leimanis, M.
Lwin, K. M.
Phyo, A. P.
Zwang, J.
Russell, B.
Nosten, F.
Renia, L.
Publication Title: 
Malaria Journal

BACKGROUND: Malaria prevalence has recently declined markedly in many parts of Tanzania and other sub-Saharan African countries due to scaling-up of control interventions including more efficient treatment regimens (e.g. artemisinin-based combination therapy) and insecticide-treated bed nets. Although continued molecular surveillance of malaria parasites is important to early identify emerging anti-malarial drug resistance, it is becoming increasingly difficult to obtain parasite samples from ongoing studies, such as routine drug efficacy trials.

Author(s): 
Ishengoma, Deus S.
Lwitiho, Sudi
Madebe, Rashid A.
Nyagonde, Nyagonde
Persson, Ola
Vestergaard, Lasse S.
Bygbjerg, Ib C.
Lemnge, Martha M.
Alifrangis, Michael
Publication Title: 
Journal of Clinical Microbiology

Alternative antischistosomal drugs are required since praziquantel is virtually the only drug available for treatment and morbidity control of schistosomiasis. Manual microscopic reading is the current "gold standard" to assess the in vitro antischistosomal properties of test drugs; however, it is labor-intensive, subjective, and difficult to standardize. Hence, there is a need to develop novel tools for antischistosomal drug discovery.

Author(s): 
Manneck, Theresia
Braissant, Olivier
Haggenmüller, Yolanda
Keiser, Jennifer

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