Publication: Modulating effects of plasma containing anti-malarial antibodies on in vitro anti-malarial drug susceptibility in Plasmodium falciparum.
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Accepted Date
2010-11-16
Issued Date
2010-11
Copyright Date
2010
Resource Type
Language
eng
ISSN
1475-2875 (electronic)
Rights
Mahidol University
Rights Holder(s)
BioMed Central
Bibliographic Citation
Monatrakul P, Mungthin M, Dondorp AM, Krudsood S, Udomsangpetch R, Wilairatana P, et al. Modulating effects of plasma containing anti-malarial antibodies on in vitro anti-malarial drug susceptibility in Plasmodium falciparum. Malar J. 2010 Nov 16;9:326.
Suggested Citation
Preeyaporn Monatrakul, ปรียาภรณ์ โมนะตระกูล, Mathirut Mungthin, Dondorp, Arjen M., Srivicha Krudsood, ศรีวิชา ครุฑสูตร, Rachanee Udomsangpetch, Polrat Wilairatana, พลรัตน์ วิไลรัตน์, White, Nicholas J., Kesinee Chotivanich, เกศินี โชติวานิช Modulating effects of plasma containing anti-malarial antibodies on in vitro anti-malarial drug susceptibility in Plasmodium falciparum.. Monatrakul P, Mungthin M, Dondorp AM, Krudsood S, Udomsangpetch R, Wilairatana P, et al. Modulating effects of plasma containing anti-malarial antibodies on in vitro anti-malarial drug susceptibility in Plasmodium falciparum. Malar J. 2010 Nov 16;9:326.. doi:10.1186/1475-2875-9-326 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/734
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Title
Modulating effects of plasma containing anti-malarial antibodies on in vitro anti-malarial drug susceptibility in Plasmodium falciparum.
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Abstract
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.
METHODS: Titres of antibodies against blood stage antigens (mainly the
ring-infected erythrocyte surface antigen [RESA]) were measured in plasma samples
obtained from Thai patients with acute falciparum malaria. 'Immune' plasma was
selected and its effects on in vitro parasite growth and multiplication of the
Thai P. falciparum laboratory strain TM267 were assessed by light microscopy. The
in vitro susceptibility to quinine and artesunate was then determined in the
presence and absence of 'immune' plasma using the 3H-hypoxanthine uptake
inhibition method. Drug susceptibility was expressed as the concentrations
causing 50% and 90% inhibition (IC50 and IC90), of 3H-hypoxanthine uptake.
RESULTS: Incubation with 'immune' plasma reduced parasite maturation and
decreased parasite multiplication in a dose dependent manner. 3H-hypoxanthine
incorporation after incubation with 'immune' plasma was decreased significantly
compared to controls (median [range]; 181.5 [0 to 3,269] cpm versus 1,222.5 [388
to 5,932] cpm) (p= 0.001). As a result 'immune' plasma reduced apparent
susceptibility to quinine substantially; median (range) IC50 6.4 (0.5 to 23.8)
ng/ml versus 221.5 (174.4 to 250.4) ng/ml (p = 0.02), and also had a borderline
effect on artesunate susceptibility; IC50 0.2 (0.02 to 0.3) ng/ml versus 0.8 (0.2
to 2.3) ng/ml (p = 0.08). Effects were greatest at low concentrations, changing
the shape of the concentration-effect relationship. IC90 values were not
significantly affected; median (range) IC90 448.0 (65 to > 500) ng/ml versus
368.8 (261 to 501) ng/ml for quinine (p > 0.05) and 17.0 (0.1 to 29.5) ng/ml
versus 7.6 (2.3 to 19.5) ng/ml for artesunate (p = 0.4).
CONCLUSIONS: 'Immune' plasma containing anti-malarial antibodies inhibits
parasite development and multiplication and increases apparent in vitro
anti-malarial drug susceptibility of P. falciparum. The IC90 was much less
affected than the IC50 measurement.