Modulating effects of plasma containing
anti-malarial antibodies on in vitro anti-malarial
drug susceptibility in Plasmodium falciparum
Preeyaporn Monatrakul1, Mathirut Mungthin2, Arjen M Dondorp1,3, Srivicha Krudsood1,4,
Rachanee Udomsangpetch5, Polrat Wilairatana1,4, Nicholas J White1,3, Kesinee Chotivanich1*
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 the3H-hypoxanthine uptake inhibition
method. Drug susceptibility was expressed as the concentrations causing 50% and 90% inhibition (IC50and IC90),
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) IC506.4 (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; IC500.2
(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. IC90values were not significantly affected; median (range) IC90448.0
(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 IC90was much less affected
than the IC50measurement.
Falciparum malaria remains the most important parasite
infection in the tropical world. Development of anti-
malarial drug resistance is a major threat for malaria
control. Early signs of low-grade resistance can be
obscured by anti-malarial immunity. The positive contri-
bution of host immunity to the therapeutic response to
anti-malarial drugs has been recognized for nearly a
century . In endemic areas, protective immunity is
acquired and maintained with repeated exposure to
Plasmodium falciparum and is an important factor
determining therapeutic outcome following anti-malarial
* Correspondence: firstname.lastname@example.org
1Department of Clinical Tropical Medicine, Faculty of Tropical Medicine,
Mahidol University, 420/6 Rajvithi, Bangkok, Thailand 10400
Full list of author information is available at the end of the article
Monatrakul et al. Malaria Journal 2010, 9:326
© 2010 Monatrakul et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
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Cite this article as: Monatrakul et al.: Modulating effects of plasma
containing anti-malarial antibodies on in vitro anti-malarial drug
susceptibility in Plasmodium falciparum. Malaria Journal 2010 9:326.
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