Decreased sensitivity of artesunate and chloroquine of Plasmodium falciparum infecting hemoglobin H and/or hemoglobin constant spring erythrocytes
Language: 
English
Abstract: 

Plasmodium falciparum infecting hemoglobin (Hb) H and/or Hb Constant Spring erythrocytes in vitro was relatively more resistant than that infecting normal erythrocytes to artesunate and chloroquine, while the sensitivity to pyrimethamine was unchanged. The 50% inhibitory concentrations (IC50) for artesunate in HbH (alpha-thal 1/alpha-thal 2), HbH (alpha-thal 1/Hb Constant Spring), and homozygous Hb Constant Spring erythrocytes were 4.5 +/- 2.8, 8.5 +/- 3.2, and 2.6 +/- 1.6 nM compared with 0.82 +/- 0.35 nM in normal erythrocytes (P less than 0.002 for all three cases). The IC50 for chloroquine were 97 +/- 46, 162 +/- 67, and 93 +/- 36 nM, respectively, in the variant erythrocytes, compared with 48 +/- 13 nM in normal erythrocytes (P less than 0.002, 0.002, and 0.02, respectively). The differences in sensitivity to artesunate and chloroquine of the parasite infecting HbH erythrocytes are probably related to their oxidative mode of action and relatively high amounts of antioxidant enzymes in the host erythrocytes. This novel example of dependence on the host of the malarial parasite drug sensitivity may have implications for chemotherapy of malaria in patients with genetically variant erythrocytes.

Author(s): 
Yuthavong, Y.
Butthep, P.
Bunyaratvej, A.
Fucharoen, S.
Item Type: 
Journal Article
Publication Title: 
The Journal of Clinical Investigation
Journal Abbreviation: 
J. Clin. Invest.
Publication Date: 
Feb-89
Publication Year: 
1989
Pages: 
502-505
Volume: 
83
Issue: 
2
ISSN: 
0021-9738
DOI: 
10.1172/JCI113910
Library Catalog: 
PubMed
Extra: 
PMID: 2643631 PMCID: PMC303707

Turabian/Chicago Citation

Y. Yuthavong, P. Butthep, A. Bunyaratvej and S. Fucharoen. Feb-89. "Decreased sensitivity of artesunate and chloroquine of Plasmodium falciparum infecting hemoglobin H and/or hemoglobin constant spring erythrocytes." The Journal of Clinical Investigation 83: 2: 502-505. 10.1172/JCI113910.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1172/JCI113910 | issn = 0021-9738 | volume = 83 | pages = 502-505 | last = Yuthavong | first = Y. | coauthors = Butthep, P., Bunyaratvej, A., Fucharoen, S. | title = Decreased sensitivity of artesunate and chloroquine of Plasmodium falciparum infecting hemoglobin H and/or hemoglobin constant spring erythrocytes | journal = The Journal of Clinical Investigation | date = Feb-89 | pmid = | pmc = }} </ref>