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QJM Advance Access originally published online on September 26, 2005
QJM 2005 98(11):789-796; doi:10.1093/qjmed/hci121
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© The Author 2005. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Pre-treatment with chloroquine and parasite chloroquine resistance in Ghanaian children with severe malaria

J.A. Evans1,2, J. May2, D. Tominski1,2, T. Eggelte3, F. Marks2, H.H. Abruquah2,4, C.G. Meyer2, C. Timmann2, T. Agbenyega4 and R.D. Horstmann2

From the 1Kumasi Centre for Collaborative Research and 4School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana, 2Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany, 3Division of Infectious Diseases, Tropical Medicine & AIDS, Academic Hospital, Amsterdam, The Netherlands

Address correspondence to Dr J.A. Evans, Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht Str. 74, D-20359 Hamburg, Germany. email: evans{at}kccr.de

Received 6 September 2004 and in revised form 12 August 2005

Background: Self-medication with anti-malarial drugs is widespread, and chloroquine (CQ) resistance is increasing. The effect of these factors on the incidence and presentation of severe malaria is uncertain.

Aim: To investigate subtype of severe malaria, duration of illness, previous CQ treatment and prevalence of Plasmodium falciparum CQ-resistance markers among children presenting with severe malaria to a teaching hospital in Ghana.

Design: Prospective clinical study.

Methods: Consecutive patients (n = 189) presenting with severe malaria were examined clinically, and blood was taken for routine haematology and malaria films. Plasma and blood cells were stored and subsequently analysed by ELISA for CQ levels (n = 168) and by PCR and restriction digest for P. falciparum chloroquine resistance transporter gene (pfcrt) mutations (n = 139).

Results: Of 47 presenting with cerebral malaria, 21 had severe anaemia and 13 respiratory distress (RDS). Twenty-nine had prostration or RDS alone, 41 severe anaemia with prostration or RDS, and 72 severe anaemia not associated with coma, prostration or RDS. Of the patients studied, 77% had CQ in their plasma, and 88% were carrying P. falciparum with a CQ-resistance genotype. Significant associations were found (i) between the CQ-resistance genotype of parasites and plasma CQ levels, (ii) between the presence of CQ in plasma and the reported duration of illness, and (iii) between the reported duration of illness and the occurrence of severe but otherwise uncomplicated anaemia.

Discussion: There was extensive prior CQ use in our patients presenting with severe malaria, and a high prevalence of parasites with the CQ-resistance genotype. CQ resistance in P. falciparum may contribute to the development of severe but otherwise uncomplicated anaemia in this setting.


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J. May, J. A. Evans, C. Timmann, C. Ehmen, W. Busch, T. Thye, T. Agbenyega, and R. D. Horstmann
Hemoglobin Variants and Disease Manifestations in Severe Falciparum Malaria
JAMA, May 23, 2007; 297(20): 2220 - 2226.
[Abstract] [Full Text] [PDF]



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