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Intensity of transmission and spread of gene mutations linked to chloroquine and sulphadoxine-pyrimethamine resistance in falciparum malaria

Talisuna, A. O., Langi, P., Mutabingwa, T. K., Van Marck, E., Speybroeck, N., Egwang, T. G., Watkins, W. W., Hastings, Ian ORCID: https://orcid.org/0000-0002-1332-742X and D'Alessandro, U. (2003) 'Intensity of transmission and spread of gene mutations linked to chloroquine and sulphadoxine-pyrimethamine resistance in falciparum malaria'. International Journal for Parasitology, Vol 33, Issue 10, pp. 1051-1058.

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Abstract

The number of malaria parasite clones per infection-multiplicity of parasite clones-is affected by the transmission intensity, multiplicity increases with increasing transmission. This affects the frequency of parasites' sexual recombination and, if several mutations in different genes are involved, can break down drug resistant genotypes. Therefore, the effects of malaria transmission intensity on the spread of drug resistance could vary depending on the number of genes involved. Here we show that, compared to low transmission, intermediate-high transmission is associated with a 20-100-fold lower risk for the mutations linked to chloroquine resistance and a 6-17 times higher risk for those linked to sulphadoxine-pyrimethamine resistance. This is consistent with the hypothesis of a multigenic basis for chloroquine resistance and a monogenic basis for that of sulphadoxine-pyrimethamine. Reducing transmission intensity could slow the spread of resistance. However, a reduction below a critical threshold (e.g. when parasite prevalence in children 2-9 years old is around 60-80%) could, paradoxically, accelerate the spread of resistance to chloroquine and possibly to other drug combinations whose basis is multigenic. Our findings have important implications for malaria control because increasing drug resistance has a substantial impact on mortality. (C) 2003 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Item Type: Article
Subjects: QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified.
QX Parasitology > Protozoa > QX 135 Plasmodia
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 770 Therapy
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1016/s0020-7519(03)00156-5
Depositing User: Martin Chapman
Date Deposited: 31 Oct 2012 18:47
Last Modified: 19 Sep 2019 11:29
URI: https://archive.lstmed.ac.uk/id/eprint/2679

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