eroding the resistance of duffy negativity to invasion by plasmodium vivax?
TRANSCRIPT
Transactions of the Royal Society of Tropical Medicine and Hygiene (2007) 101, 953—954
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LEADING ARTICLE
Eroding the resistance of Duffy negativityto invasion by Plasmodium vivax?
Geoffrey Pasvol
Department of Infection and Tropical Medicine, Imperial College London, Lister Unit,Northwick Park Hospital, Harrow HA1 3UJ, UKAvailable online 20 July 2007
KEYWORDSMalaria;Plasmodium vivax;
Summary Individuals possessing red cells negative for the Duffy blood group antigen are saidto possess absolute resistance to infection by the malarial parasite Plasmodium vivax. Now inthis issue of Transactions, initial evidence is presented from the Brazilian Amazon to suggest
Resistance;Red cells;Invasion;Duffy negativity
that P. vivax is being transmitted amongst Duffy-negative individuals. This supports data fromEast Africa where the same phenomenon has been observed. Thus the emerging picture is thatP. vivax in both South America and in Africa is now evolving pathways other than Duffy to enterred cells.
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There are indeed few polymorphisms in humans that provideabsolute, rather than relative, protection against infectiousagents. Absence of the Duffy antigen on red cells of indi-viduals mainly from West and sub-Saharan Africa, providingresistance to vivax malaria, has been upheld as the best-known paradigm of such a phenomenon (Miller et al., 1976).The genetic mechanisms of Duffy negativity are fascinatingenough: a cytosine to thymine point mutation on the DuffyB gene (FY*B) promoter, 33 bases from the initiation codon(C-33T), abolishes expression of the Duffy antigen on redcells by disrupting the binding site for the GATA-1 erythroidtranscription factor and hence transcription of Duffy mRNAin red cells but not in other cell types (Tournamille et al.,1995). The Duffy determinant is believed to be crucial forthe entry of vivax merozoites into red cells (in particular
reticulocytes). After attachment of the merozoite, the Duffyantigen is thought to be responsible for the formation of a‘moving junction’ essential for merozoite invasion. Howeverit is perfectly reasonable to argue that an organism suchE-mail address: [email protected].
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l Medicine and Hygiene. Published by Elsevier Ltd. All rights
s Plasmodium vivax, with a 48-hour cycle, should adaptnd circumvent this pathway in its human host, in whom aeneration is measured in years rather than hours. The uni-ersality of the specificity is certainly now under questionRosenberg, 2007). After all, P. falciparum appears to havet its disposal a range of pathways by which it enters redells (Pasvol, 2003).
Now in this issue of Transactions, a full frontal assault onfortress Duffy’, formerly thought to be impregnable, haseen made. In a region of the Brazilian Amazon in Southmerica, two cases of P. vivax in Duffy-negative individualsave been identified (Cavasini et al., 2007). Duffy negativ-ty is relatively common in this area (up to 60% of someopulations) as is P. vivax (Perna et al., 2007). Malaria spe-iation was done with P. vivax primers which can identifyhree variants: VK210, VK247 and a P. vivax-like variant.lasmodium vivax was also confirmed by the detection of P.ivax merozoite surface protein-1 (MSP-1) antigen antibod-es. Duffy antigens were genotyped using a commercial kit.
avasini and colleagues have identified two Duffy-negativeomozygous individuals infected with P. vivax (one with theK210 genotype and the other with VK210 plus P. vivax-likeenotypes, i.e. a mixed infection).e and Hygiene. Published by Elsevier Ltd. All rights reserved.
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These two ‘swallows may not make a summer’ or indeedgeneralization, but together with the report of Ryan et al.
2006) who recently identified four Duffy-negative individu-ls in East Africa with P. vivax infection, provide compellingvidence that P. vivax is able, albeit infrequently, to infectuffy-negative red cells. There are three main possibilitieshat could explain this observation: firstly that these para-ites were not P. vivax but variants thereof, not requiringhe Duffy antigen for invasion; secondly, that the parasite is. vivax but has evolved to use pathways other than Duffy orhirdly, that these particular individuals have unique bloodroups that serve as receptors for P. vivax. Putting these twotudies together, however, the most likely explanation woulde that we now have a situation both in East Africa and Southmerica where P. vivax is in the process of evolving receptorso invade Duffy-negative red cells. Clearly additional studiesre needed since these two have limitations, mainly that ofmall numbers. Nevertheless alternate pathways for P. vivaxntry into red cells would be entirely biologically plausiblend what we are witnessing is ‘evolution in progress’. Watchhis space!
unding: None.
onflicts of interest: None declared.
thical approval: Not required.
T
G. Pasvol
eferences
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