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Enhanced transmission of drug-resistant parasites to mosquitoes following drug treatment in rodent malaria.

Bell AS, Huijben S, Paaijmans KP, Sim DG, Chan BH, Nelson WA, Read AF - PLoS ONE (2012)

Bottom Line: Removal of drug-sensitive parasites following chemotherapy enabled resistant parasites to transmit to mosquitoes as successfully as sensitive parasites in the absence of treatment.We also show that the genetic composition of gametocyte populations in host venous blood accurately reflects the genetic composition of gametocytes taken up by mosquitoes.Our data demonstrate that, at least for this mouse model, aggressive chemotherapy leads to very effective transmission of highly resistant parasites that are present in an infection, the very parasites which undermine the long term efficacy of front-line drugs.

View Article: PubMed Central - PubMed

Affiliation: Center for Infectious Disease Dynamics, Departments of Biology and Entomology, The Pennsylvania State University, University Park, Pennsylvania, United States of America.

ABSTRACT
The evolution of drug resistant Plasmodium parasites is a major challenge to effective malaria control. In theory, competitive interactions between sensitive parasites and resistant parasites within infections are a major determinant of the rate at which parasite evolution undermines drug efficacy. Competitive suppression of resistant parasites in untreated hosts slows the spread of resistance; competitive release following treatment enhances it. Here we report that for the murine model Plasmodium chabaudi, co-infection with drug-sensitive parasites can prevent the transmission of initially rare resistant parasites to mosquitoes. Removal of drug-sensitive parasites following chemotherapy enabled resistant parasites to transmit to mosquitoes as successfully as sensitive parasites in the absence of treatment. We also show that the genetic composition of gametocyte populations in host venous blood accurately reflects the genetic composition of gametocytes taken up by mosquitoes. Our data demonstrate that, at least for this mouse model, aggressive chemotherapy leads to very effective transmission of highly resistant parasites that are present in an infection, the very parasites which undermine the long term efficacy of front-line drugs.

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Related in: MedlinePlus

Relationship between clone R gametocyte densities in mice at the time of a blood feed and in mosquito blood-meals fed on those mice.
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pone-0037172-g004: Relationship between clone R gametocyte densities in mice at the time of a blood feed and in mosquito blood-meals fed on those mice.

Mentions: The densities of R gametocytes in mouse blood on feed days and in the blood-meals of mosquitoes that fed on that mouse were highly correlated across more than 4 orders of magnitude, with a regression slope nearing 1 and an intercept not distinguishable from zero (Figure 4; F = 109.1, p<0.001, slope = 0.902±0.09, intercept = 0.16±0.26). This means that any clumping of gametocytes in host capillary beds [55], [56] is not affecting the efficiency of transmission of gametocytes to mosquitoes.


Enhanced transmission of drug-resistant parasites to mosquitoes following drug treatment in rodent malaria.

Bell AS, Huijben S, Paaijmans KP, Sim DG, Chan BH, Nelson WA, Read AF - PLoS ONE (2012)

Relationship between clone R gametocyte densities in mice at the time of a blood feed and in mosquito blood-meals fed on those mice.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3368907&req=5

pone-0037172-g004: Relationship between clone R gametocyte densities in mice at the time of a blood feed and in mosquito blood-meals fed on those mice.
Mentions: The densities of R gametocytes in mouse blood on feed days and in the blood-meals of mosquitoes that fed on that mouse were highly correlated across more than 4 orders of magnitude, with a regression slope nearing 1 and an intercept not distinguishable from zero (Figure 4; F = 109.1, p<0.001, slope = 0.902±0.09, intercept = 0.16±0.26). This means that any clumping of gametocytes in host capillary beds [55], [56] is not affecting the efficiency of transmission of gametocytes to mosquitoes.

Bottom Line: Removal of drug-sensitive parasites following chemotherapy enabled resistant parasites to transmit to mosquitoes as successfully as sensitive parasites in the absence of treatment.We also show that the genetic composition of gametocyte populations in host venous blood accurately reflects the genetic composition of gametocytes taken up by mosquitoes.Our data demonstrate that, at least for this mouse model, aggressive chemotherapy leads to very effective transmission of highly resistant parasites that are present in an infection, the very parasites which undermine the long term efficacy of front-line drugs.

View Article: PubMed Central - PubMed

Affiliation: Center for Infectious Disease Dynamics, Departments of Biology and Entomology, The Pennsylvania State University, University Park, Pennsylvania, United States of America.

ABSTRACT
The evolution of drug resistant Plasmodium parasites is a major challenge to effective malaria control. In theory, competitive interactions between sensitive parasites and resistant parasites within infections are a major determinant of the rate at which parasite evolution undermines drug efficacy. Competitive suppression of resistant parasites in untreated hosts slows the spread of resistance; competitive release following treatment enhances it. Here we report that for the murine model Plasmodium chabaudi, co-infection with drug-sensitive parasites can prevent the transmission of initially rare resistant parasites to mosquitoes. Removal of drug-sensitive parasites following chemotherapy enabled resistant parasites to transmit to mosquitoes as successfully as sensitive parasites in the absence of treatment. We also show that the genetic composition of gametocyte populations in host venous blood accurately reflects the genetic composition of gametocytes taken up by mosquitoes. Our data demonstrate that, at least for this mouse model, aggressive chemotherapy leads to very effective transmission of highly resistant parasites that are present in an infection, the very parasites which undermine the long term efficacy of front-line drugs.

Show MeSH
Related in: MedlinePlus