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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

Asexual and gametocyte densities of clone S and clone R within the 12 randomly selected mice used for mosquito blood feeds (see methods), gametocyte densities within blood-meals (denoted by crosses), prevalence of mosquito infection (percentage and numbers of infected mosquitoes at each feed) and identity of oocysts present on mid-guts 9 days post-blood feed (S: clone S genotype; R: clone R genotype; R+S: both clone genotypes).Panels A-F, non-drug-treated mice (D−); panels G–L, drug-treated mice (D+); nf: no blood feed performed due to mouse morbidity. Dotted and grey blocks show period of sham or drug treatment.
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pone-0037172-g002: Asexual and gametocyte densities of clone S and clone R within the 12 randomly selected mice used for mosquito blood feeds (see methods), gametocyte densities within blood-meals (denoted by crosses), prevalence of mosquito infection (percentage and numbers of infected mosquitoes at each feed) and identity of oocysts present on mid-guts 9 days post-blood feed (S: clone S genotype; R: clone R genotype; R+S: both clone genotypes).Panels A-F, non-drug-treated mice (D−); panels G–L, drug-treated mice (D+); nf: no blood feed performed due to mouse morbidity. Dotted and grey blocks show period of sham or drug treatment.

Mentions: Before drug treatment began on day 6 PI, there were no significant differences in parasite densities within hosts of each treatment group (Figures 1 and 2; resistant asexuals: F1,19 = 1.1, p = 0.31; resistant gametocytes: F1,19 = 0.7, p = 0.42; susceptible asexuals: F1,19 = 2.6, p = 0.13; susceptible gametocytes: F1,19 = 0.03, p = 0.86). The 10,000-fold difference in the densities of sensitive and resistant parasites we created at the beginning was maintained through to the start of drug treatment at day 6 p.i. (Figure 1– both panels; Figure 2), at which point there were only 179.5 (±26.8 [s.e.m]) resistant asexual parasites and 3.6 (±1.02) resistant gametocytes per microliter of mouse blood.


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)

Asexual and gametocyte densities of clone S and clone R within the 12 randomly selected mice used for mosquito blood feeds (see methods), gametocyte densities within blood-meals (denoted by crosses), prevalence of mosquito infection (percentage and numbers of infected mosquitoes at each feed) and identity of oocysts present on mid-guts 9 days post-blood feed (S: clone S genotype; R: clone R genotype; R+S: both clone genotypes).Panels A-F, non-drug-treated mice (D−); panels G–L, drug-treated mice (D+); nf: no blood feed performed due to mouse morbidity. Dotted and grey blocks show period of sham or drug treatment.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0037172-g002: Asexual and gametocyte densities of clone S and clone R within the 12 randomly selected mice used for mosquito blood feeds (see methods), gametocyte densities within blood-meals (denoted by crosses), prevalence of mosquito infection (percentage and numbers of infected mosquitoes at each feed) and identity of oocysts present on mid-guts 9 days post-blood feed (S: clone S genotype; R: clone R genotype; R+S: both clone genotypes).Panels A-F, non-drug-treated mice (D−); panels G–L, drug-treated mice (D+); nf: no blood feed performed due to mouse morbidity. Dotted and grey blocks show period of sham or drug treatment.
Mentions: Before drug treatment began on day 6 PI, there were no significant differences in parasite densities within hosts of each treatment group (Figures 1 and 2; resistant asexuals: F1,19 = 1.1, p = 0.31; resistant gametocytes: F1,19 = 0.7, p = 0.42; susceptible asexuals: F1,19 = 2.6, p = 0.13; susceptible gametocytes: F1,19 = 0.03, p = 0.86). The 10,000-fold difference in the densities of sensitive and resistant parasites we created at the beginning was maintained through to the start of drug treatment at day 6 p.i. (Figure 1– both panels; Figure 2), at which point there were only 179.5 (±26.8 [s.e.m]) resistant asexual parasites and 3.6 (±1.02) resistant gametocytes per microliter of mouse blood.

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