Details:

Alternative Title:
PLoS Biol
Personal Author:
Bushman, Mary ; Antia, Rustom ; Udhayakumar, Venkatachalam ; de Roode, Jacobus C.
Bushman, Mary ; Antia, Rustom ; Udhayakumar, Venkatachalam ; de Roode, Jacobus C. Less -
Description:
In the malaria parasite P. falciparum, drug resistance generally evolves first in low-transmission settings, such as Southeast Asia and South America. Resistance takes noticeably longer to appear in the high-transmission settings of sub-Saharan Africa, although it may spread rapidly thereafter. Here, we test the hypothesis that competitive suppression of drug-resistant parasites by drug-sensitive parasites may inhibit evolution of resistance in high-transmission settings, where mixed-strain infections are common. We employ a cross-scale model, which simulates within-host (infection) dynamics and between-host (transmission) dynamics of sensitive and resistant parasites for a population of humans and mosquitoes. Using this model, we examine the effects of transmission intensity, selection pressure, fitness costs of resistance, and cross-reactivity between strains on the establishment and spread of resistant parasites. We find that resistant parasites, introduced into the population at a low frequency, are more likely to go extinct in high-transmission settings, where drug-sensitive competitors and high levels of acquired immunity reduce the absolute fitness of the resistant parasites. Under strong selection from antimalarial drug use, however, resistance spreads faster in high-transmission settings than low-transmission ones. These contrasting results highlight the distinction between establishment and spread of resistance and suggest that the former but not the latter may be inhibited in high-transmission settings. Our results suggest that within-host competition is a key factor shaping the evolution of drug resistance in P. falciparum.
Subject:
[+]
Adaptation, Biological Animals Antimalarials Culicidae Disease Transmission, Infectious Drug Resistance Drug Resistance, Bacterial Host-Parasite Interactions Humans Malaria Malaria, Falciparum Plasmodium Falciparum
Source:
PLoS Biol. 16(8).
Pubmed ID:
30130363
Pubmed Central ID:
PMC6103507
Document Type:
Journal Article
Place as Subject:
Africa South of the Sahara ; South America
Africa South of the Sahara ; South America Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:1e6ebd54fe37af2121615d3ad0b066ac20251b78fba506ba39c7cf0f40515624
Download URL:
https://stacks.cdc.gov/view/cdc/59619/cdc_59619_DS1.pdf
File Type:

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