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Title:
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Relevance of Undetectably Rare Resistant Malaria Parasites in
Treatment Failure: Experimental Evidence from Plasmodium
chabaudi
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Author:
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Huijben, Silvie; Chan, Brian H. K.; Read, Andrew F.
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Abstract:
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Resistant malaria parasites are frequently found in mixed
infections with drug-sensitive parasites. Particularly early in
the evolutionary process, the frequency of these resistant
mutants is extremely low and below the level of molecular
detection. We tested whether the rarity of resistance in
infections impacted the health outcomes of treatment failure and
the potential for onward transmission of resistance. Mixed
infections of different ratios of resistant and susceptible
Plasmodium chabaudi parasites were inoculated in laboratory mice
and dynamics tracked during the course of infection using highly
sensitive genotype-specific quantitative polymerase chain
reaction (qPCR). Frequencies of resistant parasites ranged from
10% to 0.003% at the onset of treatment. We found that the rarer
the resistant parasites were, the lower the likelihood of their
onward transmission, but the worse the treatment failure was in
terms of parasite numbers and disease severity. Strikingly, drug
resistant parasites had the biggest impact on health outcomes
when they were too rare to be detected by any molecular methods
currently available for field samples. Indeed, in the field,
these treatment failures would not even have been attributed to
resistance. |
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Subject(s):
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-Malària
-Malalties parasitàries
-Malaria
-Parasitic diseases |
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Rights:
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(c) The American Society of Tropical Medicine and Hygiene, 2015
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Document type:
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Article
Article - Published version |
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Published by:
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The American Society of Tropical Medicine and Hygiene
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