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Study reveals mechanism of multidrug resistance in malaria

Malaria-infected cell bursting

Image by Peter H. Seeberger

Researchers say they have identified a mechanism of multidrug resistance in malaria that represents a major threat to antimalarial drug policy.

The team exposed a strain of malaria parasites to artemisinin (the base compound for standard therapy) long-term and found the parasites developed widespread resistance to most other antimalarial drugs.

The group also discovered that this type of resistance cannot be detected by current assays.

Françoise Benoit-Vical, PhD, of Université de Toulouse in France, and his colleagues described this work in Emerging Infectious Diseases.

The researchers set out to study resistance mechanisms in Plasmodium falciparum parasites. So they exposed the parasites to artemisinin in vitro for 5 years.

Parasites that survived in the presence of artemisinin developed resistance to most other artemisinin-based or non-artemisinin-based antimalarial therapies, including partner molecules present in combination therapies used in endemic areas.

These parasites did not exhibit any known mutation in resistance genes. However, the researchers found the parasites could circumvent the toxic effect of the drugs by quiescence.

The parasites were able to suspend their development during exposure to antimalarial agents. As soon as they were no longer subjected to antimalarial therapy, they “woke up” and began to proliferate again.

The researchers also found that multidrug resistance based on this quiescence phenomenon cannot be detected by tests currently used to analyze parasitic resistance.

“In vitro tests carried out using the patient’s blood predict high sensitivity and, therefore, the treatment’s effectiveness, while parasites are resistant because they are quiescent,” Dr Benoit-Vical said.

“As such, it is essential to conduct research with relevant and appropriate tests in the field if the multi[drug]-resistant phenomenon that we identified in vitro is also present, in order to design therapeutic strategies accordingly.”

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Malaria-infected cell bursting

Image by Peter H. Seeberger

Researchers say they have identified a mechanism of multidrug resistance in malaria that represents a major threat to antimalarial drug policy.

The team exposed a strain of malaria parasites to artemisinin (the base compound for standard therapy) long-term and found the parasites developed widespread resistance to most other antimalarial drugs.

The group also discovered that this type of resistance cannot be detected by current assays.

Françoise Benoit-Vical, PhD, of Université de Toulouse in France, and his colleagues described this work in Emerging Infectious Diseases.

The researchers set out to study resistance mechanisms in Plasmodium falciparum parasites. So they exposed the parasites to artemisinin in vitro for 5 years.

Parasites that survived in the presence of artemisinin developed resistance to most other artemisinin-based or non-artemisinin-based antimalarial therapies, including partner molecules present in combination therapies used in endemic areas.

These parasites did not exhibit any known mutation in resistance genes. However, the researchers found the parasites could circumvent the toxic effect of the drugs by quiescence.

The parasites were able to suspend their development during exposure to antimalarial agents. As soon as they were no longer subjected to antimalarial therapy, they “woke up” and began to proliferate again.

The researchers also found that multidrug resistance based on this quiescence phenomenon cannot be detected by tests currently used to analyze parasitic resistance.

“In vitro tests carried out using the patient’s blood predict high sensitivity and, therefore, the treatment’s effectiveness, while parasites are resistant because they are quiescent,” Dr Benoit-Vical said.

“As such, it is essential to conduct research with relevant and appropriate tests in the field if the multi[drug]-resistant phenomenon that we identified in vitro is also present, in order to design therapeutic strategies accordingly.”

Malaria-infected cell bursting

Image by Peter H. Seeberger

Researchers say they have identified a mechanism of multidrug resistance in malaria that represents a major threat to antimalarial drug policy.

The team exposed a strain of malaria parasites to artemisinin (the base compound for standard therapy) long-term and found the parasites developed widespread resistance to most other antimalarial drugs.

The group also discovered that this type of resistance cannot be detected by current assays.

Françoise Benoit-Vical, PhD, of Université de Toulouse in France, and his colleagues described this work in Emerging Infectious Diseases.

The researchers set out to study resistance mechanisms in Plasmodium falciparum parasites. So they exposed the parasites to artemisinin in vitro for 5 years.

Parasites that survived in the presence of artemisinin developed resistance to most other artemisinin-based or non-artemisinin-based antimalarial therapies, including partner molecules present in combination therapies used in endemic areas.

These parasites did not exhibit any known mutation in resistance genes. However, the researchers found the parasites could circumvent the toxic effect of the drugs by quiescence.

The parasites were able to suspend their development during exposure to antimalarial agents. As soon as they were no longer subjected to antimalarial therapy, they “woke up” and began to proliferate again.

The researchers also found that multidrug resistance based on this quiescence phenomenon cannot be detected by tests currently used to analyze parasitic resistance.

“In vitro tests carried out using the patient’s blood predict high sensitivity and, therefore, the treatment’s effectiveness, while parasites are resistant because they are quiescent,” Dr Benoit-Vical said.

“As such, it is essential to conduct research with relevant and appropriate tests in the field if the multi[drug]-resistant phenomenon that we identified in vitro is also present, in order to design therapeutic strategies accordingly.”

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Study reveals mechanism of multidrug resistance in malaria
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