Publication: Measuring ex vivo drug susceptibility in Plasmodium vivax isolates from Cambodia
Issued Date
2017
Resource Type
Language
eng
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Mahidol University
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BioMed Central
Bibliographic Citation
Malaria Journal. Vol. 16, (2017), 392
Suggested Citation
Suwanna Chaorattanakawee, Chanthap Lon, Soklyda Chann, Kheang Heng Thay, Nareth Kong, You, Yom, Siratchana Sundrakes, Chatchadaporn Thamnurak, Sorayut Chattrakarn, Chantida Praditpol, Kritsanai Yingyuen, Wojnarsk, Mariusz i, Huy, Rekol, Spring, Michele D., Walsh, Douglas S., Patel, Jaymin C., Lin, Jessica, Juliano, Jonathan J., Lanteri, Charlotte A., Saunders, David L. Measuring ex vivo drug susceptibility in Plasmodium vivax isolates from Cambodia. Malaria Journal. Vol. 16, (2017), 392. doi:10.1186/s12936-017-2034-2 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/2853
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Title
Measuring ex vivo drug susceptibility in Plasmodium vivax isolates from Cambodia
Author(s)
Suwanna Chaorattanakawee
Chanthap Lon
Soklyda Chann
Kheang Heng Thay
Nareth Kong
You, Yom
Siratchana Sundrakes
Chatchadaporn Thamnurak
Sorayut Chattrakarn
Chantida Praditpol
Kritsanai Yingyuen
Wojnarsk, Mariusz i
Huy, Rekol
Spring, Michele D.
Walsh, Douglas S.
Patel, Jaymin C.
Lin, Jessica
Juliano, Jonathan J.
Lanteri, Charlotte A.
Saunders, David L.
Chanthap Lon
Soklyda Chann
Kheang Heng Thay
Nareth Kong
You, Yom
Siratchana Sundrakes
Chatchadaporn Thamnurak
Sorayut Chattrakarn
Chantida Praditpol
Kritsanai Yingyuen
Wojnarsk, Mariusz i
Huy, Rekol
Spring, Michele D.
Walsh, Douglas S.
Patel, Jaymin C.
Lin, Jessica
Juliano, Jonathan J.
Lanteri, Charlotte A.
Saunders, David L.
Other Contributor(s)
Abstract
Background: While intensive Plasmodium falciparum multidrug resistance surveillance continues in Cambodia,
relatively little is known about Plasmodium vivax drug resistance in Cambodia or elsewhere. To investigate P. vivax antimalarial
susceptibility in Cambodia, 76 fresh P. vivax isolates collected from Oddar Meanchey (northern Cambodia) in
2013–2015 were assessed for ex vivo drug susceptibility using the microscopy-based schizont maturation test (SMT)
and a Plasmodium pan-species lactate dehydrogenase (pLDH) ELISA. P. vivax multidrug resistance gene 1 (pvmdr1)
mutations, and copy number were analysed in a subset of isolates.
Results: Ex vivo testing was interpretable in 80% of isolates using the pLDH-ELISA, but only 25% with the SMT. Plasmodium
vivax drug susceptibility by pLDH-ELISA was directly compared with 58 P. falciparum isolates collected from
the same locations in 2013–4, tested by histidine-rich protein-2 ELISA. Median pLDH-ELISA IC50
of P. vivax isolates was
significantly lower for dihydroartemisinin (3.4 vs 6.3 nM), artesunate (3.2 vs 5.7 nM), and chloroquine (22.1 vs 103.8 nM)
than P. falciparum but higher for mefloquine (92 vs 66 nM). There were not significant differences for lumefantrine or
doxycycline. Both P. vivax and P. falciparum had comparable median piperaquine IC50
(106.5 vs 123.8 nM), but some P.
falciparum isolates were able to grow in much higher concentrations above the normal standard range used, attaining
up to 100-fold greater IC50s
than P. vivax. A high percentage of P. vivax isolates had pvmdr1 Y976F (78%) and F1076L
(83%) mutations but none had pvmdr1 amplification.
Conclusion: The findings of high P. vivax IC50
to mefloquine and piperaquine, but not chloroquine, suggest significant
drug pressure from drugs used to treat multidrug resistant P. falciparum in Cambodia. Plasmodium vivax isolates
are frequently exposed to mefloquine and piperaquine due to mixed infections and the long elimination half-life
of these drugs. Difficulty distinguishing infection due to relapsing hypnozoites versus blood-stage recrudescence
complicates clinical detection of P. vivax resistance, while well-validated molecular markers of chloroquine resistance
remain elusive. The pLDH assay may be a useful adjunctive tool for monitoring for emerging drug resistance, though
more thorough validation is needed. Given high grade clinical chloroquine resistance observed recently in neighbouring
countries, low chloroquine IC50
values seen here should not be interpreted as susceptibility in the absence of
clinical data. Incorporating pLDH monitoring with therapeutic efficacy studies for individuals with P. vivax will help to
further validate this field-expedient method.