Publication: Intervals to Plasmodium falciparum recurrence after anti-malarial treatment in pregnancy: a longitudinal prospective cohort
Issued Date
2015
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eng
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Mahidol University
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BioMed Central
Bibliographic Citation
Malaria Journal. Vol.14, (2016), 221
Suggested Citation
Natthapon Laochan, Zaloumis, Sophie G., Mallika Imwong, Usa Lek-Uthai, Alan Brockman, Kanlaya Sriprawat, Jacher Wiladphaingern, White, Nicholas J., François Nosten, McGready, Rose Intervals to Plasmodium falciparum recurrence after anti-malarial treatment in pregnancy: a longitudinal prospective cohort. Malaria Journal. Vol.14, (2016), 221. doi:10.1186/s12936-015-0745-9 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/3159
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Title
Intervals to Plasmodium falciparum recurrence after anti-malarial treatment in pregnancy: a longitudinal prospective cohort
Abstract
Background: Plasmodium falciparum infections adversely affect pregnancy. Anti-malarial treatment failure is common.
The objective of this study was to examine the duration of persistent parasite carriage following anti-malarial treatment
in pregnancy.
Methods: The data presented here are a collation from previous studies carried out since 1994 in the Shoklo Malaria
Research Unit (SMRU) on the Thailand-Myanmar border and performed using the same unique methodology detailed
in the Materials and Methods section. Screening for malaria by microscopy is a routine part of weekly antenatal care
(ANC) visits and therapeutic responses to anti-malarials were assessed in P. falciparum malaria cases. Women with
microscopy confirmed P. falciparum malaria had a PCR blood spot from a finger-prick sample collected. Parasite DNA
was extracted from the blood-spot samples using saponin lysis/Chelex extraction method and genotyped using
polymorphic segments of MSP1, MSP2 and GLURP. Recurrent infections were classified by genotyping as novel,
recrudescent or indeterminate. Factors associated with time to microscopy-detected recrudescence were analysed
using multivariable regression techniques.
Results: From December 1994 to November 2009, 700 women were treated for P. falciparum and there were 909
recurrent episodes (481 novel and 428 recrudescent) confirmed by PCR genotyping. Most of the recurrences, 85 %
(770/909), occurred after treatment with quinine monotherapy, artesunate monotherapy or artesunate-clindamycin. The
geometric mean number of days to recurrence was significantly shorter in women with recrudescent infection, 24.5
(95 %: 23.4-25.8), compared to re-infection, 49.7 (95 %: 46.9-52.7), P <0.001. The proportion of recrudescent P. falciparum
infections that occurred after days 28, 42 and 63 from the start of treatment was 29.1 % (124/428), 13.3 % (57/428) and
5.6 % (24/428). Recrudescent infections ≥100 days after treatment occurred with quinine and mefloquine monotherapy,
and quinine + clindamycin and artesunate + atovaquone-proguanil combination therapy. Treatments containing an
artemisinin derivative or an intercalated Plasmodium vivax infection increased the geometric mean interval to
recrudescence by 1.28-fold (95 % CI: 1.09-1.51) and 2.19-fold (1.77-2.72), respectively. Intervals to recrudescence
were decreased 0.83-fold (0.73-0.95) if treatment was not fully supervised (suggesting incomplete adherence) and
0.98-fold (0.96-0.99) for each doubling in baseline parasitaemia.
Conclusions: Prolonged time to recrudescence may occur in pregnancy, regardless of anti-malarial treatment. Long
intervals to recrudescence are more likely with the use of artemisinin-containing treatments and also observed with
intercalated P. vivax infections treated with chloroquine. Accurate determination of drug efficacy in pregnancy requires
longer duration of follow-up, preferably until delivery or day 63, whichever occurs last.