Delayed Onset of Plasmodium falciparum Malaria after Doxycycline Prophylaxis in a Soldier Returning from the Central African Republic

Javelle, Émilie; Madamet, Marylin; Gaillard, Tiphaine; Velut, Guillaume; Surcouf, Corinne; Michel, R.; Garnotel, Éric; Simon, Fabrice; Pradines, Bruno

doi:10.1128/aac.01858-15

Cited by 10 publications

(13 citation statements)

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“…Using the pLDH-ELISA, P. vivax appeared significantly more susceptible to dihydroartemisinin (DHA), artesunate (AS), and chloroquine (CQ) than P. falciparum ,but less susceptible to mefloquine (MQ), and artemisone (ATM), and similarly susceptible to lumefantrine (LUM), piperaquine (PPQ) and doxycycline (DOX). It should be noted that although DOX IC 50 values were in the micromolar range, they were still below previously proposed values for resistance [ 44 ]. The present study reveals Cambodian P. vivax isolates appear to remain sensitive to CQ while resistance to other anti-malarials may be worse than previously assumed, though the absence of baseline values precludes definitive conclusions.…”

Section: Discussioncontrasting

confidence: 66%

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Measuring ex vivo drug susceptibility in Plasmodium vivax isolates from Cambodia

Chaorattanakawee

Lon

Chann

et al. 2017

Malar J

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BackgroundWhile 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 anti-malarial 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.ResultsEx 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.ConclusionThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-2034-2) contains supplementary material, which is available to authorized users.

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Section: Discussioncontrasting

confidence: 66%

“…Approximately 60% of P. vivax patients treated with chloroquine experienced a recurrence within 28 days in studies from Malaysia and Vietnam [ 24 , 52 ]. Yet chloroquine sensitivity was better preserved in studies conducted in Cambodia [ 29 , 44 ], the Brazilian Amazon [ 53 ], Myanmar [ 54 ], India [ 55 ] and Ethiopia [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Measuring ex vivo drug susceptibility in Plasmodium vivax isolates from Cambodia

Chaorattanakawee

Lon

Chann

et al. 2017

Malar J

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“…Nonetheless, there are very few reliable data available. Two studies on in vitro sensitivity tests conducted in Bangui in 2004 (before ACT were introduced) and in 2014 showed that 100% of the circulating P. falciparum strains were sensitive to the main antimalarial drugs [8,9]. A clinical study assessing the efficacy of ACT was conducted in Bangui in 2010 and showed a high level of clinical and parasitological response rate estimated to 100% for the artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) [10].…”

Section: Introductionmentioning

confidence: 99%

Molecular assessment of kelch13 non-synonymous mutations in Plasmodium falciparum isolates from Central African Republic (2017–2019)

Nzoumbou‐Boko

Panté-Wockama

Ngoagoni

et al. 2020

Preprint

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Background: Over the last decade, Artemisinin-based Combination Therapies (ACT) have contributed substantially to the decrease in malaria-related morbidity and mortality. The emergence of Plasmodium falciparum parasites resistant to artemisinin derivatives in Southeast Asia and the risk of their spread or of local emergence in sub-Saharan Africa are a major threat to public health. This study thus set out to estimate the proportion of P. falciparum isolates, with PfKelch13 gene mutations associated with artemisinin resistance previously detected in Southeast Asia. Methods: Blood samples were collected in two sites of Bangui, the capital of the Central African Republic form 2017 to 2019. DNA was extracted and nested PCR were carried out to detect Plasmodium species and mutations in the propeller domain of the PfKelch13 gene. Results: A total of 255 P. falciparum isolates were analyzed. Among them, P. ovale DNA was found in four samples (1.57%, 4/255). Of 187 samples with interpretable PfKelch13 sequences, four isolates presented a mutation in the PfKelch13 gene (2.1%, 4/187), including one non-synonymous mutation (Y653N) (0.5%, 1/187). This mutation has never been described as associated with artemisinin resistance in Southeast Asia and its in vitro phenotype is unknown. Conclusion: This preliminary study indicates the need for a larger study on samples collected across the whole country along with the evaluation of in vitro and in vivo phenotype profiles of PfKelch13 mutant parasites to estimate the risk of artemisinin resistance in the CAR.

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“…Clinical manifestations of P. falciparum malaria 2 to 9 years after infection were previously described (2,12,13). Generally, recurrence of P. falciparum infection in Europe affects (i) migrants from areas where malaria is endemic in whom malaria parasites were not initially detected (1); (ii) patients with immunocompromised conditions, such as pregnancy or coinfection with HIV or sickle cell disease (13,14); and (iii) patients undergoing chemoprophylaxis (5,15).…”

mentioning

confidence: 96%

“…The ex vivo susceptibility to antimalarial drugs was evaluated for the two samples as previously described (5). Additionally, the K13 propeller gene involved in artemisinin resistance, pfmdr1 (P. falciparum multidrug resistance 1) gene, and pfcrt (P. falciparum chloroquine resistance transporter) gene involved in quinoline resistance were se- quenced as previously described (6).…”

mentioning

confidence: 99%

Plasmodium falciparum Recrudescence Two Years after Treatment of an Uncomplicated Infection without Return to an Area Where Malaria Is Endemic

Malvy

Torrentino-Madamet

L’Ollivier

et al. 2018

Antimicrob Agents Chemother

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Delayed Onset of Plasmodium falciparum Malaria after Doxycycline Prophylaxis in a Soldier Returning from the Central African Republic

Abstract: International audienceno abstrac

Cited by 10 publications

References 12 publications

Measuring ex vivo drug susceptibility in Plasmodium vivax isolates from Cambodia

Measuring ex vivo drug susceptibility in Plasmodium vivax isolates from Cambodia

Molecular assessment of kelch13 non-synonymous mutations in Plasmodium falciparum isolates from Central African Republic (2017–2019)

Plasmodium falciparum Recrudescence Two Years after Treatment of an Uncomplicated Infection without Return to an Area Where Malaria Is Endemic

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