Abstract
Background Plasmodium vivax malaria is a major public health problem in French Guiana. Some cases of resistance to chloroquine, the first-line treatment used against P. vivax malaria, have been described in the Brazilian Amazon region. The aim of this study is to investigate a possible dispersion of chloroquine-resistant P. vivax isolates in French Guiana. The genotype, polymorphism and copy number variation, of the P. vivax multidrug resistance gene-1 (pvmdr1) have been previously associated with modification of the susceptibility to chloroquine.MethodsThe pvmdr1 gene polymorphism was evaluated by sequencing and copy number variation was assessed by real-time PCR, in P. vivax isolates obtained from 591 symptomatic patients from 1997 to 2013.ResultsThe results reveal that 1.0% [95% CI 0.4–2.2] of French Guiana isolates carry the mutations Y976F and F1076L, and that the proportion of isolates with multiple copies of pvmdr1 has significantly decreased over time, from 71.3% (OR = 6.2 [95% CI 62.9–78.7], p < 0.0001) in 1997–2004 to 12.8% (OR = 0.03 [95% CI 9.4–16.9], p < 0.0001) in 2009–2013. A statistically significant relationship was found between Guf-A (harboring the single mutation T958M) and Sal-1 (wild type) alleles and pvmdr1 copy number.ConclusionsFew P. vivax isolates harboring chloroquine-resistant mutations in the pvmdr1 gene are circulating in French Guiana. However, the decrease in the prevalence of isolates carrying multiple copies of pvmdr1 might indicate that the P. vivax population in French Guiana is evolving towards a decreased susceptibility to chloroquine.
Highlights
Plasmodium vivax malaria is a major public health problem in French Guiana
The signal from the pvmdr1 gene was normalized to the single copy pvaldolase reference gene, copy number was determined using the mathematical model described by Pfaffl [34]
Three time periods (1997–2004, 2005–2008 and 2009–2013) were considered according to the years 2005 when the P. vivax became the dominant species diagnosed in French Guiana, and 2009 when the combination of artemether and lumefantrine was adopted for the treatment of P. falciparum and mixed infections (P. falciparum/P. vivax) in French Guiana (Table 2)
Summary
Plasmodium vivax malaria is a major public health problem in French Guiana. Some cases of resistance to chloroquine, the first-line treatment used against P. vivax malaria, have been described in the Brazilian Amazon region. A total of 311 P. vivax cases were reported in French Guiana in 2014, representing 70% of the total number of malaria cases [2]. First cases of P. vivax resistance to chloroquine in South America were described in clinical studies of unsupervised chloroquine treatment in 1989 and 1992, in Colombia and Brazil, respectively [6, 7]. It was only in 1996 that the first confirmed clinical case of resistance was described in Brazil [8]. Chloroquine resistance has spread around the world over the last decade [9], and is found in Southeast Asia [10,11,12,13,14] and in Africa [15, Faway et al Malar J (2016) 15:540
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