Field-based evidence of fast and global increase of Plasmodium falciparum drug-resistance by DNA-microarrays and PCR/RFLP in Niger

Ibrahim, Maman Laminou; Steenkeste, Nicolas; Khim, Nimol; Adam, Hadiza Hassane; Konaté, Lassana; Coppée, Jean‐Yves; Ariey, Frédéric; Duchemin, Jean‐Bernard

doi:10.1186/1475-2875-8-32

Cited by 23 publications

(22 citation statements)

References 29 publications

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“…Similarly, no sign of a decrease in susceptibility to LUM has been detected. This observation is consistent with earlier molecular data showing the prevalence of mutations of P. falciparum mdr1 (Pfmdr1) sequences to be low in isolates from Niger, particularly for the Y86N mutation, which is thought to confer a selective advantage on parasites, rendering them tolerant to LUM (22,27). PYD and PIP have been developed as alternative antimalarial drugs for inclusion in ART-containing combinations for the treatment of multidrug-resistant malaria.…”

supporting

confidence: 80%

“…This observation must be viewed in light of the results of in vivo tests conducted in Niger a decade ago, for which a treatment success rate of about 85% was reported for CQ. The trend in 2011 (11% of isolates presenting a mutated codon 76) is therefore distinctly different from those reported for molecular studies carried out between 2003 and 2007 in Niger, in which the prevalence of Pfcrt 76T was reported to be between 32.4% and 50.8% (22,32). However, given the limited number of isolates examined and the short time interval between these studies, it is too soon to draw any firm conclusions about a shift toward an improved susceptibility of parasites to CQ in Niger.…”

mentioning

confidence: 40%

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Ex Vivo Responses of Plasmodium falciparum Clinical Isolates to Conventional and New Antimalarial Drugs in Niger

Issaka

Salissou

Aliyu

et al. 2013

Antimicrob Agents Chemother

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Little is known about resistance of Plasmodium falciparum to antimalarials in Sahelian countries. Here we investigated the drug susceptibilities of fresh isolates collected in Niger post-deployment of artemisinin-based combination therapies (ACTs). We found that the parasites remained highly susceptible to new (dihydroartemisinin, lumefantrine, pyronaridine, and piperaquine) and conventional (amodiaquine and chloroquine) antimalarial drugs. The introduction of ACTs in 2005 and their further deployment nationwide have therefore not resulted in a decrease in P. falciparum susceptibilities to these antimalarials. The WHO estimates that 50% of the world's population is exposed to malaria. In 2010, 216 million cases and more than 650,000 deaths from malaria were reported. Despite a decrease in the number of confirmed cases in some parts of the world, the situation remains heterogeneous and worrying in Africa (1). Together with respiratory infections and diarrheal diseases, malaria is one of the leading causes of death in Niger. Malaria transmission rates are high, with a mean incidence of 80 cases per 1,000 inhabitants. Despite the complementary nature of interventions in the field, which have strengthened in recent years, the number of cases has steadily risen over the last 20 years, reaching three million in 2010 (2, 3). There are several reasons for the deterioration of the public health situation with regard to malaria, and the increase in resistance to antimalarial drugs is considered a key factor. In Niger, infections are currently treated with combinations of drugs including an artemisinin (ART) derivative (artemisinin-based combination treatment, or ACT) (4). Since 2005, ACT has been proposed as the first-line treatment for the management of uncomplicated malaria. The use of such treatments throughout Niger was greatly expanded in 2010 by the implementation of a Global Fund Affordable Malaria Facility mechanism (5). Thereby, the drug pressure exerted on Plasmodium falciparum increases the risk of selection of parasites with altered susceptibility to antimalarials. This seems to be inevitable, as demonstrated by recent observations in Asia, which have revealed the presence of parasites less sensitive to artemisinins (6). The risk of emerging resistance to ACT makes it necessary to monitor the susceptibilities of parasites to antimalarial drugs, particularly those used in combination with artemisinin derivatives, on a regular basis and to search for new molecules with antimalarial activity.In this context, a study was carried out in Niger in 2011, at Gaya in the Dosso region, 250 km south of Niamey (3.44°N, 11.9°E), to evaluate the response of P. falciparum isolates to lumefantrine (LUM) and amodiaquine diphosphate (AQ), both of which are widely used in the ACTs distributed in Niger. In addition, responses to alternative molecules, such as pyronaridine (PYD) and piperaquine (PIP), both currently not available in Niger, as well as dihydroartemisinin (DHA) and chloroquine (CQ), were investigated. P. falciparum is...

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supporting

confidence: 80%

mentioning

confidence: 40%

Ex Vivo Responses of Plasmodium falciparum Clinical Isolates to Conventional and New Antimalarial Drugs in Niger

Issaka

Salissou

Aliyu

et al. 2013

Antimicrob Agents Chemother

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“…Using a geographical database of molecular biomarkers as described elsewhere [16], we obtained prevalence esti-mates of Pfdhps 581G from 44 locations that had been measured within AE2 years of the IPTp-SP studies. There were 20 locations within <100 miles of the pregnancy study sites and 24 locations within 100-250 miles as shown in Table 5 [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40].…”

Section: Effect Modification Of Pfdhps 581gmentioning

confidence: 99%

Influence of malaria transmission intensity and the 581G mutation on the efficacy of intermittent preventive treatment in pregnancy: systematic review and meta‐analysis

Chico

Cano

Ariti

et al. 2015

Tropical Med Int Health

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Abstractobjectives To estimate where intermittent preventive treatment (IPTp) using sulphadoxinepyrimethamine (SP) could be withdrawn as an intervention due to declining malaria transmission intensity, or due to increasing prevalence of the Plasmodium falciparum dihydropteroate synthetase resistance mutation at codon 581G.methods We conducted a systematic review and meta-analysis of protection against the incidence of low birth weight (LBW) conferred by ≥2 doses of IPTp-SP. We matched these outcomes to a proxy measure of malaria incidence in women of the same studies, applied meta-regression models to these data and conducted sensitivity analysis of the 581G mutation.results Variation in the protective effect of IPTp-SP against LBW could not be explained by malaria transmission intensity. Among primi-and secundigravidae, IPTp-SP protected against LBW where 581G was ≤10.1% [odds ratio (OR): 0.49; 95% confidence intervals (CI): 0.29, 0.81; P = <0.01] and 581G was >10.1% (OR = 0.73; 95% CI: 0.29, 1.81; P = 0.03). Random-effects models among multigravidae showed that IPTp-SP protects against LBW where 581G was ≤10.1% (OR = 0.56; 95% CI: 0.37, 0.86; P = 0.07), a finding of borderline statistical significance. No evidence of protection against LBW was observed where 581G was >10.1% (OR = 0.96; 95% CI: 0.70, 1.34; P = 0.47).conclusion There appears to be a prevalence of 581G above which IPTp-SP no longer protects against LBW. Pregnancy studies are urgently needed where 581G is >10.1% to define the specific prevalence threshold where new strategies should be deployed.

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“…They also described the assay as suitable to cope with the problem of multiplicity of infections and the determination of the most dominant haplotype representing the clinical malaria-causing clone. While the present study only worked with cultured organisms, the authors and collaborators conducted further successful field studies on the basis of the microarray system using patient samples in Tanzania [176], Niger [177], Papua New Guinea [178], and the Solomon Islands [179]. In an interesting study, the group around Hans-Peter Beck used the same technological approach to genotype polymorphisms, that is, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, and NAT2, which are known to have an impact on human malarial drug metabolisms [180].…”

Section: Malariamentioning

confidence: 99%

DNA Microarrays for Pathogen Detection

Schulze

Rubtsova

Bachmann

2015

Modern Techniques for Pathogen Detection

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Field-based evidence of fast and global increase of Plasmodium falciparum drug-resistance by DNA-microarrays and PCR/RFLP in Niger

Cited by 23 publications

References 29 publications

Ex Vivo Responses of Plasmodium falciparum Clinical Isolates to Conventional and New Antimalarial Drugs in Niger

Ex Vivo Responses of Plasmodium falciparum Clinical Isolates to Conventional and New Antimalarial Drugs in Niger

Influence of malaria transmission intensity and the 581G mutation on the efficacy of intermittent preventive treatment in pregnancy: systematic review and meta‐analysis

DNA Microarrays for Pathogen Detection

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