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The effectiveness of first-line malaria treatment underpins the success of malaria control programs. Without treatment, malaria infections usually reproduce for several months. These recurrences increase malaria morbidity and improve transmission. Basically, suboptimal parasitic clearance promotes the emergence of drug resistance. Thus, the treatment should aim at the total elimination of the parasites. The definition of the optimal dose and the monitoring of the effectiveness are based on the results of clinical trials carried out in endemic areas. Patients, although monitored for 4 weeks or longer (depending on the pharmacokinetics of drugs), are usually released within a few days when symptoms decrease and parasites become undetectable under the microscope. The drug efficacy, or even the indication of resistance, is deduced from the occurrence, timing and frequency of recurrent episodes during follow-up
For malaria caused by Plasmodium vivax the most widespread species in the world, now and historically, the path to successful treatment has been long. Early last century, Yorke 1 x 1 Yorke, W. Other observations on malaria made during the treatment of general paralysis. Trans R Soc Trop Med Hyg . 1925 ;
19 : 108-130
Abstract | Full text PDF | Scopus (11) | Google Scholar See all references have shown that only 2% of cases treated with quinine P vivax inoculated with infected blood were recurrent, whereas 57% of patients with between them treated but infected by a mosquito bite. The biological basis of this riddle was discovered only in the early 1980s: 2 x 2 Krotoski, WA, Collins, WE, Bray, and RS al. Demonstration of hypnozoites in a Plasmodium vivax infection transmitted by sporozoites . Am J Trop Med Hyg . 1982 ;
31 : 1291-1293
Crossref | PubMed | Scopus (104) | Google Scholar See all References Sporozoites inoculated by the mosquito invade hepatocytes where they develop within 1-2 weeks to release the merozoites, which invade red blood cells, but for P vivax a subset of the liver forms remain dormant in the form of hypnozoites, activating at various intervals in subsequent months to cause other episodes (ie, relapses). After the pioneering work of Werner Schulemann and his colleagues at IG Farben in Eberfield, Germany, in the 1920s, American workers produced primaquine 30 years later, 3 x 3 [19659006] Edgcomb, JH, Arnold, JD, Yount, EH Jr, Alving, AS, and Eichelberger, L. Primaquine, SN 13272, a new curative agent in P. vivax malaria: a preliminary report. J. Natl Malar Soc . 1950 ;
9 : 285-292
PubMed | Google Scholar See all References See all References An 8-aminoquinoline which remains the only homologous compound capable of eliminating hypnozoites to achieve radical cure.
The recent campaign to rid the world of malaria P vivax in the foreground, recognizing that relapses are a serious obstacle to its eradication, and recommending that chloroquine and primaquine be combined as as first-line treatment. However, primaquine, which can cause severe haemolysis in people with glucose-6-phosphate deficiency, is therefore often omitted or under-treated. Thus, in practice infections with P. vivax are frequently treated with chloroquine alone
In this context, Robert Commons and colleauges 4 4 Commons , RJ, Simpson, JA, Thriemer, K et al. The effect of the dose of chloroquine and primaquine on the recurrence of Plasmodium vivax : a systematic review of the WorldWide Global Antimalarial Resistance Network and an individual meta-analysis of patients . Lancet Infect Dis . 2018 ;
() http://dx.doi.org/10.1016/S1473-3099 (18) 30348-7
Google Scholar See all the references sought to establish whether the variations of the dose chloroquine could have an effect on the results. They selected a subset of 37 recent trials (from 2000) involving 5,240 patients from a carefully compiled database of all clinical trials against P vivax x [19659006] Commons, RJ, Thriemer, K, Humphreys, GS et al. The Vivax Surveyor: Online Mapping Database for Plasmodium vivax Clinical Trials. Int J Parasitol Medically Resistant to Resistance . 2017 ;
7 : 181-190
Crossref | PubMed | Scopus (2) | Google Scholar See all References Two highlights of this unique clustered analysis are as simple as they are convincing. First, slight increases in the target dose of chloroquine (5 mg / kg) significantly reduced the risk of recurrence within 7 to 42 days after chloroquine administration (adjusted relative risk 0.82, 95% CI). 0.97; p = 0.021), an effect that was amplified in children under 5 years of age for an increase from 25 mg / kg to 30 mg / kg (0.69, 0.40-0.86, 0 · 0058). This finding is of particular importance since the parasitic rates of P vivax peak at the age of 2 to 6 years. 6 x 6 Howes, RE, Battle, KE, Mendis, KN et al. Global epidemiology of Plasmodium vivax . Am J Trop Med Hyg . 2016 ;
95 : 15-34
Crossref | PubMed | Scopus (41) | Google Scholar See all References The second discovery is undoubtedly the most important: the concomitant administration of primaquine reduces by 90% the number of recurring episodes compared to chloroquine alone (adjusted relative risk 0 to 10, 0 · 05-0 · 17, p <0 · 0001), thereby also minimizing the selection of chloroquine-resistant lines 7 x 7 ] Chu, CS, Phyo, AP, Lwin. KM et al. Comparison of the cumulative efficacy and safety of chloroquine, artesunate and chloroquine-primaquine in Malaria to Plasmodium vivax . Clin Infect Dis . 2018 ;
() DOI: 10.1093 / cid / ciy319.
Crossref | Google Scholar See all the references
The general finding that the recommended chloroquine treatment of malaria P vivax was optimal for decades, could not have been achieved without broad collective participation under the umbrella of the Global Antimalarial Resistance Network (WWARN). Given the potential positive impact on overall morbidity, physicians and public health administrators should seriously consider a modest increase in WHO's long-standing recommendations for a total dose of chloroquine. 25 mg / kg. 8 x 8 WHO. Guidelines for the Treatment of Malaria. 3rd edition. World Health Organization ,
Geneva ; 2015
Google Scholar See all References The minimum costs incurred will certainly be offset by the resulting health and socio-economic benefits. Nevertheless, the fact that chloroquine monotherapy continues to be the most frequently administered treatment in many endemic areas P vivax is of concern, and this meta-analysis should not be considered as advocating this scheme.
The treatment of P vivax must include a hypnozoic component. Tafenoquine, another 8-aminoquinoline, which offers the elimination of hypnozoites with a single dose, approaches the approval of the US Food and Drug Administration and shares the hemolytic potential of primaquine. However, neither compound is currently suitable for administration without the availability of a reliable and inexpensive point-of-care test for glucose-6-phosphate deficiency. With P vivax malaria is now firmly in the eyes of the malaria control community, and in view of the growing number of endemic areas where chloroquine resistance is recorded, 9 x [19659005] 9 [19659006] Price, RN, Von Seidlein, L, Valecha, N, Nosten, F, Baird, JK, and White, NJ. Global range of chloroquine resistance Plasmodium vivax : systematic review and meta-analysis. Lancet Infect Dis . 2014 ;
14 : 982-991
Abstract | Full text | Full text PDF | PubMed | Scopus (119) | Google Scholar See all References The malaria community should give priority to research leading to the universal implementation of effective therapies P vivax that incorporate an anti-malarial partner. hypnozoïque. The threat of endemicity P vivax should not go away until radical healing becomes the usual treatment
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I declare that There is no conflict of interest.
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