Towards the elimination of Plasmodium vivax malaria: Implementing the radical cure

Thriemer, Kamala; Ley, Benedikt; Seidlein, Lorenz von

doi:10.1371/journal.pmed.1003494

Cited by 33 publications

(32 citation statements)

References 82 publications

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“…Very recently, in October 2021, The WHO has recommended the use of RTS,S among children in sub-Saharan Africa and in regions with moderate to high P. falciparum malaria transmission 17 . However, this vaccine shows only moderate protection against severe disease caused by P. falciparum , while efforts to develop vaccines against P. vivax remain limited, despite the enormous burden caused by this parasite species 16 , 18 . Traditional antimalarials based on chloroquine ( 1 , CQ, Fig.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and antiplasmodial activity of regioisomers and epimers of second-generation dual acting ivermectin hybrids

Singh

Fontinha

Francisco

et al. 2022

Sci Rep

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With its strong effect on vector-borne diseases, and insecticidal effect on mosquito vectors of malaria, inhibition of sporogonic and blood-stage development of Plasmodium falciparum, as well as in vitro and in vivo impairment of the P. berghei development inside hepatocytes, ivermectin (IVM) continues to represent an antimalarial therapeutic worthy of investigation. The in vitro activity of the first-generation IVM hybrids synthesized by appending the IVM macrolide with heterocyclic and organometallic antimalarial pharmacophores, against the blood-stage and liver-stage infections by Plasmodium parasites prompted us to design second-generation molecular hybrids of IVM. Here, a structural modification of IVM to produce novel molecular hybrids by using sub-structures of 4- and 8-aminoquinolines, the time-tested antiplasmodial agents used for treating the blood and hepatic stage of Plasmodium infections, respectively, is presented. Successful isolation of regioisomers and epimers has been demonstrated, and the evaluation of their in vitro antiplasmodial activity against both the blood stages of P. falciparum and the hepatic stages of P. berghei have been undertaken. These compounds displayed structure-dependent antiplasmodial activity, in the nM range, which was more potent than that of IVM, its aglycon or primaquine, highlighting the superiority of this hybridization strategy in designing new antiplasmodial agents.

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Section: Introductionmentioning

confidence: 99%

Synthesis and antiplasmodial activity of regioisomers and epimers of second-generation dual acting ivermectin hybrids

Singh

Fontinha

Francisco

et al. 2022

Sci Rep

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“…Preventing severe anemia associated with relapsing vivax malaria, particularly in very young children, is a priority to reduce morbidity and mortality in this group. Progress has been slowed by low uptake of antihypnozoiticidal treatment with 8-aminoquinoline drugs due to fears of hemolysis in patients with G6PD deficiency, compounded by lack of access to G6PD testing [ 102 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical impact of vivax malaria: A collection review

et al. 2022

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Background Plasmodium vivax infects an estimated 7 million people every year. Previously, vivax malaria was perceived as a benign condition, particularly when compared to falciparum malaria. Reports of the severe clinical impacts of vivax malaria have been increasing over the last decade. Methods and findings We describe the main clinical impacts of vivax malaria, incorporating a rapid systematic review of severe disease with meta-analysis of data from studies with clearly defined denominators, stratified by hospitalization status. Severe anemia is a serious consequence of relapsing infections in children in endemic areas, in whom vivax malaria causes increased morbidity and mortality and impaired school performance. P. vivax infection in pregnancy is associated with maternal anemia, prematurity, fetal loss, and low birth weight. More than 11,658 patients with severe vivax malaria have been reported since 1929, with 15,954 manifestations of severe malaria, of which only 7,157 (45%) conformed to the World Health Organization (WHO) diagnostic criteria. Out of 423 articles, 311 (74%) were published since 2010. In a random-effects meta-analysis of 85 studies, 68 of which were in hospitalized patients with vivax malaria, we estimated the proportion of patients with WHO-defined severe disease as 0.7% [95% confidence interval (CI) 0.19% to 2.57%] in all patients with vivax malaria and 7.11% [95% CI 4.30% to 11.55%] in hospitalized patients. We estimated the mortality from vivax malaria as 0.01% [95% CI 0.00% to 0.07%] in all patients and 0.56% [95% CI 0.35% to 0.92%] in hospital settings. WHO-defined cerebral, respiratory, and renal severe complications were generally estimated to occur in fewer than 0.5% patients in all included studies. Limitations of this review include the observational nature and small size of most of the studies of severe vivax malaria, high heterogeneity of included studies which were predominantly in hospitalized patients (who were therefore more likely to be severely unwell), and high risk of bias including small study effects. Conclusions Young children and pregnant women are particularly vulnerable to adverse clinical impacts of vivax malaria, and preventing infections and relapse in this groups is a priority. Substantial evidence of severe presentations of vivax malaria has accrued over the last 10 years, but reporting is inconsistent. There are major knowledge gaps, for example, limited understanding of the underlying pathophysiology and the reason for the heterogenous geographical distribution of reported complications. An adapted case definition of severe vivax malaria would facilitate surveillance and future research to better understand this condition.

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“…Accordingly, health care workers in P. vivax-endemic rural areas must be trained in G6PD testing. [63][64][65] The diagnosis of G6PD deficiency can be especially tricky in heterozygous women because of random X-chromosome inactivation.…”

Section: Tafenoquine and Glucose-6-phosphate-dehydrogenase Deficiencymentioning

confidence: 99%

Safety and Efficacy of Tafenoquine for Plasmodium vivax Malaria Prophylaxis and Radical Cure: Overview and Perspectives

Markus¹

2021

TCRM

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This article is inter alia a brief, first-stop guide to possible adverse events (AEs) associated with tafenoquine (TQ) intake. Safety and efficacy findings for TQ in Plasmodium vivax malaria prophylaxis and radical cure are summarized and some of the latest TQ-related studies (published in 2020 and 2021) are highlighted. In addition, little-known biological and other matters concerning malaria parasites and 8-aminoquinoline (8-AQ) drug action are discussed and some correct terminology pertinent to malaria is explained.

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Towards the elimination of Plasmodium vivax malaria: Implementing the radical cure

Cited by 33 publications

References 82 publications

Synthesis and antiplasmodial activity of regioisomers and epimers of second-generation dual acting ivermectin hybrids

Synthesis and antiplasmodial activity of regioisomers and epimers of second-generation dual acting ivermectin hybrids

Clinical impact of vivax malaria: A collection review

Safety and Efficacy of Tafenoquine for Plasmodium vivax Malaria Prophylaxis and Radical Cure: Overview and Perspectives

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