Mass drug administrations with dihydroartemisinin-piperaquine and single low dose primaquine to eliminate Plasmodium falciparum have only a transient impact on Plasmodium vivax: Findings from randomised controlled trials

Phommasone, Koukeo; Leth, Frank van; Peto, Thomas J.; Landier, Jordi; Nguyen, Thuy-Nhien; Tripura, Rupam; Pongvongsa, Tiengkham; Lwin, Khin Maung; Kajeechiwa, Ladda; Thwin, May Myo; Parker, Daniel M.; Wiladphaingern, Jacher; Nosten, Suphak; Proux, Stéphane; Nguon, Chea; Davoeung, Chan; Huy, Rekol; Adhikari, Bipin; Promnarate, Cholrawee; Chotivanich, Kesinee; Hanboonkunupakarn, Borimas; Jittmala, Podjanee; Cheah, Phaik Yeong; Dhorda, Mehul; Imwong, Mallika; Mukaka, Mavuto; Peerawaranun, Pimnara; Pukrittayakamee, Sasithon; Newton, Paul N.; Thwaites, Guy; Day, Nicholas P. J.; Mayxay, Mayfong; Hien, Tran Tinh; Nosten, F; Cobelens, Frank; Dondorp, Arjen M.; White, Nicholas J.; Seidlein, Lorenz von

doi:10.1371/journal.pone.0228190

Cited by 9 publications

(11 citation statements)

References 29 publications

(37 reference statements)

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“…As the prevalence of P. falciparum has declined, P. vivax has emerged as a significant barrier to malaria elimination in Myanmar. 19 , 35 There is also evidence of P. vivax chloroquine resistance in Myanmar, 20 – 23 including high-level resistant strains circulating in northeast Myanmar. 22 Although the prevalence of these strains is thought to be low, the success of elimination efforts based on chloroquine/primaquine could be jeopardized and intensification of P. vivax antimalarial treatment may further select and propagate resistant strains.…”

Section: Discussionmentioning

confidence: 99%

“…17 However, P. vivax remains refractory to current interventions and has become the dominant parasite in some areas. 18 , 19 Pyronaridine–artesunate is the first ACT specifically registered for P. vivax malaria, with demonstrated high clinical efficacy across Southeast Asia. 12 , 14 Chloroquine resistance has been reported in Myanmar, 20 – 23 and to plan effective P. vivax elimination programs, the efficacy of alternative therapies requires confirmation.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and Safety of Pyronaridine–Artesunate for the Treatment of Uncomplicated Plasmodium falciparum and Plasmodium vivax Malaria in Myanmar

Han

Lin

Han

et al. 2020

The American Journal of Tropical Medicine and Hygiene

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Four single-arm, prospective, clinical studies of pyronaridine-artesunate efficacy in uncomplicated Plasmodium falciparum or Plasmodium vivax malaria were conducted in Myanmar between 2017 and 2019. Eligible subjects were aged at least 6 years, with microscopically confirmed P. falciparum (n = 196) or P. vivax mono-infection (n = 206). Patients received pyronaridine-artesunate once daily for 3 days with follow-up until day 42 for P. falciparum or day 28 for P. vivax. For the primary efficacy analysis, adequate clinical and parasitological response (ACPR) in the per-protocol population at day 42 for P. falciparum malaria was 100% (88/88; 95% CI: 95.9, 100) in northern Myanmar (Kachin State and northern Shan State), and 100% (101/101; 95% CI: 96.4, 100) in southern Myanmar (Tanintharyi Region and Kayin State). Plasmodium falciparum day-3 parasite clearance was observed for 96.9% (190/196) of patients. Mutations in the P. falciparum Kelch propeller domain (K13) were detected in 39.0% (69/177) of isolates: F446I (14.7% [26/177]), R561H (13.0% [23/177]), C580Y (10.2% [18/177]), and P574L (1.1% [2/177]). For P. vivax, the day-28 ACPR was 100% (104/104; 95% CI: 96.5, 100) in northern Myanmar and 100% (97/97; 95% CI: 96.3, 100) in southern Myanmar. Across both P. vivax studies, 100% (206/206) of patients had day-3 parasite clearance. There were no adverse events. Pyronaridineartesunate had excellent efficacy in Myanmar against P. falciparum and P. vivax and was well tolerated. This study supports the inclusion of pyronaridine-artesunate in national malaria treatment guidelines for Myanmar.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Pyronaridine–Artesunate for the Treatment of Uncomplicated Plasmodium falciparum and Plasmodium vivax Malaria in Myanmar

Han

Lin

Han

et al. 2020

The American Journal of Tropical Medicine and Hygiene

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“…Past MDAs in regions surrounded by ongoing P. falciparum malaria transmission have succeeded to suppress transmission for limited periods but failed to interrupt transmission permanently probably due to residual parasite reservoirs and reimportation of infections [87]. In the presence of residual hypnozoites, the suppression of P. vivax prevalence is even shorter than P. falciparum prevalence [88]. To make a lasting impact, MDAs aiming to eliminate P. vivax malaria have to include 8-aminoquinolines.…”

Section: Alternative Approaches To P Vivax Elimination: Vaccines and Mass Drug Administrationsmentioning

confidence: 99%

“…vivax prevalence is even shorter than P . falciparum prevalence [ 88 ]. To make a lasting impact, MDAs aiming to eliminate P .…”

Section: Introductionmentioning

confidence: 99%

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

2021

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“…Primaquine (PQ) has broad therapeutic utility for treatment, prophylaxis, radical cure and prevention of transmission of malaria [ 3 ]. Mass drug administration of PQ has been suggested for clearance of residual gametocytemia in malaria endemic regions for malaria control [ 16 , 17 , 18 ]. However, hemolytic toxicity in individuals with genetic deficiency of G6PD limits the use of PQ for malaria radical cure and prevents widespread use of this drug in public health [ 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Enantioselective Interactions of Anti-Infective 8-Aminoquinoline Therapeutics with Human Monoamine Oxidases A and B

et al. 2021

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8-Aminoquinolines (8-AQs) are an important class of anti-infective therapeutics. The monoamine oxidases (MAOs) play a key role in metabolism of 8-AQs. A major role for MAO-A in metabolism of primaquine (PQ), the prototypical 8-AQ antimalarial, has been demonstrated. These investigations were further extended to characterize the enantioselective interactions of PQ and NPC1161 (8-[(4-amino-1-methylbutyl) amino]-5-[3, 4-dichlorophenoxy]-6-methoxy-4-methylquinoline) with human MAO-A and -B. NPC1161B, the (R)-(−) enantiomer with outstanding potential for malaria radical cure, treatment of visceral leishmaniasis and pneumocystis pneumonia infections is poised for clinical development. PQ showed moderate inhibition of human MAO-A and -B. Racemic PQ and (R)-(−)-PQ both showed marginally greater (1.2- and 1.6-fold, respectively) inhibition of MAO-A as compared to MAO-B. However, (S)-(+)-PQ showed a reverse selectivity with greater inhibition of MAO-B than MAO-A. Racemic NPC1161 was a strong inhibitor of MAOs with 3.7-fold selectivity against MAO-B compared to MAO-A. The (S)-(+) enantiomer (NPC1161A) was a better inhibitor of MAO-A and -B compared to the (R)-(−) enantiomer (NPC1161B), with more than 10-fold selectivity for inhibition of MAO-B over MAO-A. The enantioselective interaction of NPC1161 and strong binding of NPC1161A with MAO-B was further confirmed by enzyme-inhibitor binding and computational docking analyses. Differential interactions of PQ and NPC1161 enantiomers with human MAOs may contribute to the enantioselective pharmacodynamics and toxicity of anti-infective 8-AQs therapeutics.

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Mass drug administrations with dihydroartemisinin-piperaquine and single low dose primaquine to eliminate Plasmodium falciparum have only a transient impact on Plasmodium vivax: Findings from randomised controlled trials

Abstract: Background Mass administrations of antimalarial drugs (MDA) have reduced the incidence and prevalence of P. falciparum infections in a trial in the Greater Mekong Subregion. Here we assess the impact of the MDA on P. vivax infections.

Cited by 9 publications

References 29 publications

Efficacy and Safety of Pyronaridine–Artesunate for the Treatment of Uncomplicated Plasmodium falciparum and Plasmodium vivax Malaria in Myanmar

Efficacy and Safety of Pyronaridine–Artesunate for the Treatment of Uncomplicated Plasmodium falciparum and Plasmodium vivax Malaria in Myanmar

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

Enantioselective Interactions of Anti-Infective 8-Aminoquinoline Therapeutics with Human Monoamine Oxidases A and B

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