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NOT Open Access | High-dose chloroquine for uncomplicated Plasmodium falciparum malaria is well tolerated and causes similar QT prolongation as standard dose chloroquine in children

January 14, 2020 - 16:02 -- NOT Open Access
Ursing J, Rombo L, Eksborg S, Larson L, Bruvoll A, Tarning J, Rodrigues A, Kofoed PE
Antimicrob Agents Chemother. 2020 Jan 6. pii: AAC.01846-19

Higher chloroquine doses can effectively treat up to 93-96% of malaria infections caused by P. falciparum carrying the resistance conferring chloroquine resistance transporter (pfcrt) 76T allele. The tolerability of 50 (double standard dose) and 70 mg/kg total chloroquine doses were assessed in this study.

NOT Open Access | Improving the immunogenicity and protective efficacy of a whole‐killed malaria blood‐stage vaccine by chloroquine

January 14, 2020 - 10:00 -- NOT Open Access
Yong Fu, Xiao Lu, Feng Zhu, Yunxiang Zhao, Yan Ding, Lilin Ye, Bo Guo, Taiping Liu, Wenyue Xu
Parasite Immunology, Volume42, Issue1, January 2020, e12682

A whole‐killed malaria blood‐stage vaccine (WKV) is promising in reducing the morbidity and mortality of malaria patients, but its efficacy needs to be improved. We found that the antimalarial drug chloroquine could augment the protective efficacy of the WKV of Plasmodium yoelii. The direct antimalarial effect of chloroquine on parasites during immunization could be excluded, as the administration of chloroquine or chloroquine plus alum every two weeks had a slight effect on parasitemia, and an immunization with NP‐KLH (4‐hydroxy‐3‐nitrophenylacetyl Keyhole Limpet Hemocyanin) plus chloroquine could significantly promote the generation of NP‐specific antibodies. Additionally, alum was required for chloroquine to augment the immunogenicity of the pRBC lysate.

Doses of chloroquine in the treatment of malaria by Plasmodium vivax in patients between 2 and 14 years of age from the Brazilian Amazon basin

December 30, 2019 - 14:46 -- Open Access
Luann Wendel Pereira de Sena, Amanda Gabryelle Nunes Cardoso Mello, Michelle Valéria Dias Ferreira, Marcieni Andrade de Ataide, Rosa Maria Dias and José Luiz Fernandes Vieira
Malaria Journal 2019 18:439, 21 December 2019

A total dose of chloroquine of 25 mg/kg is recommended by the World Health Organization (WHO) to treat malaria by Plasmodium vivax. In several endemic areas, including the Brazilian Amazon basin, anti-malarial drugs are dispensed in small plastic bags at a dosing regimen based on age. This practice can lead to suboptimal dosing of the drug, which can impact treatment outcomes. The aim of the present study was to estimate the extent of sub-dosing of chloroquine in children and adolescents with vivax malaria using an age-based dose regimen, in addition to investigating the influence of age on the plasma concentrations of chloroquine and desethylchloroquine.

Coupling the Antimalarial Cell Penetrating Peptide TP10 to Classical Antimalarial Drugs Primaquine and Chloroquine Produces Strongly Hemolytic Conjugates

December 23, 2019 - 14:59 -- Open Access
Aguiar L, Biosca A, Lantero E, Gut J, Vale N, Rosenthal PJ, Nogueira F, Andreu D, Fernàndez-Busquets X, Gomes P
Molecules 2019, 24(24), 4559

Recently, we disclosed primaquine cell penetrating peptide conjugates that were more potent than parent primaquine against liver stage Plasmodium parasites and non-toxic to hepatocytes. The same strategy was now applied to the blood-stage antimalarial chloroquine, using a wide set of peptides, including TP10, a cell penetrating peptide with intrinsic antiplasmodial activity. Chloroquine-TP10 conjugates displaying higher antiplasmodial activity than the parent TP10 peptide were identified, at the cost of an increased hemolytic activity, which was further confirmed for their primaquine analogues.

Pharmacokinetics/pharmacodynamics of chloroquine and artemisinin-based combination therapy with primaquine

September 24, 2019 - 14:59 -- Open Access
André Daher, Ghait Aljayyoussi, David G. Lalloo, et al.
Malaria Journal 2019 18:325, 23 September 2019

Activation of hypnozoites of vivax malaria causes multiple clinical relapses, which contribute to the Plasmodium vivax burden and continuing transmission. Artemisinin-based combination therapy (ACT) is effective against blood-stage P. vivax but requires co-administration with primaquine to achieve radical cure. The therapeutic efficacy of primaquine depends on the generation of a therapeutically active metabolite via cytochrome P450 2D6 (CYP2D6). Impaired CYP2D6 metabolism has been associated with primaquine treatment failure. This study investigated the association between impaired CYP2D6 genotypes, drug-exposure to the long-acting ACT component (schizonticidal drugs) and tolerance and efficacy.

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NOT Open Access | Chloroquine Analogues as Leads against Pneumocystis Lung Pathogens

October 30, 2018 - 12:44 -- NOT Open Access
Ana Gomes, Ricardo Ferraz, Lauren Ficker, Margaret S. Collins, Cristina Prudêncio, Melanie T. Cushion, Cátia Teixeira and Paula Gomes
Antimicrob. Agents Chemother. November 2018 62:e00983-18

The impact of Pneumocystis pneumonia (PcP) on morbidity and mortality remains substantial for immunocompromised individuals, including those afflicted by HIV infection, organ transplantation, cancer, autoimmune diseases, or subject to chemotherapy or corticosteroid-based therapies.

Chloroquine efficacy for Plasmodium vivax in Myanmar in populations with high genetic diversity and moderate parasite gene flow

July 11, 2017 - 12:53 -- Open Access
Myo Win Htun, Nan Cho Nwe Mon, Kamala Thriemer, et al.
Malaria Journal 2017 16:281, 10 July 2017

Treatment failures after chloroquine were observed following chloroquine monotherapy, with pvmdr1 amplification present in both Myawaddy and Shwegyin.

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Efficacy of Artesunate-mefloquine for Chloroquine-resistant Plasmodium vivax Malaria in Malaysia: An Open-label, Randomized, Controlled Trial

May 26, 2016 - 16:39 -- Open Access
Matthew J. Grigg, Timothy William, Nicholas M. Anstey, et al.
Clin Infect Dis. (2016) 62 (11): 1403-1411

A randomized, controlled trial of CQ vs artesunate-mefloquine (AS-MQ) for uncomplicated vivax malaria was conducted in 3 district hospitals in Sabah, Malaysia. Primaquine was administered on day 28. The primary outcome was the cumulative risk of treatment failure by day 28 by Kaplan–Meier analysis.

A Randomized Comparison of Chloroquine Versus Dihydroartemisinin–Piperaquine for the Treatment of Plasmodium vivax Infection in Vietnam

April 12, 2016 - 16:34 -- Open Access
Phung Duc Thuan, Nguyen Thuy Nha Ca, Tran Tinh Hien, et al.
Am J Trop Med Hyg 2016 vol. 94 no. 4 879-885

All cases of recurrent parasitemia in the chloroquine arm occurred from day 33 onward, with corresponding whole blood chloroquine concentration lower than 100 ng/mL in all patients. Chloroquine thus remains efficacious for the treatment of P. vivax malaria in southern Vietnam, but DHA-PPQ provides more rapid symptomatic and parasitological recovery.

NOT Open Access | Quinoline-based antimalarial hybrid compounds

August 12, 2015 - 14:27 -- NOT Open Access
Stéphanie Vandekerckhove, Matthias D’hooghe
Bioorganic & Medicinal Chemistry, Volume 23, Issue 16, 15 August 2015, Pages 5098–5119

Quinoline-containing compounds, such as quinine and chloroquine, have a long-standing history as potent antimalarial agents.

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