scholarly journals Amodiaquine Resistance in Plasmodium falciparum Malaria in Afghanistan Is Associated with the pfcrt SVMNT Allele at Codons 72 to 76

2010 ◽  
Vol 54 (9) ◽  
pp. 3714-3716 ◽  
Author(s):  
Khalid Beshir ◽  
Colin J. Sutherland ◽  
Ioannis Merinopoulos ◽  
Naeem Durrani ◽  
Toby Leslie ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Novel Mutation ◽  
Plasmodium Falciparum Malaria ◽  
Codon 72 ◽  
Before And After

ABSTRACT Mutations in the Plasmodium falciparum genes pfcrt and pfmdr1 are selected by amodiaquine treatment in Africa. To examine the importance of these mutations in amodiaquine-treated Asian parasites, we determined pre- and posttreatment genotypes for amodiaquine treatment failures from a clinical trial in Afghanistan. The pfcrt codon 72 to 76 haplotype SVMNT was present in all samples tested, both before and after treatment. Amodiaquine did not clearly select for any pfmdr1 genotype, but a novel mutation, pfmdr1 N86F, was detected in four samples. We provide in vivo data to support the in vitro correlation between pfcrt SVMNT and increased resistance to the metabolite of amodiaquine.

scholarly journals A randomized clinical trial with high dose of chloroquine for treatment of Plasmodium falciparum malaria in Brazil

1992 ◽  
Vol 34 (5) ◽  
pp. 467-473 ◽  
Author(s):  
João Guimarães de Andrade ◽  
Ana Lúcia Sampaio Sgambatti de Andrade ◽  
Elisabeth S. O. Araujo ◽  
Renato Maurício Oliveira ◽  
Simonne Almeida Silva ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Plasmodium Falciparum ◽  
Side Effects ◽  
Falciparum Malaria ◽  
Amazon Basin ◽  
Geometric Mean ◽  
Plasmodium Falciparum Malaria ◽  
High Dose ◽  
First Choice

This clinical trial compared parasitological efficacy, levels of in vivo resistance and side effects of oral chloroquine 25 mg/Kg and 50 mg/Kg in 3 days treatment in Plasmodium falciparum malaria with an extended followed-up of 30 days. The study enroled 58 patients in the 25 mg/Kg group and 66 in the 50 mg/Kg group. All eligible subjects were over 14 years of age and came from Amazon Basin and Central Brazil during the period of August 1989 to April 1991. The cure rate in the 50 mg/Kg group was 89.4% on day 7 and 71.2% on day 14 compared to 44.8% and 24.1% in the 25 mg/Kg group. 74.1% of the patients in the 25 mg/Kg group and 48.4% of the patients in the 50 mg/Kg group had detectable parasitaemia at the day 30. However, there was a decrease of the geometric mean parasite density in both groups specially in the 50 mg/Kg group. There was 24.1% of RIII and 13.8% of RH in the 25 mg/Kg group. Side effects were found to be minimum in both groups. The present data support that there was a high level resistance to chloroquine in both groups, and the high dose regimen only delayed the development of resistance and its administration should not be recommended as first choice in malaria P. falciparum therapy in Brazil.

IN-VIVO AND IN-VITRO ASSESSMENT OF CHLOROQUINE-RESISTANT PLASMODIUM FALCIPARUM MALARIA IN ZANZIBAR

The Lancet ◽  
1983 ◽  
Vol 321 (8332) ◽  
pp. 1003-1005 ◽  
Author(s):  
IraK. Schwartz ◽  
CarlosC. Campbell ◽  
David Payne ◽  
Omar Juma Khatib
Keyword(s):  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Plasmodium Falciparum Malaria ◽  
In Vitro Assessment

scholarly journals Antigenicity of the infected-erythrocyte and merozoite surfaces in Falciparum malaria.

1979 ◽  
Vol 150 (5) ◽  
pp. 1241-1254 ◽  
Author(s):  
S G Langreth ◽  
R T Reese
Keyword(s):  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Infected Erythrocyte ◽  
Falciparum Infection ◽  
Human Erythrocytes ◽  
Cross Linking ◽  
Common Antigens

The antigenicity of altered structures induced by Plasmodium falciparum in the membranes of infected Aotus monkey and human erythrocytes was examined. Antisera were obtained from monkeys made immune to malaria. Bound antibodies were shown to be localized on the knob protrusions of infected erythrocytes of both human and monkey origin and from both in vitro and in vivo infections. Therefore, P. falciparum infection has produced similar antigenic changes in the erythrocyte surfaces of both man and monkey. Uninfected erythrocytes and all knobless-infected erythrocytes bound no antibody from immune sera. Strains of P. falciparum from widely different geographic areas that were cultured in vitro in human erythrocytes induced structures (knobs) which have common antigenicity. Merozoites were agglutinated by cross-linking of their cell coats when incubated with immune sera. The binding of ferritin-labeled antibody was heavy on the coats of both homologous and heterologous strains of the parasite, indicating that the merozoite surfaces of these strains share common antigens.

scholarly journals Phase I Clinical Trial of a Recombinant Blood Stage Vaccine Candidate for Plasmodium falciparum Malaria Based on MSP1 and EBA175

PLoS ONE ◽  
2015 ◽  
Vol 10 (4) ◽  
pp. e0117820 ◽  
Author(s):  
Chetan E. Chitnis ◽  
Paushali Mukherjee ◽  
Shantanu Mehta ◽  
Syed Shams Yazdani ◽  
Shikha Dhawan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Plasmodium Falciparum ◽  
Phase I ◽  
Falciparum Malaria ◽  
Vaccine Candidate ◽  
Plasmodium Falciparum Malaria ◽  
Blood Stage ◽  
Phase I Clinical Trial

Efficacy of dihydroartemisinin/piperaquine in patients with non-complicated Plasmodium falciparum malaria in Yaoundé, Cameroon

2021 ◽  
Author(s):  
Mélissa Mairet-Khedim ◽  
Sandrine Nsango ◽  
Christelle Ngou ◽  
Sandie Menard ◽  
Camille Roesch ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Southeast Asia ◽  
Falciparum Malaria ◽  
Gene Polymorphisms ◽  
Plasmodium Falciparum Malaria ◽  
Molecular Profile ◽  
Uncomplicated Plasmodium Falciparum Malaria ◽  
In Vitro Survival ◽  
Phenotypic Susceptibility

Abstract Background Dihydroartemisinin/piperaquine is increasingly used for the treatment of uncomplicated Plasmodium falciparum malaria in Africa. The efficacy of this combination in Cameroon is poorly documented, while resistance to dihydroartemisinin/piperaquine readily spreads in Southeast Asia. Objectives This study evaluated the clinical efficacy of dihydroartemisinin/piperaquine in Cameroon, as well as the molecular profile and phenotypic susceptibility of collected isolates to dihydroartemisinin and piperaquine. Patients and methods Dihydroartemisinin/piperaquine efficacy in 42 days was followed-up for 138 patients presenting non-complicated falciparum malaria. Piperaquine concentration was determined at day 7 for 124 patients. kelch13 gene polymorphisms (n = 150) and plasmepsin2 gene amplification (n = 148) were determined as molecular markers of resistance to dihydroartemisinin and piperaquine, respectively. Parasite susceptibility to dihydroartemisinin and piperaquine was determined using validated in vitro survival assays. Results The efficacy of dihydroartemisinin/piperaquine treatment was 100% after PCR correction. The reinfections were not associated with a variation of piperaquine concentration at day 7. Ninety-six percent (144/150) of the samples presented a WT allele of the kelch13 gene. Two percent (3/150) presented the non-synonymous mutation A578S, which is not associated with resistance to dihydroartemisinin. No duplication of the plasmepsin2 gene was observed (0/148). All the samples tested in vitro by survival assays (n = 87) were susceptible to dihydroartemisinin and piperaquine. Conclusions Dihydroartemisinin/piperaquine has demonstrated excellent therapeutic efficacy with no evidence of emerging artemisinin or piperaquine resistance in Yaoundé, Cameroon. This observation suggests that dihydroartemisinin/piperaquine could be a sustainable therapeutic solution for P. falciparum malaria if implemented in areas previously free of artemisinin- and piperaquine-resistant parasites, unlike Southeast Asia.

scholarly journals Correction: Phase I Clinical Trial of a Recombinant Blood Stage Vaccine Candidate for Plasmodium falciparum Malaria Based on MSP1 and EBA175

PLoS ONE ◽  
2015 ◽  
Vol 10 (9) ◽  
pp. e0137816 ◽  
Author(s):  
Chetan E. Chitnis ◽  
Paushali Mukherjee ◽  
Shantanu Mehta ◽  
Syed Shams Yazdani ◽  
Shikha Dhawan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Plasmodium Falciparum ◽  
Phase I ◽  
Falciparum Malaria ◽  
Vaccine Candidate ◽  
Plasmodium Falciparum Malaria ◽  
Blood Stage ◽  
Phase I Clinical Trial ◽  
Correction Phase
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