scholarly journals Multinormal In Vitro Distribution Model Suitable for the Distribution of Plasmodium falciparum Chemosusceptibility to Doxycycline

2008 ◽  
Vol 53 (2) ◽  
pp. 688-695 ◽  
Author(s):  
Sébastien Briolant ◽  
Meili Baragatti ◽  
Philippe Parola ◽  
Fabrice Simon ◽  
Adama Tall ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Normal Distribution ◽  
Geometric Mean ◽  
Distribution Model ◽  
Bayesian Mixture ◽  
Republic Of The Congo ◽  
Component C ◽  
Bayesian Mixture Modeling ◽  
Mixture Modeling Approach

ABSTRACT The distribution and range of 50% inhibitory concentrations (IC50s) of doxycycline were determined for 747 isolates obtained between 1997 and 2006 from patients living in Senegal, Republic of the Congo, and Gabon and patients hospitalized in France for imported malaria. The statistical analysis was designed to answer the specific question of whether Plasmodium falciparum has different phenotypes of susceptibility to doxycycline. A triple normal distribution was fitted to the data using a Bayesian mixture modeling approach. The IC50 geometric mean ranged from 6.2 μM to 11.1 μM according to the geographical origin, with a mean of 9.3 μM for all 747 parasites. The values for all 747 isolates were classified into three components: component A, with an IC50 mean of 4.9 μM (±2.1 μM [standard deviation]); component B, with an IC50 mean of 7.7 μM (±1.2 μM); and component C, with an IC50 mean of 17.9 μM (±1.4 μM). According to the origin of the P. falciparum isolates, the triple normal distribution was found in each subgroup. However, the proportion of isolates predicted to belong to component B was most important in isolates from Gabon and Congo and in isolates imported from Africa (from 46 to 56%). In Senegal, 55% of the P. falciparum isolates were predicted to be classified as component C. The cutoff of reduced susceptibility to doxycycline in vitro was estimated to be 35 μM.

Drug sensitivity of Plasmodium falciparum field isolates to selected antimalarial drugs in Ghana using the in-vitro DAPI assay

2020 ◽  
Author(s):  
Michael Fokuo Ofori ◽  
Emma E. Kploanyi ◽  
Benedicta A. Mensah ◽  
Emmanuel K. Dickson ◽  
Eric Kyei Baafour ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Drug Sensitivity ◽  
Geometric Mean ◽  
Antimalarial Drugs ◽  
Chloroquine Resistance ◽  
Cape Coast ◽  
African Region ◽  
Cross Sectional ◽  
Ecological Zones

Abstract Background: Malaria continues to be a major health issue globally with nine out of ten cases reported in Africa. Although the current artemisinin derived combination therapies in Ghana are still efficacious against the Plasmodium falciparum parasite, compounding evidence of artemisinin and amodiaquine resistance in the African region establish the need for a full, up-to-date understanding and monitoring of antimalarial resistance to provide evidence for planning control strategies.Methods: The study was cross-sectional and was conducted during the peak transmission seasons of 2015, 2016, and 2017 in two study sites located in different ecological zones of Ghana involving children aged 0.5-14 years presenting with symptomatic uncomplicated Plasmodium falciparum (Pf) malaria with parasitaemia greater than 1000 parasites/µl of blood. Using in vitro 4-,6-diamidino-2-phenylindole (DAPI) drug sensitivity assays, 328 Pf parasites collected were used to investigate susceptibility to five selected antimalarial drugs: chloroquine, amodiaquine, dihydroartemisinin, artesunate and mefloquine.Results: The geometric mean B (GMIC50) of five drugs against the parasites collected from Cape Coast were 9.6, 23.6, 9.1, 3.5 and 8.1nM for chloroquine, amodiaquine, artemisinin, artesunate, and mefloquine respectively in 2015. There was a 2 fold increase in the GMIC50 levels of all the drugs against the isolates collected in 2016 as compared to the 2015 data from Cape Coast .The a of the five drugs against the parasites collected from Cape Coast were significantly higher than those isolates collected from Begoro in 2016 and 2017 (P<0.001) . The chloroquine resistance ranged between 1.9% and 9.1% among isolates collected from Cape Coast but remained 0% in Begoro over the period. High amodiaquine resistance levels were recorded at both sites whilst that of artesunate resistance ranged between 4 and 10% over the study period.Conclusions: The study has assessed the antimalarial drug sensitivities of Ghanaian Pf isolates collected over 3 consecutive years. The parasites showed variable resistance levels to all the drugs used over the period. The study has demonstrated the continual return of chloroquine-sensitive parasites. The in vitro DAPI assay is a useful method for monitoring individual drugs used in combinations in Ghana for the generation of data on their sensitivities over time.

Baseline and multinormal distribution of ex vivo susceptibilities of Plasmodium falciparum to methylene blue in Africa, 2013–18

2020 ◽  
Author(s):  
Mathieu Gendrot ◽  
Marylin Madamet ◽  
Joel Mosnier ◽  
Isabelle Fonta ◽  
Rémy Amalvict ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Plasmodium Falciparum ◽  
Ex Vivo ◽  
Geometric Mean ◽  
Threshold Value ◽  
Effective Concentration ◽  
In Vitro Activity ◽  
Potential Partner ◽  
Median Effective Concentration

Abstract Background Plasmodium falciparum resistance to most antimalarial compounds has emerged in Southeast Asia and spread to Africa. In this context, the development of new antimalarial drugs is urgent. Objectives To determine the baseline in vitro activity of methylene blue (Proveblue®) on African isolates and to determine whether parasites have different phenotypes of susceptibility to methylene blue. Methods Ex vivo susceptibility to methylene blue was measured for 609 P. falciparum isolates of patients hospitalized in France for malaria imported from Africa. A Bayesian statistical analysis was designed to describe the distribution of median effective concentration (EC50) estimates. Results The EC50 ranged from 0.16 to 87.2 nM with a geometric mean of 7.17 nM (95% CI = 6.21–8.13). The 609 EC50 values were categorized into four components: A (mean = 2.5 nM; 95% CI = 2.28–2.72), B (mean = 7.44 nM; 95% CI = 7.07–7.81), C (mean = 16.29 nM; 95% CI = 15.40–17.18) and D (mean = 38.49 nM; 95% CI = 34.14–42.84). The threshold value for in vitro reduced susceptibility to methylene blue was estimated at 35 nM using the geometric mean of EC50 plus 2 SDs of the 609 isolates. This cut-off also corresponds to the lower limit of the 95% CI of the methylene blue EC50 of component D. Thirty-five isolates (5.7%) displayed EC50 values above this threshold. Conclusions Methylene blue exerts a promising efficacy against P. falciparum and is a potential partner for triple combinations.

scholarly journals Iron chelation with desferrioxamine B in adults with asymptomatic Plasmodium falciparum parasitemia [see comments]

Blood ◽  
1992 ◽  
Vol 79 (2) ◽  
pp. 308-312 ◽  
Author(s):  
VR Gordeuk ◽  
PE Thuma ◽  
GM Brittenham ◽  
S Zulu ◽  
G Simwanza ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Geometric Mean ◽  
Iron Chelation ◽  
Parasite Clearance ◽  
Placebo Treatment ◽  
Iron Complex ◽  
Double Blind ◽  
Blood Concentrations ◽  
Desferrioxamine B

Abstract To determine if iron chelation therapy has activity against human malaria, we administered desferrioxamine B in amounts of 100 mg/kg per day by continuous 72-hour subcutaneous infusions to 28 volunteers with asymptomatic Plasmodium falciparum infection in a randomized, double- blind, placebo-controlled crossover trial. Peripheral blood concentrations of P falciparum ring forms were determined at 12-hour intervals in all subjects and serum concentrations of desferrioxamine B + ferrioxamine (the iron complex of desferrioxamine B) were measured in 26 subjects. Geometric mean concentrations of asexual intraerythrocytic parasites decreased with both chelator and placebo treatment, but the decrement with desferrioxamine B was significantly greater than that with placebo (P less than .006) during both the initial and crossover periods. Compared with placebo, desferrioxamine B treatment was associated with an almost 10-fold enhancement of the rate of parasite clearance during both phases of the trial (P less than .007). Mean +/- SEM steady state concentrations of desferrioxamine B + ferrioxamine were 6.90 +/- 0.60 mumol/L at 36 hours and 7.72 +/- 0.68 mumol/L at 72 hours; in vitro, the ID50 has been reported to be approximately 4 to 20 mumol/L. No drug toxicity was detected. Parasitemia recurred in 19 of 24 participants followed-up over 1 to 6 months. We conclude that desferrioxamine B enhances the clearance of P falciparum parasitemia and that iron chelation may provide a new strategy to be developed for the treatment of malaria.

scholarly journals In Vitro Activity of Lumefantrine (Benflumetol) against Clinical Isolates of Plasmodium falciparum in Yaoundé, Cameroon

1998 ◽  
Vol 42 (9) ◽  
pp. 2347-2351 ◽  
Author(s):  
Leonardo K. Basco ◽  
Jean Bickii ◽  
Pascal Ringwald
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Activity ◽  
Geometric Mean ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Cross Resistance ◽  
In Vitro Activity ◽  
Antimalarial Agents ◽  
Fluorene Derivative

ABSTRACT The in vitro antimalarial activity of the new Chinese synthetic drug, lumefantrine, also known as benflumetol (a fluorene derivative belonging to the aminoalcohol class), was determined by an isotopic microtest against 61 fresh clinical isolates of Plasmodium falciparum and compared with that of other established antimalarial agents. The geometric mean 50% inhibitory concentration of lumefantrine was 11.9 nmol/liter (95% confidence intervals, 10.4 to 13.6 nmol/liter; range, 3.3 to 25.6 nmol/liter). The in vitro activities of lumefantrine against the chloroquine-sensitive and the chloroquine-resistant isolates did not differ (P > 0.05). There was a significant positive correlation of responses between lumefantrine and two other aminoalcohols studied, mefloquine (r = 0.688) and halofantrine (r = 0.677), and between lumefantrine and artesunate (r = 0.420), suggesting a potential for in vitro cross-resistance. Our data suggest high in vitro activity of lumefantrine, comparable to that of mefloquine, and are in agreement with the promising results of preliminary clinical trials.

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