Artemisinin resistance: current status and scenarios for containment

Dondorp, Arjen M.; Yeung, Shunmay; White, Lisa J.; Nguon, Chea; Day, Nicholas P. J.; Socheat, Duong; Seidlein, Lorenz von

doi:10.1038/nrmicro2331

Cited by 499 publications

(431 citation statements)

References 60 publications

Supporting

Mentioning

425

Contrasting

Unclassified

Order By: Relevance

“…2 This may accelerate the pace of development of drug resistance, 3 thus making it important to maintain high adherence rates to preserve the efficacy of artemisinin-based combination therapy (ACT) in Africa and elsewhere. 4 Adherence levels as high as 90% have been reported in controlled clinical trials. 5,6 These figures are likely to be an overestimation because in real-life situations caretakers are neither given detailed instruction on to how to administer the treatment nor do they receive follow-up on the use of the drugs by the child.…”

Section: Introductionmentioning

confidence: 99%

Adherence to artemether/lumefantrine treatment in children under real-life situations in rural Tanzania

Simba

Kakoko

Tomson

et al. 2012

Transactions of the Royal Society of Tropical Medicine and Hygi

View full text Add to dashboard Cite

a b s t r a c tA follow-up study was conducted to determine the magnitude of and factors related to adherence to artemether/lumefantrine (ALu) treatment in rural settings in Tanzania. Children in five villages of Kilosa District treated at health facilities were followed-up at their homes on Day 7 after the first dose of ALu. For those found to be positive using a rapid diagnostic test for malaria and treated with ALu, their caretakers were interviewed on drug administration habits. In addition, capillary blood samples were collected on Day 7 to determine lumefantrine concentrations. The majority of children (392/444; 88.3%) were reported to have received all doses, in time. Non-adherence was due to untimeliness rather than missing doses and was highest for the last two doses. No significant difference was found between blood lumefantrine concentrations among adherent (median 286 nmol/l) and nonadherent [median 261 nmol/l; range 25 nmol/l (limit of quantification) to 9318 nmol/l]. Children from less poor households were more likely to adhere to therapy than the poor [odds ratio (OR) = 2.45, 95% CI 1.35-4.45; adjusted OR = 2.23, 95% CI 1.20-4.13]. The high reported rate of adherence to ALu in rural areas is encouraging and needs to be preserved to reduce the risk of emergence of resistant strains. The age-based dosage schedule and lack of adherence to ALu treatment guidelines by health facility staff may explain both the huge variability in observed lumefantrine concentrations and the lack of difference in concentrations between the two groups.

show abstract

Section: Introductionmentioning

confidence: 99%

Adherence to artemether/lumefantrine treatment in children under real-life situations in rural Tanzania

Simba

Kakoko

Tomson

et al. 2012

Transactions of the Royal Society of Tropical Medicine and Hygi

View full text Add to dashboard Cite

show abstract

“…Although high-grade resistance has not yet been seen in southeast Asia, the artemisinin-resistant phenotype (delayed parasite clearance and treatment failure after several weeks) has been confirmed in several locations. 21,22 In the past, high-grade parasite resistance has often been used interchangeably for both the parasite phenotype, as characterised in vitro by its confirmed ability to survive a threshold concentration of the drug in standard conditions of continuous culture, and in reference to therapeutic failure after the administration of a standard dose of a drug. Therapeutic failure is used in the WHO standard in-vivo test protocol.…”

Section: Parasite Resistancementioning

confidence: 99%

“…68 Tolerance, and now resistance, has been confirmed for the artemisinin class of drugs in southeast Asia. 21,22 WHO recommends that 10% of patients remaining parasite-positive after 3 days should serve as a definition for suspected resistance. 25 A review 69 of parasite-clearance data (from more than 18 000 clinical trial patients), mostly from southeast Asia, suggests that the expected frequency of parasite positivity at 72 h after treatment with a 3 day artemisinin-based combination therapy regimen in patients with initial parasitaemia between 10 000 and 100 000 per μL of blood is less than 3%.…”

Section: Early Warning and Investigationmentioning

confidence: 99%

See 1 more Smart Citation

Mitigating the threat of artemisinin resistance in Africa: improvement of drug-resistance surveillance and response systems

Talisuna

Karema

Ogutu

et al. 2012

The Lancet Infectious Diseases

View full text Add to dashboard Cite

Artemisinin-resistant Plasmodium falciparum malaria has emerged in western Cambodia and has been detected in western Thailand. The situation is ominously reminiscent of the emergence of resistance to chloroquine and to sulfadoxine-pyrimethamine several decades ago. Artemisinin resistance is a major threat to global public health, with the most severe potential effects in subSaharan Africa, where the disease burden is highest and systems for monitoring and containment of resistance are inadequate. The mechanisms that underlie artemisinin resistance are not fully understood. The main phenotypic trait associated with resistance is a substantial delay in parasite clearance, so far reported in southeast Asia but not in Africa. One of the pillars of the WHO global plan for artemisinin resistance containment is to increase monitoring and surveillance. In this Personal View, we propose strategies that should be adopted by malaria-endemic countries in Africa: resource mobilisation to reactivate regional surveillance networks, establishment of baseline parasite clearance profiles to serve as benchmarks to track emerging artemisinin resistance, improved data sharing to allow pooled analyses to identify rare events, modelling of risk factors for drug resistance, and development and validation of new approaches to monitor resistance.

show abstract

“…Además, los medicamentos antipalúdicos como los derivados de la artemisinina y la quinina, se sintetizaron a partir de compuestos aislados de plantas (7). Recientemente, se ha reportado resistencia a las artemisininas, lo cual constituye una seria amenaza para la salud, dado que en ella se basan los esquemas de tratamiento para el paludismo no complicado por P. falciparum (8).…”

unclassified

Evaluación del efecto citotóxico y del daño genético de extractos estandarizados de Solanum nudum con actividad antiplasmodial

García-Huertas

Pabón

Arias³

et al. 2012

biomedica

View full text Add to dashboard Cite

Contribución de los autores:Paola García diseñó la investigación, realizó las pruebas experimentales, tabuló los datos, analizó los resultados obtenidos y redactó el manuscrito. Adriana Pabón asesoró las pruebas de actividad anti-Plasmodium y análisis de los resultados, y participó en la corrección del manuscrito. Carlos Arias Londoño cuantificó las sustancias rastreadoras en los extractos estandarizados. Silvia Blair participó en el diseño de la investigación y en la supervisión del desarrollo de la misma; revisó y corrigió el artículo de investigación. ARTÍCULO ORIGINAL Biomédica 2013;33:78-87 doi: http://dx.doi.org/10.7705/biomedica.v33i1.838 Evaluación del efecto citotóxico y del daño genético de extractos estandarizados de Solanum nudum con actividad anti-Plasmodium Introducción. La planta Solanum nudum es ampliamente usada en la medicina tradicional del Pacífico colombiano para tratar las fiebres y la malaria, o paludismo, y se ha convertido en una fuente de nuevas moléculas promisorias. Objetivo. Evaluar el efecto citotóxico y daño genético de extractos estandarizados de S. nudum en diferentes modelos celulares. Materiales y métodos. A 66 extractos estandarizados de S. nudum se les evaluó la actividad antiPlasmodium in vitro en dos cepas de Plasmodium falciparum, una sensible (NF54) y otra resistente (FCB2) a la cloroquina, y la citotoxicidad en células U937 y HepG2. Se seleccionaron los extractos que presentaron actividad anti-Plasmodium y baja toxicidad, y se les estimó su efecto hemolítico en eritrocitos sanos O + , el efecto mutagénico en las cepas TA98 y TA100 de Salmonella Typhimurium y el efecto genotóxico en células U937. Resultados. Se seleccionaron cinco extractos como promisorios (28MA1, 29MA1, 51MA1, 55MA1 y 61MA1), los cuales fueron activos en las cepas de P. falciparum con concentración inhibitoria 50 (CI 50 ) entre 9,8 y 54,8 µg/ml. El extracto 29MA1 fue el más selectivo para Plasmodium, con índice de selectividad de 4,4 y 14,5 para las células U937 y HepG2, respectivamente. En ningún extracto se observó efecto hemolítico a 250 µg/ml, no causaron mutaciones en las cepas TA98 y TA100 de S. Typhimurium, ni generaron efectos genotóxicos en células U937. Conclusiones. La utilización de extractos estandarizados de S. nudum contribuye con los trabajos encaminados al desarrollo de una nueva formulación farmacéutica para tratar la malaria a partir de productos naturales.Palabras clave: Solanum/toxicidad, Plasmodium falciparum, malaria/terapia, extractos vegetales, seguridad. doi: http://dx.doi.org/10.7705/biomedica.v33i1.838Evaluation of cytotoxic effect and genetic damage of standardized extracts of Solanum nudum with antiplasmodial activity Introduction. The plant Solanum nudum (Solanaceae) is extensively used for the treatment of malariarelated symptoms in traditional medicine practices in the Colombian Pacific. Recently, it has become a significant source of promising new molecules for developing a pharmaceutical malaria treatment. Objective. This research aimed to evaluate the cytotoxic ...

show abstract

Artemisinin resistance: current status and scenarios for containment

Cited by 499 publications

References 60 publications

Adherence to artemether/lumefantrine treatment in children under real-life situations in rural Tanzania

Adherence to artemether/lumefantrine treatment in children under real-life situations in rural Tanzania

Mitigating the threat of artemisinin resistance in Africa: improvement of drug-resistance surveillance and response systems

Evaluación del efecto citotóxico y del daño genético de extractos estandarizados de Solanum nudum con actividad antiplasmodial

Contact Info

Product

Resources

About