Detection of atovaquone-proguanil resistance conferring mutations in Plasmodium falciparum cytochrome b gene in Luanda, Angola

Pimentel, Sónia; Nogueira, Fátima; Benchimol, Carla; Quinhentos, Vatúsia; Bom, Joana; Varandas, Luís; Rosário, Virgı́lio do; Bernardino, Luís

doi:10.1186/1475-2875-5-30

Cited by 17 publications

(6 citation statements)

References 26 publications

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“…[309][310][311] However, the prevalence of mutations of the cytochrome b gene that confer resistance to this combination in primary isolates seems to be lower than 1 %. [312][313][314] To shield the atovaquone/ proguanil combination from emerging resistance, it has been successfully combined with artesunate (42) for the treatment of uncomplicated malaria. [315] This combination was also used for the treatment of uncomplicated as well as recrudescent multiple-resistant malaria during pregnancy.…”

Section: Mechanism Of Action and Resistancementioning

confidence: 99%

Malaria Chemotherapeutics Part I: History of Antimalarial Drug Development, Currently Used Therapeutics, and Drugs in Clinical Development

2007

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Since ancient times, humankind has had to struggle against the persistent onslaught of pathogenic microorganisms. Nowadays, malaria is still the most important infectious disease worldwide. Considerable success in gaining control over malaria was achieved in the 1950s and 60s through landscaping measures, vector control with the insecticide DDT, and the widespread administration of chloroquine, the most important antimalarial agent ever. In the late 1960s, the final victory over malaria was believed to be within reach. However, the parasites could not be eradicated because they developed resistance against the most widely used and affordable drugs of that time. Today, cases of malaria infections are on the rise and have reached record numbers. This review gives a short description of the malaria disease, briefly addresses the history of antimalarial drug development, and focuses on drugs currently available for malaria therapy. The present knowledge regarding their mode of action and the mechanisms of resistance are explained, as are the attempts made by numerous research groups to overcome the resistance problem within classes of existing drugs and in some novel classes. Finally, this review covers all classes of antimalarials for which at least one drug candidate is in clinical development. Antimalarial agents that are solely in early development stages will be addressed in a separate review.

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Section: Mechanism Of Action and Resistancementioning

confidence: 99%

Malaria Chemotherapeutics Part I: History of Antimalarial Drug Development, Currently Used Therapeutics, and Drugs in Clinical Development

2007

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“… 46 Interestingly, the mutation at 268, which is commonly found in atovaquone-resistant field isolates, is also located in this binding pocket. 47 – 49 …”

Section: How Useful Has In Vitro Resistance Been?mentioning

confidence: 99%

In vitro selection of Plasmodium falciparum drug-resistant parasite lines

Nzila

Mwai

2009

Journal of Antimicrobial Chemotherapy

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The in vitro selection of antimicrobial resistance in important pathogens can provide critical information on the genetic basis of drug resistance, and such information can be used to predict, anticipate and even contain the spread of resistance in clinical practice. For instance, the discovery of the role of pfmdr1 in mefloquine resistance in malaria parasites resulted from in vitro studies. However, the in vitro selection of resistance is difficult, challenging and time consuming. In this review, we discuss the key parameters that impact on the efficiency of the in vitro selection of resistance, and propose strategies to improve and streamline this process.

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“…Because of these advantages, DBS sample cards have been used extensively in surveillance and epidemiological studies of malaria. For example, extraction and detection/sequencing of nucleic acid material from DBS have allowed for not only malaria detection in symptomatic and asymptomatic patients 4 – 6 but also speciation, 7 determination of parasite diversity, 8 identification of drug-resistant strains, 9 , 10 and evaluation of rapid diagnostic tests on a population level. 11 – 13 Dried blood spots have also been used for the detection of antimalarial antibodies for serology-based epidemiological studies.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Plasmodium Lactate Dehydrogenase and Histidine-Rich Protein 2 Clearance Patterns via Rapid On-Bead Detection from a Single Dried Blood Spot

Markwalter

Gibson

Mudenda

et al. 2018

The American Journal of Tropical Medicine and Hygiene

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Abstract.A rapid, on-bead enzyme-linked immunosorbent assay for Plasmodium lactate dehydrogenase (pLDH) and Plasmodium falciparum histidine-rich protein 2 (HRP2) was adapted for use with dried blood spot (DBS) samples. This assay detected both biomarkers from a single DBS sample with only 45 minutes of total incubation time and detection limits of 600 ± 500 pM (pLDH) and 69 ± 30 pM (HRP2), corresponding to 150 and 24 parasites/μL, respectively. This sensitive and reproducible on-bead detection method was used to quantify pLDH and HRP2 in patient DBS samples from rural Zambia collected at multiple time points after treatment. Biomarker clearance patterns relative to parasite clearance were determined; pLDH clearance followed closely with parasite clearance, whereas most patients maintained detectable levels of HRP2 for 35–52 days after treatment. Furthermore, weak-to-moderate correlations between biomarker concentration and parasite densities were found for both biomarkers. This work demonstrates the utility of the developed assay for epidemiological study and surveillance of malaria.

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Detection of atovaquone-proguanil resistance conferring mutations in Plasmodium falciparum cytochrome b gene in Luanda, Angola

Cited by 17 publications

References 26 publications

Malaria Chemotherapeutics Part I: History of Antimalarial Drug Development, Currently Used Therapeutics, and Drugs in Clinical Development

Malaria Chemotherapeutics Part I: History of Antimalarial Drug Development, Currently Used Therapeutics, and Drugs in Clinical Development

In vitro selection of Plasmodium falciparum drug-resistant parasite lines

Characterization of Plasmodium Lactate Dehydrogenase and Histidine-Rich Protein 2 Clearance Patterns via Rapid On-Bead Detection from a Single Dried Blood Spot

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