Publications by authors named "Rotha Eam"
Indigenous emergence and spread of C469Y artemisinin-resistant in Uganda.
Antimicrob Agents Chemother
August 2024
Article Synopsis
- Artemisinin-based combination therapies (ACTs) have been the standard treatment for uncomplicated malaria in Africa for nearly 20 years, but recent studies indicate an increase in mutant parasites linked to reduced treatment effectiveness.
- The Community Access to Rectal Artesunate for Malaria project studied 697 children with severe malaria in northern Uganda, finding that a significant mutation (C469Y) was more common after the introduction of rectal artesunate, suggesting it enhances resistance.
- Genome analysis revealed that the C469Y mutation has an indigenous African origin and confirmed that parasites with this mutation show significantly reduced susceptibility to artemisinin, highlighting the urgent need for ongoing monitoring and adherence to treatment protocols to combat the rise of resistant strains.
Background: In early 2016, in Preah Vihear, Northern Cambodia, artesunate/mefloquine was used to cope with dihydroartemisinin/piperaquine-resistant Plasmodium falciparum parasites. Following this policy, P. falciparum strains harbouring molecular markers associated with artemisinin, piperaquine and mefloquine resistance have emerged.
View Article and Find Full Text PDFBackground: Artesunate-amodiaquine is a potential therapy for uncomplicated malaria in Cambodia.
Methods: Between September 2016 and January 2017, artesunate-amodiaquine efficacy and safety were evaluated in a prospective, open-label, single-arm observational study at health centers in Mondulkiri, Pursat, and Siem Reap Provinces, Cambodia. Adults and children with microscopically confirmed Plasmodium falciparum malaria received oral artesunate-amodiaquine once daily for 3 days plus single-dose primaquine, with follow-up on days 7, 14, 21, and 28.
Background: Cambodia is the epicentre of resistance emergence for virtually all antimalarial drugs. Selection and spread of parasites resistant to artemisinin-based combination therapy (ACT) is a major threat for malaria elimination, hence the need to renew the pool of effective treatments.
Objectives: To determine whether ACT resistance haplotypes could have an effect on ferroquine in vitro antimalarial activity.
Background: Given the risk of artemisinin resistance spreading from the Greater Mekong sub-region, prospective monitoring in sub-Saharan Africa should be expedited. Molecular biology techniques used for monitoring rely on the detection of k13 validated mutants by using PCR and Sanger sequencing approach, usually not available in malaria endemic areas.
Methods: A semi-automated workflow based on the easyMAG platform and the Argene Solution (bioMérieux, Marcy l'Etoile, France) as a field-based surveillance tool operable at national level was developed in four steps.
Background: In the frame of elimination strategies of Plasmodium falciparum (Pf), active case detection has been recommended as complementary approach to the existing passive case detection programs. We trialed a polymerase chain reaction (PCR)-based active detection strategy targeting asymptomatic individuals, named proactive case detection (PACD), with the aim of assessing its feasibility, the extra yield of Pf infections, and the at-risk population for Pf carriage status.
Methods: A pilot of PACD was conducted in 3 villages in Chey Saen district (Preah Vihear province, Cambodia), from December 2015 to March 2016.
Background: Western Cambodia is the epicentre of Plasmodium falciparum multidrug resistance and is facing high rates of dihydroartemisinin-piperaquine treatment failures. Genetic tools to detect the multidrug-resistant parasites are needed. Artemisinin resistance can be tracked using the K13 molecular marker, but no marker exists for piperaquine resistance.
View Article and Find Full Text PDFBackground: Recent gains in reducing the global burden of malaria are threatened by the emergence of Plasmodium falciparum resistance to artemisinins. The discovery that mutations in portions of a P. falciparum gene encoding kelch (K13)-propeller domains are the major determinant of resistance has provided opportunities for monitoring such resistance on a global scale.
View Article and Find Full Text PDFBackground: The declining efficacy of dihydroartemisinin-piperaquine against Plasmodium falciparum in Cambodia, along with increasing numbers of recrudescent cases, suggests resistance to both artemisinin and piperaquine. Available in vitro piperaquine susceptibility assays do not correlate with treatment outcome. A novel assay using a pharmacologically relevant piperaquine dose/time exposure was designed and its relevance explored in retrospective and prospective studies.
View Article and Find Full Text PDFArticle Synopsis
- There is a need for better ways to detect low levels of malaria in people who don’t show symptoms, particularly due to limitations in current testing methods.
- A study compared the effectiveness of a PCR assay using dried blood spots (5 μL) against various volumes of venous blood (50 μL, 200 μL, and 1 mL) to identify malaria parasites.
- The results indicated that larger blood samples were better at detecting malaria, with 27% of cases missed by the dried blood spot method, particularly P. vivax cases, suggesting that testing strategies need to be improved for effective malaria elimination.
Background: To achieve the goal of malaria elimination in low transmission areas such as in Cambodia, new, inexpensive, high-throughput diagnostic tools for identifying very low parasite densities in asymptomatic carriers are required. This will enable a switch from passive to active malaria case detection in the field.
Methods: DNA extraction and real-time PCR assays were implemented in an "in-house" designed mobile laboratory allowing implementation of a robust, sensitive and rapid malaria diagnostic strategy in the field.