Evaluation of an electronic clinical decision support algorithm to improve primary care management of acute febrile illness in rural Cambodia: protocol for a cluster-randomised trial.

Introduction: Acute febrile illness (AFI), traditionally attributed to malaria, is a common reason for seeking primary healthcare in rural South and Southeast Asia. However, malaria transmission has declined while health workers are often poorly equipped to manage non-malarial AFIs. This results in indiscriminate antibiotic prescribing and care escalation, which promotes antibiotic resistance and may increase healthcare costs.

Intermittent preventive treatment for forest goers by forest malaria workers: an observational study on a key intervention for malaria elimination in Cambodia.

Background: Cambodia targets malaria elimination by 2023 and all human malaria species by 2025, aligning with WHO's Mekong Malaria Elimination program. The Intermittent Preventive Treatment for Forest Goers (IPTf) project aimed at forest-specific malaria elimination. The study aims to pinpoint the main factors driving malaria transmission in Cambodian forests and evaluate the initial implementation and effectiveness of IPTf in accelerating the elimination of malaria by treating and preventing infections among at-risk populations in these areas.

Triple therapy with artemether-lumefantrine plus amodiaquine versus artemether-lumefantrine alone for artemisinin-resistant, uncomplicated falciparum malaria: an open-label, randomised, multicentre trial.

Background: Late treatment failures after artemisinin-based combination therapies (ACTs) for falciparum malaria have increased in the Greater Mekong subregion in southeast Asia. Addition of amodiaquine to artemether-lumefantrine could provide an efficacious treatment for multidrug-resistant infections.

Methods: We conducted an open-label, randomised trial at five hospitals or health centres in three locations (western Cambodia, eastern Cambodia, and Vietnam).

Choosing interventions to eliminate forest malaria: preliminary results of two operational research studies inside Cambodian forests.

Background: Rapid elimination of Plasmodium falciparum malaria in Cambodia is a goal with both national and international significance. Transmission of malaria in Cambodia is limited to forest environments, and the main population at risk consists of forest-goers who rely on forest products for income or sustenance. The ideal interventions to eliminate malaria from this population are unknown.

Engaging ethnic minority communities through performance and arts: health education in Cambodian forest villages.

Background: In Siem Pang, northeastern Cambodia, malaria transmission persists in remote forested areas populated by ethnic minorities. Engaging affected communities in health education campaigns is challenging due to language, access and literacy constraints. During 2018, a newly established medical research station conducted a health education programme in local villages harnessing traditional songs, arts and crafts, along with theatre, comedy and health talks and quizzes.

Molecular epidemiology of resistance to antimalarial drugs in the Greater Mekong subregion: an observational study.

Background: The Greater Mekong subregion is a recurrent source of antimalarial drug resistance in Plasmodium falciparum malaria. This study aimed to characterise the extent and spread of resistance across this entire region between 2007 and 2018.

Methods: P falciparum isolates from Myanmar, Thailand, Laos, and Cambodia were obtained from clinical trials and epidemiological studies done between Jan 1, 2007, and Dec 31, 2018, and were genotyped for molecular markers (pfkelch, pfcrt, pfplasmepsin2, and pfmdr1) of antimalarial drug resistance.

Tools to accelerate falciparum malaria elimination in Cambodia: a meeting report.

Cambodia targets malaria elimination by 2025. Rapid elimination will depend on successfully identifying and clearing malaria foci linked to forests. Expanding and maintaining universal access to early diagnosis and effective treatment remains the key to malaria control and ultimately malaria elimination in the Greater Mekong Subregion (GMS) in the foreseeable future.

Mass drug administrations with dihydroartemisinin-piperaquine and single low dose primaquine to eliminate Plasmodium falciparum have only a transient impact on Plasmodium vivax: Findings from randomised controlled trials.

Background: Mass administrations of antimalarial drugs (MDA) have reduced the incidence and prevalence of P. falciparum infections in a trial in the Greater Mekong Subregion. Here we assess the impact of the MDA on P.

Forest work and its implications for malaria elimination: a qualitative study.

Background: Over the last 20 years, malaria incidence has decreased across the Greater Mekong Sub-region (GMS) and the emergence of artemisinin resistance has stimulated efforts to accelerate regional elimination. In the GMS, the malaria transmission is focused increasingly in forested zones. This article describes forest-going activities and examines forest workers' attitudes to and experiences of malaria prevention and control in north-eastern Cambodia.

Polymorphisms in Pvkelch12 and gene amplification of Pvplasmepsin4 in Plasmodium vivax from Thailand, Lao PDR and Cambodia.

Background: Mutations in Pfkelch13 and Pfplasmepsin2/3 gene amplification are well-established markers for artemisinin and piperaquine resistance in Plasmodium falciparum, a widespread problem in the Greater Mekong Subregion (GMS). The Plasmodium vivax parasite population has experienced varying drug pressure dependent on local drug policies. We investigated the correlation between drug pressure from artemisinins and piperaquine and mutations in the P.

Community engagement, social context and coverage of mass anti-malarial administration: Comparative findings from multi-site research in the Greater Mekong sub-Region.

Background: Between 2013 and 2017, targeted malaria elimination (TME), a package of interventions that includes mass drug administration (MDA)-was piloted in communities with reservoirs of asymptomatic P. falciparum across the Greater Mekong sub-Region (GMS). Coverage in target communities is a key determinant of the effectiveness of MDA.

The impact of targeted malaria elimination with mass drug administrations on falciparum malaria in Southeast Asia: A cluster randomised trial.

Background: The emergence and spread of multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion (GMS) threatens global malaria elimination efforts. Mass drug administration (MDA), the presumptive antimalarial treatment of an entire population to clear the subclinical parasite reservoir, is a strategy to accelerate malaria elimination. We report a cluster randomised trial to assess the effectiveness of dihydroartemisinin-piperaquine (DP) MDA in reducing falciparum malaria incidence and prevalence in 16 remote village populations in Myanmar, Vietnam, Cambodia, and the Lao People's Democratic Republic, where artemisinin resistance is prevalent.

Asymptomatic Natural Human Infections With the Simian Malaria Parasites Plasmodium cynomolgi and Plasmodium knowlesi.

Background: In Southeast Asia, Plasmodium knowlesi, a parasite of long-tailed macaques (Macaca fascicularis), is an important cause of human malaria. Plasmodium cynomolgi also commonly infects these monkeys, but only one naturally acquired symptomatic human case has been reported previously.

Methods: Malariometric studies involving 5422 subjects (aged 6 months to 65 years) were conducted in 23 villages in Pailin and Battambang, western Cambodia.

Allele-Specific Isothermal Amplification Method Using Unmodified Self-Stabilizing Competitive Primers.

Rapid and specific detection of single nucleotide polymorphisms (SNPs) related to drug resistance in infectious diseases is crucial for accurate prognostics, therapeutics and disease management at point-of-care. Here, we present a novel amplification method and provide universal guidelines for the detection of SNPs at isothermal conditions. This method, called USS-sbLAMP, consists of SNP-based loop-mediated isothermal amplification (sbLAMP) primers and unmodified self-stabilizing (USS) competitive primers that robustly delay or prevent unspecific amplification.

Smartphones for community health in rural Cambodia: A feasibility study.

Village Malaria Workers (VMWs) are lay people trained to provide a valuable role in frontline testing and treatment of malaria in rural villages in Cambodia. Emergence of artemisinin-resistant malaria highlights the essential role of such VMWs in surveillance and early treatment of malaria. Smartphone technology offers huge potential to support VMWs in isolated and resource-poor settings.

Comparison of glucose-6 phosphate dehydrogenase status by fluorescent spot test and rapid diagnostic test in Lao PDR and Cambodia.

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy worldwide. Primaquine is the only licensed drug that effectively removes Plasmodium vivax hypnozoites from the human host and prevents relapse. While well tolerated by most recipients, primaquine can cause haemolysis in G6PD deficient individuals and is, therefore, underused.

The feasibility and acceptability of mass drug administration for malaria in Cambodia: a mixed-methods study.

Background: Mass drug administrations (MDAs) are part of the World Health Organization's Plasmodium falciparum elimination strategy for the Greater Mekong Subregion (GMS). In Cambodia, a 2015-2017 clinical trial evaluated the effectiveness of MDA. This article explores factors that influence the feasibility and acceptability of MDA, including seasonal timing, financial incentives and the delivery model.

'I could not join because I had to work for pay.': A qualitative evaluation of falciparum malaria pro-active case detection in three rural Cambodian villages.

Background: Pro-active case detection (Pro-ACD), in the form of voluntary screening and treatment (VSAT) following community mobilisation about 'asymptomatic malaria', is currently being evaluated as a tool for Plasmodium falciparum elimination in Preah Vihear Province, Cambodia.

Methods: A qualitative study was conducted to explore community understanding, perceptions, expectations and acceptability of the Pro-ACD intervention in order to identify aspects that could be improved in future Pro-ACD activities. This was ancillary to a three-round VSAT campaign, carried out in three villages between December 2015 and March 2016.

Imidazolopiperazines Kill both Rings and Dormant Rings in Wild-Type and K13 Artemisinin-Resistant Plasmodium falciparum In Vitro.

Artemisinin (ART) resistance has spread through Southeast Asia, posing a serious threat to the control and elimination of malaria. ART resistance has been associated with mutations in the kelch-13 () propeller domain. Phenotypically, ART resistance is defined as delayed parasite clearance in patients due to the reduced susceptibility of early ring-stage parasites to the active metabolite of ART dihydroartemisinin (DHA).

A Controlled Trial of Mass Drug Administration to Interrupt Transmission of Multidrug-Resistant Falciparum Malaria in Cambodian Villages.

Background: The increase in multidrug-resistant Plasmodium falciparum in Southeast Asia suggests a need for acceleration of malaria elimination. We evaluated the effectiveness and safety of mass drug administration (MDA) to interrupt malaria transmission.

Methods: Four malaria-endemic villages in western Cambodia were randomized to 3 rounds of MDA (a 3-day course of dihydroartemisinin with piperaquine-phosphate), administered either early in or at the end of the study period.

Community participation during two mass anti-malarial administrations in Cambodia: lessons from a joint workshop.

Two mass drug administrations (MDA) against falciparum malaria were conducted in 2015-16, one as operational research in northern Cambodia, and the other as a clinical trial in western Cambodia. During an April 2017 workshop in Phnom Penh the field teams from Médecins Sans Frontières and the Mahidol-Oxford Tropical Medicine Research Unit discussed lessons for future MDAs.

Closing in on the Reservoir: Proactive Case Detection in High-Risk Groups as a Strategy to Detect Plasmodium falciparum Asymptomatic Carriers in Cambodia.

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.

Art and theatre for health in rural Cambodia.

This article describes our experience using art and theatre to engage rural communities in western Cambodia to understand malaria and support malaria control and elimination. The project was a pilot science-arts initiative to supplement existing engagement activities conducted by local authorities. In 2016, the project was conducted in 20 villages, involved 300 community members and was attended by more than 8000 people.

A multi-level spatial analysis of clinical malaria and subclinical infections in Pailin Province, Cambodia.

Background: The malaria burden is decreasing throughout the Greater Mekong Subregion, however transmission persists in some areas. Human movement, subclinical infections and complicated transmission patterns contribute to the persistence of malaria. This research describes the micro-geographical epidemiology of both clinical malaria and subclinical infections in three villages in Western Cambodia.