Aung Pyae Phyo

Shoklo Malaria Research Unit

Background Tuberculosis (TB) is a chronic condition, with overlapping symptoms to those of coronavirus disease 2019 (COVID-19). There has been inconsistent evidence on whether TB is a predisposing factor for developing severe COVID-19. The aim of this report is to explore whether TB influences the severity of COVID-19. Methods COVID-19 cases at two...

Background Neglected tropical diseases (NTDs) affect most impoverished communities in developing countries, like Myanmar in Southeast Asia. NTDs have been understudied and underreported in Myanmar. Methods A systematic review of published and grey literature (1900–2023) on neglected tropical diseases (NTDs) in Myanmar was conducted. The literature...

Background Severe malaria in pregnancy causes maternal mortality, morbidity, and adverse foetal outcomes. The factors contributing to adverse maternal and foetal outcomes are not well defined. We aimed to identify the factors predicting higher maternal mortality and to describe the foetal mortality and morbidity associated with severe falciparum ma...

Background: Tuberculosis (TB) is a chronic condition, with overlapping symptoms to those of coronavirus disease 2019 (COVID-19). There has been inconsistent evidence on whether TB is a predisposing factor for developing severe COVID-19. The aim of this report is to explore whether TB influences the severity of COVID-19. Methods: COVID-19 cases at t...

Background: The northwestern border of Thailand is an area of low seasonal malaria transmission. Until recent successful malaria elimination activities, malaria was a major cause of morbidity and mortality. Historically the incidences of symptomatic Plasmodium falciparum and Plasmodium vivax malaria were approximately similar. Methods: All malar...

A major threat to the goal of eliminating malaria, in particular Southeast Asia, is the spread of Plasmodium falciparum resistant to artemisinin (ART)-based combination therapies. P218 is a drug candidate designed to combat antifolate-sensitive and -resistant parasites. However, there is no evidence that P218 is effective against ART-resistant Plas...

Background: Preterm birth is a major public health concern with the largest burden of morbidity and mortality falling within low- and middle-income countries (LMIC). Materials and methods: This sequential explanatory mixed methods study was conducted in special care baby units (SCBUs) serving migrants and refugees along the Myanmar-Thailand border....

We describe the MalariaGEN Pf7 data resource, the seventh release of Plasmodium falciparum genome variation data from the MalariaGEN network. It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented. For the first time we include dried blood spot sample...

Burkholderia pseudomallei is a soil-dwelling aerobic bacterium prevalent in tropical and subtropical regions, particularly in Southeast Asia and Northern Australia. It is the causal organism of melioidosis, a severe infection that can manifest as chronic debilitating pneumonia resembling pulmonary tuberculosis. Here, we report a case of melioidosis...

Background Understanding the effect of immunity on P. falciparum clearance is essential for interpreting therapeutic efficacy studies designed to monitor emergence of artemisinin drug resistance. In low transmission areas of Southeast Asia, where resistance has emerged, P. falciparum antibodies confound parasite clearance measures. However, variati...

This report describes the MalariaGEN Pv4 dataset, a new release of curated genome variation data on 1,895 samples of Plasmodium vivax collected at 88 worldwide locations between 2001 and 2017. It includes 1,370 new samples contributed by MalariaGEN and VivaxGEN partner studies in addition to previously published samples from these and other sources...

Introduction Understanding the human immune response to Plasmodium falciparum gametocytes and its association with gametocytemia is essential for understanding the transmission of malaria as well as progressing transmission blocking vaccine candidates. Methods In a multi-national clinical efficacy trial of artemisinin therapies (13 sites of varyin...

The emergence and spread of artemisinin-resistant Plasmodium falciparum, first in the Greater Mekong Subregion (GMS), and now in East Africa, is a major threat to global malaria elimination ambitions. To investigate the artemisinin resistance mechanism, transcriptome analysis was conducted of 577 P. falciparum isolates collected in the GMS between...

In rural areas of South and Southeast Asia malaria is declining but febrile illnesses still account for substantial morbidity and mortality. Village health workers (VHWs) are often the first point of contact with the formal health system, and for patients with febrile illnesses they can provide early diagnosis and treatment of malaria. However, for...

Background Plasmodium vivax infects an estimated 7 million people every year. Previously, vivax malaria was perceived as a benign condition, particularly when compared to falciparum malaria. Reports of the severe clinical impacts of vivax malaria have been increasing over the last decade. Methods and findings We describe the main clinical impacts...

Background Artemisinin (ART) resistance in Plasmodium falciparum is thought to occur during the early stage of the parasite's erythrocytic cycle. Here, we identify a novel factor associated with the late stage parasite development that contributes to ART resistance. Methods Rosetting rates of clinical isolates pre- and post- brief (one hour) expos...

Increasing drug resistance in Plasmodium falciparum to artemisinins and their ACT partner drugs jeopardises effective antimalarial treatment. Resistance is worst in the Greater Mekong Subregion. Monitoring genetic markers of resistance can help to guide antimalarial therapy. Markers of resistance to artemisinins ( PfKelch mutations), mefloquine (am...

Background Primaquine is the only widely available drug for radical cure of Plasmodium vivax malaria. There is uncertainty whether the pharmacokinetic properties of primaquine are altered significantly in childhood or not. Methods Glucose-6-phosphate dehydrogenase normal patients with uncomplicated P. vivax malaria were randomized to receive either...

Background: National Malaria Control Programmes (NMCPs) currently make limited use of parasite genetic data. We have developed GenRe-Mekong, a platform for genetic surveillance of malaria in the Greater Mekong Subregion (GMS) that enables NMCPs to implement large-scale surveillance projects by integrating simple sample collection procedures in rou...

MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nuc...

Background: Primaquine is the only widely available drug for radical cure of Plasmodium vivax malaria. There is uncertainty whether the pharmacokinetic properties of primaquine are altered significantly in childhood or not. Methods: Glucose-6-phosphate dehydrogenase normal patients with uncomplicated P. vivax malaria were randomized to receive eith...

Background Artemisinin and artemisinin-based combination therapy (ACT) partner drug resistance in Plasmodium falciparum have spread across the Greater Mekong Subregion compromising antimalarial treatment. The current 3-day artemether-lumefantrine regimen has been associated with high treatment failure rates in pregnant women. Although ACTs are reco...

The emergence and spread of artemisinin resistant Plasmodium falciparum , first in the Greater Mekong Subregion (GMS), and now in East Africa, is a major threat to global malaria eliminations ambitions. To investigate the artemisinin resistance mechanism, transcriptome analysis was conducted of 577 P. falciparum isolates collected in the GMS betwee...

Background Burkholderia pseudomallei is a Gram-negative bacterium found in soil and water in many tropical countries. It causes melioidosis, a potentially fatal infection first described in 1911 in Myanmar. Melioidosis is a common cause of sepsis and death in South and South-east Asia, but it is rarely diagnosed in Myanmar. We conducted a nationwid...

The emergence and spread of artemisinin resistant Plasmodium falciparum , first in the Greater Mekong Subregion (GMS), and now in East Africa, is a major threat to global malaria eliminations ambitions. To investigate the artemisinin resistance mechanism, transcriptome analysis was conducted of 577 P. falciparum isolates collected in the GMS betwee...

Background Lower respiratory infections constitute a major disease burden worldwide. Treatment is usually empiric and targeted towards typical bacterial pathogens. Understanding the prevalence of pathogens not covered by empirical treatment is important to improve diagnostic and treatment algorithms. Methods A prospective observational study in pe...

MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nuc...

Quinoline antimalarials cause drug-induced electrocardiograph QT prolongation, a potential risk factor for torsade de pointes. The effects of currently used antimalarials on the electrocardiogram were assessed in pregnant women with malaria. Pregnant women with microscopy-confirmed parasitaemia of any malaria species were enrolled in an open-label...

Background Little research has been published on the prevalence of rickettsial infections in Myanmar. In this study, we determined the seroprevalence of IgG antibodies to rickettsial species in different regions of Myanmar. Methods We collected 700 leftover blood samples from patients of all age groups in primary care clinics and hospitals in seve...

National Malaria Control Programmes (NMCPs) currently make limited use of parasite genetic data. We have developed GenRe-Mekong, a platform for genetic surveillance of malaria in the Greater Mekong Subregion (GMS) that enables NMCPs to implement large-scale surveillance projects by integrating simple sample collection procedures in routine public h...

Introduction The risk of emergence and spread of antibiotic resistance is high in Southeast Asian countries and various strategies are being used to raise awareness about appropriate antibiotic use and antibiotic resistance within communities. Public engagement in science has not been widely practised in Myanmar. We describe the use of a forum thea...

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 tr...

Background Malaria in pregnancy, including asymptomatic infection, has a detrimental impact on foetal development. Individual patient data (IPD) meta-analysis was conducted to compare the association between antimalarial treatments and adverse pregnancy outcomes, including placental malaria, accompanied with the gestational age at diagnosis of unco...

Background: Artemisinin and partner-drug resistance in Plasmodium falciparum are major threats to malaria control and elimination. Triple artemisinin-based combination therapies (TACTs), which combine existing co-formulated ACTs with a second partner drug that is slowly eliminated, might provide effective treatment and delay emergence of antimalari...

Progress in controlling malaria has slowed in recent years and the annual death toll remains above 400 000 globally, with most deaths caused by Plasmodium falciparum. The joint threats of increasing resistance to insecticides, artemisinin derivatives, and almost all other antimalarials in current use make the development of new classes of antimalar...

Background Malaria in pregnancy affects both the mother and the fetus. However, evidence supporting treatment guidelines for uncomplicated (including asymptomatic) falciparum malaria in pregnant women is scarce and assessed in varied ways. We did a systematic literature review and individual patient data (IPD) meta-analysis to compare the efficacy...

Background Artemisinin-based combination therapy (ACT) is recommended for uncomplicated Plasmodium vivax malaria in areas of emerging chloroquine resistance. We undertook a systematic review and individual patient data meta-analysis to compare the efficacies of dihydroartemisinin-piperaquine (DP) and artemether-lumefantrine (AL) with or without pri...

In The Lancet, Katherine Battle and Daniel Weiss and colleagues present new malaria maps. These maps are the result of a considerable effort and will undoubtedly be well received by individuals interested in malaria. Several novelties and improvements from earlier versions are noticeable: the data for Plasmodium falciparum now cover the entire ende...

Background Primaquine is necessary for the radical cure of Plasmodium vivax malaria, but the optimum duration of treatment and best partner drug are uncertain. A randomized controlled trial was performed to compare the tolerability and radical curative efficacy of 7-day versus 14-day high-dose primaquine regimens (total dose 7mg/kg) with either chl...

Between 2003 and 2010, 687 (23.8%) of 2885 patients treated for falciparum malaria in clinical studies in Myanmar or on the Thailand-Myanmar border had recurrent Plasmodium vivax malaria within 63 days compared with 18 (4.2%) of 429 patients since then; RR 0.176 (95%CI: 0.112-0.278); p<0.0001. Corresponding figures for 42 days follow up only were 8...

Background: Plasmodium falciparum infections with slow parasite clearance following artemisinin-based therapies are widespread in the Greater Mekong Subregion. A molecular marker of the slow clearance phenotype has been identified: single genetic changes within the propeller region of the Kelch13 protein (pfk13; Pf3D7_1343700). Global searches have...

Background: Chloroquine remains the mainstay of treatment for Plasmodium vivax malaria despite increasing reports of treatment failure. We did a systematic review and meta-analysis to investigate the effect of chloroquine dose and the addition of primaquine on the risk of recurrent vivax malaria across different settings. Methods: A systematic r...

The last two decades have seen a surge in antimalarial drug development with product development partnerships taking a leading role. Resistance of Plasmodium falciparum to the artemisinin derivatives, piperaquine and mefloquine in Southeast Asia means new antimalarials are needed with some urgency. There are at least 13 agents in clinical developme...

Following unsuccessful eradication attempts there was a resurgence of malaria towards the end of the 20th century. Renewed control efforts using a range of improved tools, such as long-lasting insecticide-treated bednets and artemisinin-based combination therapies, have more than halved the global burden of disease, but it remains high with 445 000...

Background: Potentially untreatable Plasmodium falciparum malaria threatens the Greater Mekong subregion. A previous series of pilot projects in Myanmar, Laos, Cambodia, and Vietnam suggested that mass drug administration was safe, and when added to provision of early diagnosis and treatment, could reduce the reservoir of P falciparum and interrup...

Background Malaria has declined dramatically along the Thai–Myanmar border in recent years due to malaria control and elimination programmes. However, at the same time, artemisinin resistance has spread, raising concerns about the efficacy of parenteral artesunate for the treatment of severe malaria. Case presentationIn November 2015 and April 2017...

Background Artemisinin resistance, linked to polymorphisms in the Kelch gene on chromosome 13 of Plasmodium falciparum (k13), has outpaced containment efforts in South East Asia. For national malaria control programmes in the region, it is important to establish a surveillance system which includes monitoring for k13 polymorphisms associated with t...

With the rapidly increasing abundance and accessibility of genomic data, there is a growing interest in using population genetic approaches to characterize fine-scale dispersal of organisms, providing insight into biological processes across a broad range of fields including ecology, evolution and epidemiology. For sexually recombining haploid orga...

Summary of previous population genetic analyses of the barcode data in [1] Nkhoma SC, et al. Mol Ecol. 2013; 22(2). †Given decline in malaria transmission. Figure references refer to Figures in [1]. (PDF)

Additional details and analyses regarding FST. (PDF)

Single-infection WGS data parasite sample counts per clinic and year. Clinic code: MLA (Maela), WPA (Wang Pha), MKK (Mae Kon Ken) and MKT (Mawker Thai). (PDF)

Additional details and plots of 93 and 24-SNP π^IBD. (PDF)

Single-infection barcode data parasite sample counts per clinic and year. Clinic code: MLA (Maela), WPA (Wang Pha), MKK (Mae Kon Ken) and MKT (Mawker Thai). (PDF)

Additional details and plots of co-ancestry estimates. (PDF)

Numbers of SNPs for which clinic and year variables were significant in a simple linear model. The simple linear model was as follows. Non-reference allele frequency = intercept + βclinic clinic + βyear year + ε, where ε was normally distributed with mean 0 and variance σ2. (PDF)

Additional details and analyses regarding π^IBD. (PDF)

Background: Reductions in malaria transmission decrease naturally acquired immunity, which may influence the emergence of Plasmodium falciparum artemisinin-resistant phenotypes and genotypes over time. Methods: Antibodies specific for P. falciparum antigens were determined in uncomplicated hyperparasitemic malaria patients over a 10-year period...