Southeast Asian Sites Research Articles

Host immunity to Plasmodium falciparum and the assessment of emerging artemisinin resistance in a multinational cohort

Artemisinin-resistant falciparum malaria, defined by a slow-clearance phenotype and the presence of kelch13 mutants, has emerged in the Greater Mekong Subregion. Naturally acquired immunity to malaria clears parasites independent of antimalarial drugs. We hypothesized that between- and within-population variations in host immunity influence parasite clearance after artemisinin treatment and the interpretation of emerging artemisinin resistance. Antibodies specific to 12 Plasmodium falciparum sporozoite and blood-stage antigens were determined in 959 patients (from 11 sites in Southeast Asia) participating in a multinational cohort study assessing parasite clearance half-life (PCt1/2) after artesunate treatment and kelch13 mutations. Linear mixed-effects modeling of pooled individual patient data assessed the association between antibody responses and PCt1/2.P. falciparum antibodies were lowest in areas where the prevalence of kelch13 mutations and slow PCt1/2 were highest [Spearman ρ = -0.90 (95% confidence interval, -0.97, -0.65), and Spearman ρ = -0.94 (95% confidence interval, -0.98, -0.77), respectively]. P. falciparum antibodies were associated with faster PCt1/2 (mean difference in PCt1/2 according to seropositivity, -0.16 to -0.65 h, depending on antigen); antibodies have a greater effect on the clearance of kelch13 mutant compared with wild-type parasites (mean difference in PCt1/2 according to seropositivity, -0.22 to -0.61 h faster in kelch13 mutants compared with wild-type parasites). Naturally acquired immunity accelerates the clearance of artemisinin-resistant parasites in patients with falciparum malaria and may confound the current working definition of artemisinin resistance. Immunity may also play an important role in the emergence and transmission potential of artemisinin-resistant parasites.

The Middle Pleistocene vertebrate fauna from Khok Sung (Nakhon Ratchasima, Thailand): biochronological and paleobiogeographical implications.

The fluviatile terrace deposits of Khok Sung, Nakhon Ratchasima province, have yielded more than one thousand fossils, making this the richest Pleistocene vertebrate fauna of Thailand. The excellent preservation of the specimens allows precise characterization of the faunal composition. The mammalian fauna consists of fifteen species in thirteen genera, including a primate, a canid, a hyaenid, proboscideans, rhinoceroses, a suid, cervids, and bovids. Most species correspond to living taxa but globally (Stegodon cf. orientalis) and locally (Crocuta crocuta ultima, Rhinoceros unicornis, Sus barbatus, and Axis axis) extinct taxa were also present. The identification of Axis axis in Khok Sung, a chital currently restricted to the Indian Subcontinent, represents the first record of the species in Southeast Asia. Three reptilian taxa: Crocodylus cf. siamensis, Python sp., and Varanus sp., are also identified. Faunal correlations with other Southeast Asian sites suggest a late Middle to early Late Pleistocene age for the Khok Sung assemblage. However, the Khok Sung mammalian fauna is most similar to that of Thum Wiman Nakin, dated to older than 169 ka. The Khok Sung large mammal assemblage mostly comprises mainland Southeast Asian taxa that migrated to Java during the latest Middle Pleistocene, supporting the hypothesis that Thailand was a biogeographic pathway for the Sino-Malayan migration event from South China to Java.

The problem with looting: An alternative perspective on antiquities trafficking in Southeast Asia

The 1950s and 1960s constitute a key “moment” in the history of the looting of archaeological sites in Southeast Asia. The emergence in the region at that time of a commodity market for antiquities such as pottery triggered a wave of illicit excavation of archaeological sites. Simultaneous with the trafficking of antiquities out of the Philippines and Thailand into the hands of private collectors and museums in the West during this period and subsequent decades a thriving domestic antiquities market developed. It is argued here that the valorization of antiquities as national heritage, rather than inhibiting acquisition by citizen collectors, facilitated a process wherein collecting became a form of cultural capital accumulation. It is inaccurate to categorize Thailand and the Philippines simply as “source” or “supply” nodes in the global antiquities trade. This paper aims for a more nuanced approach to the geoeconomics of antiquities consumption.

THE INVISIBLE MOATS OF THE MUN RIVER VALLEY, NE THAILAND: THE EXAMINATION OF WATER MANAGEMENT DEVICES AT MOUNDED SITES THROUGH GROUND PENETRATING RADAR (GPR)

The Mun River valley is well known for its moat-bound mounded archaeological sites that are usually associated with Iron Age occupation (~500BC- AD500). The investigation of these sites has provided a wealth of information on the changing social and environmental conditions during prehistory. In recent years, research has identified a greater diversity of site morphologies in the region, many of which, importantly, do not appear to have moats surrounding them. This paper seeks to investigate whether the apparently ‘non-moated’ mound site of Non Klang (Nong Hua Raet village) was actually moated in the past, and if such, now in-filled features can be investigated through non-destructive Ground Penetrating Radar methodology. Additionally, while large external moats can be observed in the modern day topography at sites such as Ban Non Wat, excavation has demonstrated that further, invisible, water management features exist beneath the surface within the current mound boundary of the site. These are probably Iron Age precursors to the later more extensive and still visible moats. This paper seeks to answer several fundamental questions: What application can GPR have at mounded sites in Southeast Asia? Do invisible moats exist? How will this affect our understanding of the broader prehistoric landscape in the Upper Mun River Valley?

Early Gold Ornaments of Southeast Asia: Production, Trade, and Consumption

abstract: In the last decade a variety of gold ornaments have come to light through excavations and the illegal looting of Iron Age and early historical sites in Southeast Asia. Although these gold objects are personal ornaments testifying to an innovative local craft tradition that was partly inspired by foreign technologies and styles, their role in the interregional and long-distance exchange network of the early Southeast Asian communities has been rarely considered. This study of early gold ornaments brings together important gold discoveries on sites in Viet Nam, Cambodia, Thailand, Myanmar, and southern China, and discusses similarities in production, consumption, and exchange. It further attempts to offer some new insights into sociopolitical and economic changes on a regional scale, and hopes to contribute to a longue-durée examination of trading connections across Asia. It is proposed that the first arrival of gold ornaments was closely related to the blossoming of trade activities on the terrestrial and maritime silk routes, and the political, religious, and artistic ideas that reached Southeast Asia from far-away regions such as the Greco-Buddhist and Hindu-Buddhist regions. Furthermore it is argued that gold ornaments were prestige goods and an essential part of dressing strategies through which changing elite identities were expressed.

Character and provenance of aeolian sediments in northeast Thailand

Aeolian activity is not generally associated with the humid tropics, and although reports of loess-like soils in various locations in southeast Asia exist, these mainly lack the detailed analysis to set them in meaningful spatial or historical context. This paper examines the red and yellow sandy sediments of the Khorat Plateau in northeast Thailand which have been variously referred to as ‘cover sands’, ‘loessial soils’ or ‘loess’. The sediments are referred to as having alluvial, biological as well as aeolian origin, and a date of 9–35 ka is reported. The study compares the Khorat sediments physically and geochemically with loess and aeolian sediments from other regions, as well as with other sites in southeast Asia which are reported here. The moderate degree of particle sorting and unimodal sizes of the sediments along with a sub-spherical sub-rounded form, supports previous diagnoses of an aeolian origin. Geochemical analysis of the Khorat sediments indicates severe depletion in both mobile and immobile elements, which are even more depleted than other southeast Asian loessic soils examined. This depletion, along with the only moderate particle sorting, suggests the source of the sediments to be the local weathered sandstones outcropping around the edge of the Khorat Plateau. The dissimilarity of the Khorat sediments from Upper Continental Crust (UCC) elemental values supports this, as homogenisation would occur if diverse source areas were involved. The study suggests that aeolian sediments of humid tropical regions warrant more attention as climate proxy markers, due to the dissimilarity between the present climate and conditions required for their formation.

Using isotopic evidence to assess the impact of migration and the two-layer hypothesis in prehistoric Northeast Thailand.

The nature of the agricultural transition in Southeast Asia has been a topic of some debate for archaeologists over the past decades. A prominent model, known as the two-layer hypothesis, states that indigenous hunter-gatherers were subsumed by the expansion of exotic Neolithic farmers into the area around 2000 BC. These farmers had ultimate origins in East Asia and brought rice and millet agriculture. Ban Non Wat is one of the few archaeological sites in Southeast Asia where this model can potentially be tested. The site is located in the Mun River valley of Northeast Thailand, and divided into 12 phases that span over 2,000 years, from about 1750 BC to the end of the Iron Age (ca. 500 AD). These phases exhibit successive cultural changes, and current interpretation of the site is of an early hunter-gatherer population, with agriculturalists immigrating into the later phases. We analyzed strontium, oxygen, and carbon isotopes in tooth enamel from over 150 individuals, dating from the Neolithic to Iron Age, to assess extrinsic origins and differences in diet between early and later phases. We find evidence of dietary and cultural differences between groups at Ban Non Wat during its early occupation, but little evidence for immigration from distinct environments beyond the Khorat Plateau of Northeast Thailand. The lack of consistent isotopic differences between early and later Neolithic occupants at Ban Non Wat means that the site does not conclusively support the two-layer hypothesis.

Archaeogenetic study of prehistoric rice remains from Thailand and India: evidence of early japonica in South and Southeast Asia

We report a successful extraction and sequencing of ancient DNA from carbonized rice grains (Oryza sativa) from six archaeological sites, including two from India and four from Thailand, ranging in age from ca. 2500 to 1500 BP. In total, 221 archaeological grains were processed by PCR amplification and primary-targeted fragments were sequenced for comparison with modern sequences generated from 112 modern rice populations, including crop and wild varieties. Our results include the genetic sequences from both the chloroplast and the nuclear genomes, based on four markers from the chloroplast and six from the nuclear genome. These markers allow differentiation of indica rice from japonica rice, the two major subspecies of Asian rice (O. sativa) considered to have separate geographical origins. One nuclear marker differentiates tropical and temperate forms of subspecies japonica. Other markers relate to phenotypic variation selected for under domestication, such as non-shattering, grain stickiness (waxy starch) and pericarp colour. Recovery and identification of sequences from nuclear markers was generally poor, whereas recovery of chloroplast sequences was successful, with at least one of four markers recovered in 61 % of archaeological grains. This allowed for successful differentiation of indica or japonica subspecies variety, with japonica identified in all the Thai material and a mixture of indica and japonica chloroplasts in the two Indian assemblages. Rice subspecies was also assessed through conventional archaeobotanical methods relying on grain metrics, based on measurements from 13 modern populations and 499 archaeological grains. Grain metrics also suggest a predominance of japonica-type grains in the Southeast Asian sites and a mixture of japonica and indica in the Indian sites with indica in the minority. The similar results of grain metrics and ancient DNA (aDNA) affirm that grain measurements have some degree of reliability in rice subspecies identification. The study also highlights the great potential of ancient DNA recovery from archaeological rice. The data generated in the present study adds support to the model of rice evolution that includes hybridization between japonica and proto-indica.

Governance potential for cetacean bycatch mitigation in small-scale fisheries: A comparative assessment of four sites in Southeast Asia

Bycatch of cetaceans (whales, dolphins, porpoises) in small-scale fisheries is a major global conservation threat. Mitigating bycatch is a fisheries management issue. However, investigation of the governance context of bycatch has been limited. Much-needed progress in bycatch mitigation requires integration of governance assessment in bycatch-related studies. This project assesses “conservation-relevant elements” of local governance institutions and activities that are involved in coastal and aquatic resource management (CARM) and considered important to bycatch mitigation. Research focused on four sites in Southeast Asia with small-scale fisheries bycatch of Irrawaddy dolphins (Orcaella brevirostris): Trat, Thailand; Mahakam River, Indonesia; and Malampaya Sound and Guimaras and Iloilo Straits, Philippines. Using key informant and household surveys, this project examines the extent to which conservation-relevant governance elements are active and effective in CARM, contribute to enforcement, coordinate across institutions, and engage communities. These attributes varied across sites, holding potentially significant implications for the feasibility and process of bycatch mitigation. The role of bridging organizations appears to be vital in CARM activities and current bycatch mitigation efforts, but involvement of local communities and support from external institutions are also necessary for sustained and impactful management. Insights derived from approaches such as that used here can hold lessons beyond Southeast Asia in terms of research methods (i.e., how to incorporate interdisciplinary approaches into bycatch studies), findings (i.e., what governance elements might be most conducive to bycatch mitigation), and setting priorities for conservation (i.e., at what sites is mitigation most feasible, and how can governance capacity for mitigation be enhanced).

Chapman, William: A Heritage of Ruins. The Ancient Sites of Southeast Asia and Their Conservation

Chapman, William: A Heritage of Ruins. The Ancient Sites of Southeast Asia and Their Conservation

Homogeneous population of the brown alga Sargassum polycystum in Southeast Asia: possible role of recent expansion and asexual propagation.

Southeast Asia has been known as one of the biodiversity hotspots in the world. Repeated glacial cycles during Pleistocene were believed to cause isolation of marine taxa in refugia, resulting in diversification among lineages. Recently, ocean current was also found to be another factor affecting gene flow by restricting larval dispersal in animals. Macroalgae are unique in having mode of reproduction that differs from that of animals. Our study on the phylogeographical pattern of the brown macroalga Sargassum polycystum using nuclear Internal Transcribed Spacer 2 (ITS2), plastidal RuBisCO spacer (Rub spacer) and mitochondrial cytochrome oxidase subunit-III (Cox3) as molecular markers revealed genetic homogeneity across 27 sites in Southeast Asia and western Pacific, in sharp contrast to that revealed from most animal studies. Our data suggested that S. polycystum persisted in single refugium during Pleistocene in a panmixia pattern. Expansion occurred more recently after the Last Glacial Maximum and recolonization of the newly flooded Sunda Shelf could have involved asexual propagation of the species. High dispersal ability through floating fronds carrying developing germlings may also contribute to the low genetic diversity of the species.

How to interpret informal flakes assemblages? Integrating morphological description, usewear and morphometric analysis gave better understanding of the behaviors of anatomically modern human from Song Terus (Indonesia)

Stone artifacts are the most numerous remains provided by early Holocene sites in Southeast Asia. They are thus of prime importance to understand better human behaviors of this region. However, they are typo-technologically difficult to characterize and consist mainly of informal flakes. This paper presents an innovative approach focusing on form and function to better assess the prehistoric use of stone tools in the region using a sample of flakes from the cave of Song Terus, Java, Indonesia. The integration of morphological description, usewear and morphometric analysis (Elliptical Fourier Analysis) allows a detailed characterization of tool use not possible with other methods. We demonstrate that a specific form of stone flake is not related to a particular function and vice versa. Our results show that tool production was not oriented towards the production of flakes of specific form, or to the production of flake blanks that could be modified by retouch but was a system where the control of flake shape was relaxed in favor of the selection of flakes suitable for particular tasks either during reduction or once core reduction had concluded.

From the mouths of babes: Dental caries in infants and children and the intensification of agriculture in mainland Southeast Asia

Many bioarchaeological studies have established a link between increased dental caries prevalence and the intensification of agriculture. However, research in Southeast Asia challenges the global application of this theory. Although often overlooked, dental health of infants and children can provide a sensitive source of information concerning health and subsistence change. This article investigates the prevalence and location of caries in the dentition of infants and children (less than 15 years of age) from eight prehistoric mainland Southeast Asian sites collectively spanning the Neolithic to late Iron Age, during which time rice agriculture became an increasingly important subsistence mode. Caries prevalence varied among the sites but there was no correlation with chronological change. The absence of evidence of a decline in dental health over time can be attributed to the relative noncariogenicity of rice and retention of broad-spectrum subsistence strategies. No differences in caries type indicating differences in dental health were found between the sites, apart from the Iron Age site of Muang Sema. There was a higher prevalence of caries in the deciduous dentition than the permanent dentition, likely due to a cariogenic weaning diet and the higher sensitivity of deciduous teeth to decay. The level of caries in the permanent dentition suggests an increased reliance on less cariogenic foods during childhood, including rice. The absence of a temporal decline in dental health of infants and children strengthens the argument that the relationship between caries and agricultural intensification in Southeast Asia was more complex than the general model suggests.

Prehistoric iron production technologies in the Upper Thai-Malay Peninsula: metallography and slag inclusion analyses of iron artefacts from Khao Sam Kaeo and Phu Khao Thong

This article presents a preliminary attempt to characterise Upper Thai-Malay Peninsula prehistoric iron technologies based on assemblages from two recently excavated coastal sites: Khao Sam Kaeo and Phu Khao Thong. These are the earliest known sites involved in the early trans-Asian exchange that connected the eastern Indian Ocean to the South China Sea from the mid-first millennium bc. It is from this period that iron assemblages start appearing at both continental and insular Southeast Asian sites. Three models have been offered confronting an indigenous vs. Chinese or South Asian impetus for the introduction of iron metallurgy in Southeast Asia. These models are discussed in the light of the metallographic and compositional analyses of iron and slag assemblages from these two sites using optical microscopy, scanning electron microscopy with energy dispersive spectrometry, energy dispersive X-ray fluorescence and slag inclusion analysis techniques, together with other production materials from these and other contemporaneous Southeast Asian sites.

Early Cambodian gold and silver from Prohear: composition, trace elements and gilding

Rescue excavations in Prohear, southeast Cambodia, recently saved the last untouched graves of one of the richest prehistoric sites in Southeast Asia. Many Iron Age burials dating from the 2nd century BC to the 1st century AD contained gold and silver ornaments so far unknown from archaeological contexts together with indications for the presence of an immigrated elite. A first selection of 59 objects were analysed by LA-ICP-MS to obtain detailed information about the composition, as well as minor and trace elements. The majority of the ornaments consist of electrum and auriferous silver with low copper concentrations, and two main groups indicating different alluvial gold sources can be distinguished by different concentrations of Pt, Ir, Bi and different Pd/Pt ratios, one group being related to rich burials with non-local features. The SEM and EDX analyses of four objects revealed two different gilding techniques observed for the first time in Southeast Asian artefacts: foil-fusion gilding, related to special Ag–Au–(Cu)–Sn alloys containing up to 4% tin, and depletion gilding.

Early Evidence for Pig and Dog Husbandry from the Neolithic Site of An Son, Southern Vietnam

An Son in southern Vietnam is one of a series of Neolithic (food producing) settlement/cemetery sites in Southeast Asia that appear, archaeologically, shortly before and after 2000 cal. bc. Excavations in 2009 produced a small but important assemblage of vertebrate remains that permit relative comparisons with other zooarchaeological assemblages of similar date in Thailand and northern Vietnam. At An Son, domestic dogs are present from the earliest known phases of occupation with butchery evidence and a high proportion of canid remains, suggesting they were possibly used as a food resource. Suid bones were recovered from the earliest phases of the site excavated, and pig husbandry can be identified from at least 1800 to 1600 cal. bc. There is also evidence for the use of a range of other resources including fishing, hunting and the capturing of turtles.

An automated approach for segmenting and classifying a large sample of multi-date Landsat imagery for pan-tropical forest monitoring

The TREES-3 project of the Joint Research Centre aims at assessing tropical forest cover changes for the periods 1990–2000 and 2000–2010 using a sample-based approach. This paper refers to the 1990–2000 assessment. Extracts of Landsat satellite imagery (20 km × 20 km) are analyzed for these reference dates for more than 4000 sample sites distributed systematically across the tropical belt. For the processing and analysis of such a large amount of satellite imagery a robust methodological approach for forest mapping and change detection has been developed. This approach comprises two automated steps of multi-date image segmentation and object-based land cover classification (based on a supervised spectral library), followed by an intense phase of visual control and expert refinement. Image segmentation is done at two spatial scales, introducing the concept of a minimum mapping unit via the automated selection of a site-specific scale parameter. The automated segmentation of land cover polygons and the pre-classification of land cover types mainly aim at avoiding manual delineation and at reducing the efforts of visual interpretation of land cover to a reasonable level, making the analysis of 4000 sample sites feasible. The importance of visual control and correction can be perceived when comparing to the initial automatic classification result: about 20% of the polygon labels were changed through expert knowledge by visual interpretation. The component of visual refinement of the mapping results had also a notable impact on forest area and change estimates: for a set of sample sites in Southeast Asia (~ 90% of all sites of SE-Asia) the rate of change in tree cover (deforestation) was assessed at 0.9% and 1.6% before and after visual control, respectively.

Artificial Bird Perches for the Regeneration of Degraded Tropical Peat Swamp Forest: A Restoration Tool with Limited Potential

Forest rehabilitation activities have been initiated on degraded peatland at several sites in Southeast Asia. In order to achieve rehabilitation efficiently and on the largest possible scale, cost‐effective, transferable methods need to be established. One potential method, which has previously proven successful in both temperate and neotropical forest ecosystems, is the construction of artificial bird perches outside the forest edge. These provide resting perches for frugivorous birds, encouraging them to fly out of the forest, thus increasing seed dispersal and subsequent seedling recruitment into the degraded area. This method was trialled for the first time in degraded tropical peat swamp forest in Indonesia. The results show that the perches were used by frugivorous birds, leading to a significant increase in seed dispersal; however, seedling recruitment was not increased. The frugivorous birds using the perches were degraded zone species and dispersed mainly tree species from the degraded area. Furthermore, while some seeds of forest‐area tree species were dispersed, largely only the degraded area tree species survived to seedling stage. Neither seasonality nor distance from forest edge proved to be significant factors influencing seed dispersal or seedling recruitment, the latter highlighting that seeds were principally being dispersed from within the degraded area rather than from the forest. Although artificial perches did increase seed dispersal, their use as an actual restoration tool in the process of forest regeneration on degraded tropical peatland is limited. Furthermore, when the cost‐ and effort‐to‐area factors are considered, this method is shown to be inefficient.

Palaeoecology of Southeast Asian megafauna‐bearing sites from the Pleistocene and a review of environmental changes in the region

AbstractAim To reconstruct the palaeoenvironments of megafauna‐bearing sites from Pleistocene Southeast Asia, and to describe general environmental changes in the region.Location Indochina and Sundaland, including Myanmar, Laos, Vietnam, Cambodia, Thailand, the Malay Peninsula, Borneo, Sumatra and Java.Methods This study reconstructs the habitat types of 25 Pleistocene sites in Southeast Asia through a synecological (community‐based) method. This method specifically targets medium‐ and large‐bodied mammals, and ecovariables that could be directly assessed from species lists were chosen. The methods allow the reconstruction of fossil sites as closed (continuous tree cover), mixed (heterogeneous tree cover) and open (very limited to no tree cover) through discriminant functions analysis of community guild structure.Results Four Pleistocene sites can confidently be assigned to one of the three habitat types. Tam Hang (south), a Middle Pleistocene site from Laos, is classified as mixed. Ban Fa Suai, a Middle Pleistocene site from Thailand, is also classified as mixed. Trinil, a Middle Pleistocene site from Java, is classified as open. Lastly, Hang Hum II, a Late Pleistocene site from Vietnam, is classified as open. Insufficient species are present in the fossil faunas of remaining sites to allow statistically confident habitat assignment. Nevertheless, conditional habitat assignments can be achieved, and these are largely congruent with other palaeoenvironmental evidence.Main conclusions Medium‐ and large‐bodied mammals are the most frequently recovered mammals from Pleistocene sites in Southeast Asia. Previous palaeoenvironmental reconstructions of these sites have been hampered by this body size bias, as well as by limited site and faunal descriptions. However, our analysis demonstrates that reconstructions can still be achieved for megafauna‐bearing sites in the region. The reconstructions suggest that through much of the Pleistocene, Southeast Asia had significant areas of mixed habitats, and that the widespread distribution of rain forests, such as found today, was a relatively rare phenomenon.

Efficacy and safety of a fixed-dose oral combination of pyronaridine-artesunate compared with artemether-lumefantrine in children and adults with uncomplicated Plasmodium falciparum malaria: a randomised non-inferiority trial

There is a need for new artemisinin-based combination therapies that are convenient, effective, and safe. We compared the efficacy and safety of pyronaridine-artesunate with that of artemether-lumefantrine for treatment of uncomplicated P falciparum malaria. This phase 3, parallel-group, double-blind, randomised, non-inferiority trial was undertaken in seven sites in Africa and three sites in southeast Asia. In a double-dummy design, patients aged 3-60 years with uncomplicated P falciparum malaria were randomly assigned in a 2:1 ratio to receive pyronaridine-artesunate once a day or artemether-lumefantrine twice a day, orally for 3 days, plus respective placebo. Randomisation was done by computer-generated randomisation sequence in blocks of nine by study centre. Intervention tablets contained 180 mg pyronaridine and 60 mg artesunate; control tablets contained 20 mg artemether and 120 mg lumefantrine. Both treatments were given according to bodyweight. The primary efficacy outcome was PCR-corrected adequate clinical and parasitological response (ACPR) rate at day 28 in the per-protocol population. Non-inferiority was shown if the lower limit of the two-sided 95% CI for the difference between groups was greater than -5%. This study is registered with ClinicalTrials.gov, number NCT00422084. 1272 patients were randomly assigned to treatment (pyronaridine-artesunate, n=849; artemether-lumefantrine, n=423). The per-protocol population consisted of 784 patients in the pyronaridine-artesunate group and 386 patients in the artemether-lumefantrine group. PCR-corrected ACPR rate at day 28 was 99.5% (780 patients; 95% CI 98.7-99.9) in the pyronaridine-artesunate group and 99.2% (383 patients; 95% CI 97.7-99.8) in the artemether-lumefantrine group (treatment difference 0.3%, 95% CI -0.7 to 1.8; p=0.578). There were 509 (60.0%) adverse events in 849 patients assigned to pyronaridine-artesunate and 241 (57.0%) in 423 patients assigned to artemether-lumefantrine. The most frequent drug-related adverse event was eosinophilia (pyronaridine-artesunate, 53 events [6.2%]; artemether-lumefantrine 24 events [5.7%]). 21 (2.5%) patients in the pyronaridine-artesunate group and seven (1.7%) in the artemether-lumefantrine group discontinued study drugs or were withdrawn from the study. Mild and transient increases in alanine aminotransferase and aspartate aminotransferase concentrations were seen in the pyronaridine-artesunate group but not in the artemether-lumefantrine group. Efficacy of pyronaridine-artesunate was non-inferior to that of artemether-lumefantrine for treatment of uncomplicated falciparum malaria. Pyronaridine-artesunate should be considered for inclusion in malaria treatment programmes. Shin Poong Pharmaceutical and the Medicines for Malaria Venture.