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From fragmentation to coordination: strengthening One Health research to support H5N1 preparedness in Cambodia.

OBJECTIVES: Highly pathogenic avian influenza A (H5N1) remains a major zoonotic threat, characterized by persistent transmission in Cambodia since its re-emergence in 2023. Despite strengthened surveillance and the establishment of the Inter-Ministerial Coordination Committee on One Health, limited integration of research across sectors constrains preparedness and response. This viewpoint examines how research supports the One Health system in Cambodia. METHODS: This viewpoint draws on insights obtained from the first national multistakeholder workshop on H5N1, held in March 2026. RESULTS: Fragmentation across epidemiological, clinical, behavioral, environmental, and genomic domains limits the generation of actionable evidence and delays its translation into policy. CONCLUSION: We propose the establishment of a multisectoral technical working group on H5N1 research embedded within the Inter-Ministerial Coordination Committee on One Health to align research priorities, strengthen data integration, and improve evidence-to-policy translation. This approach could enhance national preparedness while simultaneously positioning Cambodia as a model for coordinated One Health research in the Western Pacific region and beyond.

Avian influenza A (H5N1)

Parasite clearance in patients with Plasmodium vivax monoinfection treated with artesunate in Cambodia: an observational secondary analysis of trial data.

BACKGROUND: Artemisinin-based combination therapies are the frontline drugs for the treatment of malaria infections, but, for Plasmodium falciparum, the efficacy of artemisinin is threatened by the spread of resistance. Plasmodium vivax is the second most common cause of human malaria, but there is little information on its susceptibility to artemisinin due to the lack of an in-vitro culture system. This study aims to characterise the response of P vivax to artesunate using clinical, genomic, and transcriptomic data from infected individuals in Cambodia. METHODS: We analysed 161 P vivax infections from 87 patients (six female and 81 male; median age 20 years [IQR 17-26]) enrolled between Nov 10, 2021, and Nov 18, 2022, in a drug efficacy study in Cambodia and treated with 2 mg/kg/day of artesunate for 7 days. To determine clearance rates, we measured parasitaemia before, and 1 h, 2 h, 4 h, 8 h, and 16 h after the first dose of artesunate, and then at 24-h intervals during the 7 days of artesunate therapy. We also examined the parasites' genome sequences and used RNA sequencing of 31 infections to analyse changes in parasite gene expression upon treatment. FINDINGS: All infections were successfully cleared by day 3. However, 49 of the infections displayed a slow clearance after treatment, including nine (6%) infections with a parasite clearance slope half-life greater than 5 h. We observed no significant association between slow clearance and either patient or infection characteristics (including the infection's stage composition). Analyses of gene expression showed that, while fast-clearing parasites displayed significant changes in gene expression immediately upon treatment, slow-clearing parasites had a delayed gene expression response characterised notably by a downregulation of genes associated with haemoglobin endocytosis and digestion. INTERPRETATION: Some Cambodian P vivax parasites clear slowly after artesunate treatment, possibly due to a downregulation of haemoglobin metabolism that might reduce the efficiency of the artesunate. The slow clearance could allow parasites to outlast artesunate treatment and facilitate emergence of resistance to the artemisinin-combination therapy partner drug, threatening malaria elimination effort. FUNDING: US National Institutes of Health.

Adolescent

14 days of high-dose versus low-dose primaquine treatment in patients with Plasmodium vivax infection in Cambodia: a randomised, single-centre, open-label efficacy study.

BACKGROUND: Most malaria-endemic countries, including Cambodia, use a total dose of 3&#xb7;5 mg/kg of primaquine to eliminate Plasmodium vivax hypnozoites and prevent relapses. There are, however, indications that the lower dose of 3&#xb7;5 mg/kg is insufficient for tropical P vivax isolates, particularly in southeast Asia, and WHO now recommends a total dose of 7&#xb7;0 mg/kg in most countries. We aimed to determine the most effective regimen to eliminate P vivax hypnozoites to support elimination efforts of this malaria parasite. METHODS: We conducted an open-label, randomised controlled trial in Kampong Speu province, western Cambodia. Patients infected with P vivax aged at least 15 years were offered to participate. Exclusion criteria were severe malaria or other diseases requiring treatment, low haemoglobin (<8&#xb7;0 g/dL), pregnancy or breastfeeding, sensitivity to study drugs, and use of antimalarials in the preceding month. Enrolled patients were treated with an artesunate regimen of 2 mg/kg per day for 7 days. Patients with normal glucose-6-phosphate dehydrogenase (G6PD) levels were randomly assigned (2:2:1) to receive 3&#xb7;5 mg/kg (low dose [0&#xb7;25 mg/kg per day]), 7&#xb7;0 mg/kg (high dose [0&#xb7;5 mg/kg per day]), or no primaquine for 14 days. Patients with deficient G6PD levels were assigned to the no primaquine comparator arm. Patients were relocated to the study site in Aoral town where no malaria transmission occurs to ensure that they were not reinfected during their 90-day follow-up. After 90 days of relocation, G6PD-normal patients in the no primaquine arm were provided 3&#xb7;5 mg/kg of primaquine for 14 days to be taken unsupervised. At day 90, relocation was terminated, and patients were followed up monthly for 3 months until day 180. The primary outcome was P vivax recurrence within 90 days of relocated follow-up, assessed in all patients who completed treatment and complied with relocation without interruption. All patients enrolled and assigned to an intervention arm were included in the safety analysis. The study is registered on ClinicalTrials.gov and recruitment is completed (NCT04706130). FINDINGS: Between Nov 10, 2021, and Feb 10, 2024, 160 patients were enrolled and 147 were included in the primary analysis-59 were assigned to the no primaquine arm (37 assigned as G6PD deficient [median age 22 years, IQR 18-28]; 22 randomly assigned [18, 17-25]), 45 to the low-dose primaquine arm (23, 19-30), and 43 to the high-dose primaquine arm (22, 18-25). Participants were mostly male (135 [92%] of 147) and all Cambodian. 48 (81% [95% CI 69&#xb7;6-89&#xb7;2]) participants in the no primaquine arm had at least one P vivax recurrence within 90 days, as did 11 (24%, 14&#xb7;2-38&#xb7;7) in the low-dose group and two (5%, 0&#xb7;8-15&#xb7;5) in the high-dose group (p=0&#xb7;0141 for high vs low). After imputation for missing data, low-dose primaquine remained associated with more recurrences than high-dose primaquine (hazard ratio 0&#xb7;17 [95% CI 0&#xb7;04-0&#xb7;79], p=0&#xb7;0229). Both primaquine regimens were well tolerated with no serious adverse events reported. INTERPRETATION: Not providing primaquine to patients led to a considerable rate of P vivax recurrence. The risk of P vivax recurrence was substantially lower for 7&#xb7;0 mg/kg primaquine treatment compared with 3&#xb7;5 mg/kg. Tolerability and safety of both primaquine regimens in G6PD normal individuals was comparable. FUNDING: US National Institutes of Health (R01AI146590).

Humans

Mapping Sub-National Respiratory Virus Circulation in Cambodia Using Metatranscriptomic Sequencing: A Multi-Center Hospital-Based Surveillance Study.

BACKGROUND: Genomic surveillance can guide early detection of and response to emerging epidemics. Metatranscriptomic sequencing was used to investigate sub-national respiratory virus circulation in Cambodia from 2020 to 2023. METHODS: Nasopharyngeal swabs were collected from individuals aged 2&#x2009;months to 65&#x2009;years with influenza-like illness in four Cambodian hospitals. Metatranscriptomic data were generated by short-read RNA sequencing. Bernoulli space-time scan statistics were used to identify temporal virus clusters. Bayesian inference of phylogenetic trees was used to compute divergence times for temporally clustered, highly represented viruses (influenza A/H3N2 and B, Betacoronavirus 1, respiratory syncytial virus [RSV] A and B), and publicly available global influenza virus genomes. RESULTS: Of 1093 individuals, 499 (45.7%) had detectable respiratory viruses belonging to 68 distinct species. Moderate (N&#x2009;>&#x2009;20) discrete time-clusters were noted of RSV-A (37 cases), Betacoronavirus 1 (21 cases), RSV-B (22 cases), and A/H3N2 (30 cases). The posterior median of time to most recent common ancestor ranged from 0.71&#x2009;years (95% HPD 0.38-1.10) for Betacoronavirus 1 and 1.31&#x2009;years (95% HPD 0.60-3.20) for A/H3N2, to 2.75&#x2009;years (1.82-4.26) for RSV-A and 4.79&#x2009;years (2.39-7.74) for RSV-B. A/H3N2 and influenza B virus genomes mapped to clades 3C.2a1b.2a.2a and Victoria 1A.3a.2, respectively, and inter-mixed with concurrent global strains. CONCLUSIONS: Multiple respiratory viruses circulated at a sub-national level in Cambodia from 2020 to 2023 despite pandemic disruptions. Influenza virus population diversity decreased during the height of lockdown but recovered in mid-2022. Re-emerging influenza strains were distinct from historically circulating strains and clustered with contemporaneous global variants, suggesting multiple external introductions.

Humans

Characterization and evolutionary history of novel SARS-CoV-2-related viruses in bats from Cambodia.

Circulating bat coronaviruses present a significant pandemic threat, yet our understanding of their genetic diversity and evolutionary dynamics remains limited. Over 3 years, we sampled 1,462 bats in Cambodia's Steung Treng province, identifying extensive and diverse coronaviruses co-circulation. Using metatranscriptomic and amplicon sequencing, we generated 33 complete sarbecovirus genomes sequences, revealing novel lineages that cluster into four distinct groups, each associated with different Rhinolophus bat species. Our analysis highlights rapid migration and recombination of sarbecovirus lineages over short distances and timescales. Of note, the receptor-binding domains of two novel viral groups exhibit high similarity to SARS-CoV-2, and pseudovirus assays confirmed the ability of this spike protein to mediate entry into cells expressing human ACE2, suggesting a potential zoonotic risk. The observed genetic diversity underscores the urgent need for continuous surveillance to identify high-risk animal-to-human interfaces and inform pandemic preparedness.

Animals

Hemoglobin E and glucose-6-phosphate deficiency in the Khmer Air Force (Cambodia).

This study was designed to investigate the use of primaquine in malaria control in the Khmer Republic (Cambodia). Blood was drawn from 106 male Khmer Air Force troops for analysis of hemoglobin E and glucose-6-phosphate (G-6-PD) deficiency. A test group of 15 men with G-6-PD deficiency and a group of 31 normal controls were given 15 mg of primaquine each morning for 14 days. The patients were followed for hemoglobinuria and changes in hematocrit. Primaquine induced a significant, but not a dangerous, hemolysis in G-6pD-deficient Khmer troops. The G-6-PD deficiency seen in Khmer Air Force subjects was G-6-PD Mahidol. Statistically, G-6-PD Mahidol was linked to hemoglobin E.

Cambodia

G6PD deficiency with Gd(-)A like variant in a Chinese family from Cambodia.

A low rate value of G6PD was found in red blood cells from a Cambodian boy. Enzyme mapping was performed according to the WHO standard methods. G6PD presented all the characteristics of the A(-) variant encountered in the Negroes and behaved distinct from fast migrating enzymes described in China. No negro was in the ancestry of the mother.

Adult

The Ocean-Hill Brownsville and Cambodian-Kent State crises: a biobehavioral approach to human sociobiology.

The author traces the origin of his thinking on a biobehavioral systems approach to human sociobiology as it evolved from his observations and analyses of on-the-ground human behavior in local, Ocean-Hill Brownsville, and nationwide, Cambodia-Kent State, political crises, as well as from his naturalistic observations of face-to-face behavior in group psychotherapy. He argues that the resulting sociobiological paradigm--arrived at independently by several other workers--is a fruitful alternative to sociobiological models derived from population biology and genetics.

Biology

Adolescent health across Asia Pacific, 2000-23: a systematic analysis for the Global Burden of Disease Study 2023.

BACKGROUND: The Asia Pacific region is home to more than half of the world's 1&#xb7;93 billion adolescents (aged 10-24 years). Addressing adolescent health in this region is of global importance, but to date a systematic analysis of key contributors to disease in adolescents has not been done, which is a barrier to responsive action. This systematic analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 aims to provide a comprehensive assessment of adolescent health across the Asia Pacific region, at both the subregional and national levels, encompassing burden of disease, mortality, and prevalence of adolescent risk factors. METHODS: As part of GBD 2023, we obtained estimates for cause-specific mortality, disability-adjusted life-years (DALYs), and risk factor prevalence by sex for adolescents aged 10-24 years and 5-year age groups (10-14 years, 15-19 years, and 20-24 years) across 44 countries and territories (hereafter referred to collectively as Asia Pacific), grouped by seven UN subregions, from 2000 to 2023. We extracted GBD 2023 population counts and estimates of number and rate (per 100&#x2008;000 population) for mortality and disease burden (DALYs). Risk prevalence estimates were obtained directly from the Institute for Health Metrics and Evaluation, and binge drinking estimates were sourced from WHO. Estimates are reported with 95% uncertainty intervals (UIs) where possible. UIs were estimated by running 250 draws of the posterior distribution, ordering the draws, and selecting the 2&#xb7;5th and 97&#xb7;5th percentiles for each metric. FINDINGS: In 2023, in adolescents across Asia Pacific, there were 637&#x2008;496 deaths and a total disease burden of 115&#xb7;8 million DALYs, representing 34&#xb7;1% of global adolescent deaths and 40&#xb7;6% of the global adolescent burden of disease. Non-communicable diseases (NCDs; particularly mental disorders) were the leading causes of disease burden and mortality (64&#xb7;8% of DALYs and 43&#xb7;9% of deaths). Unintentional and transport injuries were also leading causes of death (14&#xb7;7% of deaths due to transport injury and 13&#xb7;3% of deaths due to unintentional injury) and leading causes of disease burden particularly among males in south-eastern Asia. In Melanesia, Micronesia, and some parts of south-eastern Asia (Cambodia, Indonesia, Laos, the Philippines, and Timor-Leste), respiratory infections and tuberculosis remained important contributors. Southern Asia had the largest reduction (1&#xb7;5% per year) in all-cause DALYs over the study period, and Australia and New Zealand (0&#xb7;2% per year) had the smallest, with females in Australia and New Zealand showing a slight increase contrary to regional trends. Eastern Asia had the largest reduction (2&#xb7;8% per year) in all-cause mortality rate and Melanesia (0&#xb7;8% per year) the smallest. Risk factors generally had between-subregion and within-subregion variation; however, some regional trends stood out, with overweight and obesity increasing in all countries across the region, and binge drinking increasing in more countries than not. In 2023, prevalence of smoking in males exceeded that in females in every country, from 40% difference in Timor-Leste to less than 1% difference in Australia. Anaemia prevalence is decreasing in all countries, but female prevalence was higher and reducing at a slower rate than in males. Bullying prevalence was slightly higher in Polynesia, Micronesia, and Melanesia combined, Australia and New Zealand, and eastern Asia compared with southern and south-eastern Asian subregions. INTERPRETATION: Several patterns were consistent across the region: the dominance of mental disorders and NCDs, the universal rise in overweight and obesity (particularly high in Oceanic countries but increasing rapidly in south and south-eastern Asia), and persistent sex-specific challenges across subregions: unintentional injuries and smoking in males, and anaemia in females. Actions to tackle shared risk factors (while accounting for context-specific local health profiles, workforce deficits, cultural factors, and health system capacity) should not be forgone due to local variation. Future research could focus on subnational variation, intersecting inequalities, and multi-sectoral interventions targeting shared risk factors. Priority actions should include regional investment in adolescent mental health services and obesity prevention, targeted injury reduction strategies for high-risk populations, and sex-specific approaches to smoking cessation and anaemia reduction, delivered through local health systems with the capacity and cultural responsiveness to meet local needs. FUNDING: Gates Foundation and Australian Government.

Humans

Genomic diversity and selection signatures in Asian Zebu Cattle: insights into adaptation and genetic erosion.

Indigenous cattle breeds in Asia are highly adapted to their local environments providing essential commodities such as meat, milk and draught power while also playing a key role in traditional ceremonies, and sports. Despite ongoing efforts to characterize and conserve these breeds, the increasing trend of indiscriminate crossbreeding of Zebu cattle with high-yielding taurine breeds, threatens their genetic diversity. This study investigates the population structure, inbreeding levels, effective population size, gene flow and identification of selection footprints of Asian Zebu (Bos indicus) cattle. Using an Axiom 60&#xa0;K SNP chip, we analyzed genotypes from 1303 cattle across 36 populations in nine countries, including seven taurine outgroups and 29 Zebu populations from Bangladesh, Cambodia, India, Myanmar, Pakistan, and Sri Lanka. Zebu populations demonstrated moderate genetic diversity, with heterozygosity levels averaging 0.356, inbreeding coefficients ranging from 0.026 to 0.074 and genetic differentiation (FST) varied between 0.01 and 0.11. Breed clusters aligned closely with their geographic locations except for Achai (Pakistan) and Baru Harak (Sri Lanka) breeds that appeared in both Zebu and taurine clusters indicating evidence of taurine admixture. Genomic analyses identified regions under selection using extended haplotype homozygosity (EHH) and fixation index (FST) methods. Candidate genes associated with key biological functions related to environmental responsiveness, including heat tolerance (HSP90AA1), immunity (RIPK3), metabolism and fertility (REC8, CLIC4, TSSK4), were identified, reflecting adaptive traits critical for Zebu survival and utility across diverse environments. These findings provide valuable insights for conservation and management strategies aimed at preserving the unique genetic diversity of Asian Bos indicus breeds.

Animals

A common DNA deletion altering the 3'UTR of mdr1 is associated with reduced mefloquine susceptibility in P. vivax parasites from Cambodian patients.

Artemisinin-combination therapies (ACTs) are now recommended for the treatment of uncomplicated malaria caused by Plasmodium vivax, the parasite responsible for the majority of malaria infections outside of Africa. We analyzed the genome sequences of 206 P. vivax parasites collected from Cambodian malaria patients and showed that more than 80% of them carried a DNA deletion located immediately downstream of the multidrug resistance 1 gene (mdr1). This 837 bp deletion overlapped with a different deletion present at low frequency in South American isolates, suggesting a functional role despite not altering the coding sequence of mdr1. Using RNA sequencing, we showed that these deletions altered the transcripts expressed from mdr1 and resulted in mRNAs with different 3' untranslated regions. In Cambodian isolates, the deletion was significantly associated with a higher expression of mdr1 and a lower ex vivo susceptibility to mefloquine. Finally, we genotyped 592 Cambodian isolates collected between 2014 and 2024 and showed that the mdr1 deletion increased in frequency in Cambodia since the introduction of mefloquine as ACT partner drug. Overall, these findings indicate that a common deletion of a non-coding sequence affects the transcription, stability, or translation of mdr1 in P. vivax parasites and could mediate reduced susceptibility to antimalarial drug(s) currently used for the treatment of uncomplicated vivax malaria.

Journal Article

Spinal cysticercosis.

Myelopathy in a Cambodian patient proved to be due to cysticercosis. Spinal cysticercosis is rare, and Indochina is an unusual place to have acquired it.

Adult

Food or freedom?

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Cambodia

Subtypes of hepatitis B surface antigen in Southeast Asia.

The prevalences of hepatitis B surface antigen (HBs Ag) subtypes in Thais, Cambodians, and Vietnamese were compared with the prevalences in Americans residing in Southeast Asia. HBs Ag was found with approximately equal frequency in Thai (43 percent) and American (39 percent) patients with hepatitis. However, higher prevalences of HBs Ag were found in asympotomatic Thais (9.5 percent), Cambodians (11.9 percent), and Vietnamese (14.3 percent) than in asymptomatic Americans (0.7 percent). Among asymptomatic Thais, the ratio of HBs Ag/adr to HBs Ag/adw was approximately 10:1, with one exception: adw was not detected in a rural population of northern Thailand. The y determinant was not found in Thais. In contrast, both d and y determinants were found in Americans. These observations conform to a geographic pattern, with ad as the predominant combination in the Far East. In Southeast Asia determinants w and r are more useful epidemiologic markers than y and d.

Animals

Influence of opium availability on addiction rates in Laos.

Crude rates of opium addiction were determined in 1972-1974 in ten communities of Laos, representing eight different ethnic groups and three provinces. In six rural communities, data were obtained by a house-to-house survey, and in four urban communities by opium den registration. Communities raising opium poppy as a cash crop had highest crude rates of addiction (7.0-9.8 addicts per 100 people). Thos involved in opium commerce had intermediate rates (4.1-5.5). Where neither opium production nor commerce was present, the communities had the lowest rates of addiction (1.8-2.3).

Agriculture