100 ancient genomes show repeated population turnovers in Neolithic Denmark.

Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1-4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5-7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.

The selection landscape and genetic legacy of ancient Eurasians.

The Holocene (beginning around 12,000 years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical and mental health of present-day populations. Using a dataset of more than 1,600 imputed ancient genomes1, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify key selection signals related to metabolism, including that selection at the FADS cluster began earlier than previously reported and that selection near the LCT locus predates the emergence of the lactase persistence allele by thousands of years. We also find strong selection in the HLA region, possibly due to increased exposure to pathogens during the Bronze Age. Using ancient individuals to infer local ancestry tracts in over 400,000 samples from the UK Biobank, we identify widespread differences in the distribution of Mesolithic, Neolithic and Bronze Age ancestries across Eurasia. By calculating ancestry-specific polygenic risk scores, we show that height differences between Northern and Southern Europe are associated with differential Steppe ancestry, rather than selection, and that risk alleles for mood-related phenotypes are enriched for Neolithic farmer ancestry, whereas risk alleles for diabetes and Alzheimer's disease are enriched for Western hunter-gatherer ancestry. Our results indicate that ancient selection and migration were large contributors to the distribution of phenotypic diversity in present-day Europeans.

Population genomics of post-glacial western Eurasia.

Western Eurasia witnessed several large-scale human migrations during the Holocene1-5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes-mainly from the Mesolithic and Neolithic periods-from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a 'great divide' genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 BP, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 BP, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a 'Neolithic steppe' cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.

Bayesian inference of admixture graphs on Native American and Arctic populations.

Admixture graphs are mathematical structures that describe the ancestry of populations in terms of divergence and merging (admixing) of ancestral populations as a graph. An admixture graph consists of a graph topology, branch lengths, and admixture proportions. The branch lengths and admixture proportions can be estimated using numerous numerical optimization methods, but inferring the topology involves a combinatorial search for which no polynomial algorithm is known. In this paper, we present a reversible jump MCMC algorithm for sampling high-probability admixture graphs and show that this approach works well both as a heuristic search for a single best-fitting graph and for summarizing shared features extracted from posterior samples of graphs. We apply the method to 11 Native American and Siberian populations and exploit the shared structure of high-probability graphs to characterize the relationship between Saqqaq, Inuit, Koryaks, and Athabascans. Our analyses show that the Saqqaq is not a good proxy for the previously identified gene flow from Arctic people into the Na-Dene speaking Athabascans.

A Case of Eosinophilic Angiocentric Fibrosis With Palatal Fistulas.

Eosinophilic angiocentric fibrosis (EAF) is a rare, but benign, tumefactive lesion of the head and neck regions. It was initially discovered in 1983 but has recently been connected to the spectrum of immunoglobulin G4-related disease (IgG4-RD). It commonly presents with symptoms of nasal obstruction, structural deformities of the external nose, and involvement of the nasal septum and lateral nasal wall. Our patient presented with a saddle nose deformity, a septal perforation, and palatal fistulas. Laboratory testing for EAF is often negative for the presence of antinuclear cytoplasmic antibodies (ANCA). A definitive diagnosis of EAF can be made through histopathological analysis of the lesion. The appearance of "onion-skin" fibrosis with perivascular infiltration of primary eosinophils is pathognomonic for EAF. While there is a presence of ulceration tissue, EAF does not have any histological signs of necrosis. EAF is a very uncommon etiology of nasal obstructive symptoms; therefore, it is necessary to rule out more conventional pathologies. Even though it appears as a malignant process, it has an excellent prognosis. The common treatment modalities for an active lesion of EAF involve either surgical resection of margins alone or a combination of corticosteroids and resection. Rituximab has also shown benefits in the management of IgG4-RD as a corticosteroid-sparing treatment. Rituximab was chosen for treatment in our patient because surgical resection was not possible due to the absence of an active lesion. In this article, we provide a brief review of EAF and provide a unique case of EAF presenting with oronasal palatal fistulas.

Evaluation of methods for estimating coalescence times using ancestral recombination graphs.

The ancestral recombination graph is a structure that describes the joint genealogies of sampled DNA sequences along the genome. Recent computational methods have made impressive progress toward scalably estimating whole-genome genealogies. In addition to inferring the ancestral recombination graph, some of these methods can also provide ancestral recombination graphs sampled from a defined posterior distribution. Obtaining good samples of ancestral recombination graphs is crucial for quantifying statistical uncertainty and for estimating population genetic parameters such as effective population size, mutation rate, and allele age. Here, we use standard neutral coalescent simulations to benchmark the estimates of pairwise coalescence times from 3 popular ancestral recombination graph inference programs: ARGweaver, Relate, and tsinfer+tsdate. We compare (1) the true coalescence times to the inferred times at each locus; (2) the distribution of coalescence times across all loci to the expected exponential distribution; (3) whether the sampled coalescence times have the properties expected of a valid posterior distribution. We find that inferred coalescence times at each locus are most accurate in ARGweaver, and often more accurate in Relate than in tsinfer+tsdate. However, all 3 methods tend to overestimate small coalescence times and underestimate large ones. Lastly, the posterior distribution of ARGweaver is closer to the expected posterior distribution than Relate's, but this higher accuracy comes at a substantial trade-off in scalability. The best choice of method will depend on the number and length of input sequences and on the goal of downstream analyses, and we provide guidelines for the best practices.

An Observational Study of Sepsis in Takeo Province Cambodia: An in-depth examination of pathogens causing severe infections.

The world's most consequential pathogens occur in regions with the fewest diagnostic resources, leaving the true burden of these diseases largely under-represented. During a prospective observational study of sepsis in Takeo Province Cambodia, we enrolled 200 patients over an 18-month period. By coupling traditional diagnostic methods such as culture, serology, and PCR to Next Generation Sequencing (NGS) and advanced statistical analyses, we successfully identified a pathogenic cause in 46.5% of our cohort. In all, we detected 25 infectious agents in 93 patients, including severe threat pathogens such as Burkholderia pseudomallei and viral pathogens such as Dengue virus. Approximately half of our cohort remained undiagnosed; however, an independent panel of clinical adjudicators determined that 81% of those patients had infectious causes of their hospitalization, further underscoring the difficulty of diagnosing severe infections in resource-limited settings. We garnered greater insight as to the clinical features of severe infection in Cambodia through analysis of a robust set of clinical data.

Performance Characteristics of a Multiplex Flow Immunoassay for Detection of IgG-Class Antibodies to Measles, Mumps, Rubella, and Varicella-Zoster Viruses in Presumptively Immune Health Care Workers.

Immunity to measles, mumps, rubella, and varicella-zoster viruses (VZV; MMRV) is a common condition of employment for health care workers (HCWs) to ensure compliance with national standards and state laws. When documentation of complete vaccination or laboratory-confirmed infection is not available, Advisory Committee on Immunization Practices (ACIP) criteria are used to guide vaccination or anti-MMRV IgG testing. We assessed the performance of the BioPlex 2200 MMRV IgG multiplex flow immunoassay (MFI; Bio-Rad Laboratories, Hercules, CA) and matched immunofluorescence assays (IFAs; MBL Bion, Des Plaines, IL) in 220 HCWs categorized by ACIP criteria for presumptive immunity to MMRV. Among HCWs presumptively immune to measles, mumps, rubella, and VZV, the Bio-Rad MFI was positive in 77.3, 85.4, 84.3, and 91.1% of HCWs, respectively. Comparatively, the Bion IFA was positive in 92.9, 91.1, and 93.5% of HCWs presumptively immune to measles, mumps, and VZV (a rubella IFA was unavailable). Among HCWs fully vaccinated against measles, mumps, and VZV, Bio-Rad MFI/Bion IFA positivity rates were 77.4%/93%, 84.8%/90.7%, and 54.5%/90.9%, respectively. The Bio-Rad MFI was positive in 83.7% of HCWs fully vaccinated against rubella. For HCWs whose last vaccination event occurred within 15 years of enrollment, 83.3, 93.3, and 74.2% were positive by the Bio-Rad measles, mumps, and rubella IgG MFIs, respectively. We show significantly decreased Bio-Rad MFI sensitivity for detection of anti-measles and anti-mumps IgG-class antibodies in presumptively immune or fully vaccinated HCWs. Although negative results typically prompt revaccination, failure to recognize presumptive immunity in individuals unable to receive live, attenuated vaccines may have employment implications.

An Investigation of Healthcare Worker Perception of Their Workplace Safety and Incidence of Injury.

Background: Managing the safety climate in health care is a promising tool for improving employee and patient safety in the health care work environment. Gaps in the theoretical and conceptual underpinnings of safety climate, as well as the evidence base for its practical application in health care remain. The purpose of this study was to evaluate the number of work injuries occurring in health care work units and associated safety climate beliefs. Methods: A retrospective analysis was conducted utilizing organizational staff survey data collected by a large medical hospital in the Midwest in 2015. Employees (n = 32,327) were invited to identify safety climate perceptions via survey. Injuries, days restricted, and days absent were identified through the Hospital's Occupational Safety and Health Administration (OSHA) log. Zero inflated negative binomial regressions used injuries as dependent variables and safety climate perceptions as independent variables. Findings: In all, 23,599 employees completed the survey (73% response rate) across 1,805 employee work units which were defined as groupings of employees reporting to a single supervisor. We found that there was an association between fewer injuries and health care workers indicating that they share responsibility for compliance with safety rules and procedures (relative risk [RR] = 0.98, 95% confidence interval [CI] = [0.98, 0.99]). Conclusion/Application to Practice: This study supports the use of a safety climate measure to assess working units' perceptions of employee safety. A continued focus on the health and safety of employees who interact directly with patients is warranted, as well as employees who do not provide direct patient care.

Determinants of Latent Tuberculosis Treatment Acceptance and Completion in Healthcare Personnel.

BACKGROUND: US public health strategy for eliminating tuberculosis (TB) prioritizes treatment of latent TB infection (LTBI). Healthcare personnel (HCP) are less willing to accept treatment than other populations. Little is known about factors associated with HCP LTBI therapy acceptance and completion. METHODS: We conducted a retrospective chart review to identify all employees with LTBI at time of hire at a large academic medical center during a 10-year period. Personal demographics, occupational factors, and clinic visit variables were correlated with LTBI treatment acceptance and completion rates using multivariate logistic regression. RESULTS: Of 470 HCP with LTBI for whom treatment was recommended, 193 (41.1%) accepted treatment, while 137 (29.1%) completed treatment. Treatment adherence was better with 4 months of rifampin than 9 months of isoniazid (95% vs 68%, P < .005). Increased age of the healthcare worker was independently associated with lower rates of treatment acceptance (odds ratio [95% confidence interval]: 0.97 [0.94-0.99] per year), as was having an occupation of clinician (0.47 [0.26-0.85]) or researcher (0.34 [0.19-0.64]). Male gender was associated with higher treatment acceptance (1.90 [1.21-2.99]). Treatment completion was associated with being from a low- (9.49 [2.06-43.73]) or medium- (8.51 [3.93-18.44]) TB-burden country. CONCLUSIONS: Geographic and occupational factors affect acceptance and completion of LTBI therapy. Short-course regimens may improve adherence. Physicians, researchers, and HCP from high-TB-burden countries have lower treatment rates than other HCP. Improving LTBI treatment in HCP will require attending to cultural and occupational differences.

Atovaquone-Proguanil in Combination With Artesunate to Treat Multidrug-Resistant P. falciparum Malaria in Cambodia: An Open-Label Randomized Trial.

BACKGROUND: Recent artemisinin-combination therapy failures in Cambodia prompted a search for alternatives. Atovaquone-proguanil (AP), a safe, effective treatment for multidrug-resistant Plasmodium falciparum (P.f.), previously demonstrated additive effects in combination with artesunate (AS). METHODS: Patients with P.f. or mixed-species infection (n = 205) in Anlong Veng (AV; n = 157) and Kratie (KT; n = 48), Cambodia, were randomized open-label 1:1 to a fixed-dose 3-day AP regimen +/-3 days of co-administered artesunate (ASAP). Single low-dose primaquine (PQ, 15 mg) was given on day 1 to prevent gametocyte-mediated transmission. RESULTS: Polymerase chain reaction-adjusted adequate clinical and parasitological response at 42 days was 90% for AP (95% confidence interval [CI], 82%-95%) and 92% for ASAP (95% CI, 83%-96%; P = .73). The median parasite clearance time was 72 hours for ASAP in AV vs 56 hours in KT (P < .001) and was no different than AP alone. At 1 week postprimaquine, 7% of the ASAP group carried microscopic gametocytes vs 29% for AP alone (P = .0001). Nearly all P.f. isolates had C580Y K13 propeller artemisinin resistance mutations (AV 99%; KT 88%). Only 1 of 14 treatment failures carried the cytochrome bc1 (Pfcytb) atovaquone resistance mutation, which was not present at baseline. P.f. isolates remained atovaquone sensitive in vitro but cycloguanil resistant, with a triple P.f. dihydrofolate reductase mutation. CONCLUSIONS: Atovaquone-proguanil remained marginally effective in Cambodia (≥90%) with minimal Pfcytb mutations observed. Treatment failures in the presence of ex vivo atovaquone sensitivity and adequate plasma levels may be attributable to cycloguanil and/or artemisinin resistance. Artesunate co-administration provided little additional blood-stage efficacy but reduced post-treatment gametocyte carriage in combination with AP beyond single low-dose primaquine.

Success of tympanic membrane repair following palatoplasty.

INTRODUCTION: Eustachian tube dysfunction, ubiquitous in patients with cleft palate, is a known risk factor for failure of tympanic membrane (TM) repair. Age may also influence the success rate. We describe a cohort of patients with cleft palate who underwent TM repair at a tertiary academic medical center. METHODS: Record query of International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes for cleft palate and otologic procedures (myringoplasty, tympanoplasty, mastoidectomy, and/or ossicular chain reconstruction) was performed for patients treated between 1984 and 2017. Successful TM repair was defined as having an intact TM on otoscopy or a non-large volume tympanogram at most-recent follow-up. RESULTS: Of 474 patients with a cleft palate, 25 (5%) underwent a TM repair, and 16 had complete records for analysis. Among these, there were 22 surgeries on 20 ears. Sixteen of 20 TM repairs were successful. The successful group underwent TM repair at a median age of 12.5 (range, 4.8 to 22.2) compared with a median age of 8.5 (range, 3.9 to 15.0) for the unsuccessful group (P=0.28). Patients whose TM repair was successful underwent TM repair a median of 9.1 years after palatoplasty (range, -1.2 to 21.2) compared with 7.2 years (range, 3.0 to 14.9) for the unsuccessful group (P=0.67). CONCLUSION: In our cohort, TM repair in cleft palate patients had an 80% success rate. In contrast to conventional teaching, age at the time of surgery and time after palatoplasty may not affect TM repair outcomes.

Trait-Based Modeling of Multihost Pathogen Transmission: Plant-Pollinator Networks.

Epidemiological models for multihost pathogen systems often classify individuals taxonomically and use species-specific parameter values, but in species-rich communities that approach may require intractably many parameters. Trait-based epidemiological models offer a potential solution but have not accounted for within-species trait variation or between-species trait overlap. Here we propose and study trait-based models with host and vector communities represented as trait distributions without regard to species identity. To illustrate this approach, we develop susceptible-infectious-susceptible models for disease spread in plant-pollinator networks with continuous trait distributions. We model trait-dependent contact rates in two common scenarios: nested networks and specialized plant-pollinator interactions based on trait matching. We find that disease spread in plant-pollinator networks is impacted the most by selective pollinators, universally attractive flowers, and cospecialized plant-pollinator pairs. When extreme pollinator traits are rare, pollinators with common traits are most important for disease spread, whereas when extreme flower traits are rare, flowers with uncommon traits impact disease spread the most. Greater nestedness and specialization both typically promote disease persistence. Given recent pollinator declines caused in part by pathogens, we discuss how trait-based models could inform conservation strategies for wild and managed pollinators. Furthermore, while we have applied our model to pollinators and pathogens, its framework is general and can be transferred to any kind of species interactions in any community.

Association Between Culture and Culture-Independent Microtyping in Recalcitrant Chronic Rhinosinusitis.

BACKGROUND:: Many different etiologies have been proposed to be responsible for the pathogenesis of chronic rhinosinusitis, including dysbiosis of the sinus microbiome. Attempts have recently been made to identify a pathogenic organism via advanced culture mechanisms. The purpose of this study is to use culture-dependent and culture-independent means of microtyping to determine whether any association exists between the quantity and quality of bacteria identified in patients with recalcitrant chronic rhinosinusitis. METHODS:: Medical records were retrospectively reviewed for patients with a history of revision sinus surgery and persistent symptoms who underwent endoscopically directed culture and underwent quantitative polymerase chain reaction analysis of the 16S ribosomal RNA of bacteria and fungi from February 1, 2014, to January 1, 2017. A total of 21 patients met the inclusion criteria. Medical records were reviewed to determine the number of bacterial isolates and relative abundance of bacteria and fungi on culture and polymerase chain reaction. RESULTS:: Using culture-independent techniques of examining purulent secretions in patients with recalcitrant chronic rhinosinusitis, an average of 3.61 isolates were identified per specimen, compared with culture-dependent methods that revealed 2.10 isolates per specimen ( P < .05). The dominant species identified on each culture was rarely the most abundant species identified using polymerase chain reaction techniques. CONCLUSIONS:: Traditional culture methodologies may fail to identify potential pathogens or the dominant pathogen in patients with recalcitrant chronic rhinosinusitis with acute exacerbations.

Maximum Likelihood Estimation of Fitness Components in Experimental Evolution.

Estimating fitness differences between allelic variants is a central goal of experimental evolution. Current methods for inferring such differences from allele frequency time series typically assume that the effects of selection can be described by a fixed selection coefficient. However, fitness is an aggregate of several components including mating success, fecundity, and viability. Distinguishing between these components could be critical in many scenarios. Here, we develop a flexible maximum likelihood framework that can disentangle different components of fitness from genotype frequency data, and estimate them individually in males and females. As a proof-of-principle, we apply our method to experimentally evolved cage populations of Drosophila melanogaster, in which we tracked the relative frequencies of a loss-of-function and wild-type allele of yellow This X-linked gene produces a recessive yellow phenotype when disrupted and is involved in male courtship ability. We find that the fitness costs of the yellow phenotype take the form of substantially reduced mating preference of wild-type females for yellow males, together with a modest reduction in the viability of yellow males and females. Our framework should be generally applicable to situations where it is important to quantify fitness components of specific genetic variants, including quantitative characterization of the population dynamics of CRISPR gene drives.

Medical Surveillance Programs for Workers Exposed to Hazardous Medications: A Survey of Current Practices in Health Care Institutions.

OBJECTIVE: To assess current medical surveillance monitoring practices for health care workers who prepare, handle, or administer hazardous medications. METHODS: A cross-sectional survey was distributed to members of the American College of Occupational and Environmental Medicine and the National Comprehensive Cancer Network. RESULTS: Forty-six of the 91 survey respondents indicated that their institution had a hazardous medication surveillance program. We identified the most frequent laboratory (complete blood count) and physical (skin) examination components. A health history was frequently used. Statistical analysis did not suggest an association between institutions with greater resources and presence of a surveillance program. CONCLUSIONS: A consensus standard for medical monitoring was not reported by the respondents. We recommend using a standardized surveillance questionnaire and applying uniform laboratory testing across institutions, in addition to establishing a national repository for surveillance data.

Seroprevalence and awareness of porcine cysticercosis across different pig production systems in south-central Cambodia.

BACKGROUND: Taeniasis/cysticercosis, caused by the pork tapeworm Taenia solium, represents an important public health and economic burden in endemic countries. However, there is a paucity of data on infection among pigs in many parts of Southeast Asia, particularly Cambodia. We aimed to estimate seroprevalence of porcine cysticercosis, and investigate husbandary practices and knowledge of the disease among livestock workers, across different pig sector units in south-central Cambodia. METHODS: A cross sectional survey was conducted among pig smallholders, commercial farms, slaughterhouses and traders/middlemen from south-central Cambodia, selected through multistage sampling in proportion to local pig populations sizes. Questionnaires were administered to 163 pig workers to obtain data pig production, trading and slaughtering practices. Sera from 620 pigs were tested for Taenia antigens using a commercial ELISA-based test. Associations between seroprevalence and pig husbandry practices were assessed using generalised linear mixed models, adjusting for random-effects at herd-level. RESULTS: Of 620 pigs sampled, 29 (4.7%) tested positive for Taenia antigens. Seropositivity was associated with type of pig sector unit (P = 0.008), with the highest seroprevalence among pigs sampled from traders/middlemen (16.7%; 95% CI: 4.4%-37.8%), smallholders (7.6%; 95% CI: 3.8%-14.1%) and slaughterhouses (4.1%; 95% CI: 2.0%-7.5%), while none of the pigs sampled from small/medium or large commercial farms tested positive. Although the vast majority of pigs were penned, practices that might facilitate human-to-pig transmission, such as use of household waste and surface water sources to feed pigs, were prevalent among smallholders. However these were not found to be significantly associated with infection. Of 163 interviewed pig workers, 115 (70.5%) were aware of porcine cysticercosis, and 78 (47.8%) also knew it could affect humans. Twenty-six (16.0%) reported having noticed lesions typical of cysticercosis in their pigs. CONCLUSIONS: Despite most pigs being kept confined in pens rather than raised in free-roaming systems, porcine cysticercosis appears to be endemic in south-central Cambodia and is associated with smallholder production. Further investigation is needed to identify which Taenia species are causing infections among pigs, and how seroprevalence and zoonotic risk may vary across the country, to understand the risks to public health and assess where interventions might be needed.

Retrospective Analysis of Fever and Sepsis Patients from Cambodia Reveals Serological Evidence of Melioidosis.

Burkholderia pseudomallei, the etiologic agent of melioidosis, is predicted to be ubiquitous in tropical regions of the world with areas of highest endemicity throughout Southeast Asia (SEA). Nevertheless, the distribution of B. pseudomallei and the burden of melioidosis in many SEA countries remain unclear. In Cambodia, only two human endemic cases of melioidosis were reported through 2008 and since then only a few hundred cases have been described in the literature. This is in sharp contrast to the annual burden of thousands of cases in surrounding areas. To further investigate the prevalence of melioidosis in Cambodia, we used a recently developed O-polysaccharide-based rapid enzyme-linked immunosorbent assay to detect B. pseudomallei-specific antibodies in serum samples obtained from 1,316 febrile illness or sepsis patients from 10 different provinces. Based on a cutoff value derived through culture-confirmed melioidosis cases, the proportion of positive samples in our cohort was approximately 12%. Regression analysis indicated that the odds of obtaining a positive result were 2.2 times higher for males than females controlling for age and province (95% confidence interval: 1.6-3.2, P < 0.001). Consistent with this, 9.2% of females were positive versus 18.2% of males (P < 0.001). Notably, 22.5% of grain or rice farmers were positive versus 10.1% of subjects with occupations not involving regular contact with soil. Positive results varied significantly by province. Collectively, the results of this study suggest that the true burden of melioidosis in Cambodia is greater than has previously been reported.

Melioidosis in lower provincial Cambodia: A case series from a prospective study of sepsis in Takeo Province.

Melioidosis is a severe infectious disease caused by the gram-negative soil bacterium Burkholderia pseudomallei. Melioidosis is well known to be a major cause of morbidity and mortality in Southeast Asia, particularly in Thailand. However, melioidosis remains underreported in surrounding areas such as Cambodia. We report a case series of melioidosis in seven patients from Takeo Province, Cambodia. The patients, aged 24-65 years, were enrolled from May 2014 to May 2015 during a one year prospective study of sepsis at Takeo Provincial Hospital. They presented with fever, rigors, dyspnea, fatigue, diaphoresis, productive cough, and skin abscesses. Six of the seven patients were also hyponatremic. B. pseudomallei was cultured from the blood of six patients and the sputum of one patient. In this manuscript, we provide a detailed description of the clinical presentation, case management and laboratory confirmation of B. pseudomallei, as well as discuss the difficulties of identifying and treating melioidosis in low resource settings.