Publications by authors named "Sayaphet Rattanavong"

46 Publications

Childhood encephalitis in the Greater Mekong region (the SouthEast Asia Encephalitis Project): a multicentre prospective study.

Lancet Glob Health 2022 07;10(7):e989-e1002

National Institute of Hygiene and Epidemiology, Hanoi, Vietnam.

Background: Encephalitis is a worldwide public health issue, with a substantially high burden among children in southeast Asia. We aimed to determine the causes of encephalitis in children admitted to hospitals across the Greater Mekong region by implementing a comprehensive state-of-the-art diagnostic procedure harmonised across all centres, and identifying clinical characteristics related to patients' conditions.

Methods: In this multicentre, observational, prospective study of childhood encephalitis, four referral hospitals in Cambodia, Vietnam, Laos, and Myanmar recruited children (aged 28 days to 16 years) who presented with altered mental status lasting more than 24 h and two of the following minor criteria: fever (within the 72 h before or after presentation), one or more generalised or partial seizures (excluding febrile seizures), a new-onset focal neurological deficit, cerebrospinal fluid (CSF) white blood cell count of 5 per mL or higher, or brain imaging (CT or MRI) suggestive of lesions of encephalitis. Comprehensive diagnostic procedures were harmonised across all centres, with first-line testing was done on samples taken at inclusion and results delivered within 24 h of inclusion for main treatable causes of disease and second-line testing was done thereafter for mostly non-treatable causes. An independent expert medical panel reviewed the charts and attribution of causes of all the included children. Using multivariate analyses, we assessed risk factors associated with unfavourable outcomes (ie, severe neurological sequelae and death) at discharge using data from baseline and day 2 after inclusion. This study is registered with ClinicalTrials.gov, NCT04089436, and is now complete.

Findings: Between July 28, 2014, and Dec 31, 2017, 664 children with encephalitis were enrolled. Median age was 4·3 years (1·8-8·8), 295 (44%) children were female, and 369 (56%) were male. A confirmed or probable cause of encephalitis was identified in 425 (64%) patients: 216 (33%) of 664 cases were due to Japanese encephalitis virus, 27 (4%) were due to dengue virus, 26 (4%) were due to influenza virus, 24 (4%) were due to herpes simplex virus 1, 18 (3%) were due to Mycobacterium tuberculosis, 17 (3%) were due to Streptococcus pneumoniae, 17 (3%) were due to enterovirus A71, 74 (9%) were due to other pathogens, and six (1%) were due to autoimmune encephalitis. Diagnosis was made within 24 h of admission to hospital for 83 (13%) of 664 children. 119 (18%) children had treatable conditions and 276 (42%) had conditions that could have been preventable by vaccination. At time of discharge, 153 (23%) of 664 children had severe neurological sequelae and 83 (13%) had died. In multivariate analyses, risk factors for unfavourable outcome were diagnosis of M tuberculosis infection upon admission (odds ratio 3·23 [95% CI 1·04-10·03]), coma on day 2 (2·90 [1·78-4·72]), supplementary oxygen requirement (1·89 [1·25-2·86]), and more than 1 week duration between symptom onset and admission to hospital (3·03 [1·68-5·48]). At 1 year after inclusion, of 432 children who were discharged alive from hospital with follow-up data, 24 (5%) had died, 129 (30%) had neurological sequelae, and 279 (65%) had completely recovered.

Interpretation: In southeast Asia, most causes of childhood encephalitis are either preventable or treatable, with Japanese encephalitis virus being the most common cause. We provide crucial information that could guide public health policy to improve diagnostic, vaccination, and early therapeutic guidelines on childhood encephalitis in the Greater Mekong region.

Funding: Institut Pasteur, Institut Pasteur International Network, Fondation Merieux, Aviesan Sud, INSERM, Wellcome Trust, Institut de Recherche pour le Développement (IRD), and Fondation Total.
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http://dx.doi.org/10.1016/S2214-109X(22)00174-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210261PMC
July 2022

Distribution of Burkholderia pseudomallei within a 300-cm deep soil profile: implications for environmental sampling.

Sci Rep 2022 05 23;12(1):8674. Epub 2022 May 23.

GET, Université de Toulouse, CNRS, IRD, UPS, Toulouse, France.

The environmental distribution of Burkholderia pseudomallei, the causative agent of melioidosis, remains poorly understood. B. pseudomallei is known to have the ability to occupy a variety of environmental niches, particularly in soil. This paper provides novel information about a putative association of soil biogeochemical heterogeneity and the vertical distribution of B. pseudomallei. We investigated (1) the distribution of B. pseudomallei along a 300-cm deep soil profile together with the variation of a range of soil physico-chemical properties; (2) whether correlations between the distribution of B. pseudomallei and soil physico-chemical properties exist and (3) when they exist, what such correlations indicate with regards to the environmental conditions conducive to the occurrence of B. pseudomallei in soils. Unexpectedly, the highest concentrations of B. pseudomallei were observed between 100 and 200 cm below the soil surface. Our results indicate that unravelling the environmental conditions favorable to B. pseudomallei entails considering many aspects of the actual complexity of soil. Important recommendations regarding environmental sampling for B. pseudomallei can be drawn from this work, in particular that collecting samples down to the water table is of foremost importance, as groundwater persistence appears to be a controlling factor of the occurrence of B. pseudomallei in soil.
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http://dx.doi.org/10.1038/s41598-022-12795-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9126866PMC
May 2022

Immunoglobulin M seroneutralization for improved confirmation of Japanese encephalitis virus infection in a flavivirus-endemic area.

Trans R Soc Trop Med Hyg 2022 May 18. Epub 2022 May 18.

Lao-Oxford-Mahosot Hospital-Wellcome Trust-Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR.

Background: The mainstay of diagnostic confirmation of acute Japanese encephalitis (JE) involves detection of anti-JE virus (JEV) immunoglobulin M (IgM) by enzyme-linked immunosorbent assay (ELISA). Limitations in the specificity of this test are increasingly apparent with the introduction of JEV vaccinations and the endemicity of other cross-reactive flaviviruses. Virus neutralization testing (VNT) is considered the gold standard, but it is challenging to implement and interpret. We performed a pilot study to assess IgG depletion prior to VNT for detection of anti-JEV IgM neutralizing antibodies (IgM-VNT) as compared with standard VNT.

Methods: We evaluated IgM-VNT in paired sera from anti-JEV IgM ELISA-positive patients (JE n=35) and negative controls of healthy flavivirus-naïve (n=10) as well as confirmed dengue (n=12) and Zika virus (n=4) patient sera. IgM-VNT was subsequently performed on single sera from additional JE patients (n=76).

Results: Anti-JEV IgG was detectable in admission serum of 58% of JE patients. The positive, negative and overall percentage agreement of IgM-VNT as compared with standard VNT was 100%. A total of 12/14 (86%) patient samples were unclassified by VNT and, with sufficient sample available for IgG depletion and IgG ELISA confirming depletion, were classified by IgM-VNT. IgM-VNT enabled JE case classification in 72/76 (95%) patients for whom only a single sample was available.

Conclusions: The novel approach has been readily adapted for high-throughput testing of single patient samples and it holds promise for incorporation into algorithms for use in reference centres.
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http://dx.doi.org/10.1093/trstmh/trac036DOI Listing
May 2022

Detection and significance of neuronal autoantibodies in patients with meningoencephalitis in Vientiane, Lao PDR.

Trans R Soc Trop Med Hyg 2022 Apr 6. Epub 2022 Apr 6.

Lao-Oxford-Mahosot Hospital-Wellcome Research Unit OX3 7JX (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR.

Background: The importance of autoimmune encephalitis and its overlap with infectious encephalitides are not well investigated in South-East Asia.

Methods: We report autoantibody testing, using antigen-specific live cell-based assays, in a series of 134 patients (cerebrospinal fluid and sera) and 55 blood donor controls (sera), undergoing lumbar puncture for suspected meningoencephalitis admitted in Vientiane, Lao People's Democratic Republic (PDR).

Results: Eight of 134 (6%) patients showed detectable serum neuronal autoantibodies, against the N-methyl-D-aspartate and gamma-aminobutyric acid A receptors (NMDAR and GABAAR), and contactin-associated protein-like 2 (CASPR2). Three of eight patients had accompanying autoantibodies in cerebrospinal fluid (two with NMDAR and one with GABAAR antibodies), and in two of these the clinical syndromes were typical of autoimmune encephalitis. Three of the other five patients had proven central nervous system infections, highlighting a complex overlap between diverse infectious and autoimmune causes of encephalitis. No patients in this cohort were treated with immunotherapy, and the outcomes were poor, with improvement observed in a single patient.

Conclusions: In Lao PDR, autoimmune encephalitis is underdiagnosed and has a poor prognosis. Empiric immunotherapy should be considered after treatable infectious aetiologies are considered unlikely. Awareness and diagnostic testing resources for autoimmune encephalitis should be enhanced in South-East Asia.
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http://dx.doi.org/10.1093/trstmh/trac023DOI Listing
April 2022

Genetic diversity of Leptospira isolates in Lao PDR and genome analysis of an outbreak strain.

PLoS Negl Trop Dis 2021 12 28;15(12):e0010076. Epub 2021 Dec 28.

Biology of Spirochetes Unit, Institut Pasteur, Paris, France.

Background: Although Southeast Asia is one of the most leptospirosis afflicted regions, little is known about the diversity and molecular epidemiology of the causative agents of this widespread and emerging zoonotic disease.

Methodology/principal Findings: We used whole genome sequencing to examine genetic variation in 75 Leptospira strains isolated from patients in the Lao PDR (Laos) between 2006 and 2017. Eleven serogroups from 4 Leptospira species and 43 cgMLST-defined clonal groups (CGs) were identified. The most prevalent CG was CG272 (n = 18, 26.8%), composed of L. interrogans serogroup Autumnalis isolates. This genotype was recovered throughout the 12-year period and was associated with deaths, and with a large outbreak in neighbouring Thailand. Genome analysis reveals that the CG272 strains form a highly clonal group of strains that have, for yet unknown reasons, recently spread in Laos and Thailand. Additionally, accessory genes clearly discriminate CG272 strains from the other Leptospira strains.

Conclusions/significance: The present study reveals a high diversity of Leptospira genotypes in Laos, thus extending our current knowledge of the pan- and core-genomes of these life-threatening pathogens. Our results demonstrate that the CG272 strains belong to a unique clonal group, which probably evolved through clonal expansion following niche adaptation. Additional epidemiological studies are required to better evaluate the spread of this genotype in Southeast Asia. To further investigate the key factors driving the virulence and spread of these pathogens, more intense genomic surveillance is needed, combining detailed clinical and epidemiological data.
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http://dx.doi.org/10.1371/journal.pntd.0010076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8746763PMC
December 2021

A spatio-temporal analysis of scrub typhus and murine typhus in Laos; implications from changing landscapes and climate.

PLoS Negl Trop Dis 2021 08 25;15(8):e0009685. Epub 2021 Aug 25.

Lao-Oxford-Mahosot-Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR.

Background: Scrub typhus (ST) and murine typhus (MT) are common but poorly understood causes of fever in Laos. We examined the spatial and temporal distribution of ST and MT, with the intent of informing interventions to prevent and control both diseases.

Methodology And Principle Findings: This study included samples submitted from 2003 to 2017 to Mahosot Hospital, Vientiane, for ST and MT investigation. Serum samples were tested using IgM rapid diagnostic tests. Patient demographic data along with meteorological and environmental data from Laos were analysed. Approximately 17% of patients were positive for either ST (1,337/8,150 patients tested) or MT (1,283/7,552 patients tested). While both diseases occurred in inhabitants from Vientiane Capital, from the univariable analysis MT was positively and ST negatively associated with residence in Vientiane Capital. ST was highly seasonal, with cases two times more likely to occur during the wet season months of July-September compared to the dry season whilst MT peaked in the dry season. Multivariable regression analysis linked ST incidence to fluctuations in relative humidity whereas MT was linked to variation in temperature. Patients with ST infection were more likely to come from villages with higher levels of surface flooding and vegetation in the 16 days leading up to diagnosis.

Conclusions: The data suggest that as cities expand, high risk areas for MT will also expand. With global heating and risks of attendant higher precipitation, these data suggest that the incidence and spatial distribution of both MT and ST will increase.
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http://dx.doi.org/10.1371/journal.pntd.0009685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386877PMC
August 2021

Antimicrobial-Resistant Strains and Their Plasmids in People, Poultry, and Chicken Meat in Laos.

Front Microbiol 2021 26;12:708182. Epub 2021 Jul 26.

Institute for Infectious Diseases, University of Bern, Bern, Switzerland.

Antimicrobial resistant (AMR) Enterobacterales are widely distributed among the healthy population of the Indochinese peninsula, including Laos. However, the local reservoir of these pathogens are currently not known and possible sources such as agricultural settings and food have rarely been analyzed. In this work, we investigated the extended-spectrum cephalosporin- (ESC-) and colistin-resistant strains (CST-R-) isolated from the gut of local people, feces of poultry, and from chicken meat (60 samples each group) in Laos. Whole-genome sequencing (WGS) analysis based on both short- and long-read sequencing approaches were implemented. The following prevalence of ESC-R- and CST-R- were recorded, respectively: local people (70 and 15%), poultry (20 and 23.3%), and chicken meat (21.7 and 13.3%). Core-genome analysis, coupled with sequence type (ST)/core-genome ST (cgST) definitions, indicated that no common AMR- clones were spreading among the different settings. ESC-R- mostly possessed and associated to IS or IS. The majority of CST-R- carried on IncX4, IncI2, IncP1, and IncHI1 plasmids similar or identical to those described worldwide; strains with chromosomal or possessing plasmid-mediated were also found. These results indicate a high prevalence of AMR- in the local population, poultry, and chicken meat. While we did not observe the same clones among the three settings, most of the and were associated with mobile-genetic elements, indicating that horizontal gene transfer may play an important role in the dissemination of AMR- in Laos. More studies should be planned to better understand the extent and dynamics of this phenomenon.
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http://dx.doi.org/10.3389/fmicb.2021.708182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350485PMC
July 2021

Molecular Detection of Pathogens in Negative Blood Cultures in the Lao People's Democratic Republic.

Am J Trop Med Hyg 2021 03 1;104(4):1582-1585. Epub 2021 Mar 1.

3Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR.

Bloodstream infections cause substantial morbidity and mortality. However, despite clinical suspicion of such infections, blood cultures are often negative. We investigated blood cultures that were negative after 5 days of incubation for the presence of bacterial pathogens using specific (Rickettsia spp. and Leptospira spp.) and a broad-range 16S rRNA PCR. From 190 samples, 53 (27.9%) were positive for bacterial DNA. There was also a high background incidence of dengue (90/112 patient serum positive, 80.4%). Twelve samples (6.3%) were positive for Rickettsia spp., including two Rickettsia typhi. The 16S rRNA PCR gave 41 positives; Escherichia coli and Klebsiella pneumoniae were identified in 11 and eight samples, respectively, and one Leptospira species was detected. Molecular investigation of negative blood cultures can identify potential pathogens that will otherwise be missed by routine culture. Patient management would have been influenced in all 53 patients for whom a bacterial organism was identified, and 2.3-6.1% of patients would likely have had an altered final outcome. These findings warrant further study, particularly to determine the cost-benefit for routine use, ways of implementation, and timing of PCR for organisms such as Rickettsia and Leptospira, which are important pathogens in rural Asia.
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http://dx.doi.org/10.4269/ajtmh.20-1348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045604PMC
March 2021

Effects of hydrological regime and land use on in-stream Escherichia coli concentration in the Mekong basin, Lao PDR.

Sci Rep 2021 02 10;11(1):3460. Epub 2021 Feb 10.

Institut de Recherche Pour le Développement (IRD), iEES-Paris, UMR 242 (IRD, SU-UPMC, CNRS, INRA, Univ. de Paris, UPEC), PO Box 5992, Vientiane, Lao PDR.

In the basin of Mekong, over 70 million people rely on unimproved surface water for their domestic requirements. Surface water is often contaminated with fecal matter and yet little information exists on the underlying mechanisms of fecal contamination in tropical conditions at large watershed scales. Our objectives were to (1) investigate the seasonality of fecal contamination using Escherichia coli as fecal indicator bacteria (FIB), and (2) establish links between the fecal contamination in stream water and its controlling factors (hydrology and land use). We present the results of (1) a sampling campaign at the outlet of 19 catchments across Lao PDR, in both the dry and the rainy seasons of 2016, and (2) a 10-day interval monitoring conducted in 2017 and 2018 at three point locations of three rivers (Nam Ou, Nam Suang, and Mekong) in northern Lao PDR. Our results show the presence of fecal contamination at most of the sampled sites, with a seasonality characterized by higher and extreme E. coli concentrations occurring during the rainy season. The highest E. coli concentrations, strongly correlated with total suspended sediment concentrations, were measured in catchments dominated by unstocked forest areas, especially in mountainous northern Lao PDR and in Vientiane province.
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http://dx.doi.org/10.1038/s41598-021-82891-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876097PMC
February 2021

Whole-Genome Assemblies of 16 Burkholderia pseudomallei Isolates from Rivers in Laos.

Microbiol Resour Announc 2021 Jan 28;10(4). Epub 2021 Jan 28.

Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos.

We report 16 genomes, including 5 new multilocus sequence types, isolated from rivers in Laos. The environmental bacterium causes melioidosis, a serious infectious disease in tropical and subtropical regions. The isolates are geographically clustered in one clade from around Vientiane, Laos, and one clade from further south.
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http://dx.doi.org/10.1128/MRA.01226-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844071PMC
January 2021

Prediction of disease severity in young children presenting with acute febrile illness in resource-limited settings: a protocol for a prospective observational study.

BMJ Open 2021 01 25;11(1):e045826. Epub 2021 Jan 25.

Faculty of Tropical Medicine, Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand.

Introduction: In rural and difficult-to-access settings, early and accurate recognition of febrile children at risk of progressing to serious illness could contribute to improved patient outcomes and better resource allocation. This study aims to develop a prognostic clinical prediction tool to assist community healthcare providers identify febrile children who might benefit from referral or admission for facility-based medical care.

Methods And Analysis: This prospective observational study will recruit at least 4900 paediatric inpatients and outpatients under the age of 5 years presenting with an acute febrile illness to seven hospitals in six countries across Asia. A venous blood sample and nasopharyngeal swab is collected from each participant and detailed clinical data recorded at presentation, and each day for the first 48 hours of admission for inpatients. Multianalyte assays are performed at reference laboratories to measure a panel of host biomarkers, as well as targeted aetiological investigations for common bacterial and viral pathogens. Clinical outcome is ascertained on day 2 and day 28.Presenting syndromes, clinical outcomes and aetiology of acute febrile illness will be described and compared across sites. Following the latest guidance in prediction model building, a prognostic clinical prediction model, combining simple clinical features and measurements of host biomarkers, will be derived and geographically externally validated. The performance of the model will be evaluated in specific presenting clinical syndromes and fever aetiologies.

Ethics And Dissemination: The study has received approval from all relevant international, national and institutional ethics committees. Written informed consent is provided by the caretaker of all participants. Results will be shared with local and national stakeholders, and disseminated via peer-reviewed open-access journals and scientific meetings.

Trial Registration Number: NCT04285021.
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http://dx.doi.org/10.1136/bmjopen-2020-045826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839891PMC
January 2021

Outcome of Japanese Encephalitis Virus (JEV) Infection in Pediatric and Adult Patients at Mahosot Hospital, Vientiane, Lao PDR.

Am J Trop Med Hyg 2020 12 21;104(2):567-575. Epub 2020 Dec 21.

1Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos.

Although Japanese encephalitis virus (JEV) infection is an important cause of acute febrile illness in Lao PDR (Laos), patient outcome has not been evaluated. We prospectively followed up 123 JEV-infected patients (70 children < 15 years and 53 adults ≥ 15 years) admitted at Mahosot Hospital, Vientiane, from 2003 to 2013. Japanese encephalitis virus infection was diagnosed by the detection of anti-JEV IgM in cerebrospinal fluid and/or IgM seroconversion. Neurological sequelae were assessed using the Liverpool Outcome Score (LOS), total (maximum score = 75), and final (maximum score = 5). The median (interquartile range [IQR]) age of the patients was 12.0 (7.5-18.8) years, and 57% were male. The median (IQR) duration of patients' follow-up was 4.5 (3.2-7.3) years. Of all patients, 10/123 (8.1%) died during hospitalization, and 13/123 (10.6%) died at home after discharge, giving a mortality of 18.7% (23/123) (33 [26.8%] patients were lost to follow-up). The frequency of neurological sequelae at the last follow-up was 61.2% (48.4% in adults and 69.4% in children, P = 0.135). The proportion of patients with severe and moderate functional impairment at the last follow-up was significantly higher in children (25%) than in adults (6.5%), P = 0.042. Half of the patients who were still alive at the last follow-up (67) and for whom LOS data were available (22) had improvements in their total and final LOS between discharge and the last follow-up. The total and final LOS at discharge were not significantly different between children and adults, but total LOS at the last follow-up was significantly higher in adults than in children (median [IQR]: 74.5 [73-75] versus 73.0 [73-75], P = 0.019).
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http://dx.doi.org/10.4269/ajtmh.20-0581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866311PMC
December 2020

Using Land Runoff to Survey the Distribution and Genetic Diversity of in Vientiane, Laos.

Appl Environ Microbiol 2020 Nov 30. Epub 2020 Nov 30.

Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos

Melioidosis is a disease of significant public health importance that is being increasingly recognized globally. The majority of cases arise through direct percutaneous exposure to its etiological agent, In the Lao People's Democratic Republic (Laos), the presence and environmental distribution of are not well characterized, though recent epidemiological surveys of the bacterium have indicated that is widespread throughout the environment in the center and south of the country and that rivers can act as carriers and potential sentinels for the bacterium. The spatial and genetic distribution of within Vientiane Capital, from where the majority of cases diagnosed to date have originated, remains an important knowledge gap. We sampled surface runoff from drain catchment areas throughout urban Vientiane to determine the presence and local population structure of the bacterium. was detected in drainage areas throughout the capital, indicating it is widespread in the environment and that exposure rates in urban Vientiane are likely more frequent than previously thought. Whole-genome comparative analysis demonstrated that Lao isolates are highly genetically diverse, suggesting the bacterium is well-established and not a recent introduction. Despite the wide genome diversity, one environmental survey isolate was highly genetically related to a Lao melioidosis patient isolate collected 13 years prior to the study. Knowledge gained from this study will augment understanding of phylogeography in Asia and enhance public health awareness and future implementation of infection control measures within Laos. The environmental bacterium is the etiological agent of melioidosis, a tropical disease with one model estimating a global annual incidence of 165,000 cases and 89,000 deaths. In the Lao People's Democratic Republic (Laos), the environmental distribution and population structure of remain relatively undefined, particularly in Vientiane Capital from where most diagnosed cases have originated. We used surface runoff as a proxy for dispersal in the environment and performed whole-genome sequencing (WGS) to examine the local population structure. Our data confirmed that is widespread throughout Vientiane and that surface runoff might be useful for future environmental monitoring of the bacterium. isolates were also highly genetically diverse, suggesting the bacterium is well-established and endemic in Laos. These findings can be used to improve awareness of in the Lao environment and demonstrates the epidemiological and phylogeographical insights that can be gained from WGS.
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http://dx.doi.org/10.1128/AEM.02112-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851688PMC
November 2020

Spatial epidemiology of Japanese encephalitis virus and other infections of the central nervous system infections in Lao PDR (2003-2011): A retrospective analysis.

PLoS Negl Trop Dis 2020 05 26;14(5):e0008333. Epub 2020 May 26.

Department of Population Health and Disease Prevention, University of California, Irvine, United States of America.

Background: Central nervous system (CNS) infections are important contributors to morbidity and mortality and the causative agents for ~50% patients are never identified. The causative agents of some CNS infections have distinct spatial and temporal patterns.

Methodology/principal Findings: Here we present the results of a spatial epidemiological and ecological analysis of CNS infections in Lao PDR (2003-2011). The data came from hospitalizations for suspected CNS infection at Mahosot Hospital in Vientiane. Out of 1,065 patients, 450 were assigned a confirmed diagnosis. While many communities in Lao PDR are in rural and remote locations, most patients in these data came from villages along major roads. Japanese encephalitis virus ((JEV); n = 94) and Cryptococcus spp. (n = 70) were the most common infections. JEV infections peaked in the rainy season and JEV patients came from villages with higher surface flooding during the same month as admission. JEV infections were spatially dispersed throughout rural areas and were most common in children. Cryptococcus spp. infections clustered near Vientiane (an urban area) and among adults.

Conclusions/significance: The spatial and temporal patterns identified in this analysis are related to complex environmental, social, and geographic factors. For example, JEV infected patients came from locations with environmental conditions (surface water) that are suitable to support larger mosquito vector populations. Most patients in these data came from villages that are near major roads; likely the result of geographic and financial access to healthcare and also indicating that CNS diseases are underestimated in the region (especially from more remote areas). As Lao PDR is undergoing major developmental and environmental changes, the space-time distributions of the causative agents of CNS infection will also likely change. There is a major need for increased diagnostic abilities; increased access to healthcare, especially for rural populations; and for increased surveillance throughout the nation.
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http://dx.doi.org/10.1371/journal.pntd.0008333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274481PMC
May 2020

Bacteremia Caused by Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae in Vientiane, Lao PDR: A 5-Year Study.

Am J Trop Med Hyg 2020 05;102(5):1137-1143

Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Although there has been an increasing incidence of bacteremia caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) across South East Asia, there are sparse data from the Lao PDR, where laboratory capacity for antimicrobial resistance surveillance is limited. We, therefore, retrospectively reviewed bacteremia caused by ESBL-producing and between 2010 and 2014 at Mahosot Hospital, Vientiane, Lao PDR. Clinical and laboratory data relating to all episodes of ESBL-E bacteremia were reviewed over the 5-year period and compared with non-ESBL-E bacteremia. Blood cultures positive for or were identified retrospectively from laboratory records. Clinical and laboratory data were extracted from research databases and case notes and analyzed using STATA. Between 2010 and 2014, we identified 360 patients with ( = 249) or ( = 111) bacteremia, representing 34.8% of all patients with clinically significant bacteremia Seventy-two (20%) isolates produced ESBL; accounted for 15.3% (55/360) and for 4.7% (17/360), respectively. The incidence of ESBL-producing bacteremia rose during the study period. By multiple logistic analysis, reported antibiotic use in the previous week was significantly associated with ESBL positivity ( < 0.001, odds ratio 3.89). Although multiresistant, most ESBL-producing and remained susceptible to meropenem (65/65; 100%) and amikacin (64/65; 98.5%). We demonstrated an alarming increase in the incidence of ESBL-E as a cause of bacteremia in Vientiane during the study period. This has implications for empiric therapy of sepsis in Laos, and ongoing surveillance is essential.
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http://dx.doi.org/10.4269/ajtmh.19-0304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204562PMC
May 2020

Estimation of Incidence of Typhoid and Paratyphoid Fever in Vientiane, Lao People's Democratic Republic.

Am J Trop Med Hyg 2020 04;102(4):744-748

Centre for International Health, University of Otago, Dunedin, New Zealand.

Typhoid conjugate vaccines represent a new tool for typhoid control. However, incidence data are needed to inform decisions about introduction. We sought to estimate typhoid and paratyphoid fever incidence in Vientiane, the capital and largest city of the Lao People's Democratic Republic (Lao PDR). We did a representative cluster survey of health-seeking behavior for fever in Vientiane from January 15, 2019 through January 26, 2019. Multipliers derived from the survey were applied to data from Typhi and Paratyphi A bloodstream infection surveillance from Mahosot Hospital, Vientiane, for the period of January 1, 2015 through December 31, 2017, to estimate enteric fever incidence. A total of 336 households representing 1,740 persons were enrolled in the healthcare utilization survey, and multipliers were derived based on responses to questions about healthcare seeking in the event of febrile illness. Of 7,997 Vientiane residents receiving blood cultures over the 2-year surveillance period at Mahosot Hospital, we identified 16 (0.2%) with Typhi and six (< 0.1%) with Paratyphi A bloodstream infection. After applying multipliers, we estimated that the annual incidence of typhoid was 4.7 per 100,000 persons and paratyphoid was 0.5 per 100,000 persons. During the study period, the incidence of typhoid and paratyphoid fever was low in Vientiane. Ongoing surveillance is warranted to identify increases in future years. Similar studies elsewhere in the Lao PDR would be useful to understand the wider enteric fever situation in the country.
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http://dx.doi.org/10.4269/ajtmh.19-0634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124915PMC
April 2020

Typhoid in Laos: An 18-Year Perspective.

Am J Trop Med Hyg 2020 04;102(4):749

Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Although typhoid is endemic to Southeast Asia, very little is known about the disease in Laos. Typhoid vaccination is not included in the national immunization program. Although sanitation has improved, one million people still do not have access to basic clean water sources. We describe the epidemiology and antimicrobial susceptibility patterns of serovar Typhi (. Typhi) infection in Laos based on isolates accrued over 18 years at Mahosot Hospital, Vientiane. All blood cultures collected from patients presenting with fever submitted to the Microbiology Laboratory at Mahosot Hospital (February 2000-December 2018) were included. This included patients from Vientiane and four provincial hospitals and one typhoid outbreak investigation. A total of 913 (1.5%) of 60,384 blood cultures were positive for Typhi. The majority of isolates with data available (712/898, 79.3%) were susceptible to all antibiotics tested, with 59 (6.5%) multidrug-resistant (MDR) isolates, mostly from one outbreak. Of 854 isolates, 12 (1.4%) were fluoroquinolone resistant. Patient admissions peaked between March and June at the end of the dry season. Although there are key limitations, these data give the first detailed epidemiological evidence of typhoid in Laos. However, estimates will be greatly influenced by access to blood culture services and health-seeking behavior. Although typhoid multidrug resistance and fluoroquinolone resistance are not currently major issues in Laos, continued surveillance and improved antibiotic stewardship are necessary to forestall worsening of the situation. Cost-effectiveness analysis is needed to inform decisions regarding typhoid vaccine introduction.
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http://dx.doi.org/10.4269/ajtmh.19-0637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124924PMC
April 2020

Evaluation of the Active Melioidosis Detect™ test as a point-of-care tool for the early diagnosis of melioidosis: a comparison with culture in Laos.

Trans R Soc Trop Med Hyg 2019 12;113(12):757-763

Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR.

Background: Melioidosis is difficult to diagnose clinically and culture of Burkholderia pseudomallei is the current, imperfect gold standard. However, a reliable point-of-care test (POCT) could enable earlier treatment and improve outcomes.

Methods: We evaluated the sensitivity and specificity of the Active Melioidosis Detect™ (AMD) rapid test as a POCT and determined how much it reduced the time to diagnosis compared with culture.

Results: We tested 106 whole blood, plasma and buffy coat samples, 96 urine, 28 sputum and 20 pus samples from 112 patients, of whom 26 (23.2%) were culture-positive for B. pseudomallei. AMD sensitivity and specificity were 65.4 and 87.2%, respectively, the latter related to 10 weak positive reactions on urine samples, considered likely false positives. The positive predictive value was 60.7%, negative predictive value was 89.3% and concordance rate between operators reading the test was 95.7%; time to diagnosis decreased by a median of 23 h.

Conclusions: Our findings confirm that a strongly positive AMD result can reduce the time to diagnosis of melioidosis. However, the AMD currently has a disappointing overall sensitivity, especially with blood fractions, and specificity problems when testing urine samples.
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http://dx.doi.org/10.1093/trstmh/trz092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6907004PMC
December 2019

Meta-transcriptomic identification of hepatitis B virus in cerebrospinal fluid in patients with central nervous system disease.

Diagn Microbiol Infect Dis 2019 Dec 1;95(4):114878. Epub 2019 Aug 1.

Unité des Virus Émergents (UVE: Aix-Marseille Univ - IRD 190 - Inserm 1207 - IHU Méditerranée Infection), Marseille, France; Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Churchill Hospital, University of Oxford, Oxford, United Kingdom.

Determining the etiological basis of central nervous system (CNS) infections is inherently challenging, primarily due to the multi-etiological nature. Using RNA sequencing, we aimed to identify microbes present in cerebrospinal fluid (CSF) of two patients suffering CNS infection, previously diagnosed with Cryptococcus sp. and Streptococcus pneumoniae infection, respectively. After meta-transcriptomic analysis, and confirmation with real-time PCR, hepatitis B virus (HBV) was detected in the CSF of two patients diagnosed with CNS syndrome. Phylogenetic analysis of the partial HBV genomes from these patients showed that they belonged to genotypes B and C and clustered with other viruses of Asian origin. In countries with high levels of HBV endemicity, the virus is likely to be found in patients diagnosed with CNS infections, although whether it contributes to symptoms and pathology, or is simply a coincidental infection, is unknown and merits further investigation.
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http://dx.doi.org/10.1016/j.diagmicrobio.2019.114878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892275PMC
December 2019

Management of Central Nervous System Infections, Vientiane, Laos, 2003-2011.

Emerg Infect Dis 2019 05;25(5):898-910

During 2003-2011, we recruited 1,065 patients of all ages admitted to Mahosot Hospital (Vientiane, Laos) with suspected central nervous system (CNS) infection. Etiologies were laboratory confirmed for 42.3% of patients, who mostly had infections with emerging pathogens: viruses in 16.2% (mainly Japanese encephalitis virus [8.8%]); bacteria in 16.4% (including Orientia tsutsugamushi [2.9%], Leptospira spp. [2.3%], and Rickettsia spp. [2.3%]); and Cryptococcus spp. fungi in 6.6%. We observed no significant differences in distribution of clinical encephalitis and meningitis by bacterial or viral etiology. However, patients with bacterial CNS infection were more likely to have a history of diabetes than others. Death (26.3%) was associated with low Glasgow Coma Scale score, and the mortality rate was higher for patients with bacterial than viral infections. No clinical or laboratory variables could guide antibiotic selection. We conclude that high-dependency units and first-line treatment with ceftriaxone and doxycycline for suspected CNS infections could improve patient survival in Laos.
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http://dx.doi.org/10.3201/eid2505.180914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478220PMC
May 2019

Viral RNA Degradation Makes Urine a Challenging Specimen for Detection of Japanese Encephalitis Virus in Patients With Suspected CNS Infection.

Open Forum Infect Dis 2019 Mar 6;6(3):ofz048. Epub 2019 Feb 6.

Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao P.D.R.

Background: Japanese encephalitis virus (JEV) is a leading cause of central nervous system (CNS) infections in Asia and results in significant morbidity and mortality. JEV RNA is rarely detected in serum or cerebrospinal fluid (CSF), and diagnosis of JEV infection is usually based on serological tests that are frequently difficult to interpret. Unlike serum or CSF, urine is relatively easy to obtain, but, to date, there has been minimal work on the feasibility of testing urine for JEV RNA.

Methods: We investigated the use of lysis buffer and a Microsep device to optimize urine storage for detection of JEV RNA by reverse transcription real-time polymerase chain reaction (RT-qPCR). The best of the studied methods was then evaluated in consecutive patients admitted to the hospital with suspected CNS infections in Laos.

Results: We demonstrated degradation of JEV RNA in urine after even short storage periods at 4°C or -80°C. Although there was no advantage in using a Microsep concentration device alone, immediate addition of lysis buffer to fresh urine improved the detection of JEV RNA at the limit of detection.

Conclusions: In 2 studies of 41 patients with acute encephalitis syndrome, 11 (27%) were positive for JEV IgM in CSF and/or serum, and 2 (4.9%) were JEV RT-qPCR positive from throat swabs. JEV RNA was not detected in any of these patients' urine samples. However, lysis buffer was only used during a prospective study, that is, for only 17/41 (41%) patient urine samples. Our findings suggest a need for larger studies testing urine for JEV RNA, with urine collected at different times from symptom onset, and using lysis buffer, which stabilizes RNA, for storage.
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http://dx.doi.org/10.1093/ofid/ofz048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411208PMC
March 2019

Evaluation of consensus method for the culture of in soil samples from Laos.

Wellcome Open Res 2018 21;3:132. Epub 2018 Nov 21.

Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, OX3 7FZ, UK.

We have previously shown that PCR following enrichment culture is the most sensitive method to detect in environmental samples. Here we report an evaluation of the published consensus method for the culture of from Lao soil in comparison with our conventional culture method and with PCR with or without prior broth enrichment. One hundred soil samples were collected from a field known to contain and processed by: (i) the conventional method, (ii-iii) the consensus method using media prepared in either Laos or Thailand, and (iv) the consensus method performed in Thailand, as well as by (v) PCR following direct extraction of DNA from soil and (vi) PCR following broth pre-enrichment. The numbers of samples in which was detected were 42, 10, 7, 6, 6 and 84, respectively. However, two samples were positive by the consensus method but negative by conventional culture, and one sample was negative by PCR following enrichment although was isolated by the conventional culture method. The results show that no single method will detect all environmental samples that contain People conducting environmental surveys for this organism should be aware of the possibility of false-negative results using the consensus culture method. An approach that entails screening using PCR after enrichment, followed by the evaluation of a range of different culture methods on PCR-positive samples to determine which works best in each setting, is recommended.
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http://dx.doi.org/10.12688/wellcomeopenres.14851.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283377PMC
November 2018

Multilocus sequence typing of Cryptococcus neoformans var. grubii from Laos in a regional and global context.

Med Mycol 2018 Oct 19. Epub 2018 Oct 19.

Oxford University Clinical Research Unit, Vietnam.

Cryptococcosis causes approximately 180 000 deaths each year in patients with human immunodeficiency virus (HIV). Patients with other forms of immunosuppression are also at risk, and disease is increasingly recognized in apparently immunocompetent individuals. Cryptococcus neoformans var. grubii, responsible for the majority of cases, is distributed globally. We used the consensus ISHAM Multilocus sequence typing (MLST) scheme to define the population structure of clinical C. neoformans var. grubii isolates from Laos (n = 81), which we placed into the global context using published MLST data from other countries (total N = 1047), including a reanalysis of 136 Vietnamese isolates previously reported. We observed a phylogeographical relationship in which the Laotian population was similar to its neighbor Thailand, being dominated (83%) by Sequence Types (ST) 4 and 6. This phylogeographical structure changed moving eastwards, with Vietnam's population consisting of an admixture of isolates dominated by the ST4/ST6 (35%) and ST5 (48%) lineages. The ST5 lineage is the predominant ST reported from China and East Asia, where it accounts for >90% of isolates. Analysis of genetic distance (Fst) between different populations of C. neoformans var. grubii supports this intermediate structure of the Vietnamese population. The pathogen and host diversity reported from Vietnam provide the strongest epidemiological evidence of the association between ST5 and HIV-uninfected patients. Regional anthropological genetic distances suggest diversity in the C. neoformans var. grubii population across Southeast Asia is driven by ecological rather than human host factors. Where the ST5 lineage is present, disease in HIV-uninfected patients is to be expected.
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http://dx.doi.org/10.1093/mmy/myy105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581559PMC
October 2018

Melioidosis in the Lao People's Democratic Republic.

Trop Med Infect Dis 2018 Feb 19;3(1). Epub 2018 Feb 19.

Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos.

Melioidosis is clearly highly endemic in Laos, although the disease has only been diagnosed regularly in humans (1359 cases) since 1999, and only a single animal case has been microbiologically confirmed. is extensively and abundantly present in soil and surface water in central and southern Laos, but the true distribution of the disease across the country remains to be determined. Surveillance is almost non-existent and diagnostic microbiology services are not yet well established, whilst awareness of melioidosis is low amongst policy-makers, healthcare providers, and the public. It is hoped that this situation will improve over the next decade as the country rapidly develops, especially as this is likely to be accompanied by a further increase in the prevalence of diabetes, meaning that more people in this predominantly agricultural population will be at risk of contracting melioidosis.
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http://dx.doi.org/10.3390/tropicalmed3010021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6136615PMC
February 2018

A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus.

Clin Infect Dis 2019 02;68(5):738-747

Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao People's Democratic Republic.

Background: Murine typhus, or infection with Rickettsia typhi, is a global but neglected disease without randomized clinical trials to guide antibiotic therapy.

Methods: A prospective, open, randomized trial was conducted in nonpregnant, consenting inpatient adults with rapid diagnostic test evidence of uncomplicated murine typhus at 2 hospitals in Vientiane, Laos. Patients were randomized to 7 days (D7) or 3 days (D3) of oral doxycycline or 3 days of oral azithromycin (A3). Primary outcome measures were fever clearance time and frequencies of treatment failure and relapse.

Results: Between 2004 and 2009, the study enrolled 216 patients (72 per arm); 158 (73.2%) had serology/polymerase chain reaction (PCR)-confirmed murine typhus, and 52 (24.1%) were R. typhi PCR positive. The risk of treatment failure was greater for regimen A3 (22.5%; 16 of 71 patients) than for D3 (4.2%; 3 of 71) or D7 (1.4%; 1 of 71) (P < .001). Among R. typhi PCR-positive patients, the area under the time-temperature curve and the fever clearance time were significantly higher for A3 than for D3 (1.8- and 1.9-fold higher, respectively; P = .005) and D7 (1.5- and 1.6-fold higher; P = .02). No patients returned with PCR-confirmed R. typhi relapse.

Conclusion: In Lao adults, azithromycin is inferior to doxycycline as oral therapy for uncomplicated murine typhus. For doxycycline, 3- and 7-day regimens have similar efficacy. Azithromycin use in murine typhus should be reconsidered. Investigation of genomic and phenotypic markers of R. typhi azithromycin resistance is needed.

Clinical Trial Registration: ISRCTN47812566.
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http://dx.doi.org/10.1093/cid/ciy563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376095PMC
February 2019

Rivers as carriers and potential sentinels for Burkholderia pseudomallei in Laos.

Sci Rep 2018 06 6;8(1):8674. Epub 2018 Jun 6.

Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos.

Burkholderia pseudomallei, causative agent of the often fatal disease melioidosis, dwells in tropical soils and has been found in freshwater bodies. To investigate whether rivers are potential habitats or carriers for B. pseudomallei and to assess its geographical distribution in Laos, we studied 23 rivers including the Mekong, applying culture-based detection methods and PCR to water filters and streambed sediments. B. pseudomallei was present in 9% of the rivers in the dry season and in 57% in the rainy season. We found the pathogen exclusively in Southern and Central Laos, and mainly in turbid river water, while sediments were positive in 35% of the B. pseudomallei-positive sites. Our results provide evidence for a heterogeneous temporal and spatial distribution of B. pseudomallei in rivers in Laos with a clear north-south contrast. The seasonal dynamics and predominant occurrence of B. pseudomallei in particle-rich water suggest that this pathogen is washed out with eroded soil during periods of heavy rainfall and transported by rivers, while river sediments do not seem to be permanent habitats for B. pseudomallei. Rivers may thus be useful to assess the distribution and aquatic dispersal of B. pseudomallei and other environmental pathogens in their catchment area and beyond.
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http://dx.doi.org/10.1038/s41598-018-26684-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989208PMC
June 2018

Detection of Japanese Encephalitis Virus RNA in Human Throat Samples in Laos - A Pilot study.

Sci Rep 2018 05 22;8(1):8018. Epub 2018 May 22.

Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR.

Japanese encephalitis virus (JEV) is the most commonly identified cause of acute encephalitis syndrome (AES) in Asia. The WHO recommended test is anti-JEV IgM-antibody-capture-enzyme-linked-immunosorbent-assay (JEV MAC-ELISA). However, data suggest this has low positive predictive value, with false positives related to other Flavivirus infections and vaccination. JEV RT-PCR in cerebrospinal fluid (CSF) and/or serum is highly specific, but is rarely positive; 0-25% of patients that fulfil the WHO definition of JE (clinical Acute Encephalitis Syndrome (AES) and JEV MAC-ELISA positive). Testing other body fluids by JEV RT-qPCR may improve the diagnosis. As a pilot study thirty patients admitted to Mahosot Hospital 2014-2017, recruited to the South-East-Asia-Encephalitis study, were tested by JEV MAC-ELISA and two JEV real-time RT-PCR (RT-qPCR) assays (NS2A and NS3). Eleven (36.7%) were JEV MAC-ELISA positive. Available CSF and serum samples of these patients were JEV RT-qPCR negative but 2 (7%) had JEV RNA detected in their throat swabs. JEV RNA was confirmed by re-testing, and sequencing of RT-qPCR products. As the first apparent report of JEV RNA detection in human throat samples, the provides new perspectives on human JEV infection, potentially informing improving JEV detection. We suggest that testing patients' throat swabs for JEV RNA is performed, in combination with molecular and serological CSF and serum investigations, on a larger scale to investigate the epidemiology of the presence of JEV in human throats. Throat swabs are an easy and non-invasive tool that could be rolled out to a wider population to improve knowledge of JEV molecular epidemiology.
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http://dx.doi.org/10.1038/s41598-018-26333-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964078PMC
May 2018

Non-typhoidal Salmonella serovars associated with invasive and non-invasive disease in the Lao People's Democratic Republic.

Trans R Soc Trop Med Hyg 2017 09;111(9):418-424

Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, 764 Vo Van Kiet, Quan 5, Ho Chi Minh City, Vietnam.

Background: Invasive non-typhoidal Salmonella (iNTS) disease is a well-described cause of mortality in children and human immunodeficiency virus (HIV)-infected adults in sub-Saharan Africa. Additionally, there is an ill-defined burden of iNTS disease in Southeast Asia.

Methods: Aiming to investigate the causative serovars of non-invasive and iNTS disease and their associated antimicrobial susceptibility profiles in the Lao People's Democratic Republic, we performed multilocus sequence typing and antimicrobial susceptibility profiling on 168 NTS (63 blood and 105 faecal) organisms isolated in Lao between 2000 and 2012.

Results: Six different serovars were isolated from blood; Salmonella enterica serovar Enteritidis (n=28), S. enterica serovar Typhimurium (n=19) and S. enterica serovar Choleraesuis (n=11) accounted for >90% (58/63) of the iNTS disease cases. In contrast, the isolates from diarrhoeal faeces were comprised of 18 different serovars, the mostly commonly identified being S. enterica Typhimurium (n=28), S. enterica Weltevreden (n=14) and S. enterica Stanley (n=15). S. enterica Enteritidis and S. enterica Choleraesuis were significantly more associated with systemic disease than diarrhoeal disease in this patient group (p<0.001).

Conclusions: We find a differing distribution of Salmonella sequence types/serovars between those causing iNTS disease and non-invasive disease in Lao. We conclude that there is a small but not insignificant burden of iNTS disease in Lao. Further clinical and epidemiological investigations are required to assess mortality and the role of comorbidities such as HIV.
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http://dx.doi.org/10.1093/trstmh/trx076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5914354PMC
September 2017

Angiostrongylus cantonensis DNA in Cerebrospinal Fluid of Persons with Eosinophilic Meningitis, Laos.

Emerg Infect Dis 2017 12;23(12):2112-2113

Definitive identification of Angiostrongylus cantonensis parasites from clinical specimens is difficult. As a result, regional epidemiology and burden are poorly characterized. To ascertain presence of this parasite in patients in Laos with eosinophilic meningitis, we performed quantitative PCRs on 36 cerebrospinal fluid samples; 4 positive samples confirmed the parasite's presence.
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http://dx.doi.org/10.3201/eid2312.171107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5708259PMC
December 2017

Clostridium difficile infection in the Lao People's Democratic Republic: first isolation and review of the literature.

BMC Infect Dis 2017 09 21;17(1):635. Epub 2017 Sep 21.

Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao People's Democratic Republic.

Background: Current knowledge of the epidemiology of Clostridium difficile infection in Asia, and in particular the Greater Mekong Subregion, is very limited. Only a few studies from Thailand and Vietnam have been reported from the region with variable testing methods and results, and no studies from Lao People's Democratic Republic (PDR). Therefore we investigated the presence of C. difficile in a single centre in the Lao PDR and determined the ribotypes present.

Method: Seventy unformed stool samples from hospital inpatients at Mahosot Hospital, Vientiane, were tested for the presence of C. difficile using selective differential agar and confirmed by latex agglutination. C. difficile isolates were further characterised by ribotyping and toxin gene detection.

Results: C. difficile was isolated from five of the 70 patients, and five different ribotypes were identified (014, 017, 020, QX 107 and QX 574).

Conclusion: This is the first isolation of C. difficile from human stool samples in the Lao PDR. These results will add to the limited amount of data on C. difficile in the region. In addition, we hope this information will alert clinicians to the presence of C. difficile in the country and will help inform future investigations into the epidemiology and diagnosis of C. difficile in Lao PDR.
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http://dx.doi.org/10.1186/s12879-017-2737-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609038PMC
September 2017
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