Publications by authors named "Manivanh Vongsouvath"

78 Publications

Evaluation of trends in hospital antimicrobial use in the Lao PDR using repeated point-prevalence surveys-evidence to improve treatment guideline use.

Lancet Reg Health West Pac 2022 Oct 9;27:100531. Epub 2022 Jul 9.

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

Background: Antimicrobial use (AMU) is a key driver of antimicrobial resistance (AMR). There are few data on AMU, to inform optimizing antibiotic stewardship, in the Lao PDR (Laos).

Methods: Point prevalence surveys (PPS) of AMU were conducted at four-month intervals in six general hospitals across Laos from 2017 to 2020, using modified Global-PPS data collection tools. The surveys focused on AMU amongst hospitalized inpatients.

Findings: The overall prevalence of inpatient AMU was 71% (4,377/6,188), varying by hospital and survey round from 50·4% (135/268) to 88·4% (61/69). Of 4,377 patients, 44% received >one antimicrobial. The total number of prescriptions assessed was 6,555. Ceftriaxone was the most commonly used (39·6%) antimicrobial, followed by metronidazole (17%) and gentamicin (10%). Pneumonia was the most common diagnosis among those prescribed antimicrobials in both children aged ≤5 years (29% among aged ≤1 year and 27% among aged >1 to ≤5years) and adults aged ≥15 years at 9%. The percentage of antimicrobial use compliant with local treatment guidelines was 26%; inappropriate use was mainly found for surgical prophylaxis (99%). Adult patients received ACCESS group antimicrobials less commonly than children (47% vs 63%, p-value<0·0001). Most WATCH group prescriptions (99%) were without a microbiological indication.

Interpretation: AMU among hospitalized patients in Laos is high with frequent inappropriate use of antimicrobials, especially as surgical prophylaxis. Continued monitoring and enhanced antimicrobial stewardship interventions are needed in Lao hospitals.

Funding: The Wellcome Trust [Grant numbers 220211/Z/20/Z and 214207/Z/18/Z] and bioMérieux.
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http://dx.doi.org/10.1016/j.lanwpc.2022.100531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283659PMC
October 2022

Perceptions and reported practices of pregnant women and mothers of children under two years of age regarding antibiotic use and resistance in Vientiane province, Lao PDR: a qualitative study.

BMC Pregnancy Childbirth 2022 Jul 16;22(1):569. Epub 2022 Jul 16.

Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden.

Background: Understanding pregnant women and mothers' perceptions towards antibiotic use and resistance is essential for appropriate antibiotic use and limiting antibiotic resistance. This study aimed to explore perceptions and reported practices of pregnant women and mothers with children under two years of age regarding correct antibiotic use and antibiotic resistance in Vientiane Province, Lao PDR.

Methods: The study employed an exploratory qualitative research design using focus groups discussions (FGDs). Participants were purposively selected based on: being pregnant at third trimester and attending antenatal care and mothers with children under two years of age, attending the health facility for postpartum visit /vaccinations. Six focus group discussions were conducted in September 2019 with a total of 55 women. The FGDs were transcribed verbatim, data were analyzed first by coding then categorizing the data as we looked for patterns and themes by using the qualitative content analysis.

Results: Most participants had some understanding of antibiotics but wrongly believed antibiotics can be used to treat viral disease. Over half of the participants had heard the term "antibiotic resistance", but often believed it was their bodies, not the bacteria that developed antibiotic resistance. During pregnancy and for their infants, women preferred to use antibiotics only when prescribed by a doctor. Outside of pregnancy however, consuming antibiotics without a prescription was commonly reported. Participants wanted more information about the indications for antibiotic use and antibiotic resistance.

Conclusions: More effort is required to increase the level of understanding, and practice of mothers to promote optimal antibiotic use. Mothers' desire to learn more, and their fundamental concern for their children, can be used to promote appropriate antibiotic use. Awareness raising should be complemented by efforts to address other determinants of inappropriate antibiotic use, including educating healthcare workers, and pharmacists and addressing health service determinants that contribute to inappropriate antibiotic use.
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http://dx.doi.org/10.1186/s12884-022-04894-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9287906PMC
July 2022

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

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

Antibiotic Prescribing in Connection to Childbirth: An Observational Study in Two Districts in Lao PDR.

Antibiotics (Basel) 2022 Mar 25;11(4). Epub 2022 Mar 25.

Department of Global Public Health, Karolinska Institutet, 171 77 Stockholm, Sweden.

Overuse and misuse of antibiotics has frequently been reported for obstetric conditions and procedures, which may impact both the mother and the unborn baby and increase antibiotic resistance. This study aimed to investigate the antibiotic prescribing pattern in connection to childbirth in two districts in Lao PDR. It is a cross-sectional observational study. Antibiotic prescription data related to childbirth was collected via reviews of medical records in two district hospitals and five health centers in Lao PDR from September 2019 to November 2020. In total, antibiotic prescription data for 1777 women were extracted from their medical records. It was found that all women received antibiotics during in-patient care irrespective of delivery mode. When in hospital, 85.5% of the women who underwent a caesarean section got antibiotic treatment for 5 days and women who had a vaginal delivery usually had antibiotic treatment for one day or less. All the women got oral antibiotics for an additional 4-5 days upon discharge. Antibiotic prescription rate in connection to childbirth was very high in comparison with the WHO guidelines, and antibiotics were used extensively in the participating health facilities. Interventions to guide appropriate prescribing behavior in relation to childbirth are urgently needed in Lao PDR.
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http://dx.doi.org/10.3390/antibiotics11040448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9029038PMC
March 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

Utility of InTray COLOREX Screen agar and InTray COLOREX ESBL agar for urine culture in the Lao PDR.

JAC Antimicrob Resist 2022 Mar 7;4(1):dlac006. Epub 2022 Feb 7.

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

Background: There is a need for simple microbiology diagnostics to enable antimicrobial resistance surveillance in low- and middle-income countries.

Objectives: To investigate the field utility of InTray COLOREX plates for urine culture and ESBL detection.

Methods: Clinical urine samples from Mahosot Hospital, Vientiane, Lao PDR were inoculated onto chromogenic media and InTray COLOREX Screen plates between June and August 2020. Urine and isolates from other clinical specimens were inoculated onto COLOREX ESBL plates. A simulated field study investigating the field utility of the InTray COLOREX plates was also completed.

Results: In total, 355 urine samples were inoculated onto standard chromogenic agar and InTray COLOREX Screen plates, and 154 urine samples and 54 isolates from other clinical specimens on the COLOREX ESBL plates. Growth was similar for the two methods (COLOREX Screen 41%, standard method 38%) with 20% discordant results, mainly due to differences in colony counts or colonial appearance. Contamination occurred in 13% of samples, with the COLOREX Screen plates showing increased contamination rates, potentially due to condensation. ESBL producers were confirmed from 80% of isolates from the COLOREX ESBL plates, and direct plating provided rapid detection of presumptive ESBL producers. also grew well on the ESBL plates, a relevant finding in this melioidosis-endemic area.

Conclusions: The InTray COLOREX Screen and ESBL plates were simple to use and interpret, permitting rapid detection of uropathogens and ESBLs, and have the potential for easy transport and storage from field sites and use in laboratories with low capacity.
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http://dx.doi.org/10.1093/jacamr/dlac006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8826549PMC
March 2022

A case-control study of the causes of acute respiratory infection among hospitalized patients in Northeastern Laos.

Sci Rep 2022 01 18;12(1):939. Epub 2022 Jan 18.

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

With the advent of highly sensitive real-time PCR, multiple pathogens have been identified from nasopharyngeal swabs of patients with acute respiratory infections (ARIs). However, the detection of microorganisms in the upper respiratory tract does not necessarily indicate disease causation. We conducted a matched case-control study, nested within a broader fever aetiology project, to facilitate determination of the aetiology of ARIs in hospitalised patients in Northeastern Laos. Consenting febrile patients of any age admitted to Xiengkhuang Provincial Hospital were included if they met the inclusion criteria for ARI presentation (at least one of the following: cough, rhinorrhoea, nasal congestion, sore throat, difficulty breathing, and/or abnormal chest auscultation). One healthy control for each patient, matched by sex, age, and village of residence, was recruited for the study. Nasopharyngeal swabs were collected from participants and tested for 33 pathogens by probe-based multiplex real-time RT-PCR (FastTrack Diagnostics Respiratory pathogen 33 kit). Attributable fraction of illness for a given microorganism was calculated by comparing results between patients and controls (= 100 * [OR - 1]/OR) (OR = odds ratio). Between 24th June 2019 and 24th June 2020, 205 consenting ARI patients and 205 matching controls were recruited. After excluding eight pairs due to age mismatch, 197 pairs were included in the analysis. Males were predominant with sex ratio 1.2:1 and children < 5 years old accounted for 59% of participants. At least one potential pathogen was detected in 173 (88%) patients and 175 (89%) controls. ARI in admitted patients were attributed to influenza B virus, influenza A virus, human metapneumovirus (HMPV), and respiratory syncytial virus (RSV) in 17.8%, 17.2%, 7.5%, and 6.5% of participants, respectively. SARS-CoV-2 was not detected in any cases or controls. Determining ARI aetiology in individual patients remains challenging. Among hospitalised patients with ARI symptoms presenting to a provincial hospital in Northeastern Laos, half were determined to be caused by one of several respiratory viruses, in particular influenza A virus, influenza B virus, HMPV, and RSV.
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http://dx.doi.org/10.1038/s41598-022-04816-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766494PMC
January 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

Knowledge, Attitudes, Perception and Reported Practices of Healthcare Providers on Antibiotic Use and Resistance in Pregnancy, Childbirth and Children under Two in Lao PDR: A Mixed Methods Study.

Antibiotics (Basel) 2021 Nov 27;10(12). Epub 2021 Nov 27.

Department of Global Public Health, Karolinska Institutet, 17177 Stockholm, Sweden.

Background: Overuse and misuse of antibiotics contribute unnecessarily to antibiotic resistance (ABR), and are thereby global health threats. Inappropriate prescriptions of antibiotics during pregnancy, delivery and early childhood are widespread across the world. This study aimed to assess knowledge, attitudes, and reported practices of healthcare providers (HCPs) and to explore their perceptions regarding antibiotic use and ABR related to pregnancy, childbirth, and children under two in Lao PDR.

Methods: This is a mixed methods study with data collection in 2019 via structured interviews among 217 HCPs (medical doctors/assistant doctors, midwives/nurses, pharmacists/assistant pharmacists and drug sellers), who prescribed/dispensed antibiotics in one rural and one urban district in Vientiane province and individual qualitative interviews with 30 HCPs and stakeholders.

Results: Of the HCPs, 36% had below average knowledge regarding antibiotic use and ABR, and 67% reported prescribing antibiotics for uncomplicated vaginal delivery. Half of the HCPs did not believe that their prescribing contributed to ABR, and only 9% had participated in antibiotic education.

Conclusion: A substantial number of HCPs had suboptimal knowledge and prescribed antibiotics unnecessarily, thereby contributing to ABR. Continuous education and regular supervision of HCPs is recommended to improve the use of antibiotics related to pregnancy, childbirth, and young children.
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http://dx.doi.org/10.3390/antibiotics10121462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8698782PMC
November 2021

Antimicrobial resistance in commensal opportunistic pathogens isolated from non-sterile sites can be an effective proxy for surveillance in bloodstream infections.

Sci Rep 2021 12 3;11(1):23359. Epub 2021 Dec 3.

Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.

Antimicrobial resistance (AMR) surveillance in bloodstream infections (BSIs) is challenging in low/middle-income countries (LMICs) given limited laboratory capacity. Other specimens are easier to collect and process and are more likely to be culture-positive. In 8102 E. coli BSIs, 322,087 E. coli urinary tract infections, 6952 S. aureus BSIs and 112,074 S. aureus non-sterile site cultures from Oxfordshire (1998-2018), and other (55,296 isolates) rarer commensal opportunistic pathogens, antibiotic resistance trends over time in blood were strongly associated with those in other specimens (maximum cross-correlation per drug 0.51-0.99). Resistance prevalence was congruent across drug-years for each species (276/312 (88%) species-drug-years with prevalence within ± 10% between blood/other isolates). Results were similar across multiple countries in high/middle/low income-settings in the independent ATLAS dataset (103,559 isolates, 2004-2017) and three further LMIC hospitals/programmes (6154 isolates, 2008-2019). AMR in commensal opportunistic pathogens cultured from BSIs is strongly associated with AMR in commensal opportunistic pathogens cultured from non-sterile sites over calendar time, suggesting the latter could be used as an effective proxy for AMR surveillance in BSIs.
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http://dx.doi.org/10.1038/s41598-021-02755-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8642463PMC
December 2021

Antimicrobial use and resistance data in human and animal sectors in the Lao PDR: evidence to inform policy.

BMJ Glob Health 2021 11;6(12)

Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Mahosot Hospital, Vientiane, Lao People's Democratic Republic.

Objectives: To review the scientific evidence base on antimicrobial use (AMU) and antimicrobial resistance (AMR) in human and animal sectors in the Lao PDR (Laos).

Methods: We reviewed all publications from July 1994 (the first article describing AMR in Laos) to December 2020. Electronic searches were conducted using Google Scholar and PubMed with specific terms relating to AMR and AMU in Lao, French and English languages.

Findings: We screened 1,357 peer-reviewed and grey reports by title and abstract and then full articles/reports. Of 80 included, 66 (83%) related to human health, nine (11%) to animal health, four (5%) to both animal and human health and one (1%) to the environment. Sixty-two (78%) were on AMR and 18 (22%) on AMU. Extended spectrum beta lactamase-producing was the greatest concern identified; the proportion of isolates increased fivefold from 2004 to 2016 (2/28 (7%) to 27/78 (35%)) from blood cultures submitted to the Microbiology Laboratory, Mahosot Hospital, Vientiane. Carbapenem resistant was first identified in 2015. Methicillin-resistant (MRSA) was uncommon, with 15 cases of MRSA from blood cultures between its first identification in 2017 and December 2020. AMR patterns of global antimicrobial resistance surveillance system (GLASS) target pathogens from livestock were less well documented. There were few data on AMU in human health and none on AMU in livestock. The first hospital AMU survey in Laos showed that 70% (1,386/1,981) of in-patients in five hospitals from 2017 to 2018 received antimicrobial(s). Antibiotic self-medication was common.

Conclusion: AMR in Laos is occurring at relatively low proportions for some GLASS pathogens, giving the country a window of opportunity to act quickly to implement strategies to protect the population from a worsening situation. Urgent interventions to roll out new guidelines with enhanced one-health antibiotic stewardship, reduce antibiotic use without prescriptions, enhance surveillance and improve understanding of AMU and AMR are needed.
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http://dx.doi.org/10.1136/bmjgh-2021-007009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8638151PMC
November 2021

Antimicrobial resistance detection in Southeast Asian hospitals is critically important from both patient and societal perspectives, but what is its cost?

PLOS Glob Public Health 2021 13;1(10):e0000018. Epub 2021 Oct 13.

Nuffield Department of Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom.

Antimicrobial resistance (AMR) is a major threat to global health. Improving laboratory capacity for AMR detection is critically important for patient health outcomes and population level surveillance. We aimed to estimate the financial cost of setting up and running a microbiology laboratory for organism identification and antimicrobial susceptibility testing as part of an AMR surveillance programme. Financial costs for setting up and running a microbiology laboratory were estimated using a top-down approach based on resource and cost data obtained from three clinical laboratories in the Mahidol Oxford Tropical Medicine Research Unit network. Costs were calculated for twelve scenarios, considering three levels of automation, with equipment sourced from either of the two leading manufacturers, and at low and high specimen throughput. To inform the costs of detection of AMR in existing labs, the unit cost per specimen and per isolate were also calculated using a micro-costing approach. Establishing a laboratory with the capacity to process 10,000 specimens per year ranged from $254,000 to $660,000 while the cost for a laboratory processing 100,000 specimens ranged from $394,000 to $887,000. Excluding capital costs to set up the laboratory, the cost per specimen ranged from $22-31 (10,000 specimens) and $11-12 (100,000 specimens). The cost per isolate ranged from $215-304 (10,000 specimens) and $105-122 (100,000 specimens). This study provides a conservative estimate of the costs for setting up and running a microbiology laboratory for AMR surveillance from a healthcare provider perspective. In the absence of donor support, these costs may be prohibitive in many low- and middle- income country (LMIC) settings. With the increased focus on AMR detection and surveillance, the high laboratory costs highlight the need for more focus on developing cheaper and cost-effective equipment and reagents so that laboratories in LMICs have the potential to improve laboratory capacity and participate in AMR surveillance.
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http://dx.doi.org/10.1371/journal.pgph.0000018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611947PMC
October 2021

Dengue diagnostic test use to identify Aedes-borne disease hotspots.

Lancet Planet Health 2021 08;5(8):e503

Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK.

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http://dx.doi.org/10.1016/S2542-5196(21)00174-1DOI Listing
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

Cluster of Angiostrongyliasis Cases Following Consumption of Raw Monitor Lizard in the Lao People's Democratic Republic and Review of the Literature.

Trop Med Infect Dis 2021 Jun 22;6(3). Epub 2021 Jun 22.

Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Mahosot Hospital, Vientiane 01000, Laos.

Angiostrongyliasis in humans causes a range of symptoms from mild headache and myalgia to neurological complications, coma and death. Infection is caused by the consumption of raw or undercooked intermediate or paratenic hosts infected with or via contaminated vegetables or water. We describe a cluster of cases involved in the shared meal of wild raw monitor lizard in the Lao PDR. Seven males, aged 22-36 years, reported headaches, abdominal pain, arthralgia, myalgia, nausea/vomiting, diarrhea, neurological effects and loss of appetite. Five were admitted to hospital. The final diagnosis was made by clinical presentation and case history, and positive PCR for two cases. All hospitalized patients recovered fully following supportive treatment. The remaining two individuals sought local home remedies and made full recovery. Whilst most published reports concern infections via consumption of molluscs, few detailed reports exist on infections that result from the consumption of reptiles and there exists little awareness in Lao PDR. This case cluster, which originates from a single meal, highlights the potential public health risk of the consumption of raw and wild-caught meat in Lao PDR and the Southeast Asia region. Without specific diagnostics, clinical history and the consideration of recent food consumption are important when evaluating patients.
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http://dx.doi.org/10.3390/tropicalmed6030107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293387PMC
June 2021

Indirect effects of 13-valent pneumococcal conjugate vaccine on pneumococcal carriage in children hospitalised with acute respiratory infection despite heterogeneous vaccine coverage: an observational study in Lao People's Democratic Republic.

BMJ Glob Health 2021 06;6(6)

Infection and Immunity, Murdoch Childrens Research Institute (MCRI), Parkville, Victoria, Australia.

Introduction: Empiric data on indirect (herd) effects of pneumococcal conjugate vaccines (PCVs) in settings with low or heterogeneous PCV coverage are limited. The indirect effects of PCV, which benefits both vaccinated and non-vaccinated individuals, are mediated by reductions in vaccine-type (VT) carriage (a prerequisite for disease). The aim of this study among hospitalised children in Lao People's Democratic Republic (Lao PDR) is to determine the effectiveness of a 13-valent PCV (PCV13) against VT pneumococcal nasopharyngeal carriage (direct effects) and the association between village-level PCV13 coverage and VT carriage (indirect effects).

Methods: Pneumococcal nasopharyngeal carriage surveillance commenced in December 2013, shortly after PCV13 introduction (October 2013). We recruited and swabbed children aged 2-59 months admitted to hospital with acute respiratory infection. Pneumococci were detected using quantitative real-time PCR and serotyped using microarray. PCV13 status and village-level PCV13 coverage were determined using written immunisation records. Associations between both PCV13 status and village-level PCV13 coverage and VT carriage were calculated using generalised estimating equations, controlling for potential confounders.

Results: We enrolled 1423 participants and determined PCV13 coverage for 368 villages (269 863 children aged under 5 years). By 2017, median village-level vaccine coverage reached 37.5%, however, the IQR indicated wide variation among villages (24.1-56.4). Both receipt of PCV13 and the level of PCV13 coverage were independently associated with a reduced odds of VT carriage: adjusted PCV13 effectiveness was 38.1% (95% CI 4.1% to 60.0%; p=0.032); and for each per cent increase in PCV13 coverage, the estimated odds of VT carriage decreased by 1.1% (95% CI 0.0% to 2.2%; p=0.056). After adjustment, VT carriage decreased from 20.0% to 12.8% as PCV13 coverage increased from zero to 60% among under 5.

Conclusions: Despite marked heterogeneity in PCV13 coverage, we found evidence of indirect effects in Lao PDR. Individual vaccination with PCV13 was effective against VT carriage.
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http://dx.doi.org/10.1136/bmjgh-2021-005187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191607PMC
June 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

Containment of Antibiotic REsistance-measures to improve antibiotic use in pregnancy, childbirth and young children (CAREChild): a protocol of a prospective, quasiexperimental interventional study in Lao PDR.

BMJ Open 2020 11 19;10(11):e040334. Epub 2020 Nov 19.

Department of Global Public Health, Karolinska Institute, Stockholm, Stockholm County, Sweden.

Introduction: Antibiotics are essential to treat infections during pregnancy and to reduce both maternal and infant mortality. Overall use, but especially non-indicated use, and misuse of antibiotics are drivers of antibiotic resistance (ABR). High non-indicated use of antibiotics for uncomplicated vaginal deliveries is widespread in many parts of the world. Similarly, irrational use of antibiotics is reported for children. There is scarcity of evidence regarding antibiotic use and ABR in Lao PDR (Laos). The overarching aim of this project is to fill those knowledge gaps and to evaluate a quality improvement intervention. The primary objective is to estimate the proportion of uncomplicated vaginal deliveries where antibiotics are used and to compare its trend before and after the intervention.

Methods And Analysis: This 3-year, prospective, quasiexperimental study without comparison group includes a formative and interventional phase. Data on antibiotic use during delivery will be collected from medical records. Knowledge, attitudes and reported practices on antibiotic use in pregnancy, during delivery and for children, will be collected from women through questionnaires. Healthcare providers' knowledge, attitudes and practices of antibiotics administration for pregnant women, during delivery and for children, will be collected via adapted questionnaires. Perceptions regarding antibiotics will be explored through focus group discussions with women and individual interviews with key stakeholders. Faecal samples for culturing of and spp. and antibiotic susceptibility testing will be taken before, during and 6 months after delivery to determine colonisation of resistant strains. The planned intervention will comprise training workshops, educational materials and social media campaign and will be evaluated using interrupted time series analysis.

Ethics And Dissemination: The project received ethical approval from the National Ethics Committee for Health Research, Ministry of Health, Laos. The results will be disseminated via scientific publications, conference presentations and communication with stakeholders.

Trail Registration Number: ISRCTN16217522; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-040334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678367PMC
November 2020

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

Diagnostic accuracy of an in-house Scrub Typhus enzyme linked immunoassay for the detection of IgM and IgG antibodies in Laos.

PLoS Negl Trop Dis 2020 12 7;14(12):e0008858. Epub 2020 Dec 7.

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

Scrub typhus is a major cause of morbidity and mortality in Southeast Asia. Diagnosis of scrub typhus is difficult due to a lack of accessible validated diagnostic tools. Despite its objectivity, the diagnostic accuracy of ELISA tests is influenced by methodological and patient factors. This study aims to evaluate the performance of a novel in-house ELISA developed in the Mahidol Oxford Tropical Medicine Research Unit (MORU) for anti-scrub typhus group IgM and IgG compared to the "gold standard" reference IFA and PCR, and to determine whether the in-house ELISA can be used as a seroepidemiological screening tool and/or stand-alone test for scrub typhus. A total of 1,976 admission and 1,438 participant follow-up sera collected in the Lao PDR (Laos) were tested with ELISA for IgM and IgG. Samples with an ELISA OD≥0.50 were tested with IFA for IgM and/or IgG. A strong positive relationship was present between ELISA ODs and IFA titers for admission IgM (r2: 0.70, p <0.005) and IgG (r2: 0.76, p<0.005), and for follow-up IgM and IgG (both r2: 0.76, p<0.005) samples. The best compromise between sensitivity and specificity for the ELISA OD cut-off is likely to be between 0.8-1.0 for IgM antibodies and 1.2-1.8 for IgG antibodies. These results demonstrate that the diagnostic accuracy of the MORU in-house scrub typhus group ELISA is comparable to that of IFA, with similar results as reported for the commonly used InBios Scrub Typhus Detect ELISA, validating the use of the in-house ELISA. The optimal ELISA cut-off would depend on the use of the test, and the desired sensitivity and specificity. Further studies are required to authenticate the use of these cut-offs in other endemic regions. This in-house ELISA has the potential to replace the imperfect IFA, which could ultimately reduce the burden of scrub typhus by improving the rate of scrub typhus diagnoses in endemic low-resource areas.
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http://dx.doi.org/10.1371/journal.pntd.0008858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746293PMC
December 2020

Automating the Generation of Antimicrobial Resistance Surveillance Reports: Proof-of-Concept Study Involving Seven Hospitals in Seven Countries.

J Med Internet Res 2020 10 2;22(10):e19762. Epub 2020 Oct 2.

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

Background: Reporting cumulative antimicrobial susceptibility testing data on a regular basis is crucial to inform antimicrobial resistance (AMR) action plans at local, national, and global levels. However, analyzing data and generating a report are time consuming and often require trained personnel.

Objective: This study aimed to develop and test an application that can support a local hospital to analyze routinely collected electronic data independently and generate AMR surveillance reports rapidly.

Methods: An offline application to generate standardized AMR surveillance reports from routinely available microbiology and hospital data files was written in the R programming language (R Project for Statistical Computing). The application can be run by double clicking on the application file without any further user input. The data analysis procedure and report content were developed based on the recommendations of the World Health Organization Global Antimicrobial Resistance Surveillance System (WHO GLASS). The application was tested on Microsoft Windows 10 and 7 using open access example data sets. We then independently tested the application in seven hospitals in Cambodia, Lao People's Democratic Republic, Myanmar, Nepal, Thailand, the United Kingdom, and Vietnam.

Results: We developed the AutoMated tool for Antimicrobial resistance Surveillance System (AMASS), which can support clinical microbiology laboratories to analyze their microbiology and hospital data files (in CSV or Excel format) onsite and promptly generate AMR surveillance reports (in PDF and CSV formats). The data files could be those exported from WHONET or other laboratory information systems. The automatically generated reports contain only summary data without patient identifiers. The AMASS application is downloadable from https://www.amass.website/. The participating hospitals tested the application and deposited their AMR surveillance reports in an open access data repository.

Conclusions: The AMASS is a useful tool to support the generation and sharing of AMR surveillance reports.
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http://dx.doi.org/10.2196/19762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568216PMC
October 2020

ACORN (A Clinically-Oriented Antimicrobial Resistance Surveillance Network): a pilot protocol for case based antimicrobial resistance surveillance.

Wellcome Open Res 2020 1;5:13. Epub 2020 Jun 1.

Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

: Antimicrobial resistance (AMR) / drug resistant infections (DRIs) are a major global health priority. Surveillance data is critical to inform infection treatment guidelines, monitor trends, and to assess interventions. However, most existing AMR / DRI surveillance systems are passive and pathogen-based with many potential biases. Addition of clinical and patient outcome data would provide considerable added value to pathogen-based surveillance. : The aim of the ACORN project is to develop an efficient clinically-oriented AMR surveillance system, implemented alongside routine clinical care in hospitals in low- and middle-income country settings. In an initial pilot phase, clinical and microbiology data will be collected from patients presenting with clinically suspected meningitis, pneumonia, or sepsis. Community-acquired infections will be identified by daily review of new admissions, and hospital-acquired infections will be enrolled during weekly point prevalence surveys, on surveillance wards. Clinical variables will be collected at enrolment, hospital discharge, and at day 28 post-enrolment using an electronic questionnaire on a mobile device. These data will be merged with laboratory data onsite using a flexible automated computer script. Specific target pathogens will be spp and . A bespoke browser-based app will provide sites with fully interactive data visualisation, analysis, and reporting tools. : ACORN will generate data on the burden of DRI which can be used to inform local treatment guidelines / national policy and serve as indicators to measure the impact of interventions. Following development, testing and iteration of the surveillance tools during an initial six-month pilot phase, a wider rollout is planned.
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http://dx.doi.org/10.12688/wellcomeopenres.15681.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250055PMC
June 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

A need to raise the bar - A systematic review of temporal trends in diagnostics for Japanese encephalitis virus infection, and perspectives for future research.

Int J Infect Dis 2020 Jun 20;95:444-456. Epub 2020 Mar 20.

Lao-Oxford-Mahosot Hospital-Wellcome Trust-Research Unit, Mahosot Hospital, Vientiane, Laos; Centre for Tropical Medicine & Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Unité des Virus Émergents (UVE: Aix-Marseille Univ-IRD 190-Inserm 1207-IHU Méditerranée Infection), Marseille, France.

Objective: Japanese encephalitis virus infection (JE) remains a leading cause of neurological disease in Asia, mainly involving individuals living in remote areas with limited access to treatment centers and diagnostic facilities. Laboratory confirmation is fundamental for the justification and implementation of vaccination programs. We reviewed the literature on historical developments and current diagnostic capability worldwide, to identify knowledge gaps and instill urgency to address them.

Methods: Searches were performed in Web of Science and PubMed using the term 'Japanese encephalitis' up to 13th October 2019. Studies reporting laboratory-confirmed symptomatic JE cases in humans were included, and data on details of diagnostic tests were extracted. A JE case was classified according to confirmatory levels (Fischer et al., 2008; Campbell et al., 2011; Pearce et al., 2018; Heffelfinger et al., 2017), where level 1 represented the highest level of confidence.

Findings: 20,212 published JE cases were identified from 205 studies. 15,167 (75%) of these positive cases were confirmed with the lowest-confidence diagnostic tests (level 3 or 4, or level 4). Only 109 (53%) of the studies reported contemporaneous testing for dengue-specific antibodies.

Conclusion: A fundamental pre-requisite for the control of JEV is lacking - that of a simple and specific diagnostic procedure that can be adapted for point-of-care tests and readily used throughout JE-endemic regions of the world.
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http://dx.doi.org/10.1016/j.ijid.2020.03.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294235PMC
June 2020

Harnessing Dengue Rapid Diagnostic Tests for the Combined Surveillance of Dengue, Zika, and Chikungunya Viruses in Laos.

Am J Trop Med Hyg 2020 06;102(6):1244-1248

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

Recent expansions of vector-borne diseases highlight the need for improved surveillance, especially in resource-poor settings. Dengue virus (DENV), chikungunya virus (CHIKV), and Zika virus (ZIKV) share the same vectors as well as similar clinical presentations, suggesting that combined surveillance would be useful. We hypothesized that blood spotted on dengue rapid diagnostic tests (RDTs) could be harnessed for sample collection in remote areas for subsequent detection of DENV, CHIKV, and ZIKV by reverse transcription real-time polymerase chain reaction (RT-qPCR). CHIKV and ZIKV dilutions were spotted on dengue RDTs (SD BIOLINE Dengue DUO, Standard Diagnostics, Gyeonggi-do, Republic of Korea), dried, and extracted. As reference, aliquots of each viral dilution were directly extracted. Using specific RT-qPCR tests, both viruses were successfully detected from RDT extracts. However, the limit of detection was slightly lower in comparison to direct extracts, two logfold for CHIKV and one logfold for ZIKV. For analysis of temperature stability, DENV dilutions were spotted on RDTs and stored for up to 2 months at -80°C, 4°C, or 35°C before testing. Storage of RDTs for 2 months at 35°C did not compromise detection of RNA by RT-qPCR; only minimal degradation was observed. This proof-of-principle study demonstrates the potential of using dengue RDTs for DENV/CHIKV/ZIKV combined surveillance in areas without access to laboratory facilities. Further investigations are needed for evaluation of tri-viral surveillance under field conditions using patient samples. Large-scale implementation of surveillance for these viruses is of crucial public health importance for the early detection of epidemics. This method also has important implications for improving understanding of the molecular epidemiology of the three viruses.
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http://dx.doi.org/10.4269/ajtmh.19-0881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253103PMC
June 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

Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia.

Genome Med 2020 01 16;12(1):11. Epub 2020 Jan 16.

Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, Victoria, 3004, Australia.

Background: Klebsiella pneumoniae is a leading cause of bloodstream infection (BSI). Strains producing extended-spectrum beta-lactamases (ESBLs) or carbapenemases are considered global priority pathogens for which new treatment and prevention strategies are urgently required, due to severely limited therapeutic options. South and Southeast Asia are major hubs for antimicrobial-resistant (AMR) K. pneumoniae and also for the characteristically antimicrobial-sensitive, community-acquired "hypervirulent" strains. The emergence of hypervirulent AMR strains and lack of data on exopolysaccharide diversity pose a challenge for K. pneumoniae BSI control strategies worldwide.

Methods: We conducted a retrospective genomic epidemiology study of 365 BSI K. pneumoniae from seven major healthcare facilities across South and Southeast Asia, extracting clinically relevant information (AMR, virulence, K and O antigen loci) using Kleborate, a K. pneumoniae-specific genomic typing tool.

Results: K. pneumoniae BSI isolates were highly diverse, comprising 120 multi-locus sequence types (STs) and 63 K-loci. ESBL and carbapenemase gene frequencies were 47% and 17%, respectively. The aerobactin synthesis locus (iuc), associated with hypervirulence, was detected in 28% of isolates. Importantly, 7% of isolates harboured iuc plus ESBL and/or carbapenemase genes. The latter represent genotypic AMR-virulence convergence, which is generally considered a rare phenomenon but was particularly common among South Asian BSI (17%). Of greatest concern, we identified seven novel plasmids carrying both iuc and AMR genes, raising the prospect of co-transfer of these phenotypes among K. pneumoniae.

Conclusions: K. pneumoniae BSI in South and Southeast Asia are caused by different STs from those predominating in other regions, and with higher frequency of acquired virulence determinants. K. pneumoniae carrying both iuc and AMR genes were also detected at higher rates than have been reported elsewhere. The study demonstrates how genomics-based surveillance-reporting full molecular profiles including STs, AMR, virulence and serotype locus information-can help standardise comparisons between sites and identify regional differences in pathogen populations.
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http://dx.doi.org/10.1186/s13073-019-0706-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966826PMC
January 2020
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