Acquisition and Loss of #CTX-M-Producing and Non-Producing #Escherichia coli in the Fecal #Microbiome of #Travelers to South #Asia (mBio, abstract)

[Source: mBio, full page: (LINK). Abstract, edited.]

Acquisition and Loss of CTX-M-Producing and Non-Producing Escherichia coli in the Fecal Microbiome of Travelers to South Asia

Edward R. Bevan, Alan McNally, Christopher M. Thomas, Laura J. V. Piddock, Peter M. Hawkey

George A. Jacoby, Editor

DOI: 10.1128/mBio.02408-18

 

ABSTRACT

Over 80% of travelers from the United Kingdom to the Indian subcontinent acquire CTX-M-producing Escherichia coli (CTX-M-EC), but the mechanism of CTX-M-EC acquisition is poorly understood. We aimed to investigate the dynamics of CTX-M-EC acquisition in healthy travelers and how this relates to populations of non-CTX-M-EC in the fecal microbiome. This is a prospective observational study of healthy volunteers traveling from the United Kingdom to South Asia. Fecal samples were collected pre- and post-travel at several time points up to 12 months post-travel. A toothpicking experiment was used to determine the proportion of cephalosporin-sensitive E. coli in fecal samples containing CTX-M-EC. MLST and SNP type of pre-travel and post-travel E. coli were deduced by WGS. CTX-M-EC was acquired by 89% (16/18) of volunteers. Polyclonal acquisition of CTX-M-EC was seen in 8/15 volunteers (all had >3 STs across post-travel samples), suggesting multiple acquisition events. Indistinguishable CTX-M-EC clones (zero SNPs apart) are detectable in serial fecal samples up to 7 months after travel, indicating stable maintenance in the fecal microbiome on return to the United Kingdom in the absence of selective pressure. CTX-M-EC-containing samples were often co-colonized with novel, non-CTX-M strains after travel, indicating that acquisition of non-CTX-M-EC occurs alongside CTX-M-EC. The same pre-travel non-CTX-M strains (<10 SNPs apart) were found in post-travel fecal samples after CTX-M-EC had been lost, suggesting return of the fecal microbiome to the pre-travel state and long-term persistence of minority strains in travelers who acquire CTX-M-EC.

 

IMPORTANCE

Escherichia coli strains which produce CTX-M extended-spectrum beta-lactamases are endemic as colonizers of humans and in the environment in South Asia. This study demonstrates that acquisition of CTX-M-producing E. coli (CTX-M-EC) in travelers from the United Kingdom to South Asia is polyclonal, which is likely due to multiple acquisition events from contaminated food and drinking water during travel. CTX-M-EC frequently persists in the fecal microbiome for at least 1 year after acquisition, often alongside newly acquired non-CTX-M E. coli strains. In travelers who acquire CTX-M-EC, pre-travel non-CTX-M E. coli remains as a minority population in the gut until the CTX-M-EC strains are lost. The non-CTX-M strains are then reestablished as the predominant E. coli population. This study has shed light on the dynamics of CTX-M-EC acquisition, colonization, and loss after travel. Future work involving manipulation of nonvirulent resident E. coli could be used to prevent colonization with antibiotic-resistant E. coli.

Keywords: Antibiotics; Drugs Resistance; Cephalosporins; E. Coli; UK; Asian region.

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#Prevalence of pretreatment #HIV #drug #resistance in West #African and Southeast #Asian countries (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Prevalence of pretreatment HIV drug resistance in West African and Southeast Asian countries

Nicole Ngo-Giang-Huong Thu, H K Huynh, Anoumou Y Dagnra, Thomas-d’Aquin Toni, Almoustapha I Maiga, Dramane Kania, Sabrina Eymard-Duvernay, Martine Peeters, Cathia Soulie, Gilles Peytavin, Claire Rekacewicz, Marie-Laure Chaix, Avelin F Aghokeng, ANRS 12333 Study Group

Journal of Antimicrobial Chemotherapy, dky443, https://doi.org/10.1093/jac/dky443

Published: 12 November 2018

 

Abstract

Background

ART in the developing world has moved to a new era with the WHO recommendation to test and immediately treat HIV-positive individuals. A high frequency of pretreatment HIV drug resistance (PDR) can compromise ART efficacy. Our study presents updated estimates of PDR in seven countries from West Africa (Burkina Faso, Cameroon, Côte d’Ivoire, Mali and Togo) and Southeast Asia (Thailand and Vietnam).

Methods

Eligible study participants were adult ART initiators, recruited from December 2015 to November 2016 in major ART clinics in each country. HIV drug resistance (HIVDR) tests were performed for all specimens and interpretation was done using the Stanford algorithm.

Results

Overall, 1153 participants were recruited and 1020 nt sequences were generated. PDR frequency among all initiators was 15.9% (95% CI: 13.8%–18.3%) overall, ranging from 9.6% and 10.2% in Burkina Faso and Thailand, respectively, 14.7% in Vietnam, 15.4% in Mali, 16.5% in Côte d’Ivoire and 19.3% in Cameroon, to 24.6% in Togo. The prevalence of NNRTI resistance mutations was 12%; NRTI and PI PDR prevalences were 4% and 3%, respectively.

Conclusions

Our study shows that in most countries PDR exceeded 10%, warranting the conduct of nationally representative surveys to confirm this trend. In the meantime, actions to prevent drug resistance, including transition from NNRTIs to more robust drug classes should be urgently implemented.

Issue Section: ORIGINAL RESEARCH

Keywords: HIV/AIDS; Antivirals; Drugs Resistance; West Africa; Asian Region.

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#Threats of #Zika virus #transmission for #Asia and its Hindu-Kush #Himalayan region (Infect Dis Poverty., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Infect Dis Poverty. 2018 May 15;7(1):40. doi: 10.1186/s40249-018-0426-3.

Threats of Zika virus transmission for Asia and its Hindu-Kush Himalayan region.

Dhimal M1,2, Dahal S3, Dhimal ML4,5, Mishra SR6, Karki KB3, Aryal KK3, Haque U7, Kabir MI8, Guin P9,10, Butt AM11, Harapan H12, Liu QY13, Chu C14, Montag D15, Groneberg DA4, Pandey BD16, Kuch U4, Müller R4.

Author information: 1 Nepal Health Research Council (NHRC), Ramshah Path, Kathmandu, Nepal. meghdhimal@gmail.com. 2 Institute of Occupational Medicine, Social Medicine and Environmental Medicine, Goethe University, Frankfurt am Main, Germany. meghdhimal@gmail.com. 3 Nepal Health Research Council (NHRC), Ramshah Path, Kathmandu, Nepal. 4 Institute of Occupational Medicine, Social Medicine and Environmental Medicine, Goethe University, Frankfurt am Main, Germany. 5 Faculty of Social Sciences, Goethe University, Frankfurt am Main, Germany. 6 The University of Queensland, Brisbane, Australia. 7 Department of Public Health, Baldwin Wallace University, Berea, Ohio, USA. 8 Department of Epidemiology, National Institute of Preventive and Social Medicine, Ministry of Health and Family Welfare, Dhaka, Bangladesh. 9 Public Health Foundation of India, Gurgaon, Haryana, India. 10 Centre for Environmental Health, Gurgaon, Haryana, India. 11 Translational Genomics Laboratory, Department of Biosciences, COMSATS Institute of Information Technology (CIIT), Islamabad, 45550, Pakistan. 12 Medical Research Unit, School of Medicine, Syiah Kuala University, Banda Aceh, Indonesia. 13 WHO Collaborating Centre for Vector Surveillance and Management, SKLID, CCID, ICDC, China CDC, Beijing, China. 14 Centre for Environment and Population Health, Griffith University, Nathan, Queensland, Australia. 15 Barts and the London School of Medicine, Centre for Primary Care and Public Health, Queen Mary University of London, London, UK. 16 Department of Health Services, Ministry of Health, Government of Nepal, Kathmandu, Nepal.

 

Abstract

Asia and its Hindu Kush Himalayan (HKH) region is particularly vulnerable to environmental change, especially climate and land use changes further influenced by rapid population growth, high level of poverty and unsustainable development. Asia has been a hotspot of dengue fever and chikungunya mainly due to its dense human population, unplanned urbanization and poverty. In an urban cycle, dengue virus (DENV) and chikungunya virus (CHIKV) are transmitted by Aedes aegypti and Ae. albopictus mosquitoes which are also competent vectors of Zika virus (ZIKV). Over the last decade, DENV and CHIKV transmissions by Ae. aegypti have extended to the Himalayan countries of Bhutan and Nepal and ZIKV could follow in the footsteps of these viruses in the HKH region. The already established distribution of human-biting Aedes mosquito vectors and a naïve population with lack of immunity against ZIKV places the HKH region at a higher risk of ZIKV. Some of the countries in the HKH region have already reported ZIKV cases. We have documented an increasing threat of ZIKV in Asia and its HKH region because of the high abundance and wide distribution of human-biting mosquito vectors, climate change, poverty, report of indigenous cases in the region, increasing numbers of imported cases and a naïve population with lack of immunity against ZIKV. An outbreak anywhere is potentially a threat everywhere. Therefore, in order to ensure international health security, all efforts to prevent, detect, and respond to ZIKV ought to be intensified now in Asia and its HKH region. To prepare for possible ZIKV outbreaks, Asia and the HKH region can also learn from the success stories and strategies adopted by other regions and countries in preventing ZIKV and associated complications. The future control strategies for DENV, CHIKV and ZIKV should be considered in tandem with the threat to human well-being that is posed by other emerging and re-emerging vector-borne and zoonotic diseases, and by the continuing urgent need to strengthen public primary healthcare systems in the region.

KEYWORDS: Aedes aegypti; Aedes albopictus; Chikungunya virus; Dengue virus; Hindu Kush Himalayas; Mountain; Poverty, Zika virus

PMID: 29759076 DOI: 10.1186/s40249-018-0426-3

Keywords: Arbovirus; Dengue Fever; Chikungunya Fever; Zika Virus; Mosquitoes; Asia Region; Aedes spp.

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#Origins of the current #outbreak of #MDR #malaria in southeast #Asia: a retrospective genetic study (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Origins of the current outbreak of multidrug-resistant malaria in southeast Asia: a retrospective genetic study

Roberto Amato, PhD, Richard D Pearson, PhD, Jacob Almagro-Garcia, PhD, Chanaki Amaratunga, PhD, Pharath Lim, MD, Seila Suon, MD, Sokunthea Sreng, Eleanor Drury, Sc, Jim Stalker, MA, Olivo Miotto, PhD, Rick M Fairhurst, MD, Prof Dominic P Kwiatkowski, FRCP

Published: 01 February 2018 / Open Access / DOI: https://doi.org/10.1016/S1473-3099(18)30068-9

© 2018 The Author(s). Published by Elsevier Ltd.

 

Summary

Background

Antimalarial resistance is rapidly spreading across parts of southeast Asia where dihydroartemisinin–piperaquine is used as first-line treatment for Plasmodium falciparum malaria. The first published reports about resistance to antimalarial drugs came from western Cambodia in 2013. Here, we analyse genetic changes in the P falciparum population of western Cambodia in the 6 years before those reports.

Methods

We analysed genome sequence data on 1492 P falciparum samples from 11 locations across southeast Asia, including 464 samples collected in western Cambodia between 2007 and 2013. Different epidemiological origins of resistance were identified by haplotypic analysis of the kelch13artemisinin resistance locus and the plasmepsin 2–3 piperaquine resistance locus.

Findings

We identified more than 30 independent origins of artemisinin resistance, of which the KEL1 lineage accounted for 140 (91%) of 154 parasites resistant to dihydroartemisinin–piperaquine. In 2008, KEL1 combined with PLA1, the major lineage associated with piperaquine resistance. By 2013, the KEL1/PLA1 co-lineage had reached a frequency of 63% (24/38) in western Cambodia and had spread to northern Cambodia.

Interpretation

The KEL1/PLA1 co-lineage emerged in the same year that dihydroartemisinin–piperaquine became the first-line antimalarial drug in western Cambodia and spread rapidly thereafter, displacing other artemisinin-resistant parasite lineages. These findings have important implications for management of the global health risk associated with the current outbreak of multidrug-resistant malaria in southeast Asia.

Funding

Wellcome Trust, Bill & Melinda Gates Foundation, Medical Research Council, UK Department for International Development, and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases.

Keywords: Malaria; Asia Region; Antibiotics; Drugs Resistance; Artemisin; Piperaquine.

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#Azithromycin #resistance in #Shigella spp. in Southeast #Asia (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Azithromycin resistance in Shigella spp. in Southeast Asia

Thomas C Darton1,2,  Ha Thanh Tuyen1,  Hao Chung The1,  Paul N Newton3,4, David A. B. Dance3,4,5,  Rattanaphone Phetsouvanh3,  Viengmon Davong3, James I Campbell1,  Nguyen Van Minh Hoang1,  Guy E Thwaites1,4, Christopher M Parry6,7,  Duy Pham Thanh1 and  Stephen Baker1,4,8*

Author Affiliations: 1 The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam; 2 Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School, Sheffield, United Kingdom; 3 Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Vientiane, Laos; 4 Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, Oxford, United Kingdom; 5 Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom; 6 Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; 7 School of Tropical Medicine and Global Health, Nagasaki University, Japan; 8 The Department of Medicine, The University of Cambridge, Cambridge, United Kingdom

 

ABSTRACT

Infection by Shigella spp. is a common cause of dysentery in Southeast Asia. Antimicrobials are thought to be beneficial for treatment, however antimicrobial resistance in Shigella spp. is becoming widespread. We aimed to assess the frequency and mechanisms associated with decreased susceptibility to azithromycin in Southeast Asian Shigella isolates and use these data to assess appropriate susceptibility breakpoints. Shigella isolated in Vietnam and Laos were screened for susceptibility against azithromycin (15μg) by disc diffusion and minimum inhibitory concentration (MIC). Phenotypic resistance was confirmed by PCR amplification of macrolide resistance loci. We compared the genetic relationships and plasmid contents of azithromycin resistant S. sonnei using whole genome sequences. From 475 available Shigella spp. isolated in Vietnam and Laos between 1994 and 2012, 6/181 S. flexneri (3.3%, MIC≥16g/L) and 16/294 S. sonnei (5.4%, MIC≥32g/L) were phenotypically resistant to azithromycin. PCR amplification confirmed a resistance mechanism in 22/475 (4.6%) isolates (19 mphA and 3 ermB). Susceptibility data demonstrated the acceptability of S. flexneri(MIC≥16g/L, zone≤15mm) and S. sonnei (MIC≥32g/L, zone≤11mm) breakpoints with <3% discrepancy. Phylogenetic analysis demonstrated that decreased susceptibility has arisen sporadically in Vietnamese S. sonnei on at least seven occasions between 2000 and 2009, but failed to become established. While the proposed susceptibility breakpoints may allow better recognition of resistant isolates, additional studies are required to assess the impact on clinical outcome. The potential emergence of azithromycin resistance highlights the need for alternative management options for Shigella infections in endemic countries.

 

FOOTNOTES

*Corresponding author: Professor Stephen Baker, the Hospital for Tropical Diseases, 764 Vo Van Kiet, Quan 5, Ho Chi Minh City, Vietnam. Tel: +84 89241761 Fax: +84 89238904 sbaker@oucru.org

Copyright © 2018 Darton et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Keywords: Antibiotics; Drugs Resistance; Shigella spp.; Azithromycin; Asian Region.

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Neutralizing #Antibody Correlates Analysis of Tetravalent #Dengue #Vaccine Efficacy Trials in #Asia and Latin America (J Infect Dis., abstract)

[Source: The Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Neutralizing Antibody Correlates Analysis of Tetravalent Dengue Vaccine Efficacy Trials in Asia and Latin America 

Zoe Moodie, Ph.D. Michal Juraska, Ph.D. Ying Huang, Ph.D. Yingying Zhuang, M.S. Youyi Fong, Ph.D. Lindsay N Carpp, Ph.D. Steven G Self, Ph.D. Laurent Chambonneau, M.Sc. Robert Small, Ph.D. Nicholas Jackson, Ph.D. Fernando Noriega, M.D. Peter B Gilbert, Ph.D.

The Journal of Infectious Diseases, jix609, https://doi.org/10.1093/infdis/jix609

Published: 29 November 2017

 

Abstract

Background

In the CYD14 and CYD15 Phase 3 trials of the CYD-TDV dengue vaccine, estimated vaccine efficacy (VE) against symptomatic, virologically-confirmed dengue (VCD) occurring between Months 13 and 25 was 56.5% and 60.8%, respectively.

Methods

Neutralizing antibody titers to the four dengue serotypes in the CYD-TDV vaccine insert were measured at Month 13 in a randomly sampled immunogenicity sub-cohort and in all VCD cases through Month 25 (2848 vaccine, 1574 placebo) and studied for their association with VCD and with the level of VE to prevent VCD.

Results

For each trial and serotype, vaccinees with higher Month 13 titer to the serotype had significantly lower risk of VCD with that serotype (hazard ratios 0.19−0.43 per 10-fold increase). Moreover, for each trial vaccinees with higher Month 13 average titer to the four serotypes had significantly higher VE against VCD of any serotype (P values < 0.001).

Conclusions

Neutralizing antibody titers post-dose three correlate with CYD-TDV VE to prevent dengue. High titers associate with high VE for all serotypes, baseline serostatus groups, age groups, and both trials. However, lowest titers do not fully correspond to zero VE, indicating that other factors influence VE.

Issue Section: Major Article

© The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Keywords: Dengue Fever; Vaccines; Asia Region; Africa Region.

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The first external quality #assessment of #isolation and #identification of #influenza viruses in #cell culture in the #Asia #Pacific region, 2016 (J Clin Virol., abstract)

[Source: Journal of Clinical Virology, full page: (LINK). Abstract, edited.]

The first external quality assessment of isolation and identification of influenza viruses in cell culture in the Asia Pacific region, 2016

Patrick C. Reading, Vivian K. Leung, Iwona Buettner, Leah Gillespie, Yi-Mo Deng, Robert Shaw, Natalie Spirason, Angela Todd, Kanta Subbarao, Aparna Singh Shah, Frank Konings, Ian G. Barr

DOI: http://dx.doi.org/10.1016/j.jcv.2017.10.018

Article Info: Publication History: Published online: November 01, 2017 – Accepted: October 31, 2017 – Received in revised form: October 27, 2017 – Received: August 1, 2017

 

Highlights

  • An external quality assessment (EQA) was developed for influenza virus isolation.
  • National Influenza Centres (NICs) in the Asia Pacific Region performed the EQA.
  • NICs used a variety of techniques to confirm and identify influenza virus isolates.
  • The EQA revealed good proficiency and highlighted the need to improve sensitivity.

 

Abstract

Background

The isolation and propagation of influenza viruses from clinical specimens are essential tools for comprehensive virologic surveillance. Influenza viruses must be amplified in cell culture for detailed antigenic analysis and for phenotypic assays assessing susceptibility to antiviral drugs or for other assays.

Objectives

To conduct an external quality assessment (EQA) of proficiency for isolation and identification of influenza viruses using cell culture techniques among National Influenza Centres (NICs) in the World Health Organisation (WHO) South East Asia and Western Pacific Regions.

Study design

Twenty-one NICs performed routine influenza virus isolation and identification techniques on a proficiency testing panel comprising 16 samples, containing influenza A or B viruses and negative control samples. One sample was used exclusively to determine their capacity to measure hemagglutination titer and the other 15 samples were used for virus isolation and identification.

Results

All NICs performed influenza virus isolation using Madin Darby canine kidney (MDCK) or MDCK-SIAT-1 cells. If virus growth was detected, the type, subtype and/or lineage of virus present in isolates was determined using immunofluorescence, RT-PCR and/or hemagglutination inhibition (HI) assays. Most participating laboratories could detect influenza virus growth and could identify virus amplified from EQA samples. However, some laboratories failed to isolate and identify viruses from EQA samples that contained lower titres of virus, highlighting issues regarding the sensitivity of influenza virus isolation methods between laboratories.

Conclusion

This first round of EQA was successfully conducted by NICs in the Asia Pacific Region, revealing good proficiency in influenza virus isolation and identification.

Abbreviations: CC (Collaborating Centre), EQA (external quality assessment), GISRS (Global Influenza Surveillance and Response System), WPR (WHO Western Pacific Region), SEAR (WHO South East Asia Region), NIC (National Influenza Centre), MDCK (Madin Darby canine kidney), HA (hemagglutination), HI (hemagglutination inhibition), IF (immunofluorescence)

Keywords: influenza, virus isolation, external quality assessment

© 2017 Published by Elsevier B.V.

Keywords: Influenza A; Influenza B; Diagnostic Tests; Asia Region.

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