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108. How to reduce household costs for people with tuberculosis: a longitudinal costing survey in Nepal.

Author

Gurung, Suman Chandra, Rai, Bhola, Dixit, Kritika, Worrall, Eve, Paudel, Puskar Raj, Dhital, Raghu, Sah, Manoj Kumar, Pandit, Ram Narayan, Aryal, Tara Prasad, Majhi, Govinda, Wingfield, Tom, Squire, Bertie, Lönnroth, Knut, Levy, Jens W, Viney, Kerri, Rest, Job van, Ramsay, Andrew, Costa, Rafaely Marcia Santos da, Basnyat, Buddha, and Thapa, Anil

Subjects
TUBERCULOSIS, GENERALIZED estimating equations, HOUSEHOLDS, DISEASE prevalence, POVERTY
Abstract

The aim of this study was to compare costs and socio-economic impact of tuberculosis (TB) for patients diagnosed through active (ACF) and passive case finding (PCF) in Nepal. A longitudinal costing survey was conducted in four districts of Nepal from April 2018 to October 2019. Costs were collected using the WHO TB Patient Costs Survey at three time points: intensive phase of treatment, continuation phase of treatment and at treatment completion. Direct and indirect costs and socio-economic impact (poverty headcount, employment status and coping strategies) were evaluated throughout the treatment. Prevalence of catastrophic costs was estimated using the WHO threshold. Logistic regression and generalized estimating equation were used to evaluate risk of incurring high costs, catastrophic costs and socio-economic impact of TB over time. A total of 111 ACF and 110 PCF patients were included. ACF patients were more likely to have no education (75% vs 57%, P = 0.006) and informal employment (42% vs 24%, P = 0.005) Compared with the PCF group, ACF patients incurred lower costs during the pretreatment period (mean total cost: US$55 vs US$87, P < 0.001) and during the pretreatment plus treatment periods (mean total direct costs: US$72 vs US$101, P < 0.001). Socio-economic impact was severe for both groups throughout the whole treatment, with 32% of households incurring catastrophic costs. Catastrophic costs were associated with 'no education' status [odds ratio = 2.53(95% confidence interval = 1.16-5.50)]. There is a severe and sustained socio-economic impact of TB on affected households in Nepal. The community-based ACF approach mitigated costs and reached the most vulnerable patients. Alongside ACF, social protection policies must be extended to achieve the zero catastrophic costs milestone of the End TB strategy. [ABSTRACT FROM AUTHOR]

Published
2021
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109. In Reply to Drs Lipman and Hackett

Author

Kanaan, Nicholas C., Peterson, Alicia L., Pun, Matiram, Thapa, Ghan B., Tiwari, Aditya, Basyal, Bikash, Holck, Peter S., Starling, Jennifer, Freeman, Thomas F., Gehner, Jessica R., Keyes, Linda, Levin, Dana R., O’Leary, Catherine J., Stuart, Katherine E., Velgersdyk, Jared L., Zafren, Ken, and Basnyat, Buddha

Published
2017
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114. In Reply to Dr Bennett

Author

McIntosh, Scott E., primary, Hemphill, Mika, additional, McDevitt, Marion C., additional, Gurung, Tsering Yangzom, additional, Ghale, Mukhiya, additional, Knott, Jonathan R., additional, Thapa, Ghan Bahadur, additional, Basnyat, Buddha, additional, Dow, Jennifer, additional, Weber, David C., additional, and Grissom, Colin K., additional

Published
2019
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115. Diagnostic host gene signature for distinguishing enteric fever from other febrile diseases

Author

Blohmke, Christoph J, primary, Muller, Julius, additional, Gibani, Malick M, additional, Dobinson, Hazel, additional, Shrestha, Sonu, additional, Perinparajah, Soumya, additional, Jin, Celina, additional, Hughes, Harri, additional, Blackwell, Luke, additional, Dongol, Sabina, additional, Karkey, Abhilasha, additional, Schreiber, Fernanda, additional, Pickard, Derek, additional, Basnyat, Buddha, additional, Dougan, Gordon, additional, Baker, Stephen, additional, Pollard, Andrew J, additional, and Darton, Thomas C, additional

Published
2019
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125. The sensitivity of real-time PCR amplification targeting invasive Salmonella serovars in biological specimens

Author

Chau Tran, Campbell James I, Tu Le, Holt Kathryn, Dunstan Sarah, Thuy Hang, Dongol Sabina, Karkey Abhilasha, Nga Tran, Chau Nguyen, Arjyal Amit, Koirala Samir, Basnyat Buddha, Dolecek Christiane, Farrar Jeremy, and Baker Stephen

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background PCR amplification for the detection of pathogens in biological material is generally considered a rapid and informative diagnostic technique. Invasive Salmonella serovars, which cause enteric fever, can be commonly cultured from the blood of infected patients. Yet, the isolation of invasive Salmonella serovars from blood is protracted and potentially insensitive. Methods We developed and optimised a novel multiplex three colour real-time PCR assay to detect specific target sequences in the genomes of Salmonella serovars Typhi and Paratyphi A. We performed the assay on DNA extracted from blood and bone marrow samples from culture positive and negative enteric fever patients. Results The assay was validated and demonstrated a high level of specificity and reproducibility under experimental conditions. All bone marrow samples tested positive for Salmonella, however, the sensitivity on blood samples was limited. The assay demonstrated an overall specificity of 100% (75/75) and sensitivity of 53.9% (69/128) on all biological samples. We then tested the PCR detection limit by performing bacterial counts after inoculation into blood culture bottles. Conclusions Our findings corroborate previous clinical findings, whereby the bacterial load of S. Typhi in peripheral blood is low, often below detection by culture and, consequently, below detection by PCR. Whilst the assay may be utilised for environmental sampling or on differing biological samples, our data suggest that PCR performed directly on blood samples may be an unsuitable methodology and a potentially unachievable target for the routine diagnosis of enteric fever.

Published
2010
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126. High-throughput bacterial SNP typing identifies distinct clusters of Salmonella Typhi causing typhoid in Nepalese children

Author

Parkhill Julian, Song Yajun, Pulickal Anoop S, Thorson Stephen, Adhikari Neelam, Basnyat Buddha, Dongol Sabina, Baker Stephen, Holt Kathryn E, Farrar Jeremy J, Murdoch David R, Kelly Dominic F, Pollard Andrew J, and Dougan Gordon

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Salmonella Typhi (S. Typhi) causes typhoid fever, which remains an important public health issue in many developing countries. Kathmandu, the capital of Nepal, is an area of high incidence and the pediatric population appears to be at high risk of exposure and infection. Methods We recently defined the population structure of S. Typhi, using new sequencing technologies to identify nearly 2,000 single nucleotide polymorphisms (SNPs) that can be used as unequivocal phylogenetic markers. Here we have used the GoldenGate (Illumina) platform to simultaneously type 1,500 of these SNPs in 62 S. Typhi isolates causing severe typhoid in children admitted to Patan Hospital in Kathmandu. Results Eight distinct S. Typhi haplotypes were identified during the 20-month study period, with 68% of isolates belonging to a subclone of the previously defined H58 S. Typhi. This subclone was closely associated with resistance to nalidixic acid, with all isolates from this group demonstrating a resistant phenotype and harbouring the same resistance-associated SNP in GyrA (Phe83). A secondary clone, comprising 19% of isolates, was observed only during the second half of the study. Conclusions Our data demonstrate the utility of SNP typing for monitoring bacterial populations over a defined period in a single endemic setting. We provide evidence for genotype introduction and define a nalidixic acid resistant subclone of S. Typhi, which appears to be the dominant cause of severe pediatric typhoid in Kathmandu during the study period.

Published
2010
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127. Diagnostic metabolite biomarkers of chronic typhoid carriage

Author

Näsström, Elin, Jonsson, Pär, Johansson, Anders, Dongol, Sabina, Karkey, Abhilasha, Basnyat, Buddha, Thieu, Nga Tran Vu, Van, Tan Trinh, Thwaites, Guy E., Antti, Henrik, Baker, Stephen, Näsström, Elin, Jonsson, Pär, Johansson, Anders, Dongol, Sabina, Karkey, Abhilasha, Basnyat, Buddha, Thieu, Nga Tran Vu, Van, Tan Trinh, Thwaites, Guy E., Antti, Henrik, and Baker, Stephen

Abstract

Background: Salmonella Typhi and Salmonella Paratyphi A are the agents of enteric (typhoid) fever; both can establish chronic carriage in the gallbladder. Chronic Salmonella carriers are typically asymptomatic, intermittently shedding bacteria in the feces, and contributing to disease transmission. Detecting chronic carriers is of public health relevance in areas where enteric fever is endemic, but there are no routinely used methods for prospectively identifying those carrying Salmonella in their gallbladder. Methodology/Principal findings: Here we aimed to identify biomarkers of Salmonella carriage using metabolite profiling. We performed metabolite profiling on plasma from Nepali patients undergoing cholecystectomy with confirmed S. Typhi or S. Paratyphi A gallbladder carriage (and non-carriage controls) using two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS) and supervised pattern recognition modeling. We were able to significantly discriminate Salmonella carriage samples from non-carriage control samples. We were also able to detect differential signatures between S. Typhi and S. Paratyphi A carriers. We additionally compared carriage metabolite profiles with profiles generated during acute infection; these data revealed substantial heterogeneity between metabolites associated with acute enteric fever and chronic carriage. Lastly, we found that Salmonella carriers could be significantly distinguished from non-carriage controls using only five metabolites, indicating the potential of these metabolites as diagnostic markers for detecting chronic Salmonella carriers. Conclusions/Significance: Our novel approach has highlighted the potential of using metabolomics to search for diagnostic markers of chronic Salmonella carriage. We suggest further epidemiological investigations of these potential biomarkers in alternative endemic enteric fever settings.

Published
2018
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128. Clinical recommendations for high altitude exposure of individuals with pre-existing cardiovascular conditions: A joint statement by the European Society of Cardiology, the Council on Hypertension of the European Society of Cardiology, the European Society of Hypertension, the International Society of Mountain Medicine, the Italian Society of Hypertension and the Italian Society of Mountain Medicine

Author

Parati, Gianfranco, Agostoni, Piergiuseppe, Basnyat, Buddha, Bilo, Grzegorz, Brugger, Hermann, Coca, Antonio, Festi, Luigi, Giardini, Guido, Lironcurti, Alessandra, Luks, Andrew M, Maggiorini, Marco, Modesti, Pietro A, Swenson, Erik R, Williams, Bryan, Bärtsch, Peter, Torlasco, Camilla, Parati, Gianfranco, Agostoni, Piergiuseppe, Basnyat, Buddha, Bilo, Grzegorz, Brugger, Hermann, Coca, Antonio, Festi, Luigi, Giardini, Guido, Lironcurti, Alessandra, Luks, Andrew M, Maggiorini, Marco, Modesti, Pietro A, Swenson, Erik R, Williams, Bryan, Bärtsch, Peter, and Torlasco, Camilla

Abstract

Take home figureAdapted from Bärtsch and Gibbs2 Physiological response to hypoxia. Life-sustaining oxygen delivery, in spite of a reduction in the partial pressure of inhaled oxygen between 25% and 60% (respectively at 2500 m and 8000 m), is ensured by an increase in pulmonary ventilation, an increase in cardiac output by increasing heart rate, changes in vascular tone, as well as an increase in haemoglobin concentration. BP, blood pressure; HR, heart rate; PaCO2, partial pressure of arterial carbon dioxide.

Published
2018

130. Changing Antimicrobial Resistance Trends in Kathmandu, Nepal: A 23-Year Retrospective Analysis of Bacteraemia

Author

Zellweger, Raphaël M., primary, Basnyat, Buddha, additional, Shrestha, Poojan, additional, Prajapati, Krishna G., additional, Dongol, Sabina, additional, Sharma, Paban K., additional, Koirala, Samir, additional, Darton, Thomas C., additional, Boinett, Christine, additional, Thompson, Corinne N., additional, Thwaites, Guy E., additional, Baker, Stephen, additional, and Karkey, Abhilasha, additional

Published
2018
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133. Nail the Diagnosis

Author

Adhikari, Sudeep, primary, Sigdel, Keshav Raj, additional, Paudyal, Buddhi, additional, and Basnyat, Buddha, additional

Published
2018
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138. Diagnostic metabolite biomarkers of chronic typhoid carriage

Author

Näsström, Elin, primary, Jonsson, Pär, additional, Johansson, Anders, additional, Dongol, Sabina, additional, Karkey, Abhilasha, additional, Basnyat, Buddha, additional, Tran Vu Thieu, Nga, additional, Trinh Van, Tan, additional, Thwaites, Guy E., additional, Antti, Henrik, additional, and Baker, Stephen, additional

Published
2018
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139. Clinical recommendations for high altitude exposure of individuals with pre-existing cardiovascular conditions

Author

Parati, Gianfranco, primary, Agostoni, Piergiuseppe, additional, Basnyat, Buddha, additional, Bilo, Grzegorz, additional, Brugger, Hermann, additional, Coca, Antonio, additional, Festi, Luigi, additional, Giardini, Guido, additional, Lironcurti, Alessandra, additional, Luks, Andrew M, additional, Maggiorini, Marco, additional, Modesti, Pietro A, additional, Swenson, Erik R, additional, Williams, Bryan, additional, Bärtsch, Peter, additional, and Torlasco, Camilla, additional

Published
2018
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140. Tuberculosis in Staff and Students of Patan Hospital

Author

Shrestha, Poojan, primary, Shakya, Mila, primary, Caws, Maxine, primary, Shrestha, Surendra, primary, Karki, Bibek, primary, Shrestha, Shreejana, primary, Karki, Dan Bahadur, primary, Maharjan, Bhagwan, primary, Shrestha, Bhawana, primary, Arjyal, Amit, primary, Karkey, Abhilasha, primary, Prajapati, Krishna G., primary, and Basnyat, Buddha, primary

Published
2018
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142. Reduced Acetazolamide Dosing for Acute Mountain Sickness Prevention Study: A Comparison of 62.5 vs 125 mg BID (the RAD AMS prevention study)

Author

McIntosh, Scott, primary, Hemphill, Mika, additional, McDevitt, Marion, additional, Gurung, Tsering Yangzom, additional, Ghale, Mukhiya, additional, Knott, Jonathan, additional, Thapa, Ghan Bahadur, additional, Basnyat, Buddha, additional, Dow, Jennifer, additional, Weber, David, additional, and Grissom, Colin, additional

Published
2017
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144. A 23-year retrospective investigation of Salmonella Typhi and Salmonella Paratyphi isolated in a tertiary Kathmandu hospital

Author

Zellweger, Raphaël M., primary, Basnyat, Buddha, additional, Shrestha, Poojan, additional, Prajapati, Krishna G., additional, Dongol, Sabina, additional, Sharma, Paban K., additional, Koirala, Samir, additional, Darton, Thomas C., additional, Dolecek, Christiane, additional, Thompson, Corinne N., additional, Thwaites, Guy E., additional, Baker, Stephen G., additional, and Karkey, Abhilasha, additional

Published
2017
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145. Work in Hypoxic Conditions-Consensus Statement of the Medical Commission of the Union Internationale des Associations d'Alpinisme (UIAA MedCom)

Author

Küpper, Thomas, Milledge, Jim S., Hillebrandt, David, Kubalová, Jana, Hefti, Urs, Basnyat, Buddha, Gieseler, Ulf, Pullan, Richard, Schöffl, Volker, Küpper, Thomas, Milledge, Jim S., Hillebrandt, David, Kubalová, Jana, Hefti, Urs, Basnyat, Buddha, Gieseler, Ulf, Pullan, Richard, and Schöffl, Volker

Abstract

Objectives: The Commission gives recommendations on how to provide health and safety for employees in different kinds of low oxygen atmospheres. So far, no recommendations exist that take into account the several factors we have outlined in this report. Methods: The health and safety recommendations of several countries were analysed for their strength and deficiencies. The scientific literature was checked (Medline, etc.) and evaluated for relevance of the topic. Typical situations of work in hypoxia were defined and their specific risks described. Specific recommendations are provided for any of these situations. Results: We defined four main groups with some subgroups (main risk in brackets): short exposure (pressure change), limited exposure (acute altitude disease), expatriates (chronic altitude disease), and high-altitude populations (re-entry pulmonary oedema). For healthy unacclimatized persons, an acute but limited exposure down to 13% O2 does not cause a health risk. Employees should be advised to leave hypoxic areas for any break, if possible. Detailed advice is given for any other situation and pre-existing diseases. Conclusions: If the specific risk of the respective type of hypoxia is taken into account, a pragmatic approach to provide health and safety for employees is possible. In contrast to other occupational exposures, a repeated exposure as often as possible is of benefit as it causes partial acclimatization. The consensus statement was approved by written consent in lieu of a meeting in July 2009

Published
2017

146. Findings of Cognitive Impairment at High Altitude: Relationships to Acetazolamide Use and Acute Mountain Sickness.

Author

Phillips, Lara, Basnyat, Buddha, Chang, Yuchiao, Swenson, Erik R., Harris, N. Stuart, Phillips, Lara, Basnyat, Buddha, Chang, Yuchiao, Swenson, Erik R., and Harris, N. Stuart

Abstract

Phillips, Lara, Buddha Basnyat, Yuchiao Chang, Erik R. Swenson, and N. Stuart Harris. Findings of cognitive impairment at high altitude: relationships to acetazolamide use and acute mountain sickness. High Alt Med Biol. 18:121-127, 2017. OBJECTIVE: Acute mountain sickness (AMS) is defined by patient-reported symptoms using the Lake Louise Score (LLS), which provides limited insight into any possible underlying central nervous system (CNS) dysfunction. Some evidence suggests AMS might coexist with altered neural functioning. Cognitive impairment (CI) may go undetected unless a sensitive test is applied. Our hypothesis was that a standardized test for mild CI would provide an objective measure of CNS dysfunction, which may correlate with the symptoms of AMS and so provide a potential new tool to better characterize altitude-related CNS dysfunction. We compared a cognitive screening tool with the LLS to see if it correlated with CNS dysfunction. METHODS: Adult native English-speaking subjects visiting Himalayan Rescue Association aid stations in Nepal at 3520 m (11,548 ft) and 4550 m (14,927 ft) were recruited. Subjects were administered the LLS and a slightly modified version of the environmental Quick mild cognitive impairment screen (eQmci). Medication use for altitude illness was recorded. Scores were compared using the Spearman's correlation coefficient. Data also included medication use. RESULTS: Seventy-nine subjects were enrolled. A cut-off of three or greater was used for the LLS to diagnose AMS and 67 or less for the eQmci to diagnose CI. There were 22 (28%) subjects who met criteria for AMS and 17 (22%) subjects who met criteria for CI. There was a weak correlation (r(2) = 0.06, p = 0.04) between eQmci score and LLS. In matched subjects with identical LLS, recent acetazolamide use was associated with significantly more CI. CONCLUSION: Field assessment of CI using a rapid standardized tool demonstrated that a substantial number of subjects were found to have

Published
2017

147. An extended genotyping framework for Salmonella enterica serovar Typhi, the cause of human typhoid

Author

Wong, Vanessa K., Baker, Stephen, Connor, Thomas R., Pickard, Derek, Page, Andrew J., Dave, Jayshree, Murphy, Niamh, Holliman, Richard, Sefton, Armine, Millar, Michael, Dyson, Zoe A., Dougan, Gordon, Holt, Kathryn E., Parkhill, Julian, Feasey, Nicholas A., Kingsley, Robert A., Thomson, Nicholas R., Keane, Jacqueline A., Weill, François- Xavier, Le Hello, Simon, Hawkey, Jan, Edwards, David, Harris, Simon R., Cain, Amy K., Hadfield, James, Hart, Peter J., Thieu, Nga Tran Vu, Klemm, Elizabeth, Breiman, Robert F., Watson, Conall H., Edmunds, W. John, Kariuki, Samuel, Gordon, Melita A., Heyderman, Robert S., Okoro, Chinyere, Jacobs, Jan, Lunguya, Octavie, Msefula, Chisomo, Chabalgoity, Jose A., Kama, Mike, Jenkins, Kylie, Dutta, Shanta, Marks, Florian, Campos, Josefina, Thompson, Corinne, Obaro, Stephen, MacLennan, Calman A., Dolecek, Christiane, Keddy, Karen H., Smith, Anthony M., Parry, Christopher M., Karkey, Abhilasha, Dongol, Don, Basnyat, Buddha, Arjyal, Amit, Mulholland, E. Kim, Campbell, James I., Dufour, Muriel, Bandaranayake, Don, Toleafoa, Take N., Singh, Shalini Pravin, Hatta, Mochammad, Newton, Paul, Dance, David, Davong, Viengmon, Onsare, Robert S., Isaia, Lupeoletalalelei, Thwaites, Guy, Wijedoru, Lalith, Crump, John A., de Pinna, Elizabeth, Nair, Satheesh, Nilles, Eric J., Thanh, Duy Pham, Turner, Paul, Soeng, Sona, Valcanis, Mary, Powling, Joan, Dimovski, Karolina, Hogg, Geoff, Farrar, Jeremy, Mather, Alison E., Amos, Ben, Addenbrooke's Hospital, Cambridge University NHS Trust, The Wellcome Trust Sanger Institute [Cambridge], London School of Hygiene and Tropical Medicine (LSHTM), University of Oxford [Oxford], Cardiff University, Barts Health NHS Trust [London, UK], Centre for Sytems Genomics, University of Melbourne, Department of Engineering [Cambridge], University of Cambridge [UK] (CAM), Liverpool School of Tropical Medicine (LSTM), University of Liverpool, Institute of Food Research [Norwich], Institute for Astronomy [Honolulu], University of Hawai‘i [Mānoa] (UHM), Bactéries pathogènes entériques (BPE), Institut Pasteur [Paris], Atmospheric Chemistry Observations and Modeling Laboratory (ACOML), National Center for Atmospheric Research [Boulder] (NCAR), INM-8, Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Global Disease Detection Division, Centers for Disease Control and Prevention, Department of Applied Mathematics and Theoretical Physics (DAMTP), University College of London [London] (UCL), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institut National de Recherche Biomédicale [Kinshasa] (INRB), University of Malawi, Universidad de la República [Montevideo] (UCUR), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Department of Mathematics and Statistics [Toronto], York University [Toronto], Department of Mathematical Sciences [Varanasi], Banaras Hindu University [Varanasi] (BHU), Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Mahidol University [Bangkok]-Mahosot Hospital, Public Health England [London], Nuffield Department of Clinical Medicine [Oxford], This work was supported by a number of organizations. The Wellcome Trust Sanger Institute authors were funded by Wellcome Trust Award #098051. V.K.W. was supported by the Wellcome Trust (#098051) and the National Institute of HealthResearch (NIHR) Cambridge Biomedical Research Centre (BRC). N.F. was supported by the Wellcome Trust Research Fellowship #WT092152MA. N.F., R.S.H. and this work were supported by a strategic award from the Wellcome Trust for the MLW ClinicalResearch Programme (#101113/Z/13/Z). C.P. was funded by The Wellcome Trust Mahidol University Oxford Tropical Medicine Research Programme, supported by the Wellcome Trust of Great Britain (Major Overseas Programmes—Thailand Unit CoreGrant), the European Society for Paediatric Infectious Diseases and University of Oxford-Li Ka Shing Global Health Foundation. D.D., P.N. and V.D. were supported by the Wellcome Trust (core grant #089275/H/09/Z). Z.A.D. was supported by the WellcomeTrust (Strategic award #106158). K.E.H. was supported by the NHMRC of Australia (fellowship #1061409) and the Victorian Life Sciences Computation Initiative (VLSCI, grant #VR0082). C.A.M. was supported by a Clinical Research Fellowship fromGlaxoSmithKline and PJH by a UK Medical Research Council PhD studentship. This work forms part of an EU FP7 Marie Curie Actions Industry Academia Partnerships and Pathways (IAPP) Consortium Programme, entitled GENDRIVAX (Genome-drivenvaccine development for bacterial infections), involving the Wellcome Trust Sanger Institute, KEMRI Nairobi and Novartis Vaccines Institute for Global Health. The Institut Pasteur (IP) authors were funded by the IP, the Institut de Veille Sanitaire and by theFrench Government ‘Investissement d’Avenir’ programme (Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence, grant #ANR-10-LABX-62-IBEID). C.H.W. was supported by the UK Medical Research Council (MRC, MR/J003999/1).C.O. was supported by Society in Science, The Branco Weiss Fellowship, administered by the ETH Zurich. A.K.C. was supported by the MRC (#G1100100/1). J.J. was supported by the antibiotic resistance surveillance project in DR Congo, funded by Project 2.01 of the Third Framework Agreement between the Belgian Directorate General of Development Cooperation and the Institute of Tropical Medicine, Antwerp, Belgium. F.M. was supported by a research grant from the Bill and Melinda Gates Foundation. J.A.C. was supported by the joint US National Institutes of Health-National Science Foundation Ecology and Evolution of Infectious Disease program (#R01 TW009237) and the UK Biotechnology and Biological Sciences Research Council (BBSRC, BB/J010367/1), and by UK BBSRC Zoonoses in Emerging Livestock Systems awards #BB/L017679, #BB/L018926 and #BB/L018845. S.K. was supported by the NIH Grant Number R01 AI099525-02. S.B. is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (#100087/Z/12/Z). S.O. was supported by the National Institute Of Allergy And Infectious Diseases of the National Institutes of Health (#R01AI097493). C.D. was supported by the University of Oxford-Li Ka Shing Global Health Programme. A.E.M. was supported by a Biotechnology and Biological Sciences Research Councilaward (#BB/M014088/1). P.T. was supported by the Wellcome Trust of Great Britain (Major Overseas Programmes—Thailand Unit Core Grant) and University of Oxford-Li Ka Shing Global Health Foundation., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Dyson, Zoe A [0000-0002-8887-3492], Holt, Kathryn E [0000-0003-3949-2471], Apollo - University of Cambridge Repository, University of Oxford, Biotechnology and Biological Sciences Research Council (BBSRC), Institut Pasteur [Paris] (IP), and Universidad de la República [Montevideo] (UDELAR)

Subjects
0301 basic medicine, DNA, Bacterial, Genotype, Science, Population, General Physics and Astronomy, Biology, Salmonella typhi, complex mixtures, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Typhoid fever, Article, 03 medical and health sciences, medicine, Cluster Analysis, Humans, Typhoid Fever, education, Genotyping, Phylogeny, Genetics, education.field_of_study, Multidisciplinary, Geography, business.industry, Haplotype, Subclade, General Chemistry, Sequence Analysis, DNA, medicine.disease, bacterial infections and mycoses, 3. Good health, Biotechnology, 030104 developmental biology, Haplotypes, Microbial genetics, bacteria, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

The population of Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, exhibits limited DNA sequence variation, which complicates efforts to rationally discriminate individual isolates. Here we utilize data from whole-genome sequences (WGS) of nearly 2,000 isolates sourced from over 60 countries to generate a robust genotyping scheme that is phylogenetically informative and compatible with a range of assays. These data show that, with the exception of the rapidly disseminating H58 subclade (now designated genotype 4.3.1), the global S. Typhi population is highly structured and includes dozens of subclades that display geographical restriction. The genotyping approach presented here can be used to interrogate local S. Typhi populations and help identify recent introductions of S. Typhi into new or previously endemic locations, providing information on their likely geographical source. This approach can be used to classify clinical isolates and provides a universal framework for further experimental investigations., Typhoid fever is caused by Salmonella enterica serovar Typhi (S. Typhi). This study examines ∼2,000 clinical isolates of S. Typhi to show highly structured/geographically restricted genomes except rapidly disseminating H58 subclade, and design a genotyping framework for tracking the disease.

Published
2016

149. Assessment and Translation of the Antibody-in-Lymphocyte Supernatant (ALS) Assay to Improve the Diagnosis of Enteric Fever in Two Controlled Human Infection Models and an Endemic Area of Nepal

Author

Darton, Thomas C., primary, Jones, Claire, additional, Dongol, Sabina, additional, Voysey, Merryn, additional, Blohmke, Christoph J., additional, Shrestha, Rajendra, additional, Karkey, Abhilasha, additional, Shakya, Mila, additional, Arjyal, Amit, additional, Waddington, Claire S., additional, Gibani, Malick, additional, Carter, Michael J., additional, Basnyat, Buddha, additional, Baker, Stephen, additional, and Pollard, Andrew J., additional

Published
2017
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150. Co-trimoxazole versus azithromycin for the treatment of undifferentiated febrile illness in Nepal: study protocol for a randomized controlled trial

Author

Pokharel, Sunil, primary, Basnyat, Buddha, additional, Arjyal, Amit, additional, Mahat, Saruna Pathak, additional, KC, Raj Kumar, additional, Bhuju, Abhusani, additional, Poudyal, Buddhi, additional, Kestelyn, Evelyne, additional, Shrestha, Ritu, additional, Phuong, Dung Nguyen Thi, additional, Thapa, Rajkumar, additional, Karki, Manan, additional, Dongol, Sabina, additional, Karkey, Abhilasha, additional, Wolbers, Marcel, additional, Baker, Stephen, additional, and Thwaites, Guy, additional

Published
2017
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