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Title: Modeling and Cost Benefit Analysis to Guide Deployment of POC Diagnostics for Non-typhoidal Salmonella Infections with Antimicrobial Resistance

Abstract

Invasive non-typhoidal Salmonella (NTS) is among the leading causes of blood stream infections in sub-Saharan Africa and other developing regions, especially among pediatric populations. Invasive NTS can be difficult to treat and have high case-fatality rates, in part due to emergence of strains resistant to broad-spectrum antibiotics. Furthermore, improper treatment contributes to increased antibiotic resistance and death. Point of care (POC) diagnostic tests that rapidly identify invasive NTS infection, and differentiate between resistant and non-resistant strains, may greatly improve patient outcomes and decrease resistance at the community level. Here we present for the first time a model for NTS dynamics in high risk populations that can analyze the potential advantages and disadvantages of four strategies involving POC diagnostic deployment, and the resulting impact on antimicrobial treatment for patients. Our analysis strongly supports the use of POC diagnostics coupled with targeted antibiotic use for patients upon arrival in the clinic for optimal patient and public health outcomes. We show that even the use of imperfect POC diagnostics can significantly reduce total costs and number of deaths, provided that the diagnostic gives results quickly enough that patients are likely to return or stay to receive targeted treatment.

Authors:
ORCiD logo [1];  [2];  [2];  [2]; ORCiD logo [1]; ORCiD logo [1];  [2]
+ Show Author Affiliations
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  2. Univ. of Portland, Portland, OR (United States)
Publication Date:
Research Org.:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE Laboratory Directed Research and Development (LDRD) Program
OSTI Identifier:
1558981
Report Number(s):
LA-UR-19-27175
Journal ID: ISSN 2045-2322
Grant/Contract Number:  
89233218CNA000001
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 9; Journal Issue: 1; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Biological Science; Mathematics

Citation Formats

Manore, Carrie Anna, Graham, Todd, Carr, Alexa, Feryn, Alicia, Jakhar, Shailja, Mukundan, Harshini, and Highlander, Hannah Callender. Modeling and Cost Benefit Analysis to Guide Deployment of POC Diagnostics for Non-typhoidal Salmonella Infections with Antimicrobial Resistance. United States: N. p., 2019. Web. doi:10.1038/s41598-019-47359-2.
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Manore, Carrie Anna, Graham, Todd, Carr, Alexa, Feryn, Alicia, Jakhar, Shailja, Mukundan, Harshini, & Highlander, Hannah Callender. Modeling and Cost Benefit Analysis to Guide Deployment of POC Diagnostics for Non-typhoidal Salmonella Infections with Antimicrobial Resistance. United States. https://doi.org/10.1038/s41598-019-47359-2
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Manore, Carrie Anna, Graham, Todd, Carr, Alexa, Feryn, Alicia, Jakhar, Shailja, Mukundan, Harshini, and Highlander, Hannah Callender. Fri . "Modeling and Cost Benefit Analysis to Guide Deployment of POC Diagnostics for Non-typhoidal Salmonella Infections with Antimicrobial Resistance". United States. https://doi.org/10.1038/s41598-019-47359-2. https://www.osti.gov/servlets/purl/1558981.
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@article{osti_1558981,
title = {Modeling and Cost Benefit Analysis to Guide Deployment of POC Diagnostics for Non-typhoidal Salmonella Infections with Antimicrobial Resistance},
author = {Manore, Carrie Anna and Graham, Todd and Carr, Alexa and Feryn, Alicia and Jakhar, Shailja and Mukundan, Harshini and Highlander, Hannah Callender},
abstractNote = {Invasive non-typhoidal Salmonella (NTS) is among the leading causes of blood stream infections in sub-Saharan Africa and other developing regions, especially among pediatric populations. Invasive NTS can be difficult to treat and have high case-fatality rates, in part due to emergence of strains resistant to broad-spectrum antibiotics. Furthermore, improper treatment contributes to increased antibiotic resistance and death. Point of care (POC) diagnostic tests that rapidly identify invasive NTS infection, and differentiate between resistant and non-resistant strains, may greatly improve patient outcomes and decrease resistance at the community level. Here we present for the first time a model for NTS dynamics in high risk populations that can analyze the potential advantages and disadvantages of four strategies involving POC diagnostic deployment, and the resulting impact on antimicrobial treatment for patients. Our analysis strongly supports the use of POC diagnostics coupled with targeted antibiotic use for patients upon arrival in the clinic for optimal patient and public health outcomes. We show that even the use of imperfect POC diagnostics can significantly reduce total costs and number of deaths, provided that the diagnostic gives results quickly enough that patients are likely to return or stay to receive targeted treatment.},
doi = {10.1038/s41598-019-47359-2},
journal = {Scientific Reports},
number = 1,
volume = 9,
place = {United States},
year = {Fri Aug 02 00:00:00 EDT 2019},
month = {Fri Aug 02 00:00:00 EDT 2019}
}
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https://doi.org/10.1038/s41598-019-47359-2
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Clonal Differences between Non-Typhoidal Salmonella (NTS) Recovered from Children and Animals Living in Close Contact in The Gambia
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Incidence of invasive salmonella disease in sub-Saharan Africa: a multicentre population-based surveillance study
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State Dependent Parameter metamodelling and sensitivity analysis
journal, December 2007

  • Ratto, Marco; Pagano, Andrea; Young, Peter
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A Systematic Review of the Incidence, Risk Factors and Case Fatality Rates of Invasive Nontyphoidal Salmonella (iNTS) Disease in Africa (1966 to 2014)
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Community-acquired bloodstream infections in Africa: a systematic review and meta-analysis
journal, June 2010

Epidemiology, Pathogenesis, Genoserotyping, Antimicrobial Resistance, and Prevention and Control of Non-Typhoidal Salmonella Serovars
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Prevalence of Salmonella Excretion in Stool: A Community Survey in 2 Sites, Guinea-Bissau and Senegal
journal, March 2016

  • Im, Justin; Nichols, Chelsea; Bjerregaard-Andersen, Morten
  • Clinical Infectious Diseases, Vol. 62, Issue suppl 1
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Non-typhoidal salmonella bacteraemia among HIV-infected Malawian adults: high mortality and frequent recrudescence
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