methicillin-resistant staphylococcus aureus in children

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Methicillin-Resistant Staphylococcus aureus in Children Living with Industrial Hog Operation Workers Bayesian Network Risk Models Jacqueline MacDonald Gibson, Associate Professor Department of Environmental Sciences and Engineering Gillings School of Global Public Health University of North Carolina at Chapel Hill November 1, 2018

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Page 1: Methicillin-Resistant Staphylococcus aureus in Children

Methicillin-Resistant Staphylococcus aureus in Children Living with Industrial Hog Operation Workers

Bayesian Network Risk Models

Jacqueline MacDonald Gibson, Associate ProfessorDepartment of Environmental Sciences and Engineering

Gillings School of Global Public HealthUniversity of North Carolina at Chapel Hill

November 1, 2018

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Outline

• Introduction Antibiotic use in livestock Prior evidence of risk to humans

• MethodsData set from eastern North Carolina—high-intensity hog farmingBayesian network learning algorithmsModel evaluation and selection

• Results Insights on risk factors Bayesian network model accuracy

• Conclusions: interventions to decrease risk

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Modern Livestock Production: Breeding Ground for Antibiotic Resistance?

71% of domestic antibiotic use is for livestock production —mostly subtherapeuticSOURCES: Wendy Nicole, Env. Health Perspectives, 2015; FDA, 2015

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Use of Medically Important Antibiotics for Livestock Is Increasing

0.E+00

2.E+06

4.E+06

6.E+06

8.E+06

1.E+07

1.E+07

2008 2009 2010 2011 2012 2013 2014 2015 2016

Kg

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d in

Liv

esto

ck

YearSOURCE: FDA, 2015, Antimicrobials Sold or Distributed for Use in Food-Producing Animals

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Staphylococcus aureus Bacteria Can Transmit from Hogs to Humans

• S. aureus can acquire antibiotic resistance in hogs

• Resistant strains can pass to humans

• Example: methicillin-resistant S. aureus (MRSA)

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First Documented Case of MRSA Transmission from Hogs in 2004

• 6-month-old Dutch infant

• Parents also colonized

• Remained colonized for months despite aggressive treatment

• Source traced to hogs on the family’s farm

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Mounting Evidence of Hog-to-Human Transmission Since 2004

SOURCE: George, Stewart, and MacDonald Gibson, in review, Environmental Health Perspectives.

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Percentage of Human Subjects Colonized with Hog-Associated MRSA

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Prevalence of Human S. aureus Infections Resistant to Methicillin is High

Prevalence of invasive S. aureus infections resistant to methicillin

How much does animal use of antibiotics contribute?

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Objective

• Characterize risk factors for MRSA transmission to hog workers’ children

• Build a predictive model to assess potential interventions

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Methods

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Data from Hog Workers in Eastern North Carolina (NC)

• 198 children living with hog workers

• MRSA colonization tested via nasal swabs

• Questionnaires administered to adult household members

Eastern NC has among highest industrial hog operation densities in world.

SOURCE: Wing et al., 2000.

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Questionnaire Included 98 Potential Explanatory VariablesParent MRSA

Recent hospitalization

Daycare

Age, gender, race

Education

Race

Handwashing

Household pet

Jobs

Workplace hygiene . . .

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Previously Published Analysis Found Only Four of 98 Items Influenced Risk

“The other IHO work activities and factors evaluated . . . were null or non-interpretable due to insufficient numbers.”

Factor Prevalence RatioTake work clothing home

12

Use disinfectant 6Work with nursery pigs

2.2

Handle dead pigs 3.2

Risk Factors Identified by Log-Binomial Regression

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We Tested 17 BayesiaLab Algorithms to Build Predictive Model, Gain Insights

Model Taboo Equivalence Class

Max Weight Tree

Augmented Naïve Bayes

Add Prior Evidence

1 1 2 3*2 1 2 3* 43 1 2*4 1 2* 35 1 2*6 1 2* 3. . .13 1 2…17 1*

*With variable selection

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Accuracy Tested in Cross-Validation

• Five-fold cross validation

• Repeated 20 times- Different random train/test split each time

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Area Under Receiver-Operating Characteristic (ROC) Curve Used as Metric

Diagnostic accuracy = area under curve (1=perfect)

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-18-Diagnostic accuracy = area under curve (1=perfect)

Trade-off between specificity and sensitivity

Area Under Receiver-Operating Characteristic (ROC) Curve Used as Metric

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Results

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14% of Workers’ Children Colonized

By comparison, 6% of children in community referent group were colonized.

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17 Algorithms Yielded Four Model Structures

1. Taboo EQ Augmented naïve Bayes, variable selection

3. Taboo remove if mutual information p>0.2 Augmented naïve Bayes

2. Net 1 + Prior evidence

3. Net 3 + Prior evidence

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Occam’s Razor

1. Taboo EQ Augmented naïve Bayes, variable selection

Entia non suntmultiplicanda praeternecessitatem.[

More things should not be used than are necessary.

- William of Occam, 14th

Century

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The Most Parsimonious Model Had High Accuracy

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Accuracy Was Well Preserved Under Cross-Validation

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Model Shows Workplace Strategies for Decreasing Risks

Bringing home work clothing or mask

Leaving work clothing and mask at hog operation

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Model Also Reveals Surprising Health Insurance Association

Risk increases with company insurance

Risk decreases with public insurance

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Web-Based, User-Friendly Version for Communicating Results

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Limitations

Small sample sizeCross-sectional studyBut . . .

- Strong performance for sample size

No MRSA MRSAPredict No MRSA

83% 7%

Predict MRSA

13% 93%

High sensitivity with reasonable false-positive rate

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Future: Use Simulator to Promote Interventions

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Summary

• Bayesian network identified factors associated with MRSA transmission risk- Bringing PPE home

- Company insurance

- Contact with hog manure

• Web-based platform could help communicate effects of interventions

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Acknowledgements

• Funding sources- Thrasher Research Fund award 10287

- National Science Foundation grant 1316318

• Collaborators- Jill R. Stewart, UNC

- Sarah M. Hatcher, UNC

- Sarah M. Rhodes, UNC

- Devon Hall, Rural Empowerment for Community Health

- Christopher D. Heaney, Johns Hopkins

- Households, other researchers assisting with study design and data analysis