Use of Multiplex Polymerase Chain Reaction (PCR)-Based

Use of Multiplex Polymerase Chain Reaction (PCR)-Based Diagnostic

Testing for Enteric Infections in New York City (NYC), 2014–2016

Julia Latash, MPHCDC/CSTE Applied Epidemiology Fellow

New York City Department of Health and Mental Hygiene

Enteric Disease Surveillance• Based on bacterial culture

– Cases defined as culture-confirmed– Isolation necessary for

• antimicrobial susceptibility testing • serotyping • pulsed-field gel electrophoresis• whole genome sequencing

Multiplex PCR Testing in NYC

• Began receiving multiplex results in 2014• Gastrointestinal syndromic panels• No isolation of microorganism

Multiplex PCR GI Testing in NYC, 2014–2016

• NYC residents diagnosed in 2014–2016 • Positive laboratory test for selected enteric

bacteria and parasites

Routinely investigated pathogens Non-routinely investigated pathogensCryptosporidium (CSP) Entamoeba (AMB)

Cyclospora (CYC) Campylobacter (CAM)Non-typhoidal Salmonella (SAL) Giardia (GIA)

Shiga toxin-producing E. coli (STEC) Shigella (SHG)Non-cholera Vibrio (VIB) Non-plague Yersinia (YER)

Percentage of labs testing NYC residents using multiplex tests, 2014–

2016

2%

8%

13%

0%

2%

4%

6%

8%

10%

12%

14%

2014 2015 2016

Perc

enta

ge

Diagnosis year

Reported infections with multiplex testing — NYC, 2014–2016

4,611

4,723

4,092

3440 1,005

<1%

9%

20%

0%

5%

10%

15%

20%

25%

0

1,000

2,000

3,000

4,000

5,000

6,000

2014 2015 2016 Infe

ctio

ns w

ith m

ultip

lex

test

ing

Infe

ctio

ns

Diagnosis Year

Number of infections diagnosed with a multiplex testNumber of ifections diagnosed without a multiplex testPercentage of infections diagnosed with a multiplex test

Testing cascade, reported infections —NYC, 2014–2016

Additional testing performed at public health lab (PHL)n = 713

Positive result at public health labn = 458

Any additional testing performedn = 816

Multiplex testing performedn = 1,448

Infections reported to NYCn = 14,874

Any additional testing performed —NYC, 2014–2016

89% 87%93%

87%92%

33%

21%12%

77%

63%

0%10%20%30%40%50%60%70%80%90%100%

0

50

100

150

200

250

300

350

400

450

CSP CYC SAL STEC VIB AMB CAM GIA SHG YER

Infe

ctio

ns w

ith a

dditi

onal

test

ing

Infe

ctio

ns

Pathogen

Number of infections with multiplex and additional testingNumber of infections with only multiplex testingPercentage of infections with multiplex and additional testing

Additional testing performed at a PHL— NYC, 2014–2016

99% 100% 99% 99% 100%100%

7% 25%

99% 98%

0%

20%

40%

60%

80%

100%

0

50

100

150

200

CSP CYC SAL STEC VIB AMB CAM GIA SHG YER

Infe

ctio

ns w

ith c

onfir

mat

ory

test

ing

at a

PH

LInfe

ctio

ns

Pathogen

Number of infections with confirmatory testing at a PHLNumber of infections with confirmatory testing at a reference labPercentage of infections with confirmatory testing at a PHL

Positive confirmatory test at a PHL —NYC, 2014–2016

79%

100%91%

27%

50%

67%

100%

60%67%

34%

0%10%20%30%40%50%60%70%80%90%100%

020406080

100120140160180200

CSP CYC SAL STEC VIB AMB CAM GIA SHG YER

Infe

ctio

ns w

ith a

pos

itive

conf

irmat

ory

test

Infe

ctio

ns

Pathogen

Number of infections with a positive confirmatory testNumber of infections with a negative or indeterminate confirmatory testPercentage of infections with a positive confirmatory test

Median (interquartile range) time between specimen collection, result

notification—NYC, 2014–2016 5 (IQR: 3-6)

2 (IQR: 2-3)

0

1

2

3

4

5

6

7

Multiplex tests Non-multiplex tests

Days

Factors Associated with Multiplex PCR GI Test Receipt in NYC, 2014–2016

• Infection with routinely investigated pathogens (CSP, CYC, SAL, STEC, VIB)

• Specimens tested at labs using multiplex tests

Factors consideredDiagnosis year Age

Sex RaceEthnicity County of residence

Hospitalization status Exclusion statusInternational travel Area-based poverty

Factors Associated with Multiplex PCR GI Test Receipt in NYC, 2014–2016

Factors strongly associated with multiplex test receipt

Diagnosis in 2016Hispanic ethnicity

Residence in Bronx, Manhattan

Hospitalization

• Multivariable logistic regression

Factors Associated with Multiplex PCR GI Test Receipt in NYC, 2014–2016

Factors strongly associated with multiplex test receipt

Diagnosis in 2016Hispanic ethnicity*Residence in Bronx,

Manhattan*Hospitalization*

• Multivariable logistic regression

*likely due to types and locations of labs performing testing

Use of Multiplex PCR GI Tests in NYC –Findings

• Multiplex use increased over time• Timelier reporting, but additional testing

needed for public health action• Proportions of infections with reflex testing,

positive confirmatory tests varied by pathogen

Use of Multiplex PCR GI Tests in NYC –Follow Up

• NYC Health Code amended December 5, 2016– Reflex to culture if positive culture-independent

result– Report positive and negative reflex culture result– Submit isolates/broth to public health lab

Acknowledgements

Sharon BalterVasudha ReddyHaeNa WaechterBruce Gutelius

This study/report was supported in part by an appointment to the Applied Epidemiology Fellowship Program administered by the Council of State and Territorial Epidemiologists (CSTE) and funded by the Centers for Disease Control and Prevention

(CDC) Cooperative Agreement Number 1U38OT000143-04.

NYC Bureau of Communicable Disease

NYC Public Health Laboratory

NYS Wadsworth Center

Many others…

Ana Maria FireteanuRobert FitzhenryLisa AlleyneMarcelle Layton

Erlinda AmorosoLan LiKatelynn DevinneyGeneral Surveillance Unit

Morgan MoyColleen CourtneyMicrobiology Section

Jennifer Rakeman

Thank you!Questions: jlatash1@health.nyc.gov

Additional slides

Positive confirmatory test at a public health lab: STECs — NYC, 2014–2016

27%

68%

0%

10%

20%

30%

40%

50%

60%

70%

80%

020406080

100120140160180

All STECs Shiga toxin-positive STECs

Infe

ctio

ns w

ith a

pos

itive

conf

irmat

ory

test

Infe

ctio

ns

STEC infections

Number of infections with a positive confirmatory testNumber of infections with a negative or indeterminate confirmatory testPercentage of infections with a positive confirmatory test

Criteria for excluded food handlers to return to work in NYC

Disease 2 follow-up stools

2 sets of 2 follow-up stools taken 30

days apart

3 follow-up stools

Campylobacteriosis X

Cholera X

Salmonellosis X

Shigellosis X

STEC infection X

Typhoid / paratyphoid fever X

Yersiniosis X

Amebiasis X

Cryptosporidiosis X

Giardiasis X

Criteria for excluded child care worker or attendee to return to school in NYC

Disease Until asymptomatic

2 follow-up stools

2 sets of 2 follow-up

stools, taken 30 days apart

3 follow-up stools

Campylobacteriosis X

Cholera XSalmonellosis X

Shigellosis XSTEC infection X

Typhoid / paratyphoid fever

X

Yersiniosis XAmebiasis X

Cryptosporidiosis XGiardiasis X

Criteria for excluded health care workers to return to work in NYC

Disease Until asymptomatic

2 follow-up stools

2 sets of 2 follow-up

stools, taken 30 days apart

3 follow-up stools

Campylobacteriosis X

Cholera XSalmonellosis X

Shigellosis XSTEC infection X

Typhoid / paratyphoid fever

X

Yersiniosis XAmebiasis X

Cryptosporidiosis XGiardiasis X