The Year in Review: Best Papers 2014 Trish M. Perl, MD, MSc Professor of Medicine, Pathology and Epidemiology Johns Hopkins University Senior Epidemiologist Johns Hopkins Health.

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Transcript The Year in Review: Best Papers 2014 Trish M. Perl, MD, MSc Professor of Medicine, Pathology and Epidemiology Johns Hopkins University Senior Epidemiologist Johns Hopkins Health.

The Year in Review: Best Papers 2014
Trish M. Perl, MD, MSc
Professor of Medicine, Pathology
and Epidemiology
Johns Hopkins University
Senior Epidemiologist
Johns Hopkins Health System
[email protected]
Disclosures
• Disclosures: Pfizer (advisory board), Merck (grant),
Medimmune (grant)
C. difficile
N Engl J Med 2015;372:825-34.
C. difficile
N Engl J Med 2015;372:825-34.
Methods
• Active population and laboratory based surveillance in 10
geographic areas across the US
• Stools were positive for either antigen or PCR in persons > 1 year
old
• Cases classified as community or healthcare associated
• A sample of cases were cultured and underwent molecular typing
Findings
• 15,461 cases identified
• 65.8% healthcare associated; 24.2% had onset during
hospitalization
• Incident cases in the US is 453,000 with the rate higher in females
(RR 1.26 95% CI 1.25-1.27); whites (RR 1.72 95% CI 1.56-2.0); >
65 years (RR 8.65 95% CI 8.16-9.31)
• Estimated first occurrences was 83,000 and deaths--29,300
• NAP1 strain more prevalent in HCA (30.7%) than community
infections (18.8%)
Findings
Findings: Burden of Disease
Findings: Recurrences and Death
Summary
• C. difficile is more common than previously thought
• Most cases are associated with medical care but do not manifest in
the hospital—they are seen by you!
• Almost 25% of the cases are recurrences
• Certain populations of patients are at higher risk of recurrence and
death
Ebola
What about the specifics
Science 2014:345;1369
Luna et al. Crit Care Res Pract 2014: 480463
Methods
• 1st case confirmed on May 25th in Sierra Leone
• Sequenced 99 isolates from patients in Sierra Leone
• Tests run on two different platforms
History of Ebola Outbreaks
Dating of the Outbreak
Diversity of Mutations
Person to Person Transmission: Using Genetic Clues
Acquisition of Genetic Variation Over Time
Overall Summary
• The Ebola outbreak in Sierra Leone resulted from the simultaneous
introduction of two different strains from Guinea, likely from funeral
attendees
• Intra and inter-host variation illucidates the epidemiology and
transmission patterns
• Substitution rate is twice as high during the outbreak as in between
outbreaks
• 5 authors died of Ebola while doing this important work
N Engl J Med 2014;371:2083-91.
Ebola Clinical Disease
•
•
•
•
7th Ebola outbreak in Congo btw July 26 and Oct 7, 2014
69 suspect or documented cases; 7 HCW
49 deaths
Ebola Zaire Species, Genetic analysis demonstrated 99.2%
similarity of the virus with that of the Kikwit outbreak; 96.8%
similarity with virus circulating in West Africa
Ebola Virus’s
Named after the Ebola river in the Democratic Republic of
Congo, it was first discovered in 1976.
 5 species
 Ebola Zaire
 Ebola Sudan
 Ebola Ivory Coast
 Ebola Bundibugyp
 Ebola Reston
 Primarily found in Africa except E. Reston found in the
Philippines (animal only)
24
DRC
Epidemiology of the Outbreak
Clinical Features: Ebola
Mortality
Clinical and laboratory
features associated with non
fatal disease
• Respiratory rate < 25
• Lower temperature
• Lower BUN
• Lower creatinine
• Alk Ptase
• ALT
• AST
-
Clinical Features: Ebola
Chertow et al. NEJM 2014; 371:2054-7
Clinical Features: Ebola
• Case finding and testing helped modulate the outbreak.
• The virus has been relatively stable over the past 20 years.
• Triphasic illness and clinical features are non specific; fatigue,
myalgias and conjunctivitis were hallmarks. Although not asked
hiccups are a feature.
• Mortality remains high, although there are clinical and laboratory
features that can be used to predict improved survival
Clinical Trials
The Ongoing Screening Question
• 13 ICUs randomized to rapid or conventional screening for MRSA
and resistant GNRs
• 3 phases
– Phase 1: 6 month--wash in of best practice
– Phase 2: 6 months assessment of compliance with CHG bathing and hand
hygiene
– Phase 3: 12-15 month cluster randomized clinical trial of rapid (VRE, MRSA,
resistant GNRs) versus conventional screening (VRE, MRSA) with contact
precautions for carriers
• Outcome: acquisition of MDROs
Compliance with HH
• 7 ICUs randomized to conventional; 6 to rapid
screening
• HH compliance increased from 52-69% from
phase 1-2; and 77% in phase 3; CHG bathing
increased from 0-100% between phase 1 and 2.
MDRO Acquisition
Impact of Interventions
Summary
• Impact of HH and CHG bathing on MDRO
screening
• No impact of screening although these finding
may not impact areas where there is poor
compliance with HH and the use of CHG bathing
Mers CoV
Al Hasa Intra-Hospital Outbreak
Outbreak based in multiple
hospitals in Al Hasa serving a
governate of 1.1 million of rural
and urban dwellers
Initial focus was in two dialysis
units and several ICUs
Team performed chart review,
survey collection to investigate
hospital based outbreak
Assiri et al, NEJM, 2013
Al Hasa Epidemic Curve: The Story of
Intra-Hospital Transmission
Assiri et al, NEJM, 2013
Cases
• 21/23 (+2 probable cases)
acquired by person-toperson transmission in HD
units, ICUs, or in-patient
units in 3 facilities
• Among 217 household
contacts and > 200 HCW
contacts, MERS-CoV
infection developed in
• 5 family members (3
laboratory-confirmed)
• 2 HCW (both
laboratory-confirmed)
Assiri et al, NEJM, 2013
Identifying Timing of Symptom Onset
and Spatial Location
Assiri et al, NEJM, 2013
Transmission Maps
Assiri et al, NEJM, 2013
New York Times, 2013
Transmission Maps
Estimated incubation Period to be 5.2 days (95% CI 2.2 to 12.4 days) (SARS 4.0
(95% CI 1.8, 10.6 days))
Estimated Serial Interval to 7.6 days (95% CI 3.0 to 19.4 days) (SARS Median 8.4
days)
Assiri et al, NEJM, 2013
Genetic Mapping: Al Hasa Outbreak
Genetic Distance of Al-Hasa Isolates
from Other MERS CoV Isolates
Cotten et al, Lancet, 2013
MERS-CoV Is Widespread Among Camels In The
Arabian Peninsula
• Neutralizing antibodies against MERS-CoV were found
in all camel sera from Jordan (n=11) ; all samples from
other livestock species were negative. Reusken C. Euro Surveill.
2013 Dec 12;18(50)
• MERS-CoV neutralizing antibodies were present in all
samples from 151 dromedary camels from the UAE in
2003 and 60% of 651 camels in 2013. Meyer B. Emerg Infect Dis
2014 Apr;20(4)
• PCR testing and partial genomic sequencing confirmed
the presence of MERS-COV in 3/14 camels with which 2
human cases in Qatar had contact. Haagmans BL Lancet Infect
Dis. 2013 Dec 16
• Recently- likely proven transmission from pet camel to
human Perera et al. Eurosurveillance 2013; 18 and Azhar NEJM 2014; 370
Azhar et al. NEJM 2014:DOI: 10.1056/NEJMoa1401505
Azhar et al. NEJM 2014:DOI: 10.1056/NEJMoa1401505
Azhar et al. NEJM 2014:DOI: 10.1056/NEJMoa1401505
Summary
• All cases have been directly or indirectly linked through
travel to or residence in the Arabian Gulf.
• Among symptomatics respiratory symptoms almost
universal; GI symptoms in ¼; most with comorbidities, age
~50.
• Asymptomatic illness recognized.
• Sequencing data suggests multiple, ongoing community
introductions, and human-to-human spread especially in
families and healthcare.
• Camels may be an important link although a wide diversity
in viral sequences noted.