Trish M. Perl, MD, MScProfessor of Medicine, Pathology

and EpidemiologyJohns Hopkins University

Senior EpidemiologistJohns Hopkins Health System

tperl@jhmi.edu

The Year in Review: Best Papers

2014

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

Luna et al. Crit Care Res Pract 2014: 480463 Science 2014:345;1369

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’sNamed 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-to-person 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, 2013New York Times, 2013

Transmission Maps

Assiri et al, NEJM, 2013

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)

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.