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Trish M. Perl, MD, MSc Professor of Medicine, Pathology and Epidemiology Johns Hopkins University Senior Epidemiologist Johns Hopkins Health System

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Presentation on theme: "Trish M. Perl, MD, MSc Professor of Medicine, Pathology and Epidemiology Johns Hopkins University Senior Epidemiologist Johns Hopkins Health System"— Presentation transcript:

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

2 Disclosures Disclosures: Pfizer (advisory board), Merck (grant), Medimmune (grant)Disclosures: Pfizer (advisory board), Merck (grant), Medimmune (grant)

3 C. difficile N Engl J Med 2015;372:

4 C. difficile N Engl J Med 2015;372:

5 Methods Active population and laboratory based surveillance in 10 geographic areas across the USActive population and laboratory based surveillance in 10 geographic areas across the US Stools were positive for either antigen or PCR in persons > 1 year oldStools were positive for either antigen or PCR in persons > 1 year old Cases classified as community or healthcare associatedCases classified as community or healthcare associated A sample of cases were cultured and underwent molecular typingA sample of cases were cultured and underwent molecular typing

6 Findings 15,461 cases identified15,461 cases identified 65.8% healthcare associated; 24.2% had onset during hospitalization65.8% healthcare associated; 24.2% had onset during hospitalization Incident cases in the US is 453,000 with the rate higher in females (RR % CI ); whites (RR % CI ); > 65 years (RR % CI )Incident cases in the US is 453,000 with the rate higher in females (RR % CI ); whites (RR % CI ); > 65 years (RR % CI ) Estimated first occurrences was 83,000 and deaths--29,300Estimated first occurrences was 83,000 and deaths--29,300 NAP1 strain more prevalent in HCA (30.7%) than community infections (18.8%)NAP1 strain more prevalent in HCA (30.7%) than community infections (18.8%)

7 Findings

8 Findings: Burden of Disease

9 Findings: Recurrences and Death

10 Summary C. difficile is more common than previously thoughtC. 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!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 recurrencesAlmost 25% of the cases are recurrences Certain populations of patients are at higher risk of recurrence and deathCertain populations of patients are at higher risk of recurrence and death

11 Ebola

12 What about the specifics Luna et al. Crit Care Res Pract 2014: Science 2014:345;1369

13 Methods 1 st case confirmed on May 25 th in Sierra Leone1 st case confirmed on May 25 th in Sierra Leone Sequenced 99 isolates from patients in Sierra LeoneSequenced 99 isolates from patients in Sierra Leone Tests run on two different platformsTests run on two different platforms

14 Clades

15 History of Ebola Outbreaks

16 Dating of the Outbreak

17 Diversity of Mutations

18 Person to Person Transmission: Using Genetic Clues

19 Acquisition of Genetic Variation Over Time

20 Overall Summary The Ebola outbreak in Sierra Leone resulted from the simultaneous introduction of two different strains from Guinea, likely from funeral attendeesThe 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 patternsIntra and inter-host variation illucidates the epidemiology and transmission patterns Substitution rate is twice as high during the outbreak as in between outbreaksSubstitution rate is twice as high during the outbreak as in between outbreaks 5 authors died of Ebola while doing this important work5 authors died of Ebola while doing this important work

21 Overall Summary

22 N Engl J Med 2014;371:

23 Ebola Clinical Disease 7 th Ebola outbreak in Congo btw July 26 and Oct 7, th Ebola outbreak in Congo btw July 26 and Oct 7, suspect or documented cases; 7 HCW69 suspect or documented cases; 7 HCW 49 deaths49 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 AfricaEbola 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

24 Ebola Virus’s Named after the Ebola river in the Democratic Republic of Congo, it was first discovered in  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

25 DRC

26 Epidemiology of the Outbreak

27 Clinical Features: Ebola

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30 Mortality Clinical and laboratory features associated with non fatal disease Respiratory rate < 25 Lower temperature Lower BUN Lower creatinine Alk Ptase ALT AST -

31 Clinical Features: Ebola Chertow et al. NEJM 2014; 371:2054-7

32 Clinical Features: Ebola Case finding and testing helped modulate the outbreak.Case finding and testing helped modulate the outbreak. The virus has been relatively stable over the past 20 years.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.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 survivalMortality remains high, although there are clinical and laboratory features that can be used to predict improved survival

33 Clinical Trials

34 The Ongoing Screening Question 13 ICUs randomized to rapid or conventional screening for MRSA and resistant GNRs13 ICUs randomized to rapid or conventional screening for MRSA and resistant GNRs 3 phases3 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: month cluster randomized clinical trial of rapid (VRE, MRSA, resistant GNRs) versus conventional screening (VRE, MRSA) with contact precautions for carriers Outcome: acquisition of MDROsOutcome: acquisition of MDROs

35 Compliance with HH 7 ICUs randomized to conventional; 6 to rapid screening7 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.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.

36 MDRO Acquisition

37 Impact of Interventions

38 Summary Impact of HH and CHG bathing on MDRO screeningImpact 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 bathingNo impact of screening although these finding may not impact areas where there is poor compliance with HH and the use of CHG bathing

39 Mers CoV

40 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

41 Al Hasa Epidemic Curve: The Story of Intra-Hospital Transmission Assiri et al, NEJM, 2013

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44 Cases Cases 21/23 (+2 probable cases) acquired by person-to- person transmission in HD units, ICUs, or in-patient units in 3 facilities21/23 (+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 inAmong 217 household contacts and > 200 HCW contacts, MERS-CoV infection developed in 5 family members (3 laboratory-confirmed)5 family members (3 laboratory-confirmed) 2 HCW (both laboratory-confirmed)2 HCW (both laboratory-confirmed) Assiri et al, NEJM, 2013

45 Identifying Timing of Symptom Onset and Spatial Location Assiri et al, NEJM, 2013

46 Transmission Maps Assiri et al, NEJM, 2013 New York Times, 2013

47 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)

48 Genetic Mapping: Al Hasa Outbreak

49 Genetic Distance of Al-Hasa Isolates from Other MERS CoV Isolates Cotten et al, Lancet, 2013

50 Transmission Map-Genetic Evidence Cotten et al, Lancet, 2013 Eliminating some transmissions that were inconsistent with genetic evidence has little effect on natural history parameters estimated from Al Hasa outbreak Estimated incubation period = 5.1 days (95% CI 2.2 to 11.9 days) (SARS 4.0 (95% CI 1.8, 10.6 days)) Estimated Serial Interval = 7.2 days (95% CI 3.0 to 17.7 days) (SARS Median 8.4 days)

51 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 Dec 12;18(50)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 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 Meyer B. Emerg Infect Dis 2014 Apr;20(4)MERS-CoV neutralizing antibodies were present in all samples from 151 dromedary camels from the UAE in 2003 and 60% of 651 camels in 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 Dec 16PCR 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 Dec 16 Recently- likely proven transmission from pet camel to human Perera et al. Eurosurveillance 2013; 18 and Azhar NEJM 2014; 370Recently- likely proven transmission from pet camel to human Perera et al. Eurosurveillance 2013; 18 and Azhar NEJM 2014; 370

52 Azhar et al. NEJM 2014:DOI: /NEJMoa

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55 Summary All cases have been directly or indirectly linked through travel to or residence in the Arabian Gulf.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.Among symptomatics respiratory symptoms almost universal; GI symptoms in ¼; most with comorbidities, age ~50. Asymptomatic illness recognized.Asymptomatic illness recognized. Sequencing data suggests multiple, ongoing community introductions, and human-to-human spread especially in families and healthcare.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.Camels may be an important link although a wide diversity in viral sequences noted.


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