Re-emergence of old viruses

Transcription

1 Re-emergence of old viruses Erin Mathes, MD Associate Professor of Dermatology and Pediatrics University of California, San Francisco American Academy of Dermatology Annual Meeting, February 2018 Disclosures Pierre-Fabre Investigator; Zosano Pharma - Consultant ; Rodan + Fields - Consultant

2 It s a small world Measles Varicella Rubella Coxsackievirus The Plan

3 Measles (Rubeola) >90% transmission rate Live attenuated vaccine introduced in months & 4-6 years Vaccine efficacy: 1 dose = 93%; 2 doses = 97% Vaccine reduced mortality ~80% Mortality rates (pneumonia, encephalitis): 4-10% in developing countries 0.3% in US

4 Measles was declared eliminated in the US in Eliminated = no continuous disease transmission in an area for more than 12 months (Eradicated = complete and permanent worldwide reduction to zero new cases)

5 CDC Data Majority of cases are in unvaccinated Imported from outbreaks abroad France Ohio Amish Philipines Disneyland Minnesota

6 Measles: herd immunity Measles is very, very infectious Need up to 90-95% vaccination for herd immunity

7 Evolution of a vaccine program. Kathryn M. Edwards et al. Pediatrics 2016;138:e by American Academy of Pediatrics

8 Vaccine Hesitancy Vaccine refusal and alternate schedules lead to declining herd immunity and outbreaks. 3% of parents refuse all vaccines; 15-20% delay or refuse some White, well educated Physician communication is key 47% will ultimately accept vaccines if you persist New physicians are less likely to believe that vaccines are safe and effective, less familiar with diseases and complication Kathryn M. Edwards et al. Pediatrics 2016;138:e

9 Measles: Clinical Course Infectious window: 5 days before rash onset to 4 days after Incubation Prodrome Rash days Asymptomatic 2-3 days Fever + 3C s (cough, coryza, conjunctivitis) 7 days Craniocaudal spread Still febrile Slide courtesy of Iris Ahronowitz, MD

10 Modified measles Hay CM et al. N Engl J Med Jul 24;371(4):

11 Measles: What do I do? Diagnosis: PCR from throat, nasal swab, urine (3-9 days) IgM titers (detectable 3 days after rash starts) Immediate airborne respiratory isolation! Notification requirements: Report to DPH immediately if measles suspected Obtain travel and contact history Treatment: supportive

12 Have you seen varicella or zoster in the last year?

13 VZV Vaccine Live attenuated virus vaccine given at mos & 4-5 years in US Vaccine failure rate ~10-15% Reduced outbreaks, severe disease and death No infant deaths from varicella from 5 month old w/primary varicella

14 Rash after Varicella Vaccination Associated with improved long-term immunity to varicella Injection site vesicles (1-3%) Atypical varicella: generalized varicella-like rash (1-6%) Zoster (rare, <<<1%) Slide courtesy of Bree Zimmerman,MD

15 14% of vaccinated cases Breakthrough Varicella: Varicella infection in an immunized patient Milder (<50 lesions, shorter duration) Can be widely distributed with many lesions Maculopapular cases reported +/- Fever & pruritus Confirmatory Tests: DFA lesion, PCR Saliva Weinmann S et al. J Infect Dis Mar 1;197 Suppl 2:S Watanabe M, et al. Pediatr Infect Dis J Dec 15 Watson B, et al. Pediatrics 1993;91;17

16 How/Why did these kids get zoster? 9 month-old 11 year-old 15 month-old

17 Zoster in children Immunosuppressed & immune competent No history of varicella infection in up to 50% of pediatric cases Wild-type or vaccine strain virus Incidence increases with age Kurlan JG, et al. Arch Dermatol Oct;140(10):

18 Does Vaccination prevent Zoster? Overall decrease incidence 79% lower in vaccinated children Increased incidence in vaccinated 1-2 year olds 90% due to vaccine-strain Slide courtesy of Bree Zimmerman, MD Son M et al. J Infect Dis Jun 15;201(12): Weinmann S. J Infect Dis Dec 1;208(11):

19 Wild-Type Wild-type vs. Vaccine strain zoster Oka Vaccine strain Older Thoracic distribution Morphology Symptoms Younger Lumbar and cervical distribution ~ 75% ipsilateral to vaccine site Galea SA et al. J Infect Dis Mar 1;197 Suppl 2:S Weinmann S. J Infect Dis Dec 1;208(11): Guffey DJ et al. Cutis Mar;99(3): Slide courtesy of Bree Zimmerman, MD

20 Diagnosis & Treatment Lesional DFA to confirm dx Can send viral swab in holding media to Merck Acyclovir may shorten disease course if started within hours Kids do well without treatment

21 How/Why did these kids get zoster? 9 month-old Early exposure Sub-clinical infection 11 yo s/p BMT Immunocompromised 15 month-old Vaccine associated

22 Rubella Declared eliminated in the US in 2004 Vaccine licensed 1969 Goal of vaccine program is to prevent congenital infection Live attenuated virus vaccine, mo and 4-6 yrs 95% seroconversion Contraindicated in pregnant women and immunocompromised

23 Vaccine Rubella in Cutaneous Granulomas of Immunodeficiency Patients Vaccine strain of rubella virus isolated in granulomas Not found in non-lesional skin or controls Slide Courtesy of Dana Feigenbaum, MD Bodemer et al. Clin Microbiol Infect. 2014; 20: Neven et al. Clin Infect Dis 2016

24 Vaccines and Immunodeficiency Avoid live vaccines for patients with immunodeficiency (or immunosuppression) Measles, Mumps, Rubella, Varicella, Rotavirus Emerging data suggests that patients with immunosuppression (cancer, transplant, rheum conditions) mount immune responses to vaccines Safety yet to be determined Kho MM, et al. Vaccine Jan 3;35(1): Leung TF, et al. Eur J Haematol May;72(5):353-7.

25 Findings in CVA6 Outbreak of More severe/extensive rash than classic HFMD More perioral lesions than classic HFMD Late: onychomadesis, acral peeling Very rare severe systemic disease Many school-aged or adults: low herd immunity Emerging Infectious Diseases 2012 BMC Infect Diseases 2011 Emerg Infectious Disease 2009 Mathes E, et al. Pediatrics Jul;132(1):e Hubiche T, et al. Pediatr Infect Dis J Apr;33(4):e92-8.

26 CVA6 Cutaneous Findings Vesiculobullous & erosive (99%) Locus minoris (19%) Eczema coxsackium (55%) Pseudo purpuric (17%) Photos courtesy of I. Frieden, K. Cordoro Mathes EF, et al. Pediatrics 2013;132:e149 e157

27 Other Coxsackiums Incontinentia pigmenti Epidermolytic ichthyosis Darier s Pediatr Dermatol. e280 e281, Pediatr Dermatol May-Jun;32(3):e132-3 JAAD 1999;40: BJD 1973; 88:391

28 How to Confirm CVA6 Sick contacts with HFMD Diagnostic tests: Enterovirus PCR of Skin, Oropharynx, Serum CVA6 doesn t grow in culture Histopathology: ballooning of epidermal keratinocytes and reticular degeneration of the epidermis relative sparing of the stratum corneum. Neutrophil or lymphocytic infltrate Laga et al. J Cutan Pathol 2016: 43:

29 Coxsackievirus A6 Not a new virus, but did not widely circulate in the US until recently CDC Enterovirus surveillance : CVA-6 ranked 40 th, 0.1% of enterovirus in the US

30 Where did our CVA6 come from? France/Finland China/Taiwan Mirand et al. Virology 2012.

31 Why are we seeing this now? # of cases of CVA6 CVA6 introduced from abroad Viral recombination Low herd immunity Global warming? time (years)

32 Climate and Enteroviruses Enteroviruses may prefer 20 o C and 80% humidity 1 o C, or 1% humidity increase à ~ % increase in cases 1 week delay in increase c/w incubation period Huang Y, et al. BMC Infect Dis. 2013; 13: 134.

33 Re-emergence of Old Viruses The world is smaller (and warmer) than it used to be Vaccinations save lives. Intrinsic and extrinsic factors prevent 100% efficacy. Attenuated viruses can cause disease If you think you are seeing something new and different, or old and eliminated call your public health department collect specimens in viral holding media and refrigerate Check out the CDC website

34 Thank you!