OVERVIEW OF MEASLESDavid Jay Weber, M.D., M.P.H., FSHEA, FIDSA, FRCM (London)

Professor of Medicine, Pediatrics, EpidemiologyMedical Director, Hospital Epidemiology

Associate Chief Medical Officer, UNC HospitalsUniversity of North Carolina at Chapel Hill

Thanks to Dr. Peyton Thompson for some slides

MEASLES: HISTORY

In the 9th century, a Persian doctor published one of the first written accounts of measles disease. Francis Home, a Scottish physician, demonstrated in 1757 that measles is caused by an infectious agent in the

blood of patients. In 1912, measles became a nationally notifiable disease in the United States, requiring U.S. healthcare providers

and laboratories to report all diagnosed cases. In the first decade of reporting, an average of 6,000 measles-related deaths were reported each year.

In the decade before 1963 when a vaccine became available, nearly all children got measles by the time they were 15 years of age. It is estimated 3 to 4 million people in the United States were infected each year. Also each year, among reported cases, an estimated 400 to 500 people died, 48,000 were hospitalized, and 1,000 suffered encephalitis (swelling of the brain) from measles.

First measles vaccine licensed in US in 1963 (inactivated); current vaccine licensed in US in 1968 (attenuated) Measles was declared eliminated (absence of continuous disease transmission for >12 mo) from the US in 2000.

https://www.cdc.gov/measles/about/history.html

MEASLES: EPIDEMIOLOGY

Measles is a highly contagious virus (single-stranded, enveloped RNA virus with 1 serotype) that lives in the nose and throat mucus of an infected person (rho = 18, i.e., 1 infected person infects on average 18 other susceptible persons).

Reservoir: Humans (only natural host) Transmission is via airborne particles (when infected patient coughs or sneezes) Measles virus can survive for up to 2 hours in an airspace where an infected patient coughed or sneezed Incubation period: 7-21 days (average 14 days) Contagious period: 4 days before onset of rash to 4 days after onset of rash Groups at risk for measles complications: Children

Measles vaccine (inactivated) licensed 1963Measles vaccine (live attenuated) licensed 1968MMR required for school entry by many states in early 1980sTwo doses of MMR first recommended in 1989ACIP, APP, AAFP harmonized their 2nd dose recommendations (before elementary school entry) in 1998

https://www.cdc.gov/measles/cases-outbreaks.html

https://www.cdc.gov/measles/cases-outbreaks.html

Source: WHO Measles

Contagious period

MEASLES: PICTURES

Koplik spots Skin of patientAfter 3 days ofmeasles

Child with a classic measles rash after four days.

Eyes of a child with measles.

MEASLES: DIAGNOSIS

Summary Detection measles specific IgM; PCR for measles RNA (serum, throat swab, NP swab); 4-fold increase measles IgG

in acute and convalescent samples (10 days apart); virus isolation in cell culture Throat or nasopharyngeal swabs

Detection of measles RNA and measles virus isolation most successful when samples collected on 1st day rash through the 3rd day following rash onset (virus may still be recovered through day 10 following rash onset). Detection of measles RNA by RT-PCR may be successful as late as 10-14 days post rash onset.

Serology Collect acute-phase sample as soon as diagnosis suspected. If the acute-phase serum sample collected ≤3 days

after rash onset is negative, and the case has a negative (or not done) result for RT-PCR, a second serum sample collected 3–10 days after symptom onset is recommended because, in some cases, the IgM response is not detectable until 3 days after symptom onset.

MUMPS, MEASLES, RUBELLA (MMR) VACCINE Measles vaccine (administered as MMR): Efficacy

One dose of vaccine (~95% efficacy); Two doses of vaccine (>99 efficacy) Demonstration of immunity

Immunization with 2 doses of measles virus-containing vaccine (the first dose administered at age ≥12 months; the second dose no earlier than 28 days after the first dose)

Lab evidence of immunity (measles immunoglobulin G [IgG] in serum) – equivocal results are considered negative Birth before 1957 (for HCP all persons have a serology obtained, if negative they receive MMR x 2)

Immunization 1st dose at 12-15 months (for travel or outbreaks, 1st dose may be provided to infants 6-11 months of age – in these

cases children should receive 2 additional doses at recommended ages) 2nd dose at 4-6 years of age (2nd dose should always be provided at least 28 days after 1st dose) If appropriately immunized, boosters are not recommended

Contraindications: Pregnancy, immunocompromised (except HIV with CD4 >200), anaphylaxis to vaccine component

MEASLES IMMUNITY IN HCP BORN BEFORE 1957

Weber DJ, et al. Infect Control Hosp Epidemiol 2010;31:655-657

MUMPS, MEASLES, RUBELLA (MMR) VACCINE: CAVEATS MMR may be provided to persons whose households include pregnant women, infants, or immunocompromised persons

(MMR may be provided to HCP who work with all types of patients) Self-reported doses or history of vaccination, or documentation of physician-diagnosed disease are NOT acceptable

criteria for evidence of immunity Although birth before 1957 is considered evidence of immunity, healthcare facilities should consider vaccinating HCP

born before 1957 who do not have other evidence of immunity. During outbreaks of measles in healthcare facilities, or in healthcare facilities serving a measles outbreak area, 2 doses of measles vaccine are recommended for HCP, regardless of year of birth. UNC Hospitals no longer considers birth before 1957 as evidence of immunity (a measles titer is obtained)

Persons who received the inactivated measles vaccine (no longer available in the United States) should be considered unvaccinated and should be revaccinated with 2 doses of MMR vaccine. Only

PROOF OF IMMUNITY FOR HCP

Vaccine Birth before 1957

MD Dx + Serology Self Report Documented Vaccination

Mumps 1 Yes3 No Measles 1 Yes3 No Rubella 1,2 No No Varicella No Yes No Hepatitis B No >10 MIU/mL4 No Pertussis No No No No Influenza No No No No

1Consider immunization of HCP born before 1957, recommend immunity during an outbreak;2All HCP of childbearing potential should be immunized; 3requires lab confirmation;4Obtain 1-2 months post last vaccine dose Weber DJ, Schaffner W. ICHE 2011;32:912-4

MEASLES: PEP AND EXPOSURE MANAGEMENT

Active measles: Visitors, exclude from hospital; HCP furlough until 7 days after rash appears (CDC, 1998) If HCP immunocompromised, furlough for duration of illness

If exposed and unimmunized, provide first dose of MMR (HCP are furloughed from 5th day after 1st exposure through 21st day after last exposure and/or 4 days after rash appears) – HCP are furloughed even if they receive IgG Vaccine provided within 72 hours of exposure will prevent or modify disease

If exposed and had 1 dose of MMR, provide 2nd dose of MMR (if at least 28 days since 1st dose): If provided within 72 hours of first exposure, HCP may continue to work but should monitor themselves for symptoms; if MMR no provided within 72 hours of first exposure, HCP are furloughed from 5th day after 1st exposure through 21st day after last exposure and/or 4 days after rash appears

IgG may be used for exposed non-immune persons who are at high risk for severe disease (must be provided within 6 days of exposure)

MEASLES: PEP AND EXPOSURE MANAGEMENT

IgG may be provided for PEP within 6 days of exposure to prevent or modify measles: Pregnant women (non-immune), infants

MEASLES: INFECTION PREVENTION

Airborne isolation Private room, direct out exhausted air, >12 air exchanges per hour, negative pressure All HCP entering room MUST wear an N95 respirator (requires clearance from occupational health plus

fit testing yearly) – N95 respirator MUST be worn even if the healthcare provider is immune If airborne isolation room NOT available, have patient wear a mask (HCP should still wear an N95

respirator), ideally place patient in a negative pressure room, ideally place a HEPA device in the room Maintain isolation for at least 4 days after rash onset

Screen visitors to make sure that they are not contagious or potentially in the incubation phase of measles

Terminal cleaning followed by UV disinfection

USE OF ROOMS THAT CONTAINED A PATIENTWITH MEASLES

A room housing a patient with measles needs to remain unused by another patient for at least 2 hours if the air exchange rate is not known

If the air exchange rate is known, use table to determine time to 99.9% clearance

CDC. MMWR 2005;54(RR-17):page 20

CAVEATS FOR THE CLINICAL STAFF Make sure that you are immune to measles Suspect measles in any person with appropriate signs and/or symptoms – remember rash is a late sign If measles is suspected:

Obtain an immunization history: almost all cases of measles in the US occur in persons not vaccinated or inadequately vaccinated (i.e., 1 dose)

Obtain a travel history: almost all index cases are not only inadequately immunized but also have acquired measles abroad

Immediately isolate patient in a single room – place mask on patient Wear N95 respirator for care of the patient (dispose of N95 each time you leave the room) Page Infection Preventionist on call at: 919-216-2935

All vendors (look for badge), contractors, and shadowers MUST adhere to UNC Hospitals’ vaccination requirements

EMERGING PATHOGENS: ENVIRONMENTAL SURVIVAL AND TRANSMISSION, GERMICIDAL

ACTIVITY AND CONTROL MEASURESDavid Jay Weber, M.D., M.P.H.

Professor of Medicine, Pediatrics, EpidemiologyAssociate Chief Medical Officer, UNC Hospitals

Medical Director, Hospital EpidemiologyUniversity of North Carolina at Chapel Hill

Disclosures: Consultant to Germitec, PDI, Merck, Pfizer

INFECTION PREVENTION ISSUES Pathogen: Family Filovirdae (RNA virus, enveloped) Endemic location: West and Central Africa (reservoir: bats?) Transmission :Person-to-person, direct (blood or body fluids) and indirect (contaminated

needles/syringes); sexual (semen); zoonotic (nonhuman primates, bats) Incubation period: 6-12 (range, 2-21) Infectivity (rho): 1.5-2.0 (infectious period; 6-12 days, range 2-21) Biosafety level: 4 Isolation: Contact (full body protection, no exposed surfaces), N95, eye protection Hospital outbreaks: Well described (HCP at high risk) Environmental control: Dedicated (preferably) disposable equipment (sterilize reusable

equipment), use EPA disinfectant with non-enveloped virus claim

Weber DJ, et al. AJIC 2016;44:e91-e100

ENVIRONMENTAL CONTAMINATION, EBOLA TREATMENT CENTER, SIERRA LEONE, DETECTION OF RNA

Swab Location Positive swab samples/TotalPatient personal effects 1/5Patient clothing 2/5Patient blanket 1/3Patient’s mattress 4/8Floor with body fluids next to patient 1/4Floor with no visible contamination next to patient 1/8Head of bed rail 2/8Biological waste buckets 2/4IV bags and tubing 1/5Urine catheter bag assembly 2/5

Sites negative for Ebola: Patient food/water, towel , toys; foot of bed rail, curtains, chairs; all general ward surfaces Poliquin P, et al. JID 2016;214(S3):S145-52

SURVIVAL OF EBOLA VIRUS(Makona varient)

Cook BW, et alViruses 2015;7:1975-1986

SUSCEPTIBILITY OF EBOLA VIRUS TO ANTISEPTICS AND DISINFECTANTS

Cook BW, et al Viruses 2015;7:1975-1986

EBOLA: INFECTION PREVENTION Isolate patients in a single room with bathroom PPE: All body surfaces should be covered (see CDC donning and doffing protocols)

Avoid aerosol generating procedures Only essential HCP should provide care

Use dedicated HCP Keep a log of persons entering the room – monitor health of HCP

Environmental infection control Use dedicated equipment (disposal preferable) – disinfected/sterilize all reusable

equipment Frequent hand hygiene Use EPA registered hospital disinfectant with label claim for non-enveloped

viruses for surface disinfection; discard all linens, nonfluid impermeable items

https://www.cdc.gov/vhf/ebola/clinicians/cleaning/hospitals.html

CANDIDA AURIS: HISTORY First identified as a new species in 2009 from the external ear canal of a Japanese

patient Microbiology

Cannot be identified by commercial methods for yeast identification Usually resistant to fluconazole, often resistant to amphotericin B, exhibits reduced

susceptibility to voriconazole and itraconazole; resistance may develop on therapy Epidemiology

Transmission: Person-to-person (direct and indirect via environment); also via donor derived lung transplant (Azar 2017)

Most commonly clinical syndromes: fungemia, otologic infections Nosocomial outbreaks have been reported in a number of countries Risk factors for infection: immunosuppression, co-morbidities, central lines, Foley catheters,

recent surgery, parental nutrition, broad spectrum antibiotics, ICU care, and residence in a skilled nursing home

Mortality (fungemia): 28%-66% (Sears 2017)

GEOGRAPHICAL DISTRIBUTION OF CANDIDA AURIS(as of 31 March 2019)

Lamoth Fl Kontoyiannis DP. J Infect Dis 2018;217:516-520.Sekyere JO. Microbiologyopen. 2018 Jan 1 (Epub ahead of print

https://www.cdc.gov/fungal/candida-auris/tracking-c-auris.html

C. AURIS, CLINICAL CASES, US(as of 31 March 2019)

Confirmed cases = 613

Probable cases = 30

Colonized = 1,123

States = 11

https://www.cdc.gov/fungal/candida-auris/tracking-c-auris.html

CANDIDA AURIS: OUTBREAKS

Reference Location Colonized/Infected Molecular Linkage OutbreakControlled

Ryan-Gaitan, 2018 Europe 140/41 BSI Yes NoArauz, 2018 Panama NA/9 No NABiswal, 2017 India Many/3 BSI NA YesCalvo, 2016 Venezuela NA/18 BSI Yes NA

Schelenz, 2016 London NA/50 Yes No

TRANSMISSION AND PERSISTENCE OF CANDIDA AURIS

Colonization of patients Colonization of patients is common; multiple sites involved (Biswal 2017)

Role of HCP HCP may be colonized; uncommon (Schelenz 2017) HCP hands may transiently carry C. auris (Biswal 2017)

Role of environment Environmental contamination common (Lesho 2018, Biswal 2017, Schelenz 2017,

Valladhaneni 2016): mattresses, furniture, sinks, and medical equipment Prolonged environmental survival on environmental surfaces; >14 days (Piedrahita 2017,

Welsh 2017) Prolonged survival (>7 days) on contaminated bedding (Biswal 2017)

NOSOOCOMIAL OUTBREAK OF C. auris(Biswal M, et al. JHI 2017;97:363-370)

ENVIRONMENTAL SURVIVAL OF CANDIDA AURIS

Piedrahita C, et al. ICHE 2017;38:1107-1109 Welsh RM, et al. J Clin Microbiol 2017;55:2996-3005

CANDIDA AURIS:SUSCEPTIBILITY TO DISINFECTANTS

In laboratory testing, sporicidal and improved hydrogen peroxide disinfectants were highly effective against C. auris, C. glabrata, and C. albicans. The widely used quaternary ammonium disinfectantsexhibited relatively poor activity against all of the Candida species. Cadnum et al. ICHE 2017;38:1240

EFFICACY OF ANTISEPTICS AND DISINFECTANTS AGAINST C. AURIS

Study design: In vitro study of germicide efficacy against C. auris and C. albicans Method: Disc-based quantitative carrier test with an inoculum of ~106 organisms with

5% fetal calf serum and 1 minute exposure time at room temperature (challenging test conditions)

Results: Study demonstrated >3-log10 reduction (12/22, 55%) and 2-log10 reduction (15/22,

68%) for C. auris C. auris was less susceptible to 0.55% ortho-phthalaldehyde, 2% chlorhexidine, 4%

chlorhexidine, and 1% chloroxylenol compared to C. albicans. C. auris was more susceptible to 70% ethanol, compared to C. albicans. Several germicides (21.7% QAC] 3% hydrogen peroxide, 5.25% sodium

hypochlorite [1:50 dilution], 0.5% triclosan) had

EFFICACY OF ANTISEPTICS AND DISINFECTANTS AGAINST C. AURIS

EFFICACY OF ANTISEPTICS AND DISINFECTANTS AGAINST C. AURIS

Effectiveness of surface disinfectants (level of evidence) Effective: Chlorine >1000 ppm (good); hydrogen peroxide 1.4% (moderate);

phenolics 5%? (low); alcohols 29.4% (low); peracetic acid 2000 ppm (low) Ineffective: Quats - 2% didecyldimethyl ammonium chloride; alkyl dimethyl

ammonium chlorides; didecyldimethyl ammonium chloride/dimethylbenzylammonium chloride

Ku TSN, et al. Frontiers in Microbiol 2018;9:726

EFFICACY OF UVC TOINACTIVATE C. AURIS

Goal: Assess inactivation by UVC Methods: UVC (Optimum) used at

5 ft for specified time; 106 CFU with 5% FCS applied to stainless-steel carriers.

Results: C. auris less susceptible to UVC than other Candida spp.

Conclusion: Use C. difficile cycle time (data) to inactivate C. auris

Cadnum JL, et al. ICHE 2018;39:94-96

C. AURIS: INFECTION PREVENTION

Place patients in a single room using standard and contact isolation Emphasize hand hygiene Screen roommates; consider point prevalence surveys (swab

patient’s axilla and groin) Flag patient in case of re-admission Environmental infection control

EVS should use proper PPE Monitor cleaning practices Avoid quaternary ammonia products for surface disinfection; use a disinfectant

EPA registered against C. difficile (Like K)

https://www.cdc.gov/fungal/candida-auris/c-auris-infection-control.html#disinfection

CONCLUSIONS

CRE Environmental contamination: Yes (low frequency) Environmental survival: Hours Environmental transmission: Yes Antisepsis and disinfection: Standard

C. auris Environmental contamination: Yes (frequent) Environmental survival: Hours to days Environmental transmission: Yes Antisepsis and disinfection: Standard antisepsis (CHG or EtOH); Avoid quaternary ammonium

compounds for surface disinfection

CONTINUOUS ROOM DECONTAMINATION TECHNOLOGIES

David Jay Weber, M.D., M.P.H.Professor of Medicine, Pediatrics, EpidemiologyAssociate Chief Medical Officer, UNC Hospitals

Medical Director, Hospital EpidemiologyUniversity of North Carolina at Chapel Hill

Disclosures: Consultant to Germitec, PDI, Merck, Pfizer

CONTINUOUS ROOM DISINFECTION Surface disinfectants (“self-

disinfecting” surfaces) Heavy metals: Silver, copper, others Persistent disinfectants Others: Altered topography (micro-

patterned), polycationic and light-activated antimicrobial surfaces, bacteriophage-modified surfaces

Remote methods High-intensity narrow-spectrum light UV-A irradiation Low dose continuous hydrogen

peroxide

Weber DJ, et al. Curr Opin Infect Dis 2016;29:424-431 Adhart C, et al. JHI 2018 (Epub ahead of print)

ADVANTAGES OF CONTINUOUSROOM DISINFECTION

• Allows continued disinfection (may eliminate the problem of recontamination)• Patients, staff and visitors can remain in the room• Does not require an ongoing behavior change or education of personnel• Self-sustaining once in place• Once purchased might have low maintenance cost• Technology does not give rise to health or safety concerns• No (limited) consumable products

SURFACE DISINFECTANTS: PERSISTENCE

Surface disinfectant PersistencePhenolic No

Quaternary ammonium compound Yes (undisturbed)Alcohol No

Hypochlorite NoHydrogen peroxide No

Silver Yes

Rutala W, White M, Gergen M, Weber D. ICHE 2006;27:372-77

EFFICACY OF A PERSISTENT CHEMICAL DISINFECTANT

Goal: Assess the persistent antimicrobial activity of a novel disinfectant

Methods: Surfaces were inoculated , treated with the novel disinfectant, allowed to dry, and then abraded using a standardized abrasion machine under multiple alternating wet and dry wipe conditions (N=12) interspersed with 6 re-inoculations. After 24 hours, the surface was re-inoculated a final time and ability of the disinfectant to kill >99.9% of 9 test microbes within 5min was measured on 3 test surfaces (glass, Formica, and stainless steel).

The novel persistent disinfectant proved successful decontamination against a variety of pathogens

Test Pathogen Mean Log10 Reduction, 95% CI n=4

S.aureus* 4.4 (3.9, 5.0)S.aureus (formica) 4.1 (3.8, 4.4)S.aureus (stainless steel) 5.5 (5.2, 5.9)VRE ≥4.5 E.coli 4.8 (4.6, 5.0) Enterobacter sp. 4.1 (3.5, 4.6)Candida auris ≥5.0K pneumoniae 1.5 (1.4, 1.6)CRE E.coli 3.0 (2.6, 3.4)CRE Enterobacter 2.0 (1.6, 2.4)CRE K pneumoniae 2.1 (1.8, 2.4)

Rutala W, Gergen M, Sickbert-Bennett E, Anderson D, Weber D. Unpublished.

OVERVIEW OF MEASLESMEASLES: HISTORYMEASLES: EPIDEMIOLOGYSlide Number 4Slide Number 5Slide Number 6Slide Number 7Slide Number 8MEASLES: PICTURESMEASLES: DIAGNOSISMUMPS, MEASLES, RUBELLA (MMR) VACCINEMEASLES IMMUNITY IN HCP BORN BEFORE 1957MUMPS, MEASLES, RUBELLA (MMR) VACCINE: CAVEATSPROOF OF IMMUNITY FOR HCPMEASLES: PEP AND EXPOSURE MANAGEMENTMEASLES: PEP AND EXPOSURE MANAGEMENTMEASLES: INFECTION PREVENTIONUSE OF ROOMS THAT CONTAINED A PATIENT�WITH MEASLESCAVEATS FOR THE CLINICAL STAFFEMERGING PATHOGENS: ENVIRONMENTAL SURVIVAL AND TRANSMISSION, GERMICIDAL ACTIVITY AND CONTROL MEASURESINFECTION PREVENTION ISSUESENVIRONMENTAL CONTAMINATION, EBOLA TREATMENT CENTER, SIERRA LEONE, DETECTION OF RNASURVIVAL OF EBOLA VIRUS�(Makona varient)SUSCEPTIBILITY OF EBOLA VIRUS TO ANTISEPTICS AND DISINFECTANTSEBOLA: INFECTION PREVENTIONCANDIDA AURIS: HISTORYGEOGRAPHICAL DISTRIBUTION OF CANDIDA AURIS�(as of 31 March 2019)C. AURIS, CLINICAL CASES, US�(as of 31 March 2019)CANDIDA AURIS: OUTBREAKSTRANSMISSION AND PERSISTENCE OF CANDIDA AURISNOSOOCOMIAL OUTBREAK OF C. auris�(Biswal M, et al. JHI 2017;97:363-370)ENVIRONMENTAL SURVIVAL OF CANDIDA AURISCANDIDA AURIS:�SUSCEPTIBILITY TO DISINFECTANTSEFFICACY OF ANTISEPTICS AND DISINFECTANTS AGAINST C. AURISEFFICACY OF ANTISEPTICS AND DISINFECTANTS AGAINST C. AURISEFFICACY OF ANTISEPTICS AND DISINFECTANTS AGAINST C. AURISEFFICACY OF UVC TO�INACTIVATE C. AURISC. AURIS: INFECTION PREVENTIONCONCLUSIONSCONTINUOUS ROOM DECONTAMINATION TECHNOLOGIESCONTINUOUS ROOM DISINFECTIONADVANTAGES OF CONTINUOUS�ROOM DISINFECTIONSURFACE DISINFECTANTS: PERSISTENCEEFFICACY OF A PERSISTENT CHEMICAL DISINFECTANT