07/03/2014 1 Influenza, TB, Pertussis and Other Respiratory Diseases Ann-Christine Nyquist MD, MSPH Professor of Pediatrics, Sections of Infectious Diseases and Epidemiology Medical Director, Infection Prevention and Control and Occupational Health 18th Annual Fellow’s Course in Hospital Epidemiology and Infection Control July 9, 2014 Disclosures No Relevant Disclosures
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Influenza, TB, Pertussis and Other Respiratory Diseases
Ann-Christine Nyquist MD, MSPHProfessor of Pediatrics, Sections of Infectious Diseases and
EpidemiologyMedical Director, Infection Prevention and Control and
Occupational Health
18th Annual Fellow’s Course in Hospital Epidemiology and Infection Control
July 9, 2014
Disclosures
No Relevant Disclosures
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Objectives
• Discuss epidemiology, diagnosis and transmission of respiratory viruses, pertussis, and TB
• Highlight the role of respiratory viruses, pertussis, TB as causes of nosocomial infections
• Review methods to prevent healthcare-associated respiratory viral infections, pertussis, and TB
Respiratory Viruses
• Influenza
• RSV
• Human metapneumovirus
• Coronaviruses
• Rhinoviruses
• Adenoviruses
• Bocavirus
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Jul Aug Sept Oct Nov Dec Jan Feb Mar Apr May Jun
Seasonal Incidence of Common ChildhoodInfections
Diseases of Infancy and ChildhoodTextbook L. Emmett Holt 1906
Chapter XII Influenza synonym: la grippe
Influenza is an infectious, communicable disease, which is now generally admitted to be due to the bacillus described by Pfeiffer in 1892.
Treatment…..The fumigation of apartments after attacks should be regularly practiced, preferably with formalin gas; this with isolation will do much to control house epidemics…The cough which persists after influenza is best controlled by cod-liver oil and creosote, used as after acute bronchitis.
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Influenza Virus
15th Century Italians– “to influence”; illness influenced by
the stars and planets
Family Orthomyxoviridae– “myxo” mucus– enveloped, segmented, single-
stranded RNA
Influenza A first isolated 1933; Influenza B 1940
15 hemagglutinin (HA) and 9 neuraminidase (NA) subtypes– Only H1N1, H2N2, H3N2 subtypes
associated with widespread epidemics in humans
Clinically Relevant Influenza Viruses Type A Potentially severe illness
Epidemics and pandemicsRapidly changingBirds, swine, horses, seals, humans
Type B Usually less severe illnessEpidemicsMore uniformHumans
Type C Usually mild or asymptomatic illness Minimal public health impactHumans, swine
Centers for Disease Control and Prevention. Influenza Prevention and Control. Influenza. Available at: http://www.cdc.gov/ncidod/diseases/flu/fluinfo.htm.
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Influenza: A Continuously Changing Virus
Polymerase Proteins (PP)
Hemagglutinin (HA) *cell entry
Neuraminidase (NA)*cell escape
M1, M2
Nucleoprotein (NP)
Adapted from: Hayden FG et al. Clin Virol. 1997:911-942.
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RNA
Hemagglutinin
NeuraminidaseAntibodies
Sialic acid
Antigenic Drift (A & B)
Antigenic Shift (A only)
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15 countries 553 cases - 323 deaths
Update March 2013: Avian influenza A (H7N9)
Avian Influenza: Sick Chickens
Blue Comb
Swollen Wattle
Congestion and Blood Spots on
Hocksand Shanks
Vesicleson comb
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Transmission of Influenza Person to person Droplet spread-
– small particle aerosols Fomite contamination
– Steel and plastic 24-48 hrs– Cloth,paper,tissues 8-12 hrs– Hands 5 min (high viral titer)
Principal site of replication- columnar epithelium Incubation period- 18 hrs to 5 or more days (avg 2-3 days) Virus shedding 3-7 days Viral titers are generally higher in young children with shedding
lasting 10 days or longer
Children are a “Vector”
Influenza uniquely allows children to spread its virus– children less sick than adults– Higher viral titer– longer viral excretion
School-age children have the highest attack rates of influenza– disease rates peak first in children during an outbreak
Schools facilitate the infection– 1918 and 1957 first cases appeared in the spring but real
outbreaks began in fall after school began– 1968 pandemic mild- “interrupted” by school holiday break
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Influenza Symptoms by Age Group
Influenza Sign/Symptom Children Adults Elderly
Cough (nonproductive) ++ ++++ +++
Fever +++ +++ +
Myalgia + ++ +
Headache ++ ++ +
Malaise + ++ +++
Sore throat + ++ +
Rhinitis/nasal congestion ++ ++ +
Abdominal pain/diarrhea + – +
Nausea/vomiting ++ – +
++++ Most frequent sign/symptom; + Least frequent; – Infrequent
Monto AS, et al. Arch Intern Med. 2000;160:3243-3247; Cox NJ, Subbarao K. Lancet. 1999;354:1277-1282.
Role of Children in Influenza Epidemiology
Adapted from: Elveback LR et al. Am J Epidemiol. 1976;103:152-165.
Family members &other close contacts
Other children
Day care, preschool and school-age children
Communityincluding high-risk populations
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Talbot TR ICHE 2005;26:882 Stott DJ Occ Med 2002;52:249 Foy HM Am J Epi 1987;126:506 Weingarten S AJIC 1989;17:202 Lester RT ICHE 2003;24:839
Healthcare-Associated Influenza
• Outbreaks reported in most care areas
• Influenza infection causes minimal or nosymptoms in up to 25%
• Such workers still shed (and spread) virus
• 76.6% HCP work while ill with ILI
• Worked mean 2.5 days while ill with ILI
Risk of HA-ILI in Acute Care Setting
Vanhems P et al Arch Intern Med 2011;171:151+
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Transmission of Respiratory Pathogens
• Some pathogens can be spread by various sizes of particles that travel in the air Larger droplets
• Pertussis (whooping cough)
• Influenza
Smaller aerosols• M. tuberculosis
• Direct spread via contact with the environment is also suspected
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Moghadas SM et al BMC Medicine 2009;7:73+
Influenza Shedding
How Long Are Surfaces Contaminated ?
RSV survives on environmental surfaces – 7 hours on countertops– 5 hours on gloves– 2 hours on cloth– 30 minutes on skin and paper tissue
RSV can be cultured from hands for up to 25 minutes after contact with contaminated surfaces
Cultured from stethoscopes, hospital environment
Rotavirus survives for up to 7 months on surfaces, weeks in water and for up to 4 hours on human hands
Influenza survives for up to 24-48 hrs on steel and plastic, 8-12 hrs on cloth/paper tissues and 5 minutes on hands (high viral titer)
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Prevention of Healthcare-Associated Respiratory Viral Infections
• Hand Hygiene/Respiratory Hygiene & Cough Etiquette
• Early Identification of Cases
• Patient Cohorting
• Source Control
• Isolation Precautions/PPE
• Antivirals
• Vaccination
Prevention of Healthcare-Associated Respiratory Viral Infections
• Hand Hygiene/Respiratory Hygiene & Cough Etiquette
• Early Identification of Cases
• Patient Cohorting
• Source Control
• Isolation Precautions/PPE
• Antivirals
• Vaccination
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Respiratory Hygieneand Cough Etiquette
• Cover your mouth and nose when you cough or sneeze.
• Practice good hand hygiene at all times.
• Keep 6 feet or more between you and anyone with respiratory symptoms unless wearing appropriate protection.
Prevention of Healthcare-Associated Respiratory Viral Infections
• Hand Hygiene/Respiratory Hygiene & Cough Etiquette
• Early Identification of Cases
• Patient Cohorting
• Source Control
• Isolation Precautions/PPE
• Antivirals
• Vaccination
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Early Identification of Cases
• Screening for symptoms at facility entry Both patients & visitors
Clinical Presentation: ILI and Laboratory-Confirmed Influenza
Babcock HM et al 2006;27:266+
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Influenza: Diagnosis• Gold standard = isolation of virus from
respiratory secretions Takes 3-5 days to isolate
• Viral antigen detection: Various assays used (IF, RIA, ELISA) Low sensitivity for nH1N1, H5N1 and in
extremes of age
• PCR• Serology: Requires paired samples, 10-14 days apart
Source Control
• Place surgical mask on patient
• Data from households and dormitories have found use of masks reduce transmission of ILI
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Prevention of Healthcare-Associated Respiratory Viral Infections• Hand Hygiene/Respiratory Hygiene & Cough
Etiquette
• Early Identification of Cases
• Patient Cohorting
• Source Control
• Isolation Precautions/PPE
• Antivirals
• Vaccination
CDC Transmission-Based Precautions
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N-95 vs. Mask
• Keeps small droplets from going IN
• A respirator
• Filters particles 1 m with a filter efficiency of >95%
• Not effective if wet
• Fit-test annually
• Keeps large droplets from going IN
• Keeps air, secretions, YOUR viral infection from going OUT
N-95 Mask
Loeb M et al JAMA 2009;302:1865+
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PPE: Respiratory Viruses
Virus Type of Precautions
Seasonal Influenza Droplet
RSV Contact
hMPV Contact
Rhinovirus Droplet
Parainfluenza Contact
SARS-HCoV Contact, Airborne, Eye Protection
Other HCoV ??? Contact or Droplet
Prevention of Healthcare-Associated Respiratory Viral Infections• Hand Hygiene/Respiratory Hygiene & Cough
Etiquette
• Early Identification of Cases
• Patient Cohorting
• Source Control
• Isolation Precautions/PPE
• Antivirals
• Vaccination
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Influenza Antivirals
Adamantanes– Amantidine & rimantidine– M2 ion channel inhibitors– Effective against type A viruses only (Rx & prophylaxis)
Neuraminidase inhibitors– Oseltamivir (Tamiflu) & zanamivir (Relenza)– Effective against type A & B viruses (Rx & prophylaxis)
Issues– Resistance among seasonal influenza viruses– Resistance among some H5N1 viruses– None approved for Rx or prophylaxis for children < 1yr– Unproven effectiveness for Rx of H5N1 infection
Prevention of Healthcare-Associated Respiratory Viral Infections• Hand Hygiene/Respiratory Hygiene & Cough
pleomorphic bacillus• Humans only known host• Transmission via contact with
respiratory secretions (droplet precautions)
• Incubation period 6-20 days (usually 7-10 days) Catarrhal stage (mild URI
sx- most contagious) Paroxysmal stage (severe cough, whoop) Convalescent stage
• Duration 6-10 weeks
When Is Pertussis Communicable?
• Persons with pertussis become highly infectious during the catarrhal stage.
• Some individuals, especially infants, may be infectious for a longer period than shown above.
Reference:1. CDC. The Pink Book. 10th ed. 2007:81-100. Available at: http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/pert.pdf. Accessed September 17, 2007.
-2 -1 0 1 2 3 4 5 6 7 8 9 10 11 12
Weeks of cough
Catarrhal stage
Paroxysmal stage
Convalescent stage
Paroxysmal cough onset
Typical period of communicability
Exposure
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Dramatic Growth inReports of Adult and Adolescent Pertussis
References:1. Güriş D, et al. Clin Infect Dis. 1999;28:1230-1237. 2. CDC. MMWR. 2002;51(4):73-76. 3. CDC. MMWR. 2003;50(53):9.4. CDC. MMWR. 2004;51(53):23. 5. CDC. MMWR. 2005;54(31):777. 6. National Center for Immunization and Respiratory Diseases, CDC. Pertussis Surveillance Reports for 2004 & 2005.
• Transmission of pertussis to household members has been documented.
• Young infants get pertussis primarily from family members, and are at high risk of morbidity and mortality.
• Adolescents get pertussis from household contacts and schoolmates.
• Adults get pertussis from work andhousehold contacts; parents (adult and adolescent) give pertussis to their infants.
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Reasons for Increased Pertussis Incidence• Increased reporting Improved recognition of cases in adults and
adolescents Reporting criteria changed in 1995
• Confirmation through PCR• Epidemiologic links
Serology
• Increasing incidence Waning protection from childhood vaccination
or prior infection Delay or refusal of vaccines
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Parental Refusal of Pertussis Vaccination is Associated With an Increased Risk of Pertussis Infection in ChildrenCase‐control study of Kaiser Permanente Colorado Health Plan 1996‐2007; each pertussis case matched to 4 randomly selected controlsFindings
• 156 lab confirmed pertussis cases; 595 matched controls• 18 (12%) pertussis vaccine refusers among cases; 3 (0.5%) among controls • Vaccine refusers had a 23‐fold increased risk for pertussis when compared with vaccine acceptors; 11% of all pertussis cases were attributed to parental vaccine refusal
Glanz JM et al. Pediatrics 2009;123:1446‐1451
Clinical Pearls regarding Pertussis Clinical Presentation and Lab Diagnostics (1)
• Afebrile with increasing cough duration and severity
• Coryza is associated with illness onset; does not become purulent as with most viral respiratory infections
• Paroxysmal cough‐ patient does not inhale until he has run out of breath ( possibly resulting in inspiratory “whoop”)
• Most infants will have close exposure to adolescent or adult with prolonged afebrile cough illness
• Cough in pertussis is not truly productive
• Sweating periods occur in adolescents and adults in between coughing episodes
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Clinical Pearls regarding Pertussis Clinical Presentation and Lab Diagnostics (2)
• PCR and culture are most useful in the first 3 weeks after illness onset
• Serology should not be used to diagnose pertussis in patients < 1 year after inoculation with acellular or whole‐cell vaccine formulation
• IgG anti‐PT ELISA is preferred to IgA anti‐PT testing ( IgA response following infection less common therefore potential for false negative result)
• Discourage use of DFA; discourage use of ELISA that uses whole B. pertussis as antigen
Diagnosis of Pertussis
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Diagnosis of Pertussis• Culture = “Gold standard"
3 – 7 days to complete Low sensitivity Lower positivity rates w/ prior immunization, increasing age, prior
antibiotics, improper collection of specimens
• PCR: 1 – 2 days to complete Remains positive longer More sensitive than culture Not standardized Pseudo-outbreaks due to single target PCR
• Serology Different tests used to measure serum antibodies Diagnosis depends on definition used Not standardized
AAP 2012 Red Book
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Antimicrobial Treatment and Prophylaxis for Adults
Primary agents Alternative agent
Azithromycin Erythromycin Clarithromycin TMP-SMX
500mg in a single dose on
day 1 then 250mg per day
on days 2-5
2g/d in 4 divided doses for 14 days
1g/d in 2 divided doses
for 7 days
TMP 320mg/d, SMX 1600mg/d in 2 divided doses
for 14 days
Pertussis Infection Control:Droplet Precautions
• Requires close contact (3ft)• Mask: worn in room• Gloves: If handle secretions• Do not need negative
pressure room
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Pertussis Vaccines
• Whole-cell DTP (1948): Suspension of Bp inactivated by heat & formaldehyde
Efficacy ~80%
Local and systemic adverse events (encephalopathy)
• Acellular vaccine (1996): Antigens extracted from B. pertussis organisms by
purification methods
Efficacy 63 – 89%; Tdap = 92%
Local and systemic side effects less common
Vaccine Alphabet Soup
• DTaP
• Tdap
• Td
Infant and children
Adolescents & adults
Adult booster (former?)
Tetanus component
Diphtheria component
Pertussis component
Size of letter denotes size of dose
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Vaccine Indications
• DTaP: All children at 2, 4, & 6 months Booster at 15-18 months & age 4-6 years
• Tdap: Adolescents aged 11-18 yrs (11-12yrs preferred) All adults age 19-64 yrs if last Td ≥ 10 yrs ago Pregnant women in each pregnancy (27- 36 wks) Adults 65+ if infant contact Give <10 yrs since Td: if risk for pertussis
exposure, close contacts of infants Includes wound management
Hospital-based Outbreaks of Pertussis• Texas, 2004 (MMWR 2008;57:600)
11 newborns at a hospital develop pertussis after exposure to a nurse with the disease
• Washington, 2004 (ICHE 2007;28:537) 10 cases of pertussis among hospital staff, community
contacts; index cases were ED MD and RT• Kentucky, 2003 (ICHE 2006; 27:541) Pertussis in a 2 mth old preemie traced to a nurse in
intermediate care nursery 72 infant patients and 72 HCWs given prophylaxis
• Pennsylvania, 2003 (CID 2006;42:981) 17 symptomatic cases of pertussis among HCPs after 1
day exposure to infant with pertussis
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ACIP Recommendations for Use of Tdap in Health-care Personnel (HCP)
• HCP with direct patient contact in hospitals or ambulatory care settings should receive a single dose of Tdap as soon as feasible Priority for HCP with direct contact with infants Interval as short as 2 years since last Td is
recommended
• Other HCP should receive Tdap according to routine recommendations; interval as short as 2 years since last Td is encouraged
• Hospitals and ambulatory care facilities should provide Tdap for HCP and use approaches that maximize vaccination rates; education, convenience, no charge
Reference:1. CDC. MMWR. 2006;55(RR-17):1-44.
Outbreaks in Healthcare FacilitiesSetting Index Case Staff
CasesPatient Cases
Diagnostic Method Reference
Acute care hospital Infant, HCW 5 2 Culture, serology Kurt 1972
Acute care hospital HCW 15 2 ELISA, PCR Bassinet 2004
Nursery, NICU HCW 4 1 PCR, Serology, Culture MMWR 2005
Pediatric unit Infant 17 2 Culture, PCR, link MMWR 2005
Pediatric unit HCW 4 2 Culture, PCR, Serology MMWR 2005
Heme-Onc unit HCW 10 0 PCR Boulay 2006
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Pertussis in Healthcare Workers• Waning immunity
• Regular contact with infected patients Risk of infection 1.7- fold greater than general pop.
• Annual incidence of infection 2 – 8%
• Cost of outbreaks reported as $44–75K
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HCW Exposures to Pertussis
• Large quaternary pediatric care network
• Jan 1, 2002‐July 18, 2011
• 1193 confirmed HCW pertussis exposures
• 219 index cases
• 38.8% infants < 6 months of age
• 7 were HCWs ( 3.2%)
• 77.5% occurred in ED or ambulatory care site
Kuncio DE et al. Pediatrics 2014;133:15‐21.
HA Pertussis Outbreak- Arizona, 2011
• Index case: 4 week old female, 28 wk gestation• Admitted for apnea felt to be secondary to GE reflux
• Cough lasted 26 days, no isolation; sick sibling visited
• Pertussis identified upon transfer to another hospital; initial hospital had 10 HCPs who worked during cough illness
• 15 pertussis cases among 5 infants and 10 HCP in NICU
• Cost to hospital $97,745
Yasmin S et al. JPIDS 2014;3:81‐4.
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Pertussis Post-Exposure Prophylaxis
• Give antibiotics to close contacts and to persons at high risk for having severe pertussis
• Close contact of a symptomatic patient with pertussis Face-to-face exposure within 3 feet Direct contact with respiratory, oral, or nasal secretions Share a confined space in close proximity for ≥ 1 hour
• Persons at high risk for having severe disease Infants < 1 year of age Immunocompromised persons Persons with underlying medical conditions (e.g., chronic
lung disease, CF)
PEP for Vaccinated HCWs
NEW (2011):
April 2012:Vaccinated HCP still need PEP CID 2012;54(7):938–45Conclusions. Using the predefined definition of pertussis infection, noninferiority for preventing pertussis following exposure was not demonstrated for daily symptom monitoring of Tdap-vaccinated HCP without PEP when compared with antibiotic PEP. However, the small number of exposed HCP warrants further study of this approach.
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Tuberculosis
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Why Worry About TB?• Prevalence: 13.7 million people• Annual Incidence: 9.2 million• ~ 1.3 million deaths per year
TB: Clinical Syndromes
• Latent: Infected but progression halted
• Disease: Primary: Initial infection
progresses
Reactivation:• Pulmonary
• Extrapulmonary
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Latent TB Infection (LTBI) Pulmonary TB Disease
Inactive, contained tubercle bacilli in the body
Active, multiplying tubercle bacilli in the body
TST or blood test results usually positive
TST or blood test results usually positive
Chest x-ray usually normal Chest x-ray usually abnormal
Sputum smears and cultures negative
Sputum smears and cultures may be positive
No symptoms Symptoms such as cough, fever,
weight loss
Not infectious Often infectious before treatment
Primary Tuberculosis
Gohn Complex~ 90% do not disseminate
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Primary:• Traditionally
disease of childhood
• Now increasingly in adults
• Progressive 5%– Children
(meningitis, GI, bone)
– Adults (pulmonary)
Reactivation:•Long delay
•Change in T-cell immunity
•Cavitary - high inoculum
~ 5% of Primary Cases in Children Disseminate w/i 5 yrs.