Transcript Pediatric Pathogens and Impact on the Adult Population

Pediatric Pathogens and
Impact on the Adult
Population
APRIL KILGORE, MD, FAAP
ASSISTANT PROFESSOR OF PEDIATRICS
PEDIATRIC INFECTIOUS DISEASE
MARSHALL UNIVERSITY SCHOOL OF MEDICINE
Disclosure

My presentation does not include discussion of
any commercial products or services

I will not be discussing investigational products
or unlabeled uses

I have no financial interests or relationships with
manufacturers or commercial products
Objectives



Participants will understand the changing
epidemiology of childhood infectious disease
including Respiratory syncytial virus (RSV), Human
metapneumovirus (hMPV), and Bordatella pertussis
Participants will recognize the impact of these
diseases on the adult population and the
implications for clinical care/management
Participants will know the infection control related
issues for patients in the hospital/chronic care
setting
Respiratory Syncytial Virus
Background
Respiratory syncytial virus (RSV) first discovered
in 1956 as respiratory pathogen in chimpanzees
 1957 identified as cause of epidemic
bronchiolitis in infants
 Long believed to be primarily a pediatric
pathogen, however increasingly recognized as
important pathogen in adults
 Evidence indicates second to influenza as cause
of serious viral respiratory disease in adults

Virology




RNA virus of the family Paramyxoviridae
Viral structure consists of a nucleocapsid core
surrounded by lipid layer
3 glycoproteins embedded in
lipid layer: G, F, SH
Human RSV classified two major
groups, A and B

Each contain subgroups based
on antigenic differences in G protein
Virion varies in size and shape 120-300nm
http://phil.cdc.gov/PHIL_Images/092020
02/00006/PHIL_2175_lores.jpg
Epidemiology
Yearly epidemics of
respiratory illnesses during
winter months in
temperate climates
 Epidemic curve usually
broader than influenza
with longer periods of
activity
 Primary infection almost
universal by 2 years of
age

http://www.cdc.gov/surveillance/nrevss/rsv/natltrend.html
Epidemiology: CommunityDwelling Adults

Early estimates limited by diagnostic tools

Reverse transcriptase polymerase chain
reaction (RT-PCR) has allowed more accurate
estimates of disease

Zambon et al examined adults > 45 years visiting
GP during winter for respiratory illness
 RSV
identified in 10-22% of subjects
 Influenza
identified in 13-42%
Epidemiology: CommunityDwelling Adults
2001 prospective study Rochester, NY of elderly
and high risk adults over 4 winter seasons 6
 RSV infection confirmed in 3-7% of healthy
elderly enrollees & 4-10% of high risk adults
(chronic cardiopulmonary conditions)

 89%
were symptomatic
 Illness in 17-29% prompted office visits
 Among high risk patients, 9% visited the ED, 16% were
hospitalized and 4% died
Epidemiology: Adults and
Hospitalizations

2007 study examined hospitalizations for
influenza and RSV among adult population in
large HMO14
 Indirect
measure utilizing discharge diagnosis and
ICD-9 codes for “pneumonia and influenza”
Influenza and RSV associated hospitalization rates per 10,000 person-periods
Risk Group
Age (years)
Viral period
Pneumonia and Influenza
Low
65+
Any Flu
18.7 (10.2-27.1)
Low
65+
RSV only
5.1 (0.7-9.5)
High
65+
Any Flu
55.6 (41-70.2)
High
65+
RSV only
23.4 (13.9-32.9)
Adapted from Mullooly et al. Influenza and RSV associated hospitalizations among adults. Vaccine 2007;25:846-855
Epidemiology: Community
Acquired Pneumonia


Estimates of RSV contribution vary widely
Falsey et al. conducted large study of hospitalized adults
with pneumonia




Utilized RT-PCR for diagnosis
RSV identified in 4.4% of cases
3rd most common identified pathogen after S. penumoniae (6%) ,
and Influenza (5%)
Composite data from the past 30 years indicate RSV
accounts for


2-5% OF CAP throughout the year
5-15% during winter months
Epidemiology: Long-Term Care
Facilities




First outbreaks in nursing homes in 1970s
Surveillance studies estimate5

Infection rates 1-18%

Pneumonia rates 0-33%

Death 0-5% of those infected
Clustering of cases suggests nosocomial spread by
healthcare workers
Other closed populations at risk- senior day care centers 7

10% of acute respiratory tract infections in participants

5% of day care staff
Clinical Manifestations: Adults

No clinically distinct illness in adults

Characterized by nasal congestion and cough

Ranges from mild URI to severe respiratory disease
Relative Frequencies of Symptoms with RSV and Influenza
Symptom
RSV
Influenza
Rhinorrhea
++++
++
Wheezing
++++
++
Dyspnea
+++
++
Sputum production
+++
++
Fever
+
++++
Myalgias
+
++++
GI symptoms
0
++
Adapted from
Falsey, Ann.
Respiratory Syncytial
Virus infection in
Adults. Seminars in
Respiratory and
Critical Care
Medicine;
28(2)2007:171-181
Diagnosis


Diagnosis on clinical grounds difficult in adults
Four methods diagnosis

Viral culture




Sensitivity 20-45%
Enzyme immune assay (rapid tests)

Sensitivity 50-90%

Varies on prevalence of RSV in community
RT-PCR

Most sensitive and specific method available

Detects 30% more infections than viral isolation techniques
Serology

Limited by pre-existing antibodies and need for acute and convalescent
Treatment

Symptomatic supportive care

Fluids, oxygen, and antipyretics mainstay of
care

No FDA approved anti-viral medications for
adults

Published reports of ribiviran use in elderly
patients with severe disease
Infection Control
From Tang J, Nicolle A, Pantelic J, Jiang M, Sekhr C,
Cheong D, Tham K (2011). "Qualitative Real-Time
Schlieren and Shadowgraph Imaging of Human
Exhaled Airflows: An Aid to Aerosol Infection Control
Infection Control
Viral shedding in infants up to 21 days
 Shedding in young adults averages 3-6 days
with range 1-12 days
 Shedding in older adults not well studied

 Presumably
shorter in healthy adults
 Longer in patients with COPD

Spread via contact with contaminated
secretions via large droplets or fomites
 Can
survive on surfaces for many hours
Infection Control

Infection control practices1,20





Hand washing key to prevention
Contact isolation with use of gown and gloves recommended
Mask use per standard precautions
Patients with known infection single room or cohorted
HAI1,20

During community outbreaks can consider

Screening of symptomatic patients

Cohorting of infected patients and staff

Excluding visitors with current or recent respiratory tract infections

Excluding staff with respiratory tract illness from caring for susceptible
patients

Emphasizing contact precautions and hand hygiene

Limiting sibling visitation
Infection Control

When can they come out of isolation?
 Immunocompromised
adult and pediatric patients
 Official
guidelines warn of extended shedding but give no
duration recommendations
 What

have we done to address this?
If prolonged hospitalization and primary team wishes to
discontinue PCR, isolation can be discontinued when patient has
been asymptomatic for at least 5 days AND respiratory PCR is
negative
Human Metapneumovirus (hMPV)
Background




2001 first described as respiratory pathogen by van
den Hoogen and colleagues in the Netherlands
Identified in specimens collected over a 20 year
period from patients with respiratory tract disease
during the winter months
The then unidentified isolates caused cytopathic
effects largely indistinguishable from RSV
Serologic studies show high rate of antibodies in
populations worldwide and evidence circulating
dating back to 1958
Virology

RNA virus of the Paramyxoviridae family with
lipid bilayer envelope of host cell origin

Genetically related to avian pneumovirus (AVP)
aka turkey rhinotracheitis virus
 Causes
URI in turkeys and other avian species
 Suggestive
of origination from bird species
Epidemiology

Predominantly in winter
months in temperate
climates

May exhibit yearly variation

2 Major genotypes that
often co-circulate

Almost all children infected
by 5 years of age

Older age at primary
infection than RSV
http://www.cdc.gov/surveillance/nrevss/hmpv/natltrend.html
Epidemiology: CommunityDwelling Adults




Less well studied than epidemiology of RSV
Estimates of symptomatic infection generally < 5%8
2001 study in the Netherlands hMPV infection rate
3% in adults with symptomatic respiratory illnesses16
2003 two year prospective study in Rochester NY9
Cohorts of young and older adults studied
 4.5% of illnesses associated with hMPV infection
 Significant yearly variation with rates of 1.5% and 7% during
years 1 and 2 of the study period respectively
 High risk adults had more severe disease and more
hospitalizations

Epidemiology: Long Term Care
Facilities

Multiple reports in the literature of outbreaks

June-July 2006 outbreak in Sacramento
California in 148 bed facility13
 26
residents and 13 staff with acute respiratory illness
 31%
ill residents developed pneumonia and 5 %
hospitalized
 RT-PCR
confirmed hMPV in 5 of 14 specimens and no
other cause identified
Epidemiology: Long Term Care
Facilities

January-February 2006 outbreak of severe disease
in facility in Canada 2
27% of residents developed respiratory or constitutional
symptoms
 Attack rate on most affected ward 72%
 Fatality rate 50% among confirmed cases (3/6) and 9.4%
among possible cases (9/96)


Spring Summer 2011 outbreak in facility in Oregon11
Attack rate 36% among residents
 3 health care workers affected
 Fatality rate of confirmed and possible cases 31%

Clinical Manifestations

Vary based on age and health status

Clinical symptoms indistinct from other viral
respiratory infections

Patients requiring hospitalization typically elderly
with chronic cardiac or lung disease
Clinical characteristics of young versus older adults with hMPV
Clinical Feature
Elderly (n=13)
Young (n=11)
Hoarseness
46%
91%
Dyspnea
69%
9%
Wheezing
62%
9%
Length of stay
17.4 ± 9.4
8.5 ± 3.4
Adapted from Falsey, Ann et al.
Human metapneumovirus
infections in young and elderly
adults.
JID 2003;187(1-March):785-790
Clinical Manifestations

Evidence of role in COPD exacerbations,
pneumonia in immunosuppressed patients, and
severe illness with ARDS

Most common diagnoses of patients admitted
with hMPV are exacerbation of COPD, bronchitis,
and pneumonia8
Diagnosis

Serology


Viral culture


Difficult to perform and can take up to three weeks to see
cytopathic effects
Immunofluorescence



Limited by pre-existing antibodies and need for acute and
convalescent testing
Rapid testing available
Sensitivity approaches that of RT-PCR
RT-PCR

Testing modality with greatest sensitivity and specificity
Treatment

Symptomatic supportive care

Fluids, oxygen, and antipyretics mainstay of
care

No FDA approved anti-viral medications

Susceptible in vitro to Ribavirin but no controlled
clinical data to assess benefit
Infection Control

Route of transmission not established
Likely similar to RSV since closely related and similar epidemiology
 Infection probably through direct or close contact with
contaminated secretions


Infection control practices1,20
Contact precautions for duration of illness
 Masks according to standard precautions
 Patients with known infection single room or cohorted


HAI
Problematic as symptoms in staff and patients may be mild
 Emphasis on hand hygiene and adherence to contact precautions

Bordatella pertussis
Background
“The lung is so irritated that, in its attempt by every effort to cast forth the
cause of the trouble, it can neither admit breath nor easily give it forth again.
The sick person seems to swell up, and, as if about to strangle, holds his
breath clinging in the midst of his jaws. …”
DeBaillou describing the first
documented whooping cough
epidemic in 1578



In 1679 Syndenham named the illness pertussis
which means violent cough
In 1900 Bordet and Gengou discovered the
organism which causes whooping cough and by
1906 they had developed media to support culture
and detailed morphology and virulence
Pertussis is caused by a fastidious, strictly aerobic
gram negative coccobacillus
Epidemiology





Humans are the only known hosts of B. pertussis
Transmission occurs by close contact with cases via
aerosolized droplets
Cases occur year round with peaks in late
summer/autumn
In immune-naïve population, it is estimated a
primary case will result in 17 secondary cases18
In households up to 80% of immunized contacts of
symptomatic cases acquire infection 4

Mild or unrecognized atypical disease to classic pertussis
Epidemiology





Prior to routine vaccination large burden of disease and
high mortality rates in infants
The first whole-cell vaccine introduced in 1940s
Very successful and resulted in tremendous decrease in
disease incidence
In pre-vaccine era, natural infection(s) resulted in
boosted immune response
Since routine vaccination and reduction in natural
disease, now see waning immunity over time



Result is increase in cases in people > 10 years of age
Waning maternal immunity and transplacental antibody
Increase in pertussis in very young infants
Epidemiology

Currently approximately 50% of cases reported are in adults and
adolescents4





Reservoir of infection for infants who are unimmunized or partially
immunized
Based on epidemiologic studies, most infants infected by adolescents or
adults in the household
Highest rates of mortality among infants and elderly4,17
Case fatality rates approximately 1% in infants < 2 months and
<0.5% in infants 2-11 months17
Recent studies have highlighted risk in elderly17


Older patients with longer hospitalizations for pertussis
Although pertussis related deaths rare in adults, most in persons > 50 years
of age and majority > 65
Clinical Manifestations: 3 Stages
Classic Disease

Catarrhal
Nonspecific sings and symptoms following 7-10 day incubation period
 Often mistaken for viral URI


Paryoxysmal
Typically starts second week of illness
 Hallmark coughing spells
 Cough paroxysm
low lung volumes
 Post-tussive emesis and syncope reported


vigorous inspiration
Convalescent
Slow transition after 2-3 months of paroxysmal stage
 Persistent cough that is less frequent and less severe

Clinical Manifestations

Adults and adolescents with prior
infection/immunization highly variable
presentation
 Often
mild and atypical
 Most common symptom is a persistent cough
 Frequently pertussis not suspected by clinician and
therefore not diagnosed
 Pertussis estimated to be the cause in 12-32% of
adolescents and adults with prolonged cough (> 3
weeks)4
Laboratory Diagnosis



Culture

B. pertussis fastidious and requires special culture media resulting in false
negatives

Delay in transport and plating, as well as duration of illness at time of
collection, and prior antibiotics contribute to high rate false negatives

Sensitivity only 30-60%
PCR

Able to detect small number of organisms

Unaffected by prior antibiotics

Used more frequently due to better sensitivity and specificity
Challenges in testing

Must obtain specimen from ciliated respiratory epithelium of posterior
nasopharynx

Cotton swabs toxic to organism and calcium alginate interfere with PCR, so
dacron swabs preferred
Treatment
If considering testing then should also consider
treating
 Treatment during catarrhal phase may decrease
duration of illness
 Treatment at later stages does not affect
duration of illness but reduces shedding and
spread
 Macrolides preferred and usually eradicate B.
pertussis in 5 days

Infection Control Considerations


Untreated may remain contagious for > 1 month
Post exposure prophylaxis 1

Household and close contacts
If unimmunized or under immunized: age appropriate vaccine and
chemoprophylaxis
 If immunized but in household with high risk individual :
chemoprophylaxis
 Monitor closely for symptoms 21 days after last contact and evaluate
and treat when appropriate


Child care
Prophylaxis for household and close contacts
 Providers and exposed children observed for 21 days after last contact
 Children and providers with confirmed pertussis excluded until
completed 5 days of antimicrobial therapy or 21 days if untreated

Infection Control Considerations

Post exposure prophylaxis1
 Schools
 Students
and staff with pertussis excluded until completed 5
days antimicrobial therapy or 21 days from onset of
symptoms if untreated
 Immunization
given
 Consider
status reviewed and age appropriate vaccines
excluding persons with cough illness pending eval
by physician
Infection Control Considerations

Post exposure prophylaxis1
 Health
 Tdap
Care Settings
may not preclude need for antimicrobial prophylaxis
 Antimicrobial
prophylaxis recommended for ALL health care workers
(HCW) regardless of immunization status who have unprotected
exposure to pertussis AND are likely to have contact with high risk patient
 Other
HCW should receive antimicrobial prophylaxis or be monitored for
21 days and treated at first sign symptoms
 Patients
and caregivers who are close contacts or high risk contacts of
patient or HCW with pertussis should receive antimicrobial prophylaxis
and if appropriate, vaccination
 HCW
with suspected pertussis or cough illness within 21 days of exposure
should be excluded pending 5 days of antimicrobial therapy or 21 days if
refuse treatment
Infection Control Considerations

Isolation1,20
 Droplet
precautions for until patient has completed 5
days of effective therapy
 If
appropriate therapy not given then droplet
precautions until 3 weeks after onset of cough
Measles
Background
Recorded epidemics of measles date back to
the 10th century
 Repeated epidemics have occurred throughout
the ages in Europe, Asian, and ultimately
America
 The first live attenuated measles vaccine
licensed for use in 1963
 2001 Measles declared eradicated from the US
with the only cases imported

Virology

Large RNA virus of the family
Paramyxoviridae

Virion composed of outer lipoprotein
envelope and internal nucleocapsid

Labile and inactivated rapidly by
heat, UV light, and lipid solvents
•Photo Credit: Cynthia S. Goldsmith
•Content Providers(s): CDC/ Courtesy of Cynthi
S. Goldsmith; William Bellini, Ph.D.
Epidemiology




Although declared eradicated in
2001, importation of cases
continues15
From 2001-2012 median number of
cases annually in US was 60
This year to date 159 cases have
been reported in 16 states
82% cases unimmunized and 9%
unknown immunization status

Of those unimmunized, 79% had
philosophical objections and 13% were
infants too young to be immunized
http://www.cdc.gov/mmwr/preview/mm
wrhtml/mm6236a2.htm#fig2
Epidemiology

2013 outbreaks15
 11%
required hospitalization
4
patients diagnosed with
pneumonia
 No
deaths reported
 Source
of outbreaks
continues to be WHO
European Region
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm
6236a2.htm#fig2
Clinical Manifestations

Prodrome
Onset characterized by fever, cough, coryza, conjunctivitis
 Koplik spots, bluish white spots on bright red mucosal
surface, usually appear on approximately day 10 and are
pathognomonic


Exanthem stage
Characteristic rash appears on day 14 after exposure
 Rash starts on hairline and spreads from head to feet in
centrifugal manner
 Exanthem begins to clear on day 3-4 of rash and typically
lasts 6-7 days

Clinical Manifestations:
Complications



Pneumonia10

Very common and reported in 50-75%

Young infants have clinical picture of bronchiolitis

Clinical course can progress to severe pulmonary disease and ARDS
Encephalitis10

0.5 to 1 per 1000 cases

20-40% of patients with encephalitis have evidence of brain damage
Subacute Sclerosing Panencephalitis (SSPE)10

Rare, incidence in pre-vaccine era after infection with wild type measles 1 case per 100,000
population

Stage 1 progressive psychointellectual disturbances

Stage 2 convulsive and motor disorders

Stage 3 pre-terminal stage with rapid decrease in cortical activity ultimately progression to
vegetative state

Progression over months to years
Laboratory Diagnosis

Viral culture

PCR
 Can

be performed on throat swab specimens
Serology
 Acute
and convalescent titers
 Single
positive IgM suggests diagnosis
Treatment
Supportive care for typical measles
 Vitamin A supplements recommended in certain
situations 1,10

 Reduced
morbidity in Vitamin A deficient children
 Enhanced IgG and total lymphocyte numbers
 Children 6 months to 2 years who require
hospitalization
 Children > 6 months with suspected vitamin A
deficiency
Infection Control Considerations






Transmitted by direct contact with infectious droplets or
airborne spread
Airborne transmission precautions indicated for 4 days
after onset of rash in healthy children and duration of
illness in immunosuppressed 1,20
Negative airflow room with 6-12 changes per hour
Susceptible HCW should not enter patient rooms
If susceptible persons must enter then N-95 mask should
be worn
People with documented immunity do not need to wear
a mask
Infection Control Considerations
Vaccination recommended for all people who
work or volunteer at health care facilities and
who may be in contact with patients with
measles1
 Adequate evidence of immunity 1

 Documentation
of 2 doses live-virus measles vaccine
 Laboratory evidence of immunity or confirmation of
disease
 Birth before 1957
References
1.
2.
3.
4.
5.
6.
7.
American Academy of Pediatrics. RedBook: The report of the committee on
infectious diseases 2012
Boivin, G. et al. An outbreak of severe respiratory tract infection due to human
metapneumovirus in a long-term care facility. CID 2007;44(1-May): 1152-1158
Caram et al. Respiratory Syncytial Virus outbreak in a long-term care facility
detected using reverse transcriptase polymerase chain reaction: an argument for
real-time detection methods. J Am Geriatric Soc 2009;57:482-485
Cornia, P et al. Does this coughing adolescent or adult patient have pertussis?
JAMA 2010;304(8):890-896
Falsey, Ann. Respiratory Syncytial Virus infection in Adults. Seminars in Respiratory
and Critical Care Medicine; 28(2)2007:171-181
Falsey AR. Et al. Respiratory syncytial virus infection in elderly and high-risk adults.
N Engl J Med 2005;28:1749-1759
Falsey AR et al. Acute respiratory tract infection in daycare centers for older
persons. J Am Geriatr Soc 1995;45:30-36
References
8.
9.
10.
11.
12.
13.
14.
15.
Falsey, Ann. Human metapneumovirus infection in adults. The Pediatric Infectious
Disease Journal 2008;27(10):s80-s83
Falsey, Ann et al. Human metapneumovirus infections in young and elderly adults. JID
2003;187(1-March):785-790
Feigan and Cherry’s Textbook of Pediatric Infectious Diseases 6th edition. Saunders
Elsevier Philadelphia PA 2009
Liao, R. et al. An outbreak of severe respiratory tract infection due to human
metapneumovirus in a long-term care facility for the elderly in Oregon. Journal of
Clinical Virology 2012;53:171-173
Liss, HP, Bernstein, J. Ribavirin aerosol in the elderly. Chest 1998;93:1239-1241
Louie, J. et al. A summer outbreak of human metapneumovirus infection in a longterm-care facility. JID 2007;196(1-September):705-708
Mullooly et al. Influenza and RSV associated hospitalizations among adults. Vaccine
2007;25:846-855
MMWR. Centers for Disease Control and Prevention. September 13, 2013 / 62(36);741743
References
16.
17.
18.
19.
20.
21.
Osterhaus A, Fouchier R. Human metapneumovirus in the community. Lancet
2003;111:1407-1410
Ridda, I. et al. The importance of pertussis in older adults: A growing case for
reviewing vaccination strategy in the elderly. Vaccine 2012; 30: 6745-6752
Schellekens, J. Et al. Pertussis sources of infection and routes of transmission in
the vaccination era. Pediatr Infect Dis J 2005;24: S19-S24
Senzilet, L et al. Pertussis is a frequent cause of prolonged cough illness in
adults and adolescents. CID 2001;32(15 June): 1691-1697
Siegel, J et al. 2007 guideline for isolation precautions: preventing transmission
of infectious agents in healthcare settings. The Healthcare Infection Control
Practices Advisory Committee
Zambon et al. Contribution of influenza and respiratory syncytial virus to
community cases of influenza-like illness: an observational study. Lancet
2001;358:1410-1416