1. Pediatric Pathogens and Impact on the Adult Population
April Kilgore, MD, FAAP
Assistant Professor of Pediatrics
Pediatric Infectious Disease
Marshall University School of Medicine

2. 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

3. 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

4. Respiratory Syncytial Virus

5. 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

6. 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 nm

7. 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

8. Epidemiology: Community-Dwelling 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%

9. Epidemiology: Community-Dwelling 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

10. 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 ( )
RSV only
5.1 ( )
High
55.6 ( )
23.4 ( )
Adapted from Mullooly et al. Influenza and RSV associated hospitalizations among adults. Vaccine 2007;25:

11. 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

12. 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

13. 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
Adapted from Falsey, Ann. Respiratory Syncytial Virus infection in Adults. Seminars in Respiratory and Critical Care Medicine; 28(2)2007:

14. 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

15. 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

16. 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

17. 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

18. Infection Control Infection control practices1,20 HAI1,20
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

19. 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

20. Human Metapneumovirus (hMPV)

21. 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

22. 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

23. 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

24. Epidemiology: Community-Dwelling 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

25. 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

26. 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%

27. 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%
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):

28. 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

29. Diagnosis Serology Viral culture Immunofluorescence RT-PCR
Limited by pre-existing antibodies and need for acute and convalescent testing
Viral culture
Difficult to perform and can take up to three weeks to see cytopathic effects
Immunofluorescence
Rapid testing available
Sensitivity approaches that of RT-PCR
RT-PCR
Testing modality with greatest sensitivity and specificity

30. 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

31. 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

32. Bordatella pertussis

33. 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 they had developed media to support culture and detailed morphology and virulence
Pertussis is caused by a fastidious, strictly aerobic gram negative coccobacillus

34. 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

35. 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

36. 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

37. 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 vigorous inspiration
Post-tussive emesis and syncope reported
Convalescent
Slow transition after 2-3 months of paroxysmal stage
Persistent cough that is less frequent and less severe

38. 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

39. Laboratory Diagnosis Culture PCR Challenges in testing
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

40. 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

41. 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

42. 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 status reviewed and age appropriate vaccines given
Consider excluding persons with cough illness pending eval by physician

43. Infection Control Considerations
Post exposure prophylaxis1
Health Care Settings
Tdap 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

44. 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

45. Measles

46. 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

47. 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 Cynthia S. Goldsmith; William Bellini, Ph.D.

48. Epidemiology
Although declared eradicated in 2001, importation of cases continues15
From 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

49. Epidemiology 2013 outbreaks15 11% required hospitalization
4 patients diagnosed with pneumonia
No deaths reported
Source of outbreaks continues to be WHO European Region

50. 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

51. 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

52. Laboratory Diagnosis Viral culture PCR Serology
Can be performed on throat swab specimens
Serology
Acute and convalescent titers
Single positive IgM suggests diagnosis

53. 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

54. 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

55. 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

56. References
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):
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:
Cornia, P et al. Does this coughing adolescent or adult patient have pertussis? JAMA 2010;304(8):
Falsey, Ann. Respiratory Syncytial Virus infection in Adults. Seminars in Respiratory and Critical Care Medicine; 28(2)2007:
Falsey AR. Et al. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med 2005;28:
Falsey AR et al. Acute respiratory tract infection in daycare centers for older persons. J Am Geriatr Soc 1995;45:30-36

57. References
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):
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:
Liss, HP, Bernstein, J. Ribavirin aerosol in the elderly. Chest 1998;93:
Louie, J. et al. A summer outbreak of human metapneumovirus infection in a long- term-care facility. JID 2007;196(1-September):
Mullooly et al. Influenza and RSV associated hospitalizations among adults. Vaccine 2007;25:
MMWR. Centers for Disease Control and Prevention. September 13, 2013 / 62(36);

58. References
Osterhaus A, Fouchier R. Human metapneumovirus in the community. Lancet 2003;111:
Ridda, I. et al. The importance of pertussis in older adults: A growing case for reviewing vaccination strategy in the elderly. Vaccine 2012; 30:
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):
Siegel, J et al 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: