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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

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Pediatric Pathogens and Impact on the Adult Population

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  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 120-300nm http://phil.cdc.gov/PHIL_Images/09202002/00006/PHIL_2175_lores.jpg

  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 http://www.cdc.gov/surveillance/nrevss/rsv/natl-trend.html

  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” Adapted from Mullooly et al. Influenza and RSV associated hospitalizations among adults. Vaccine 2007;25:846-855

  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 Adapted from Falsey, Ann. Respiratory Syncytial Virus infection in Adults. Seminars in Respiratory and Critical Care Medicine; 28(2)2007:171-181

  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 antibodiesand 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 • 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 http://www.cdc.gov/surveillance/nrevss/hmpv/natl-trend.html

  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 Adapted from Falsey, Ann et al. Human metapneumovirus infections in young and elderly adults. JID 2003;187(1-March):785-790

  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 • 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 1906 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 • 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 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/mmwrhtml/mm6236a2.htm#fig2

  49. 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/mm6236a2.htm#fig2

  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

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