At the end of this session, participants will be able to:

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Advanced Concepts in Pediatric Tuberculosis: Infection Control, Source Case and Contact Investigation Ana M. Alvarez, M.D. Associate Professor Division of Pediatric Infectious Diseases and Immunology University of Florida College of Medicine/Jacksonville Objectives At the end of this session, participants will be able to: Compare contagiousness of children of different ages with pulmonary TB, and apply this to planning investigations Discuss importance and indications for source case investigation Plan evaluation for contacts of patients with various forms of TB disease Discuss infection control guidelines for a child hospitalized with TB disease 1

Key Terms Case A particular patient with TB disease. All TB cases are reportable. Contact (AKA: Exposed person) Someone who has been exposed to M. tuberculosis by sharing air space with a person with infectious TB. Index case The first case or patient who comes to attention as indicator of a potential public health problem. Source case The case or person who was the original source of infection for secondary cases or contacts; can be, but is not necessarily, the index case. Case 2

Index Case 2 y/o AA male presented to ER with 8 day history of fever and cough. He was diagnosed with pneumonia and was prescribed amoxicillin. After 5 days, his fever was not better, so he was admitted to the hospital for IV antibiotics. He was started on ceftriaxone, and then vancomycin was added. However, fever persisted. PMH: no significant illness, no surgeries or hospitalizations Index Case Family/Social history: lives with mother and 2 older siblings. Has attended a Daycare Center since the age of 7 months. No travel history, no history of contacts with adults with HIV, IVDU, homeless, incarcerated. Physical exam was normal, with the exception of Tmax of 41 degrees. 3

4

Index Case TST was placed and read as 10 mm of induration Gastric aspirates x 3 were sent Patient was started on INH, Rif, and PZA, and fever resolved after 3 days. He was discharged home to continue meds under DOT. Gastric aspirate cultures were negative Case 2y/o AA male with a clinical case of pulmonary TB. What would you do next? a. Obtain biopsy of hilar lymph nodes to confirm TB. b. Since patient is responding to anti-tb therapy, just complete 6 months of therapy c. Plan and conduct a contact investigation d. Plan and conduct a source-case investigation 5

Source-Case Investigations Source-case Investigations Seeks the source of recent M.tuberculosis infection TB in children <5 years of age typically indicates recent transmission. Young children usually do not transmit TB to others. The source-case is usually an adult/adolescent care-giver. A source-case investigation should be considered for children <5 y/o (especially <2) with TB. 6

Importance of Source-case Investigations Public health measure Identify the individual who infected the child, who is probably transmitting TB to others Diagnostic measure Isolating the organism from the source case provides likely drug susceptibility of the child s organism Yield is higher than yield of diagnostic microbiology in children Source-case Investigation for Child with LTBI Search for source of infection for child with LTBI is not likely to be productive and cost-efficient Recommended only with infected children <2 years of age, and only if data are monitored to determine the value of the investigation Relative recent transmission! 7

Procedures for Source-Case Investigation Same procedure as standard contact investigation Patient or guardians best informants (associates) Focus on associates who have symptoms of TB disease Should begin with closest associates, and expand if appropriate Back to our case Source case investigation was conducted All household tested negative (TST) Investigation was expanded to the Daycare Center (DCC) 3 DCC staff had +TST, but negative CXR One DCC worker had neg TST, but history of chronic cough, and was eventually diagnosed with Pulmonary TB (cavitary, smear positive) This was the source case! What next? 8

Contact Investigations A Crucial Prevention Strategy On average, 10 contacts are identified for each person with infectious TB in the U.S. 20% 30% of all contacts have LTBI 1% of contacts have TB disease Of contacts who will ultimately have TB disease, approximately 50% develop disease in the first year after exposure 5 Benefits of Contact Investigations Finding and treating additional TB disease cases (potentially interrupting further transmission) Finding and treating persons with LTBI to avert future cases 9

Importance of Contact Investigation How are pediatric cases discovered? Active Contact investigation: 25-80% Screening of high risk groups: 3-35% Passive Symptomatic children: 15-45% Contact Investigation Responsibilities Health departments are responsible for conducting contact investigations Contact investigations are complicated activities that require Many interdependent decisions Time-consuming interventions 10

Decisions to Initiate a Contact Investigation Public health officials must decide which Contact investigations should be assigned a higher priority Contacts to evaluate first Decision to investigate an index patient depends on presence of factors used to predict likelihood of transmission Factors that Predict Likely Transmission of TB Anatomical site of the disease Positive sputum bacteriology Radiographic findings (cavitation) Behaviors/procedures that increase aerosolization of respiratory secretions Age HIV status Administration of effective treatment 11

Characteristics of the Index Patient Associated with Increased Risk of TB Transmission Pulmonary, laryngeal, or pleural TB Acid-fast bacilli (AFB) positive sputum smear Cavitation on CXR Adolescent or adult patient No or ineffective treatment of TB disease Determining the Infectious Period Sets time frame for testing contacts most likely to be at risk for infection Information to assist with determining infectious period Approximate dates TB symptoms were noticed Bacteriologic results Extent of disease Start is 3 months before TB diagnosis (recommended) Earlier start should be used in certain circumstances (e.g., patient aware of illness for longer period of time) 12

Assigning Priorities to Contacts Priorities based on likelihood of infection and hazards to the contact if infected Factors for Assigning Contact Priorities Characteristics of the index/source patient Characteristics of contacts Age Immune status Other medical conditions Exposure Patient has pulmonary, laryngeal, or pleural TB with cavitary lesion on chest radiograph or is AFB sputum smear positive Household contact High Contact <5 years of age High Contact with medical risk factor (HIV or other medical risk High factor) Contact with exposure during medical procedure High (bronchoscopy, sputum induction, or autopsy) Contact in a congregate setting High Contact exceeds duration/environment limits (limits per unit High time established by the health department for high-priority contacts) Contact is 5 years and 15 years of age Contact exceeds duration/environment limits (limits per unit time established by the health department for medium-priority contacts) Any contact not classified as high or medium priority is assigned a low priority. Medium Medium 13

Back to our case A full scale Contact Investigation was conducted 52 children exposed within the previous 3 months were identified and tested (ROS, Physical exam, TST and CXR) 24 children had + TST 5 children were diagnosed with Pulmonary TB (1 with meningitis) 18 children had LTBI 28 children had TST and - CXR <5y/o started on window prophylaxis 2 more children had +TST after 10 weeks (re-test) Day Care Settings: High Priority for Contact Investigation Children < 5 years of age Prolonged exposure Close contact Depending on the size of the daycare center Crowding Poor ventilation 14

General Population vs Day Care Setting On average, 10 contacts are identified for each person with infectious TB in the U.S. 52 exposed children identified 20% 30% of all contacts have LTBI 38% of children had LTBI 1% of contacts have TB disease, half of them in the first year after exposure 12% of children developed TB disease All of them developed it within 6 months Evaluation of contacts Testing for TB Infection All high or medium priority contacts who do not have a documented previous positive TST/IGRA or previous TB disease should receive a TST or IGRA at the initial encounter TST interpretation 5 mm induration is positive for any contact If TST/IGRA negative Repeat same test in 8-10 weeks (window period) If second TST is positive after initial negative Contact is classified as recently infected 15

Evaluation of contacts Medical Evaluation All contacts with positive TST/IGRA or who report any symptoms consistent with TB disease should undergo further examination and testing for TB disease History & Physical CXR Other tests as indicated Window-Period Prophylaxis Decision to treat contacts with a negative TST/IGRA should take the following factors into consideration The frequency, duration, and intensity of exposure Risk factors for TB disease Age of the contacts Medical conditions 16

Management of Contacts Younger than 5 years of age Evaluation TST CXR Review of symptoms and physical exam (PE) Primary prophylaxis ( window ) If TST, CXR, and PE are neg, start INH until repeat TST in 8-10 weeks If repeat TST is neg, stop INH If repeat TST is pos, treat as LTBI Prophylactic Treatment Prophylactic treatment (after TB disease is excluded) of presumed M. tuberculosis infection recommended for persons With HIV infection Taking immunosuppressive therapy for organ transplant Taking anti-tumor necrosis factor alpha (TNF-α) agents Since LTBI cannot be excluded, these contacts should be treated with 9 months of INH 17

A story that never ends Seven months later, a high school student with no risk factors was diagnosed with Pulmonary TB (cavitary, smear positive). Where did he get it from? Grandson of a friend of the CCC source case, with occasional contact with her before her diagnosis Had not been identified as a contact in the previous investigation MTB isolate was genotypically identical to source case. A story that never ends Contact investigation conducted at the High School Initial: 197contacts identified (same classrooms, sports teammates, bus-riders) 1 st TST: 16+ (8%) 2 nd TST: 18+ /103 (17%) Expanded: 206 additional contacts TST: 8+ (4%) None with TB disease 18

Determining When to Expand a Contact Investigation Consideration of the following factors recommended Extent of recent transmission Unexpectedly large rate of infection or TB disease in high-priority contacts Evidence of second-generation transmission TB disease in any contacts who had been assigned low priority Infection in any contacts aged <5 years Contacts with change in skin test status from negative to positive A story that never ends It keeps going, and going One month later, a 7 m/o old male, cousin of the high school student, was diagnosed with Pulmonary TB He was identified as a contact, and had been evaluated by PCP Asymptomatic, TST negative No CXR, no further intervention A month later, presented with fever, wheezing and productive cough CXR with right hilar adenopathy and RUL infiltrate Gastric aspirates smear and cx - POSITIVE 19

And it keeps going, and going This baby attended a small Child Care Center Because of extensive disease, significant cough, and + smear, and anxiety, a Contact Investigation was conducted at the CCC 4 workers 8 infants All evaluations were negative Why not contact investigations in young children? Transmission Airborne infection Inhalation of droplet nuclei produced by an adult or adolescent with pulmonary or laryngeal TB Infectiousness correlates with the number of organisms expelled 20

Why not contact investigations in young children? Very low yield! Most children with TB are not contagious because compared to adults they are less likely to Have a productive cough Generate force to aerosolize the organisms Have large numbers of organisms Children with extrapulmonary TB are not infectious unless disease of larynx or open abscesses/lesions When to consider contact investigations in children Transmission of TB from children can occur, but usually due to exceptional circumstances Adult-type disease: cavitary, extensive upper lobe disease Procedures creating aerosolization of bacilli Bronchoscopy Induced sputum By the way, gastric aspirates are NOT associated with transmission! 21

Infection Control Recommendations for Preventing M. tuberculosis Transmission in Health-Care Settings 22

Fundamentals of Infection Control Administrative Controls Environmental Controls Respiratory Protection Fundamentals of Infection Control Administrative controls: reduce risk of exposure via effective IC program Assign responsibility for IC in the facility Conduct annual facility risk assessment by examining Institute IC plan to ensure TB suspects found, isolated, evaluated, treated Ensure recommended laboratory services are available For HCWs, implement effective work practices and test as classification indicates Ensure equipment is properly cleaned, disinfected, and sterilized Educate, train, and counsel HCWs, patients, visitors about TB 23

Fundamentals of Infection Control Environmental controls: prevent spread and reduce concentration of droplet nuclei Primary controls: ventilation technologies Natural ventilation vs mechanical ventilation Use of AII room Secondary controls: HEPA filters and ultraviolet germicidal irradiation (UVGI) Fundamentals of Infection Control Environmental Controls Characteristics of AII room: Single-patient room with private bathroom Negative pressure relative to hallway Air sent outdoors or through HEPA filter Six or more air changes per hour (in some settings 12 or more air changes per hour are recommended) Visitors should use N95 respirator 24

Fundamentals of Infection Control Respiratory protection controls: further reduce risk of exposure in special areas and circumstances Consists of using personal protective equipment in areas with increased risk of exposure Should be used by persons Entering rooms of suspected/confirmed TB patients Around cough- or aerosol-producing procedures In settings where administrative and environmental controls will not prevent the inhalation of infectious droplet nuclei Respirator for Health-Care Workers HCW N95 Respirator Designed to filter out droplet nuclei from being inhaled by the health-care worker and other individuals. Should properly fit different face sizes and features. Should NOT be worn by the patient. 25

Surgical Mask for Persons with Infectious TB Disease Patient Surgical mask Designed to stop droplet nuclei from being spread (exhaled) by the patient. Should NOT be worn by the health-care worker. Risk Factors for Infectiousness Presence of productive cough Cavitation or extensive upper lobe disease Positive AFB smear of sputum Involvement of larynx Failure to cover mouth/nose with cough Cough-inducing or aerosol=generating procedures (bronchoscopy, sputum production, aerosolized medications) 26

Isolation of the Hospitalized Adult Patient with TB or suspected TB Airborne infection isolation HCW and visitors wear at least N95 mask Discontinuation of isolation Suspected TB Another diagnosis excludes TB or 3 negative AFB sputum smear results Confirmed TB Effective therapy and Clinical improvement and 3 negative AFB sputum smear results Isolation of the Hospitalized Pediatric Patient with TB or suspected TB Children with TB, especially <10 y/o, are rarely infectious Nosocomial transmission in pediatric setting rare Adults accompanying children into the hospital may be the source case and potentially infectious Emphasis on infection control should be on these adults Isolate children until infectiousness excluded in patient and adults accompanying patient CXR is critical component of evaluation Until evaluation is complete, limit visitation or visitors should wear masks in common areas 27

TB among Adult Visitors of Children with Suspected TB at a Children s Hospital Adult caretakers accompanying admitted children Screening for TB prior to admission CXR as part of screening Isolation if child potentially contagious or of delay in obtaining accompanying adults CXR 59 children enrolled 8 required isolation 105 adults screened 15% had abnormal CXR compatible with TB Infect Control and Hosp Epidemiol 2002; 23:568-72 Management of the Newborn whose Mother has LTBI Mother has reactive TST or IGRA and normal CXR If mother is asymptomatic, no separation Mother should be treated for LTBI after the initial postpartum period Newborn needs no further evaluation Other household members should be evaluated for TB infection or disease This should not delay newborn s discharge from the hospital Mother can breastfeed the infant 28

Management of the Newborn whose Mother has Suspected TB Mother has clinical signs/symptoms or abnormal CXR c/w TB disease Evaluate mother ASAP (e.g. sputum for AFB, etc) Separate mother and infant until evaluation complete If TB suspected/confirmed, separate them until mother receiving adequate therapy she wears a mask, and she understands and follows infection-control measures Mother can breastfeed the infant after at least 2 weeks of adequate treatment AND when considered not contagious Management of the Newborn whose Mother has Suspected TB Mother has clinical signs/symptoms or abnormal CXR c/w TB disease If mother has TB disease, evaluate infant for congenital TB If excluded, begin INH Repeat TST when infant is 3-4 mo old If negative, discontinue INH If positive, re-evaluate for TB disease If no disease, complete 9 mo of INH Once INH started for infant, separation no longer necessary unless there is suspicion for MDR TB 29

Management of the Newborn whose Mother has Suspected TB Mother has clinical signs/symptoms or abnormal CXR c/w TB disease If mother has TB disease, and MDR is suspected/proven Separate mother and infant until mother considered no longer contagious Consider BCG vaccination for infant (if HIV negative) if separation from mother is not possible Management of the Newborn whose Mother has Suspected TB Mother has abnormal CXR findings but no evidence of TB disease Separation not necessary Mother should receive LTBI treatment Household should be investigated for TB 30

Prevention of Transmission in the Community Child care Children with TB can attend child care if they are receiving appropriate therapy If source case child care worker, other children in center should be evaluated Child with TB not contagious unless adult-type disease School Children can attend school if receiving appropriate therapy School contacts of children with adult-type disease should be investigated by Health Department Take-Home Messages The diagnosis of TB in a child is a sentinel event representing recent transmission of TB in the community A source case investigation should be considered when a young child is diagnosed with TB Do not forget non-family care-givers Contact investigations are an essential component of TB prevention Daycare centers represent a high priority for contact investigation Young children are rarely contagious, but the source-case is Use window prophylaxis in young children 31

Main References American Academy of Pediatrics. Tuberculosis. In: Pickering, Baker, Kimberlin, Long, ed. Red Book: 2012 Report of the Committee on Infectious Diseases. Elk Grove Village, IL: American Academy of Pediatrics; 2012. Centers for Disease Control and Prevention. Guidelines for the Investigation of Contacts of Persons with Infectious Tuberculosis: Recommendations from the National Tuberculosis Controllers Association and CDC. MMWR 2005; 54 (No. RR 15) Centers for Disease Control and Prevention. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005. MMWR 2005; 54 (No. RR-17). 32