3/20/2012. Robert S. Baltimore, M.D. Tuberculosis in childhood. Infectious Diseases Update. CT-AAP Critical Issues in School Health Conference

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1 Infectious Diseases Update CT-AAP Critical Issues in School Health Conference Robert S. Baltimore, M.D. Professor of Pediatrics and Epidemiology Yale University School of Medicine March 29, 2012 Hot Topics For Today: Plan/Outline Tuberculosis Rates: USA/Connecticut Screening Skin Test IGRA- Blood tests Latent Active Meningitis Meningococcal Vaccine Update Influenza Rates: USA/Connecticut Immunization recommendations Schools Pneumococcal vaccine New Prevnar 13 - Update Immunization recommendations Tuberculosis in childhood 1

2 Winchester Clinic Pediatric TB Clinic Second Floor Bridge over Howard Avenue Age Birth to 18 years plus Attendings: Robert S. Baltimore, M.D., Director Hal Bornstein, M.D. Meets: First and Third Wednesdays of Each Month 1:00 PM to ~4:00 PM Appointments: Do you need to refer all TB infection to this clinic? No Do you need to refer all TB disease to this clinic? It is a good idea. Reported TB Cases- US Rate* of tuberculosis (TB) cases, by state/area United States, 2010 * Per 100,000 population. 2

3 85 cases of tuberculosis (TB) were reported in 2010, a 10.5% decrease from 2009 (95 cases). 63 cases (74%) were pulmonary, while 22 (26%) were extra-pulmonary. The case rate for Connecticut was 2.4/100,000 population in 2010 compared to 2.7/100,000 in This represents an 11.1% decrease in case rate from 2009 to (78%) of the TB cases were born outside the United States or Puerto Rico/Other US Territories. Foreign-born cases came from 26 different nations. Nations with five or more cases included: India 9 Philippines 6 Guatemala 5 Haiti 5 Vietnam 5 Number and rate* of tuberculosis (TB) cases among U.S. born and foreign born persons, by year United States, Source: National TB Surveillance System. * Per 100,000 population. 3

4 TABLE. Number and rate* of tuberculosis cases and percentage change, by race and ethnicity United States, % change from 2009 to Population 2010 Race/Ethnicity No. Rate No. Rate No. Rate Hispanic 3, , ,419,324 49,876,874 Non Hispanic Black 2, , ,681,544 38,045,114 Asian 3, , ,686,083 14,021,770 White 1, , ,851,24 200,140,743 0 Other ,368,359 7,544,914 Unknown Total 11, , ,006,55 309,629,415 0 * Per 100,000 population. Provisional data as of February 26, Based on U.S. Census population data. Persons included in this category are American Indian or Alaskan Native (2009, n = 101, rate: 4.3 per 100,000 population; 2010, n = 146, rate: 6.1), Native Hawaiian or other Pacific Islander (2009, n = 75, rate: 16.7; 2010, n = 94, rate: 20.6), and multiple race (2009, n = 38, rate: 0.8; 2010, n = 29, rate: 0.6). Transmission and Progression of TB Lung apices Bone growth plates vertebrae kidneys 4

5 High-Risk Groups for Tuberculosis in North America Increased Risk of Becoming Infected Foreign-born persons from high-prevalence countries Residents of jails and prisons Residents of nursing homes Homeless persons Users of illegal drugs Poor and medically indigent persons Health care workers who care for high-risk patients Children exposed to adults in high-risk groups Age <4 years Recent infection (within 2 years) FROM CT- DPH Website Recommended Testing Schedule Routine tuberculin testing of all students at school entry or for any of the required examinations is not recommended. The current low rates of transmission of tuberculosis in all parts of Connecticut do not justify it. TUBERCULOSIS SCREENING GUIDELINES FOR CONNECTICUT SCHOOLS Connecticut Department of Public Health, Infectious Diseases Section June 2011 Students not already known to have a positive test should be tested if they have any of the following risk factors for TB infection: a. were born in a high risk country of the world (see attached list of countries Appendix B) and do not have a record of a TST or IGRA (e.g. QuantiFERON - TB Gold In-Tube test (QFT-GIT) or T-SPOT.TB test) performed in the United States (U.S.); b. have traveled to a high risk country, stayed for at least a week with substantial contact with the indigenous population since the previously required examination; c. have had extensive contact with persons who have recently come to the U.S. from high risk countries since the previously required examination; d. had contact with person(s) suspected to have TB; or e. lives with anyone who has been in a homeless shelter, jail or prison, uses illegal drugs or has HIV infection. A history of BCG vaccination is not a contraindication to testing nor should it be considered in interpretation of the skin test result 5

6 New; Short Course Treatment For LTBI What is Latent TB Infection? Persons with latent TB infection do not feel sick and do not have any symptoms. They are infected with M. tuberculosis, but do not have TB disease. The only sign of TB infection is a positive reaction to the tuberculin skin test or TB blood test. Persons with latent TB infection are not infectious and cannot spread TB infection to others. Overall, without treatment, about 5 to 10% of infected persons will develop TB disease at some time in their lives. About half of those people who develop TB will do so within the first two years of infection. For persons whose immune systems are weak, especially those with HIV infection, the risk of developing TB disease is considerably higher than for persons with normal immune systems. Candidates for the Treatment of Latent TB Infection Groups Who Should be Given High Priority for Latent TB Infection Treatment People who have a positive IGRA result or a People who have a positive IGRA result or a TST reaction of 5 or more millimeters TST reaction of 10 or more millimeters HIV infected persons Recent contacts of a TB case Persons with fibrotic changes on chest radiograph consistent with old TB Organ transplant recipients Persons who are immunosuppressed for other reasons (e.g., taking the equivalent of >15 mg/day of prednisone for 1 month or longer, taking TNF α antagonists) Recent immigrants (< 5 years) from highprevalence countries Injection drug users Residents and employees of high risk congregate settings (e.g., correctional facilities, nursing homes, homeless shelters, hospitals, and other health care facilities) Mycobacteriology laboratory personnel Children under 4 years of age, or children and adolescents exposed to adults in highrisk categories Treatment Regimens for Latent TB Infection Drug(s) Duration Interval Minimum Doses Isoniazid 9 months Daily 270 Twice weekly 76 6 months Daily 180 Twice weekly 52 Isoniazid & Rifapentine 3 months Once weekly 12 Rifampin 4 months Daily 120 Note: Rifampin (RIF) and Pyrazinamide (PZA) should not be offered to persons with LTBI. RIF and PZA should continue to be administered in multidrug regimens for the treatment of persons with TB disease. 6

7 Latent TB Infection Treatment Regimens Isoniazid (INH) and Rifapentine (RPT) 1 3 month regimen of INH and RPT is an option equal to 9 month INH regimen for treating LTBI in certain groups, such as otherwise healthy people, 12 years of age and older, who were recently in contact with infectious TB or who had tuberculin skin test conversions or positive blood test for TB* Must use directly observed therapy (DOT) *MMWR. Recommendations for Use of an Isoniazid Rifapentine Regimen with Direct Observation to Treat Latent Mycobacterium tuberculosis Infection Isoniazid (INH) and Rifapentine (RPT) Regimen The 12 dose regimen of INH and RPT does not replace other recommended LTBI treatment regimens; it is another effective regimen option for otherwise healthy patients aged 12 years who have predictive factor for greater likelihood of TB developing, which includes recent exposure to contagious TB, conversion from negative to positive on an indirect test for infection (i.e. interferon-γ release assay or tuberculin test), and radiographic findings of healed pulmonary TB. This regimen is not recommended for Children younger than 2 years old, People with HIV/AIDS who are taking antiretroviral treatment, People presumed to be infected with INH or RIFresistant M. tuberculosis, and Pregnant women or women expecting to become pregnant within the 12 week regimen. Latent TB Infection Treatment Regimens Rifampin Rifampin (RIF) given daily for 4 months is an acceptable alternative when treatment with INH is not feasible. In situations where RIF cannot be used (e.g., HIV infected persons receiving protease inhibitors), rifabutin may be substituted. RIF daily for 4 months 120 doses within 6 months 7

8 Case from Primary Care I A woman brings her 4 year old son, MB, to your clinic for his well child check. She brings with her a school physical form which suggests placing a PPD and asks if her son must get this done. M has been a very healthy child except for the occasional cold. Mrs. B assures you that they do not currently know of anyone with active tuberculosis or other high risk behaviors. You notice a scar on Micah s left shoulder. Asking the mom about this, you find out that M was born in Armenia and a BCG vaccination was placed shortly after birth. MB returns to the clinic 3 days later to have his tuberculin skin test interpreted. You find that the indurated area around the injection site measures 12mm. Case from Primary Care II You obtain a thorough history and perform a targeted physical examination, which are normal. You obtain a chest x ray which is also normal. You conclude that although he is asymptomatic with a negative chest x ray, his positive tuberculin skin test and risk factor profile puts him in the category of [latent] TB infection. You tell the mother you are reassured that he doesn t have active tuberculosis. She sighs in relief and says, Great, so we can go now? 8

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10 Decision Rules for a "Positive" Mantoux Tuberculin Reaction 5 mm Contacts to infectious TB cases Abnormal chest radiograph or signs and symptoms HIV-infected and other immunosuppressed patients 10 mm Other high-risk individuals 15 mm Individuals with no risk factors Case From Primary Care III At this point, M should be started on prophylactic therapy and monitored appropriately. Referral to a TB clinic is not necessary for most cases. First line therapy for LTBI consists of a 9 month regimen of daily INH (approximately 10 15mg/kg daily, up to 300mg/day). In cases where the patient has contracted the infection from a source known to be INH resistant, daily rifampin should be used for 6 months. In cases where the patient has had a known multi drug resistant TB source, consultation with a pediatric infectious disease specialist is indicated before starting therapy. 10

11 Case from Primary Care IV Side effects of the medication should be reviewed. In general, INH is well tolerated by children, however known toxicities include hepatitis, peripheral neuropathy, hypersensitivity reactions, and GI distress 17year old from Mexico. CC. Hemoptysis x 1 week. Cough and night sweats 11

12 Calcified node T cell interferon release assays (IGRAs) for diagnosing TB: What are they? What are they good for? 12

13 Problems Solutions Diagnostic specificity of the TST is confounded in BCG vaccinated persons, and sensitivity is reduced in vulnerable populations, Including immunocompromised persons and children The advent of T cell interferon release assays (IGRAs) may offer a realistic alternative to the TST. Currently, there are only 2 forms of IGRAs using antigens specific to Mycobacterium tuberculosis: Either interferon γ secretion is measured in whole blood by the enzyme linked immunosorbent (ELISA) assay, or interferon γ secreting T cells are enumerated by the enzyme linked immunospot (ELISpot) assay. The stimulation of effector T cells in whole blood with a specific antigen(s) or mitogen, and the subsequent simple quantification of the resulting IFN-γ in the plasma, is the basis of the QuantiFERON technology. FROM CT DPH Website Although a QFT-GIT test can be performed in lieu of the placement of a TST, at times patients may have both a TST and a QFT-GIT performed. To decrease confusion and clinical dilemmas when there is discordance between the two tests, the results of the two tests should be taken together to make clinical decisions regarding the LTBI status of patients and recommendations for treatment. A medical epidemiologist in the CTDPH TB Program is available for consultation regarding discordant test results and treatment decisions 13

14 Starke,JR. Cur Opin Pediatr 19: Starke,JR. Cur Opin Pediatr 19: Influenza PHIL ID #11214 Photo Credit: C. S. Goldsmith and A. Balish, CDC Download High Resolution Description: Negative stain EM image of the 2009 H1N1 Influenza A/CA/4/09 14

15 National Institutes of Health; Structure of the influenza virion. The hemagglutinin (HA) and neuraminidase (NA) proteins are shown on the surface of the particle. The viral RNAs that make up the genome are shown as red coils inside the particle and bound to ribonucleoproteins (RNPs). CDC Recommendations for childhood flu vaccination Before Only children >6 months with certain medical conditions 6 23 months encouraged when feasible 6 23 months recommended 6 59 months recommended Everyone over 6 months old Flu viruses included in the seasonal vaccine for WHO recommended that the Northern Hemisphere's seasonal influenza vaccine contain the following three vaccine viruses: an A/California/7/2009 (H1N1) like virus, an A/Perth/16/2009 (H3N2) like virus, and a B/Brisbane/60/2008 like virus. 15

16 Special Instructions for Children 6 months through 8 years of Age Children 6 months through 8 years of age who did not receive at least one dose of the vaccine, or whom it is not certain whether the was received, should receive 2 doses of the seasonal vaccine. The first dose should be given as soon as vaccine becomes available, and the second dose should be given 28 more days after the first dose. The first dose primes the immune system; the second dose provides immune protection. Children who only get one dose but need two doses can have reduced or no protection from a single dose of flu vaccine. Two doses are necessary to protect these children. If your child needs the two doses, begin the process early, so that children are protected before influenza starts circulating in your community. Be sure to follow up to get your child a second dose if they need one. It usually takes about two weeks after the second dose for protection to begin. ACIP recommends that children 6 months through 8 years of age receive 2 doses of the flu vaccine with a minimal interval of 4 weeks unless they have received: 1. At least 1 dose of 2009 H1N1 flu vaccine last season; and 2. At least 1 dose of seasonal flu vaccine prior to the flu season or 2 doses of seasonal flu vaccine. 3. If a child has fulfilled both of these requirements, they only need 1 flu vaccine. FIGURE 1. Influenza vaccine dosing algorithm for children aged 6 months through 8 years --- Advisory Committee on Immunization Pract Alternate Text: The figure above shows influenza vaccine dosing algorithm for children aged 6 months through 8 years for the influenza s 16

17 Number and percentage of respiratory specimens testing positive for influenza, by type, surveillance week, and year World Health Organization and National Respiratory and Enteric Virus Surveillance System collaborating laboratories, United States, October 2, 2011 February 11, 2012 Percentage of all deaths attributable to pneumonia and influenza (P&I), by surveillance week and year 122 U.S. Cities Mortality Reporting System, United States, * 17

18 Neighborhood Socioeconomic Status Among Children Hospitalized With Influenza: New Haven County, Connecticut, Connecticut Epidemiologist. Volume 30, No. 6 September 2010 Schools CDC Recommendations Encourage Vaccination Against Flu Advise the sick to stay home Separate sick students and staff (for those ill separate room go home) Discourage attendance at school events by sick people Respiratory etiquette and hand hygiene Perform environmental cleaning (no additional disinfection beyond routine cleaning) Early treatment of students and staff at high risk for complications Consider selective school dismissal Components of Universal Respiratory Etiquette (also known as Respiratory Hygiene/Cough Etiquette) Applies to all patients, persons accompanying patients, visitors Source control measures Cover the mouth/nose when coughing Give the patient a surgical mask to wear Use tissues if surgical mask is not available to contain secretions Hand hygiene after contact with respiratory secretions. Spatial separation of person with respiratory infections in common waiting areas. 18

19 Prevnar 13 The Journal of Infectious Diseases 2010; 201:32 41 BOX. Updated recommendations for administration of 23 valent pneumococcal polysaccharide vaccine (PPSV23) among adults aged 19 years Advisory Committee on Immunization Practices (ACIP), United States PPSV23 should be administered to adults aged years with chronic or immunosuppressing medical conditions, including those who have asthma. Adults aged years who smoke cigarettes should receive PPSV23 and smoking cessation guidance. Routine PPSV23 use is no longer recommended for Alaska Natives or American Indians aged <65 years unless they have medical indications for PPSV23. However, in certain situations, public health authorities may recommend PPSV23 for Alaska Natives and American Indians aged years who are living in areas where the risk for invasive pneumococcal disease is increased. All persons should be vaccinated with PPSV23 at age 65 years. Those who received PPSV23 before age 65 years for any indication should receive another dose of the vaccine at age 65 years or later if at least 5 years have passed since their previous dose. Those who receive PPSV23 at or after age 65 years should receive only a single dose. ACIP does not recommend routine revaccination for most persons for whom PPSV23 is indicated. A second dose of PPSV23 is recommended 5 years after the first dose for persons aged years with functional or anatomic asplenia and for persons with immunocompromising conditions. ACIP does not recommend multiple revaccinations because of uncertainty regarding clinical benefit and safety. 19

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21 Prevnar 13 FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE Prevnar 13 is a vaccine approved for use in children 6 weeks through 5 years of age (prior to the 6th birthday). Prevnar 13 is indicated for active immunization for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F. Prevnar 13 is also indicated for the prevention of otitis media caused by Streptococcus pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. No otitis media efficacy data are available for serotypes 1, 3, 5, 6A, 7F, and 19A. Based on available safety, immunogenicity and disease burden data, ACIP recommends that a single supplemental PCV13 dose be given to healthy children aged months and to children with underlying medical conditions up to age 71 months who already have completed a schedule of PCV7. In one study, a single dose of PCV13 in children aged 12 months who had received 3 previous doses of PCV7 induced an antibody response comparable to the 3 dose infant PCV13 series, and the safety profile of this supplemental dose was comparable to that after a fourth dose of PCV13 21

22 Meningococcal Vaccine- New Recommendations At what age does my preteen or teen need it? All years olds should be vaccinated with meningococcal conjugate vaccine (MCV4). Now, a booster dose should be given at age 16 years. For adolescents who receive the first dose at age 13 through 15 years, a one-time booster dose should be administered, preferably at age 16 through 18 years, before the peak in increased risk. Adolescents who receive their first dose of MCV4 at or after age 16 years do not need a booster dose. Adolescents age 16 through 18 years can get the booster dose at any time. The minimum interval between doses is 8 weeks. As an adult, do I need it? \ You should get either the MPSV4 vaccine or the MCV4 vaccine if: You are a college freshmen living in a dormitory You are a military recruit You have a damaged spleen or your spleen has been removed You have terminal complement deficiency You are a microbiologist who is routinely exposed to Neisseria meningitidis (the causal pathogen) You are traveling or residing in countries in which the disease is common. 22

23 Infants and Children The meningococcal conjugate vaccine (MCV4) is recommended for certain high risk children from ages 9 months through 10 years. The high risk children for whom this vaccine is recommended include children who travel to, and United States citizens who reside in, countries where meningococcal meningitis is hyperendemic or epidemic (e.g. the African Meningitis Belt), persons with persistent complement component deficiencies (e.g., C5-C9, properdin, factor H, or factor D), persons with functional or anatomic asplenia, and children who are in a defined risk group during a community or institutional meningococcal disease outbreak. However, 9 through 23 month old children with functional or anatomic asplenia are NOT recommended to receive the vaccine. A 2-dose primary series is recommended for any child with the risk factors described above whose first dose was received before their second birthday. Persons at increased risk because of complement component deficiencies and persons with functional or anatomic asplenia should receive a two dose primary series 2 months apart and then get a booster dose every 5 years. Children aged 9 months-6 years at increased risk are recommended to be revaccinated 3 years after their primary series, and then at 5 year intervals if they remain at risk. In October 2010, ACIP voted to recommend a two-dose primary series of MCV4 given 2 months apart for 2 through 54 year olds with medical risk factors (complement component deficiency, functional or anatomic asplenia). In April 2011, ACIP voted to recommend MCV4 for children 9 through 23 months of age with certain medical risk factors (complement component deficiency). TABLE. Summary of MenACWY D recommendations for children aged 9 through 23 months at high risk for invasive meningococcal disease Advisory Committee on Immunization Practices (ACIP) Risk group Primary series Booster dose Children aged 9 through 23 months at high risk for invasive meningococcal disease (except children with functional or anatomic asplenia)* 2 doses, 3 months apart Initial booster 3 years after completing the primary series Catch up dose if dose 2 is not received on Continued boosters at 5 year intervals after the schedule: at the earliest opportunity initial booster Children at high risk for invasive meningococcal disease with functional or anatomic asplenia 2 doses, 2 months apart, beginning at age 2 years and 4 weeks after completion of PCV13 vaccine series Initial booster 3 years after completing the primary series Continued boosters at 5 year intervals after the initial booster Abbreviations: MenACWY D = quadrivalent meningococcal conjugate vaccine; PCV13 = 13 valent pneumococcal conjugate vaccine. * Children who have persistent complement component deficiencies (e.g., C5 C9, properdin, factor H, or factor D), children who are traveling to or residents of countries where meningococcal disease is hyperendemic or epidemic, and children who are in a defined risk group during a community or institutional meningococcal outbreak. If the person remains at increased risk. END 23