Current Issues About DTP •Diphtheria and Tetanus have been rare in Thailand •Pertussis is still present esp. in adolescents and adults, but hard to make diagnosis •TT should have been replaced by dT (10-25% of Thai adolescent and adult are susceptible to diphtheria) •DTwP-HB has been used widely in EPI •Still found problems of AEFI >> rationale for widely use of DTaP
Diphtheria-Tetanus-Pertussis •Whole cell is effective, however, –Reactogenic. Rate of serious adverse effects: Anaphylaxis 1 : 100,000 doses Seizure in 48 hr. 1 : 1750 doses HHE 3.5-291 : 100,000 doses Prolong crying > 3 hr. 1 : 100 doses T > 40.5 in 48 hr. 0.3 : 100 doses –Not recommend in > 6 year-old –DTPw induced immunity decline 50% in 6-12 years, after childhood vaccine most adults are susceptible. DTaP as efficacious but less reactogenic
Acellular pertussis Vaccines Japanese Experiences of adverse reactions •Fever >38 C : 2-4% •Local redness >5 cm: 8-9% (less in 1 st dose) •Serious & sequelae DTaP vs DTwP: 0.25 vs 0.4/10 6 •Serious & death DTaP vs DTwP: 0.10 vs 0.15/10 6 Overall side effects are much less than whole cell, however, serious effects still may occur Aoyama. JID 1996:174s264-9
DTaP in EPI will reduce AEFI The main obstacle of getting DTaP in EPI is cost!
Current Issues About MMR •EPI cannot afford 2 doses of MMR. Are Urabe or L-Zagreb strains safe enough for infants? •Recent outbreaks in Thailand (mostly in unvaccinated infants and children) •Seems to be good control for congenital rubella, but no documentation •No link between MMR and autism
Rate of Aseptic Meningitis Caused By MMR From Various Mumps Strain *This is a schematic diagram of the range of reported rates of vaccine-associated aseptic meningitis attributed to different mumps vaccine strains from the present review. The figure is not to scale and is not a representation of statistical difference between strains.
Reducing the Burden of Congenital Rubella Syndrome (CRS) •Incidence of CRS worldwide 1995-1996 = 0.6-2.2 /1000 live birth •CRS is difficult to diagnose –mainly clinical SS; deafness, blindness and mental retardation, may not all presented –Serology is unreliable for infants –Rubella in adults is mostly asymptomatic •WHO suggest either: –Selective vaccination in women of childbearing age –Elimination of rubella Best JM. JID 2005;192:1890-7 Thailand • No surveillance for CRS • Serological study in pregnant women found susceptible in 18% • Try to eliminate rubella by universal vaccination in children
Current Issues About HBV •Vaccine at birth works well •HBIG is expensive, and sometimes not available. •Vaccine works well even without HBIG. Need to vaccinate ASAP. Also need second dose at 1 month-old in those with HBsAg positive mothers •Should serology be checked in pregnant women if HBIG is not available? •How to encourage susceptible adolescent and adult to get vaccine
Chongsrisawat V. Tropical Medicine & International Health 2006;11:1496-1502. Seroprevalence of hepatitis B surface antigen (HBsAg), anti-HBs and anti-HBc among children below the age of 18 years born before and after hepatitis B vaccine integration into expanded programme on immunization (EPI) % No. 584 581 583 1328 1328 1328 2299 2283 2290 901 508 57 Year 2004 1999 2004 1999 Born before EPI Born after EPI 4.3 18.4 15.8 3.4 32.8 0.7 55 2.9 56.4 6.3 15.7 0.7
What would be the estimate cost benefit of HBIG in Thailand •Siriraj Hospital Scenario : Antenatal care clinic in 2003 –HBsAg + = 341/8017 (4.29%) –HBeAg + = 123/341 (36%), HBeAg- = 218 (64%) Expected cases of chronic infection (eAg-, +) –Vac + HBIG 341 doses = 2+6 –Vac + HBIG 123 doses = 2+6 –Vac only, no HBIG = 2+12 To prevent 6 cases –Test HBsAg 8017 cases (125 Baht) = 1,002,125 Baht –Test HBeAg 341 cases (250 Baht) = 85,250 Baht –HBIG 123 doses (500 Baht) = 61,500 Baht Total 1,148,875 Baht to prevent 6 cases (191,479 Baht / case)
Poovorawan Y. JAMA 1989;261:3278-81. <1 mlU/mL 1-9.9 mlU/mL 10-99.9 mlU/mL 100-999.9 mlU/mL >1000 mlU/mL Anti-HBs Antibody Levels Following Recombinant HB Vaccine at Birth, 1, 2, 12 Months in Infants with HBs Ag-HBe Ag Positive Mothers
Draw back of Mouse-Brain Vaccine •Short span protection (3-5 yr) •Required multiple dose (>3 doses) and boosting 2-3 primary series, boost q 3 hr. till 10-15 yo. •Adverse events caused by myelin basic protein (now <2 ng/ml); – hypersensitivity reaction: urticaria, angioedema –ADEM <1:100,000 (acute disseminated encephalomyelitis) urticari a (incide nce 18- 64/10, 000 doses)
•Licensed in China in 1989 •Registered in China, Korea, Nepal, India, Sri Lanka, and Thailand •Large scale use in china show efficacy reduced JE in china 2.5/100,000 in 1990 to <0.5/100,000 in 2004 •No serious A/E reported in 30 days in 13,266 children (JID 1997;176:1366-9) •Efficacy in 5 studies using 2 doses, 1 year apart (N>500,0000)= 95-100% (Vaccine 2000;18:1-25) •A study in Nepal showed an efficacy of 99.3% after a single dose in that year, and 98.5% in the following year (Bista MB. Lancet 2001;358:791-5, Ohrr H. Lancet 2005;366:1375-8) Live Attenuated Virus SA-14-14-2 JE Vaccine http://www.who.int/vaccine_research/documents/Vector_Borne_Viral_Infections.pdf
Frequency of Adverse Events of Inactivated Mouse Brain Derived VS Live Attenuated SA 14-14-2 JE Vaccines Report of the Bi-Regional Meeting on Japanese Encephalitis, WHO 2005 Reaction type Frequency of reported adverse events Inactivated mouse brain derived Live attenuated PHK (SA 14-14-2) Local reactions – tenderness, redness, swelling 20%<1% Mild systemic – headache, myalgia, GI symptoms, low-grade fever 10-30%Fever < 0.5% Total 21% Hypersensitivity (delayed onset common) 1-64:10,000None reported Acute encephalitis1:50-75,000 to 1:millionNone reported
Recommendation for Live JE •2 doses at 9-12 month of age, 3-12 months apart, replacing mouse brain vac. •Live JE can effectively boost immunity in those who primed with mouse brain vaccine •For those who received mouse-brain derived killed vaccine (expert opinion): Mouse brain vaccine Live JE Interval 1 dose2 dose Any 2-3 doses1 dose 1 year >4 dose Do not need
Influenza in Hospitalized Patients in Thailand •Influenza was identified in 11% of hospitalized in CAP patients •Annual incidence 18-111/100,000 population •Cost: US$ 23-66 millions economy losses with loss of productivity 56% of all cost •Influenza occurred in 75 (OR=7.1) year-old, and those with chronic respiratory disease (OR=11.6) Simmerman JM, et al. The cost of influenza in Thailand. Vaccine 2006 Katz MA, et al. Who get hospitalized for influenza pneumonia in Thailand? Vaccine 2004
Priority for Seasonal Influenza Vaccine in Thailand Priorities - Senior citizen w chronic illness (at chest, geriatric, endocrine, heart, DM) - Health care workers - Children (esp. < 2 year-old) Recommended strains for Influenza vaccine 2008-2009 (both northern and southern A/Brisbane 59/2007(H1N1), A/Brisbane 10/2007 (H3N2, B/Florida 4/2006
Oseltamivir Resistance in H1N1 2008-9 Season; USA % of oseltamivir resistance •2007-200810.9% •2008-200998% (50 strains tested) Recommendation for antiviral Rx from CDC •If suspect influenza, regardless of rapid test, and with H1N1 circulating, or confirmed H1N1: Use Zanamivir or Oseltamivir + Rimantadine • If suspect or confirm of H3N2 or B: Use Oseltamivir or Zanamivir www.cdc.gov
Zaman K. NEJM 2008;359:1-10. Effectiveness of Maternal Influenza Immunization in Mothers and Infants Infant < 6mo # of case VE =63% VE =29% VE =31% N = 340 Preg 3 rd trimester
Current Issues About Hib Vaccine •Thailand has a much lower disease burden than the western countries •In Thailand, invasive Hib diseases found almost all in younger than 2 years of age. Almost all healthy Thai children are immune by 2 yo. •Hib vaccine has in used widely in private market, mostly in combined vaccine, and can induce herd immunity. •The booster dose may not need, but can give as combine vaccine. •The cost benefit of Hib vaccine in EPI is not clear.
Hib Disease Burden in Thailand A prospective study of meningitis in Lampang and Phisanulok: Population < 5 yo = 105,269 NRate/10 5 <5yo Potential meningitis (LP)598 568 Probable meningitis2826 Laboratory confirmed 76.7 Hib 43.8 (1.0-9.7) N.meningitidis 2<3 S.pneumoniae 1 (+1 pos H/C) <3 ATB detected in CSF 20/455 (4.4%) Rerks-Ngarm S. Vaccine 2004;22:975-83.
HbCV Recommended Schedule Age start PRP-T PRP-OMP 2-6 mo. 0,2,4, (boost) 0,2,(boost) 7-11 mo. 0,2,(boost) 0,2,(boost) 12-14 mo. 0,(boost) 0,(boost) 15-24 mo. single single Healthy Thai children do not need Hib after 2 yo., and may not need booster dose (but OK to give booster)
Morris SK. Lancet Infect Dis 2008;8:435-443. Countries that have introduced Hib vaccine and infant Hib coverage, 2006