Tuberculosis control in Japanexperience & perspective

Akira ShimouchiSpecial Advisor for TB ControlNishinari District, Osaka City

Senior Advisor, The Research Institute of Tuberculosis Japan Anti-Tuberculosis Association

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1. TB burden & epidemiologytrend & present

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Annual reduction rate 1960s-70s:10%, 80s-90s: 3%, since 2000 : 5% RIT/JATA 3

1951 TB control law

1961 Universal health insurance coverage

(INH, SM, PAS 2 y)

(INH, RFP, SM/EB 9m)

(RHEZ/RH 6-9m)

Cohort analysis

DOT in urban area

QFT

16.1

Declaration of TB emergency

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Reformed TB control programmes

After stagnation of notification rate reduction in 1980s, since mid 1990s, global standardized treatment :2HREZ/4RH and cohort analysis of treatment outcome for evaluation has been introduced nationwide.

Since 2000, DOT has gradually been introduced for inpatients for all hospitals, and for homeless patients for ambulant treatment in urban areas.

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Annual reduction rate is larger in younger age group than in older age group.RIT/JATA 6

Based on the tuberculin survey in the past, the oldest age group is estimated to have the highest prevalence rate of TB infection.RIT/JATA 7

The curve of notification rate by age group reflects that of prevalence of infection. Therefore reactivation of infected person is main mechanism of developing TB in the elderly.

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High TB endemic areas remain in west Japan where TB incidence was high in the past. TB transmission is occurring in mega cities such as Tokyo, Osaka, Nagoya and Kobe.

Geographical difference of TB notification rate, Japan 2013

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n/a)

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2. TB in the elderly &

main control activities

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Stagnation of reduction is now occurring at the oldest age group.RIT/JATA 12

Main indicators of national TB control programme2011-2015

2011 2012 2013 2014Noti fication rate of a l l TB (per 100,000) 17.7 16.7 16.1 15.1* less tha 15Retreatment rate of PTB (%)† 7.7 6.7 6.3 7% or lessTreatment fa i lure/defaulter rate(%) 3.6 4.0 4.4 5% or less* preliminary report

among newly registered PTB cases¶ result of new smear (+) pulmonary TB registered in previous year.

Target would be achieved.Target has been achieved.

Target by2015

Related with improved treatment support

In order to reduce TB notification (incidence) rate, early case finding and early treatment, and LTBI treatment need to be expanded.

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Active case finding

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Active case finding (TB screening) has lower rate of sputum positive PTB rate than other modes of case finding.

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The elderly have more chances to visit medical facilities with high morbidity with any symptoms.

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The older TB patients, the less often with cavitary lesions.RIT/JATA 17

3. TB in children

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Number Rate 0-14 yrs 0-4 yrs (Rate) 0-14 yrs 0-4 yrs (Rate)1965 44,180 175.61970 18,197 73.41975 4,905 18.0 28 22 (0.221)1980 1,893 6.9 22 14 (0.164)1985 1,088 4.21990 518 2.3 9 4 (0.061) 10 8 (0.122)1995 340 1.7 8 8 (0.136) 8 8 (0.136)2000 220 1.2 7 4 (0.069) 3 3 (0.052)2005 117 0.67 3 1 (0.018) 3 1 (0.018)2006 85 0.49 0 0 1 1 (0.018)2007 92 0.53 0 0 0 02008 95 0.55 0 0 1 1 (0.019)2009 73 0.43 1 1 (0.019) 4 3 (0.056)2010 89 0.53 0 0 0 02011 84 0.50 1 0 2 1(0.019)2012 63 0.38 1 1(0.019) 0 02013 66 0.40 2 2(0.038) 0 0

Extra-pulmonary tuberculosis: Cases are counted independently. Rate: per 100,000 -: Not available

Trend of number & rates of pediatric TB patients and sereous extra-pulmonarytuberculosis, 1965-2012

Year

Newly notified all TB aged 0-14 yrs TB meningitis Miliary TB

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More than half of pediatric TB patients were found by contact examination.

0-4 5-9 10-14 Total (%) School TB screening byquestionnaire/interview

0 0 1 1 1.6

Family contactinvestigation

17 7 8 32 50.8

Other contactinvestigation

1 2 1 4 6.3

At clinics/hospitals withsymptoms

10 2 10 22 34.9

Others 2 1 1 4 6.3

Total 30 12 21 63 100

Number of newly notified pediatric TB patients by age and modeof detection, Japan 2012

mode of detection

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Less than 1 per 100,000 pop. Under 5. (Effect of BCG.)(In US, it is more than 1 per 100,000 pop. Under 5. )

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BCG vaccination

From 2005, BCG had been mostly given before 6 months of age. Since then BCG related osteomyelitis increased from 1 per 1 million to 3.6 per 1 million. In addition, based on the above information, since 2013, BCG is given from 5 to 8 months, at latest by 12 months of age to prevent osteomyelitis.BCG would be continued as long as risk of TB development still surpass the frequency and severity of side effects.

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4. Latent TB infection (LTBI) treatment

Age group for method for LTBI diagnosis: (guidelines March 2014)Under 5 : TST [IGRA(QFT, T-SPOT)]5-12 : IGRA & TST 13 and over: IGRAThe elderly: consider balance between prevalence of infection & possible side effect of treatment

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Effort has been made to increase LTBI treatment. But geographical difference by prefecture of the above indicators is still large.RIT/JATA 24

5. MDR TB

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Drug resistance rate obtained by national surveillance in 2013

73 of DST results of registered patients available in the surveillance. 64% of MDR reported from Tokyo and Osaka.Long standing XDR patients are now receiving treatment including Delamanid with strict conditions for patients and institutions.RIT/JATA 26

6.TB in foreign-born persons

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Foreign born patients consist of 5% of all ages and 40% of 20s of all patients.RIT/JATA 28

Mainly come from high prevalence countries.RIT/JATA 29

More transfer out and defaulted rate among foreign born patients.RIT/JATA 30

during treatment, 2006-2012, Osaka City, Japantreatment success transfer out

n=108 n=17(%) (%) p value

sex male 81.8 18.2 0.093female 91.5 8.5

age 20 or less 83.1 16.9 0.13830 or over 91.7 8.3

job yes 91.9 8.1 0.193no 84.1 15.9

entry to Japan within 5 years 81.5 18.5 0.0675 year or more 94.1 5.9

insurance yes 89.5 10.5 0.059no 72.2 27.8

way of case finding TB screening with chest x-ray 89.3 10.7 0.281found at clinic/hospital 84.1 15.9

fluency in Japanese fluent 91.1 8.9 0.051daily conversation only or less 78.6 21.4

sputum smear positive 81.0 19.0 0.060negative 92.2 7.8

treatment outcome: excluding other factors except for treatment success & transfer out

Characteristics of foreign born patients transferred out to mother countries

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Variables Subject x % Odds ratio 95%CL pNationalitiesJapanese 14125 121 0.9 1 (reference)Foreigners (entry within 5 yrs) 299 21 7.0 2.7 1.8-4.2 <0.001Foreigners (entry over 5 yrs ago) 193 2 1.0 1.0 0.5-2.0 ns

Treatment historywith previous treatment 13913 85 0.6 1 (reference)without previous treatment 1326 67 5.1 3.6 3.0-4.4 <0.001

Variables Subject x % Odds ratio 95%CL pNationalitiesJapanese 1214 56 4.6 1 (reference)Foreigners (entry within 5 yrs) 11 5 45.5Foreigners (entry over 5 yrs ago) 10 0 0.0

3.8 1.1-13.2 0.036

MDRStatistical test results by variable associated with MDR TB, Japan, 2007-2009

Statistical test results by variable associated with MDR TB, Japan, 2007-2009among foreign born patients with previous treatment

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7. TB in Urban poor areas

Osaka City (pop:2.6m)as an example

with worst notification rate in Japan39.4/100,000

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Osaka CityAirin Area

Nishinari

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Factors of high TB prevalence in Osaka City(1)High TB prevalence in the past negative heritage(2)Daily labourers, unemployed, and homeless stay

concentrated in inner city areas.Rate of receiving poverty scheme among TB patients:

Osaka City 31%, Kawasaki City 15%, Nation average 8%.(3)Ageing of population progresses.(4)Patient’s Delay partly refuse to consult with doctors

lack of understanding, financial reason.Thus TB transmission still continues.(5)High day/night pop.rate 138(3.6m/2.6m

High chances of get infected in working places.But low rate of TB/HIV pts.

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Sapporo, Sendai, Chiba, Yokohama, Kawasaki, Nagoya, Kyoto, Osaka, Kobe, Hiroshima, Kitakyushu, Fukuoka, Tokyo(23 districts) etc.

Poverty relief rate and TB notification rate in 19 large cities in Japan, 2012

Osaka City

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Clu

ster

ing

size

(n)

Non Beijing type Beijing type (ancient) Beijing type (modern)

5

100200202-2-04 (2733 strains)

200606-6-08 (191strains)

Results of VNTR analysis among homeless patients in Osaka City(1515-

yyy5-MIRUU-

gU-VNTR + 4 hypere -

pr variable loci)- ypNTR + 4 hypeVNV er- ariavav

Clustering rategggggg)able locii)ria

41.6%

200220032004

Non Beijing type Beijing type (ancient) Beijing type (modern)

5

10

15Clustering rategggggg 38.2%

200620072008

WadaT et al, Tuberculosis 89, 2009,252-55

TB transmission still occurs among homeless.RIT/JATA 37

Yes No CrudeOR

95% CI P -value AdjustedOR*

95%CI P -value

Less than 40 16 3562 1

40 and above 16 1047 1.24

Female 15 856 1

Male 66 3753 0.7

Without previous treatment 40 4141 1

With previous treatment 41 509 7.89

Any district except Nishinari 46 3307 1

Homeless, Nishinari District 35 1348 1.73

Crude OR – crude odds ratio; Adjusted OR – adjusted odds ratio; CI – confidence interval.* Logistic regression adjusted for the four variables in this table.

0.249 - - -

Multidrug resistance

Age 0.70–2.21 0.462 - -

Comparison between multidrug resistant TB cases and all other positive pulmonary TBcases, Osaka City, Japan, 2001 to 2008

Residence 1.07–2.81 0.0027 1.580.99–2.52 0.053

Treatment 4.96–11.57 < 0.001 7.574.78–11.98 < 0.001

-

Sex 0.38–1.28

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Homeless & residents of Nishinari District had been risk factor for MDR TB.

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n % n % n % n % n % n % n % n % n %2001 681 63 9.3 23 3.4 18 2.6 579 37 6.4 14 2.4 10 1.7 102 26 25.5 9 8.8 8 7.82002 664 50 7.5 27 4.1 17 2.6 546 29 5.3 15 2.7 6 1.1 118 21 17.8 12 10.2 11 9.32003 651 37 5.7 19 2.9 16 2.5 568 33 5.8 16 2.8 13 2.3 83 4 4.8 3 3.6 3 3.62004 633 36 5.7 11 1.7 7 1.1 541 32 5.9 7 1.3 4 0.7 92 4 4.3 4 4.3 3 3.32005 632 26 4.1 10 1.6 5 0.8 555 19 3.4 4 0.7 2 0.4 77 7 9.1 6 7.8 3 3.92006 644 38 5.9 9 1.4 4 0.6 571 28 4.9 6 1.1 2 0.4 73 10 13.7 3 4.1 2 2.72007 620 45 7.3 18 2.9 12 1.9 548 35 6.4 7 1.3 5 0.9 72 10 13.9 11 15.3 7 9.72008 505 27 5.3 11 2.2 9 1.8 446 18 4 5 1.1 4 0.9 59 9 15.3 6 10.2 5 8.5

H – isoniazid; R – rifampicin* All smear positive pulmonary tuberculosis cases that drug susceptibility result is available.

any H

Number and proportion of smear-positive pulmonary TB cases with drug resistance to isoniazid and/or rifampicin by treatmentstatus, Osaka City, Japan, 2001 to 2008

any R any RH Allcases*

any H any R any RHYear Combined Without previous treatment With previous treatment

Allcases*

any H any R any RH Allcases*

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Reduction of MDR patients

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TB Control Strategy in high endemic (Airin Area) for the homeless & the poor

Residents in Airin Area: 25,800 in 0.62km2Case notification rate: 400 per 100,000TB Screening with CXR(1) The homeless at the year-end, new year days shelter

1,900 in Osaka City, mainly in Airin(2) Workers registered for Cleaning of the Town Project for the elderly (55 and over) (1,000~)(3) Residents who are on poverty relief scheme (9,000)Detect abnormal shadow sputum AFB, AFB (+) hospitalized, AFB (-) OPDTreatment support by daily DOT by TB staffStay in apartment or welfare institution.

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Results of TB screening (CXR & AFB)April 2013- March 2014

Target Mainly homeless & those people receiving cash benefit on poverty scheme

• No. screened 8109• TB patients 58 • Case finding rate 0.72% (720 per 100,000)• S(+)PTB patients 20• S(+) rate 34.5%

reference TB case finding rate by TB screening in Osaka City excluding Nishinari Ward in 2012. 0.09%(6/7042)

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Case finding rate by TB screening for the high risk is as eight times high as for the general public.WHO recommends TB screening among high risk group (C.F. rate >0.1%) and in high risk area (C.F. rate of > 1%).(Systematic screening for active TB, WHO 2013)RIT/JATA

PHN visits apartment of TB patients for DOTS. Also provide with nutritious food. RIT/JATA 43

After was introduced, persons were explained about the findings of chest x-ray on the spot. Most of TB suspects agreed to visit medical facilities for further examination. Before, one third did not come back to obtain x-ray results.RIT/JATA 44

Almost plateau in 1980s-90s (Lost 20 years).

But it started to decline after 2000 when new programme started.RIT/JATA 45

8. Emphasized future activities based onNational guidelines for TB control ,2011-2015

with new suggestions(1) Active case finding: TB screening by chest x-ray• The elderly: at the start of utilization of service of

hospitals and nursing homes as part of TB control in all institutions to prevent transmission to HCW etc.

• The homeless: at the time of utilization of shelters, registration for working arrangement.

• Foreign born persons: at the entrance of Japanese schools and firms. New immigrant policy is needed.

• Prisoners on entry (under Ministry of Judge)

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(2) Treatment supportEstablish network for treatment support between medical facilities/ pharmacies, public health offices, and welfare offices, etc. Daily DOT for homeless

Support for LTBI treatment Foreign born patients: medical translator, referral system to

their own countries to continue treatment(3) Contact examination

Intensify contact investigation with full utilization of IGRA without age limitation (including the elderly)

(4) Expansion of targets of LTBI treatmentImmuno-suppresive patients the elderly with fibrotic lesion in chest X-ray

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(6) Gene-epidemiology using VNTRStandard loci (JATA12) + highly variable loci

Currently all cases are tested in contact examination. All notified culture positive cases should be testedto detect unknown transmission link and

to evaluate transmission rate for long term.(7) National TB surveillance systemImprove data entry on DST results by health staffEstablish quality assurance of TB laboratory between private /public laboratories, medical facilities and RIT.

(8) BCGContinue BCG for children within the first year of birth.

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