of niE

RI:GIONAL OFFICE

FOR

niE WISTI:RM PACtFIC

of lhe

Worrel Heal!ll

Or!Jani•qfiian ManlUa

FIMAL

REPORT

OM

RECENT DEVELO' PMENTS IN tHE DOMICILIARY

rltEA

l"MENT

0 F TUBE ICULOSIS

IN

GHINA (TAIWAN)

•

WPRO

75

(China)

Cbi.ns

17

:RECEN'l DEVELO~ IN THE IXMICILIARY ~

OF !LUBERCOU>SIS IN c:HIBA (TAIWAN) by

H.i'.

L:1n1

M.D.

Director~ Taiwan Provincial TubercuJ.osis Control. Centre

and

Akio !l!anaka~

M.D.

WBD statistician

Regional. TubercuJ.osis Advisory i'eam

Worl.d Heal.th Organization

Regional. Ott1ce for the Western Eacific Man1l.a1 Phillppines

August

J.!:66

'- WPR/267/66

~

'

Foreword

Since

1963

a

new

phase in the extension of tuberculosis control in i'aiwan bas been put into operation by the Chinese Government, with

wm

technical. advice and with assistance from UNICEF in the form of equipment, supplies and field al.lowances.

These operations are being conducted, on behalf of the Tuberculosis Control Collllll1ttee of the Provincial Health Department, in ~ch of the f'our areas into which Taiwan is divided for tuberculosis control, i.e., by the Taipei, Taichung, Chiayi arJd i'ainan Tuberculosis Control Centres, under the technical. guidance of' the Taipei Centre.

f; A special feature of this extension was a study carried out between August

1963

and January

1965

ccxqpar:l.ng three types of supervision of domicil-

! 1.aey treatment and chemopropb;yl.sx:Ls of tuberculosis.

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Part I of this report will deal with the general organization and execution of this programme, and will outline sane of the main results obtained.

Part II will deal. specifi~ with the ccxqpar:Lson of supervision by the three types of sta:U.

SUbsequent parts will deal. in detail with other aspects of tuberculosis epidemiology and control that may cane

to

light during this phase of the programme.

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CONTENTS

PART I - EXTENSION OF DOMICILIARY TREAiMENT AND CREM>PRO-

PHYLAXIS OF 'l'UBERCULOSIS IN TAIWAN •••••••••••• • • • • • l l.

4.

5·

INTRODUCTION

. ...

^,

... .

METHODS e a e . e e ... e . e . e a a e e e • . a a e a . e e ea • . • • a a • • • a e e a I a . e e . a .

2.1 2.2 2.}

2.4

2-5

2.6

General .•....•••••.•••...•.••...•..••••. · · • · • Case-finding ..••...•.•.•••..••••...•.•••..•.•.•...

Regimens of treatment •••••••••••••••••••••••••••••

Health education ••••••••••••••••••••••••••••••••••

Recruitment and training of auxiliary workers •••••

Control and a.ssessment of the project •••••••••.•• • RECORDS AND THEIR ANALYSIS ••••••••.••••••.•.••••••••••••

REBULTS

. ... .

Initial ftndings ••••••••••••••••••••••••••••••••••

Consideration of treetment •••••••••••••••••••••.••

StJ1..14ARY AND CONCWSIONS

...

PART

n -

A COMPARISON OF THREE TIPEl3 OF SUPERVISION OF DOMICILIARY 'l'REATMElfr AND CBlKlPROPBYLAXIS

l.

2.

4.

FOR WBERCUWSIS IN TAIWAN

...

INTRODUCTION

...

METHODO:WGICAL CONSIDERATIONS

...

...

...

Drug collection

Drug adml.nistre.tion

...

Supervision a.a measured by the extent

of home visiting

...

Rediological cbsnges under treatment

...

Chsnges in bacteriological status under treatment ••

CONCWSION

...

ANNEX l List of Statistical Tables ANNEX 2 - List of Figures

TABLES 1

to

63

FIGtJR1!:3 I to XXI Appendices 1 to

4

l l l 2 2

3

4

3

5

5 8

5 lO

12 l2 l}

13 13 14 15

16 l6

16

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PARr I

EX.'lENSION OF DCM[CILIARY ~ AND Cll'PH>PROPIM.AXIS OF !I.'UBERCUIDSIS IN TAIWAN

1. INTRODUCTION

A new stage in intensity, duration and superv.Lsion of tuberc~osis contro~ activities in !raiwan was set in motion in ~9631 when, in trial.

areas

throughout the is.l.and with a total. popuation of over one-third of a million

peop~, mass case-finding was conducted and followed by danicil.iary treat- ment for twelve months of ~patients with active tuberculosis (bacteriol...

ogically confirmed or radio~ogica1ly suspect or both) and domiciliary chemo- prophylaxis for the same period of positive tuberculin reactors under the age of five years (in the absence of previous BOG vaccination) •

2. MEI'HO:OO 2.1 Gene~

!lbis tria~ was carried out in 60 se~ected areas in Taiwan, each with a population of'

5000

to

6000

peop~ 1 and each being a part of' the territory covered by one hea~th station - a basic community health unit1

one in each of' the total

361

townships.

One-quarter of' these sixty s~ected areas fell within the region which is covered each by a provincial. tuberculosis contro~ centre (i.e.

fifteen each of the four regions in the province). Moreover each of' these groups of fifteen was divided into three subgroups (i.e. of :five districts each), and one-third of' ~districts was ~ocated to each of' three types of' superv.l.sion to be tried and compared, viz.

(a) existing heal.th station staff';

(b) vo~untary workers in addition to (a);

(c) paid lay home visitors in addition to (a).

!thus twenty areas throughout Taiwan were al.located to each of' (a), {b) and (c). Of' the twenty-two administrative divisions of' Taiwan Province (counties and cities), seventeen were represented in the trial - those ~eft out being the smsll.er and more remote counties. In general,

sets of three heal.th stations were taken fran each county or city represented, but in three counties two sets of three (i.e. six health stations) were

taken. !lhis s~ection was made so as to. avoid areas which had already undergone large..scal.e (COIIIIIIUlli.ty) chest :x;..rsy examination, and also to obtain good community support f'or the operation. However, care was taken, within each county or city, to pie!k sets of three health stations which were as s1 mi 1 a r and comparable to each other as possib~ ₁ so that the al.loca- tion of different methods of superv.l.sion to each of the three would not introduce a aystematic bias.

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Within the are~ of each health station selected, a sector was chosen, as far as possible by random methods, with a populatb between 5000 and 6000, as indicated above.

Details of the areas fi~ selected are shown in ~le l.

2.2 case-finding

This extended to two main groups in the study areas: tbose aged 20 and over, and those under 5 years of age. The former group was initial.ly

X..~d, the lAtter received a tuberculin test.

case-finding, which lasted from August l$63 to January l$64, represented a joint effort by the local community office, which prepared lists of people in the two examins.tion groups, health station and health bureau staff, which visited homes and carried out tests, and a mobile 70 mrn pbotot'luorograph1c unit which was responsible for chest radiography.

After the initial test, follow-up invol.ved BOO vaccination of tuberculin-negative children and chemoprophylaxis of positive reactors where no evidence of previous BOO vaccination was found. Among adul.ts With radiol.ogical abnomalities follow-up invol.ved bacteriological examina- tion of sputum and lAryngeal. swabs for tubercl.e bacilli and then, in the cases with proven or suspect active tubercul.ous l.esions, treatment for twelve months.

X..ray films were read by two medical officers independentzy of each other at the nearest tubercul.osis control centre, and abnomal. fil.ms were later reviewed by a senior medical. officer of the iaipei i'uberculosis Control Centre.

At l.east three specimens of sputum, or three laryngeal swabs, were aimed at, nol'ID8.l.ly taken on three consecutive days from those

discovered to have pulmonary abnormalities on X..ray; both swabs and sputum were cultured for tubercle bacilli, but the sputa were also examined by direct smear.

.

^.

2.3

Regimens of treatment

All radiological suspects (i.e. peopl.e with shadows indicative of pulmonary tuberculosis) were advised to take isoniazid (INH), 300 mgm daizy, in a single morning dose, for one

year.

Supplies of

nm

were made

available

to

them at the heaJ.th stations, and the patients vere asked to collect the drug every month.

In the case of bacterioJ.ogica~ proven disease, "moderate:cy advanced disease with cavitation" and "far advanced disease, with or with- out cavitation'', COlllbined treatment was instituted. !l.bis meant an injection ot l. gm of streptom;ycin six days a veek for six month$ ( norma.J.zy at the heal.th station) plus a da.1ly dose of 300 mg of INH (no~ taken at

the

time of the injection, and on SUildays), then INH alone for the remaining six months. For patients who devel.oped side-reactions to streptomycin,

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•

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Para-Amino-Salicylic Acid {PAS) was substituted in a daily total dose of lD mgs (in four divided doses), continued for twe~ve months, together with Iml: as before.

!l.'uberc~n positive chUdren ·without BOO scar. were given J.OO mgm of

Jli1H

daily f'or one year, irreapective of age and weight. Supplles.

of tab~ets were simi~ly avaihbl.e at the health stations and were expected to be co~ected monthly.

2.4 Health education

Health education was regarded as an important part of the operation and was extended to the patients ₁ their familles and the chUdren' s parents at the beginning of' the treatmerxt, during cllnic attendance and on home visits. Pro~onged reiuJ,arity of' treatment was stressed and the possib~e side etf'ects of' drugs exp~ned.

2.5 Recruitment and training of auxiliary workers

As indicated earller, in addition to the regular health station staf'f ₁ two other groups of' peopl.e were under observation and trial as supervisors of the domici~ treatment prograume: vo~untary workers

(main:cy

part-time) an4 paid lay home visitors.

The vo~untary workers included such peopl.e as ~ocal government otf'icials, 4-H Cl.ub workers, members of women's organizations, tuberculosis patients themse~ves etc. !!.'hey came from the community in which the proJect was operating, and no apecial quallf'ications were expected of them, except eagerness and interest to serve the community for its duration. The number of' vo~untary workers varied greatly depending on local conditions, but as they were mostly part-time he~ers, more than one was usually acquired in any one area.

lay home visitors were chosen among unmarried girls between l.8 and

30

years of age who bad comp~eted at least junior high schoo~ educa- tion, who could speak the local dial.ect and Mandarin, and who could ride a bicyel.e. The number to be employed was to depend on the workload and eventuaJ.l.y one was designated f'or each study area, except for two areas in which two visitors each were required. In the s~ection of' these ^lay home visitors a pre~inary examination was he1d, consisting of an oral test to gauge their personality, manner and inte~gence by means of an impromptu apeech, and a written test based on a questionnaire covering social and educational. background and interests. Having thus narrowed the f1e1d candidates, the remainder attended a pre-service training course hating ten to fourteen days and centred on the case-f1nd1ng campaign,

after which a final test was given, to assess basic know~edge of tuberculosis arid practical case III&Jlag8lllellt. Successf'ul. candidates were then emp~oyed at the rate of

N!l.'$

600 per month for one year, a s~montly bonus of NT$ l200 being awarded in addition to those who had carried out their duties satisfac- torily.

Pre-service training courses were organized in the local. COIIIIIII.Ul.-

ities and were attended by health station workers, and vo~untary workers as we~ as by the lay home visitors. Bel.ection and training was the

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responsibillty of committees illc~udil:lg health station and health bureau directors, tuberculosis contro~ centre statf and l.ocal goverameut o:tticials.

In addition to basic ~ctures on tuberculosis dellvered at the healtl1 station, participants rece:Lved traiD1Dg at the var:Low. proJect activities ill progress, such as tuberculos:Ls ccmf'erences, househoM meet-·

illgs, home v:l.s:Lts, case-finding (radiol.oe;ical, bacteriol.og:Lcal and tuber ..

cul1D testing), health education, drug admiD:Lstration, etc. A~ of 120 health station personne1,

6.5

lay home vis:Ltor candidates and

76

voJ.untary workers attended these courses of :Lnstruct:Lon.

2.6 Contro~ and assessment of the project

Lay home visitors were :Lnstrw:ted to visit at home ~ patients and children under treatment twi.ce a month on the average ₁ wh~ vo~untary

. . . . I

workers and health station staff. were asked to make visits as often as they • could 1118Dage. All three groups were asked to trace patients and chUdren

under treatment who f~ to report for injections or to co~ct drugs ---

within a few days of defaulting. •

At the time of home visits enquiries were made as to regularity of treatment being followed, and tab~ts lett in the bottle fran current therapy were counted; in the case of those taking drugs at home ₁ urine tests were carried out :tor

nm

or PAS or both.

Follow-up bacteriol.ogical eyaminations on forwarded specimens were carried out at tbe tuberculosis control centres (both smears and cultures).

These eyami nations were carried out every three months tor non-intectioUB patients, and monthl.y in bacillary/cavitary cases :tor the first six months -- thereafter every three months. Radiol.ogical follow-up of all cases under treatment vas carried out by the ^mob~ team atter six months and again at the end of the year.

Each tuberculosis control ceutre formed one supervisory team consisting ot a senior medical officer and a senior nurse :tor regio~

supervision of the project ₁ under general coutrol of the project J.eader.

Both technical and administrative i\speC't!s of the operation were checked tvice a month ill each st~ area. The supervisory teams were also respon-.

sible tor tra.1n1ng ot l.ocal staff.

In addition, each tuberculosis ^contra~ centre provided a senior nurse as assessment oi'ticer, actillg independently of the supervisory tel!lll.

Each week the ceutral statistical otf'ice

(the

Statistical Unit of the Taipei Tuberculosis Control Centre) selected at random ten persons under treatmerrt from each ot a set of three stwcy areas within a county or city.

This was done for each contra~ cerrtre region and the Dames were c()!!ll!llm1 cated to the assessmerrt officer ₁ and to this assess:ment otf'icer only. She then paid a surprise visit to the se~cted person and illdependently 1 to

~

^a) enquire about drug sdmin1stration₁ b) count residual tabl.ets₁ and

c) perform urine tests for

:nm and/

^or

^PAS.

•

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The assessment of'f'icers were requested to be as objective as possible and to retrain f'rom making comments or giving instructions to the patients or their families.

). RECORJlS AND THEIR ANALISIS

The f'ollowing record forms were used in the ^st~:

l

a) s1;anderd examination ^{card -} tor case-f'inding and f'ollow-u;p b) drug administration record .form - f'oJ: treatment

c) home visiting· record form - tor local staff visiting homes d) assessmeut record card - tor assessment otticers.

t For facsimiles see ~pendix.

Case-finding resul.ts were tabul.ated at the four control centres

• and then submitted to the central statistical of'f'ice with a list of' patients.

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Af'ter completion of' ^the final exam1nation a.f'ter one year, ^all forms tor all patients were forwarded to the central statistical of'f'ice together with ^all X-ray films. There a final radiological assessment ^{was made} and all records needed for analysis were coded and sent to International Business Ma.ch1ne

(IBM) ₁ Taipei, for tabulation.

4.

REBUmS

The raw data have been grou;ped and tabulated ful.ly in the tables appended; however, the main findings and achievements can be set out as follows:

4.1

Initial findings

4.1.1

stw1y popuJ.ation

For all the st~ areas, the total population vas over

300

000 p~ople. Of these,

:/3.Cf/.,

were aged 20 and over, while 15.~ were under

5

years. Thus ₁ diagnostic and control measures were directed at over one-halt of' the total population. The proportions actually X-rayed and tul.ly tuber- cul.in-tested were a little lower, viz. 32.~ and 13.1~ respectively, over

8$

o£ the target grou;ps nevertheless, (Tables 2 and

3).

4.1.2

X-ray examination

Abnormal X-ra.ys were reported in 7.1~ of' ^all rad.1ophotographs, and roughly two-thirds of' these (61.4~ of' the abnormal X-rays, or

4."'

of' all X-ra.ys taken) Showed signs suspicious of tubercul.osis, while about one- third

(:/3.6'1>

of' abnormal X-rays, or 2. 7j of' all X-rays) had evidence of' non-tubercul.ous abnormalities (Table 4) •

II

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Bacteriological exam1DA.tion

All peopl.e with radiological abnormal1ties were asked to submit to bacteriological follow-up ₁ and over 9~ of them co-opera-ted. ot those tested, one in eight gave .results positive for tubercle bac1l.l.1₁ vhUe the proportion among those with rad1ol.ogical suspicion of tuberculosis was higher

(18.5'1>).

N.B. Tubercle bac1lli were recovered from a few non- tuberculous X-ray suspects.

4.J..4

Treatmezrt

Eventually nearly

5000

people were pu:t on treatment, tor purposes of detailed st~ and analysis ₁ however ₁ a number were excl.uded f'rom the series. These com,prised those :who died during the ;year of' treatment, those who J.ei't the study areas in the time ₁ and those who ₁ upon f'iDA.J. assessment ₁ mainly radiological, were transferred from. the "tuberculosis ·suspect"

category to other groups, (incl.uding non-tuberculous patholog;y₁ healed lesions, and normal.). In addition, a smaJ.J. number of records were not avail.able for final ans.l.ysis and had :Likewise to be excl.uded.

4.J..4.J.

Adults' series (Tabl.e

6)

S;ynoptical.J.;y the adult series can be sUIIIII8rized thus:

El.igibl.e for X-ra;y X-ra;yed

Radiol.og1cal abnormalities Tuberculosis suspects Pat1ezrts treated

Series for analysis (Tabl.e 5.)

(after deducting

?1'7

reassessmentt~ . l.26 Cleaths

253 emigrants from study areas

l l sundries - dossiers unava1J.abl.e) Analysis based on the

4J.85

patients showed that:

(a) Rougb.l.;y .three-fifths coul.d be cl.assed as ^having ndn1mal tuberculosis.

One-fiitb. were cl.assed as moderately adV&Zlced, . but .•

without cavitation.

Nearly one-tenth showed moderate advanced disease with cavitation.

Other groups were: Far advanced without cavitation Far advanced With cavitation Pleural effusion

. (6o.51>)

(20.~)

! ^{9.l!j) 2.91o)} _7.J.1t)

o.J.1t)

(b) OVer two-thirds of the cases were male (68.~)(Table

8).

(c) The age distribution showed a peak between 40 and 49 ;years of age (Tabl.e

7): ·

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(d) Nearly three quarters of the patients were being treated for tuberculosis for the first time (70.~), while the remainder had been treated previously, (Table 9) •

4.1.4.2 Children's series

Of the children under

.5

years Of

ase

over ~· COIJIPleted tuber- Culin

test~

(i.e., tested and reactions

read~.

The proportion of reactors averaged

5·

~~ and over one-half of these children had no evidence of

preVious BCG vaccination (»). This left 1"'"5 children to receive prophy- lactic INH, but this number was reduced to 1267 for purposes of analysis, as a result of deaths, migration and unavailability of records, (Table 3) •

Comparison of subgroups

This can be discussed under two main headings:

(a) (b)

differences between the regions of each tuberculosis control centre,

differences between the gl'O\.TIIS of areas with different k1Dds of s~rvision of treatment.

4.1 •

.5.1

By region

Only general, and possibly invidious ₁ couments can be made under this heading: e.g. in ranldng the efficiency of the four centres using the

criteria of completeness of radiophotography ₁ bacteriological examination and tuberculin testing. Tainan came out at the top of the list, followed by Ch1ayi₁ Taichung and Taipei 1D that order. Again, the proportions of children under

.5

years of

ase

reacting to tuberculin showed up ditterences in the

extent to which BCG vaccination had been carried out to date. Correlations between the prevalence of active tuberculosis and the proportion of positive

childhood reactors is not so easy to establi(lh or interpret but may indicate that in Tainan large-scale case-finding had been less advanced than else- where ₁ judging by the relatively and absolutely higher prevalence both 1D

children and adults.

4.1.5.2

By

types of supervision

Comparison between the groups S\.Tilervised by health station workers alone, and by those assisted by voluntary workers or 1~ home visitors, is naturally important 1D the assessment of the relative merits and results of the three types of s~rvision. Not only were statistically significant differences in the prOportions between these groups not detected in respect of' the chief' measured criteria, but the actual differences

were

^{small and}

of dOubtful logical ilqportailce; thus the three groups may be regarded as essentiall.y homogeneous as required for a ~ison of' their results. At

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all. events this question will be more ~ discussed in Part II. Full aud val1d comparisons of work loads for the three groups or tor individual st1.¥cy areas is not easy ₁ but by way of example the range of bacteriologically positive cases per area may be·cited to show its extent: tuere were as fev as zero ₁ and as many as 33 such cases in any one study district •

4.2 Consideration of treatment

It will be recall.ed that although · clear-cut criteria in the select- ion of patients for treatment were

laid

^down in the prOtocol, the final classification of patients took place only at the end of the trial, erables l3 aZJd l4) • This introduced the complicating factor that a considerable number of patients "Which shoul.d have received combined therapy were in fact treated with Ilm alone in accordance with the initial classification. This group varied f'ran 24.~ of' "far advanced patients with cavitation" (correspond-

•

ing to 71 patients) to Y.}.5'J, of' "moderately advanced patients with cavitation" • {correspoud.i.ng to l56 patients). That reclassification was DOt the only factor

responsible for incomplete therapy is ^shown by the fact that 15.~ of bacter-

iologically positive cases

(128

cases) were treated by I11H

alone,

and l . $ of • treatable patients (69 patients) were not treated at all. A :further factor

with bearing on the evaluation of supervised treatment is that bacteriological con:f'irmation usually followed the begj nn1 ng of treatment ₁ so that streptOIJI1'c1n therapy

was

often added, 'Where applicable, in the second or third month of treatment ₁ and suspended six months later, i.e. ₁ in the seventh or eisbth month.

ot all the adul.ts receiVing· INH, 1.$ had to discontinue the drug because o:r side effects. ot a much smaller number taking PAS, 8. ~ had to

stop it 'While 9.fYI, had to give up streptomycin. Among the children taking INH,

o.4cto

^{had to} discontinue therapy because of side effects. Severe side effects necessitating suspension of' therapy usually occurred within the first three or f'our months, and earlier with streptomycin (Tabl.esl5₁ l6).

4.2.l Regula.rity

4.2.1.1 In drug coll.ection

· The fi:r;st index

ot

regularity and e,ssiduity.·of treatment for the two series (41.85 adults and 1.267 c:hildren receiViDS the~peutic aud ProtmY- lactic treatment, respectiVely, f'or 12 months in each case) is based on the proportion of indi.viduals coll.ecting supplies of' oral

dru8s

to be taken at home or attending f'or treatment at the health station. These proportions were worked out for eac:h successive month of treatment and can be seen in cleta1l. in Tables 17-1.8 and in Fip. l-2. Sulllllarizing these, it c~ be stated that, in the case o:£ the adults, nearly 9$ attended in the first lliouth₁ but the proportion decllned subsequently ₁ reac:hing a fairly steady val;u.e around

8$

in the last f'i ve months; the average proportion attending or ca~cting

treatment was 88.~. This may be quated in a different way; it is a8 thouah eac:h patient ₁ instead of' taking treatment f'or l2 months ₁ took on the aVerage ₁ treatment f'or l0.7months (Table 19). In the

case

of the cb11dren₁ the proportion dropped f'rom 98.~ in the f'irst month to less thaD ~ at the eDd of the year, with the averaae

at

85.$. This may be looked upon as the equivalent of' each c:h1ld collecting treatment f'or 10.3 months inStead of'

~ I

the 'Whole 12 moxrths (Table 20, Fig. 3).

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It is in conJunction with tbis ~sis .that the moat signii'icazrt d1ff'erences between groups (b;y supemsion) were recorded - these resul.ts will be considered ill detail in Part

n.

The next index of efficient ~rap;y is based on the proportions ot persons in the two series who collected treatment without defaul.t every month, tor total l.engths ot siX and twel.ve months (see Tabl.es 2l. ud 2}, Fig. 4). Among the adul.ts,

8o.$

collected their treatment regular~

(m.on~) tor six months, but after twel.ve months, this proportioJ:!. ^had dropped to 73·4~. Among the children the corre~ va,lues were

78.:fl,

and

69

.l.~. Here again there were signii'icant d1ff'erences according to the type ot s~sion.

4.2.1.2 By urine test

I t is DOt

enouah

to .col.l.ect drugs - they must · al.so be taken. The most rel.iabl.e 1ndex of selt..edm1n1 atration o:l! the drugs vas the test perto~

b;y the assessment officers on the urine of patients and chil.clren under therapy.

The pl'Qtocol. envisaged approximate~

one

test on the urille of each person receiving or taking treatmeut during the ;year. In fact, tests were carried out (once) on between one-halt and two-thirds of the groups ill question

(Iml in adul.ts and children; PAS ill adul.ts). The average proportion of Iml excretors among adul.ts was (:bl,, with irregul.ar monthly tl.uctuations ₁

thousb

in general. biaher figures were obtained ill the first six months than in the second half' or the year (Tabl.e 25₁ Fig. 5). The average proportion or PAS excretors among those al.l.egedl.;y tski ng the drug was 6J..

:fl.

₁ again w1 th ir- regul.ar rl.uctuations, but .a teDdency tor lower figures in the second halt Of the year (Table 26). Amorlg children supposed to be taking

nm,

the

averaae excreting rate vas 5l..~ with a similar telqporal pattern (Table 27).

Ditterences between groups under diti'erent supervision were l.ess marked here, aDd in general. not statistically significant (Tables 28,

29,

30₁ Fig.

6). .

4.2.1.} By tablet counts

These reaul.ts are corro~rated i~

a

^general.~ by the f':indings

~· involving tablet counts at the. tiiDe· of 1;he visit .or :tile assesment nurses.

•

The proportion· ot occasions wbeQ the theoretical llUIIIber of' tablets vas found

(:t

J.CJ1, tol.erance ~gin) was o~ 34:-~·(Dm-adul.ts), 20.l.1o (PAS- adul.ts), and 26.21o (Iml-chil.dren). Of the rema:hVler, most showed an excess

over

the theoretical number of' tablets eJC;Pected in their possession. Thus, tor instance ₁ about oue-third of' the adul.ts. had an Iml smpl.us exceeding the elq)ected number by 2CJ1,; .however, there were small numbers of' people (6-J.CJI.) with l.ess than the anticipated number of' tabl.ets 1D their possession - these

incident~ do DOt incl.ude those wbo were di.scovered DOt to have collected their tabl.ets to.r a month or more (l.O.~ of those visited by smprise)

(Tabl.es

31-.36

1 Fig. 7-l.3). Significance tests tor di.tterences between the three supez:rtsion groups showed positive results, as w1l.l. be seen 1D Part

n.

Cbanps ^1D radiol.ogical. signs

Six mont.hs after the

start

of treatmezrt there was a radioJ.osical.

assessmezrt of the patients. This covered. about a~ of' .the patients aDd

ot the Dl.llllber examined, about

one-third (33.5'1a)

showed improvement, a small.

- ~0 -

proportion (2.4~) deterioration and the remainder (64.~~) no perceptib~e change. AB many as possible of' these patients were X-rayed. again a:tter another six months ¹ treatment ₁ and in gene~ there was less evidence of' change in this second period. This radio:Logicu quiescence was the common- est f'1nd1ng both in the grou,p that showed initiu improvement and in the group that deteriorated at first ('lable 4~, Fig. ~7).

Taking the series of' adults as a whole, 82.~ were re..;x-rayed at the end of' a year's treatment, and by comparison with the initiu X-ray 59 .1~ showed no chrmge, ~. 9'1> showed il!lProvement 1 and 4. (1/, deterioration.

On the whole, advanced non-cavitary disease responded best, and the ~east

response was noticed in advanced cavitary disease and in minilllal lesions.

There were no significant differences between ~ groups tmdar different supervision (Table 42, Fig. W).

Speciu note was taken of' the proportion of cavity c:Losures: ~3.~

c:Losed in the first six months, and a f'Urther 5.~~ in the second six months. • The rate of' new cavity formation in those without cavities at first was less

than ~~ in each six months period, but higher in the first six months.

About ~(1/, of cavities that c:Losed in the first six months reopened in the • second h~ of the year. There were no significant differences in rates

among the groups under different supervision (Tables

4.5-48,

Fig. ~9).

Cha!!ges ⁱⁿ bacterio~ogicu status

Of those e-xamined at six months who were originally positive, 11-~~ had become sputum-negative but it must be borne in mind that this resul.t was based on examination of a single specimen. On the same basis,

2.4~ of those origjnaJJy negative had become positive. Follow-up at ~ve

months of those positive at six months showed a further

47.£4.

conversion to negative (this was higher among those who had become positive cbJr1ng treat- ment than among those initiUly positive). Assessment at twel.ve months of as many as possib~e {84..~) of those who had or:lgjnally been positive showed that of this totu

75.£4.

^had beca~~e negative, wh1l.e

3.r:J!,

of those initial.q negative had now become positive. Minima] l.esions were ^the main contributor to the former grou,p ₁ while advanced, cavitary lesions contributed most to the second. In generu, there were no significant differences between groups under di.ff'erent supervision (at any rate as far as conversion to negative status went) (Tables· 50-52·₁ Fig. 20 and 2l).

5.

SlJ!.H.RY AND CONCLUSIONS

:Between August

1963

and January

1965,

a study was conducted in Taiwan to test domicillary treatment ^and chemoprophylaxis of' tubercul.osis on a new scal.e of intensity and supervision.

While ostensibly the study was designed to COfiiP8.re the val.ue and resul.ts of three ditf'ereut types of' supervision, it cl.ear}Jr al,so offered an opportunity to assess case-finding, therapy ₁ and follow-up ₁ both in their technicu and adm1n:Jstrative aspects, as well as shedding further l.igb.t on the patients' co-operation and their role in tubercul.osis control..

•

"

..

•••

•

•

•

- l l -

Two groups in the st~ population scattered over 60 districts throughout Taiwan were screened and :f'ollowed-up, viz. the adult population

(20 years ^and over) SDi the children under

5

years. In the latter group, positive reactors to tuberculin in the absence of' previous :SCG vaccination were given INK prophyl.actical.J.y for twe~ve months, wh1J.e in the former group, those showing rad1olog1cal. abnormal.ities were submitted

to

bacterio-

logi~ tests ₁ and :f'inally bOth bacteriologically proven cases and radio-

~ogi~ suspects of tuberculosis were treated for the disease for ^twe~ve months. In the st~ population, 4.4~ of' the adults screened were treated, and 2.g/, ^of' the children tested. In terms of the total. population, ~.~

was treated. A lllin1mulll estimate of treatable (probab.cy active) pulmonary tuberculosis in the population was L4~, and the correspODdiog ~ue for infectious pulmonary tuberculosis was 0.2(;fl.. ·

From the detailed w;bles appended, it is possible

to

gauge the completeness of' each ^staae of' case-:f'ind1ng, and so the e:f'ficiency of' this aspect ^of' tuberculosis ^contro~ which depends ^~ge.cy on ^contro~ staff' ₁ particula.r.cy their capabUity in discharging the responsibility. of' educa- tion o:f' the public •

tJnHke case-f'in<Hng, treatD!nt which is ^~ge.cy domiciliary and seU-adzn1n1stered₁ depends more on the co-operation of the patients. In this .st~ ₁ both the i'requency and regula:city of' co~ction of' drug supplies was measured and.~o an estimate

was

formed of the extent and regularity nth vhich these drugs -were ^actual.cy ingested. With varying degree of

supervision( 88.~ of the adults, aDd

85.$

of' the ch1l.dreD collected (on the averaae J their drugs :f'or the llhole trtu period of one year, uthough

init~ the proportions were higher, ^and towards the elld of the period:, J.ower. On the other hand, the proportion of cases llho₁ individual.ly, collected their drugs without de:f'ault throughout the ^twe~ve months

was

73.4~ for adults ^and 69-~~ for ~dren. Estimates of' drug seU-sdministra- tion -were based on surprise visits for tablet counts and urine tests (for excretion o:f' products of' drugs) • ^These indicated that betveen 2$ ^and

3':Jf.

(approx.) of' INK-takers were regular (by tablet counts), but excretion tests

yie~d higller figures -between 5~~ and fBI, approximate.cy.

In measuring the more objective criteria of tuberculosis treat- ment, viz. bacteriological conversion₁ radiological improvement (including especially cavity c~osure) ₁ the st~ again yielded valuable data tor comparison with other series: e.g.

36.g!,

showed radiologi~ im,p:r:ovement;

~$ of iDitially cavitated cases showed closure, but the total proportion ot cavitary disease dropped on.cy from ~6.~ to ~5.4~ over the period.

or

those iDitially bacteriological.cy positive, 75.£4 converted to negative, llhile

:J1.

of' the initially negative reverted to positive.

There are many BlM!Cial features of' this ^study llhich deserve further anal.ysis; these ₁ and the detailed com;parisons of the methods of' supervision ~.be dealt nth in subsequent parts of . this report •

-12-

PARr II·

A COMPARISON OF~ TXPES OF SUPERVISION OF DaaCILIARI TBEATMI!:Rr . .AMD CllEMCIPROPRYLAXIS FOR 'rUBERCULOSIS

IN 'l'AIWAN

The comparative stuq ot chemotherapy conducted at the TubercuJ.oai.s Chemotherapy Centre in Madras, IDdia has clear~ shown that

treatment

wi.th IIm and PAS can give results as good in the heme as in a S&ll&torium or hospital. .Hovever, the conditions UDder llhicb. outpatient treatu.nt was carried

o\rt

in that stuq wre not natural.. 'J!he work

vas

doDe by a large ₁ highly trained, well equipped and aevoted team llhicb. could well attord the time to obtain the confidence of patients and familles ₁ and to supervise them ^close~.

!rherefore it can be assumed that, 1f the ~evel of regularity in drug collection and adm1n1 stration had been lower then it actual.ly was, the results of home treatmeut migb.t not have been comparabl.e wi.th those obtai.Ded in hospitals. ~ the other hand, it is generally believed that tAe main reason for the failure of treatment ( whi.cb. is not 1Df'reque~ seen in the

~ outpatients clin1cs elsewhere) is the patients ^{1 ·} failure to take drugs

regular~ for a suff'icie~ long period of time during the course of treat- ment.

For this reason, it can be postulated that the key 1oo success ot a cSomic111ar;y chemotherapy programme lies in adequate supervision of patients over their collection.BDd taking of drugs.

The present starting pattern of the health stations in Taiwan

cert~ cannot previae en adequate amount of supervision tor patients ₁ especial.l;y when a large number of patients is discovered at one time. In view of such a situation, the possib111ty of exploiting the hwilan resources of the ccmmnm1ty for the supervision ot. tuberculous patients has. been

considered. !he emplo)'lllent of aux1.l.iar;y workers to help the existing health station workers in supervising domicillar;y chemotherapy is oae such possib111 ty.

However, before me]d ng recCIIIIJI8Ddations to the Govel'D11811t for the em;plo)'lllent of ~home visitors in the health stations on a general scal.e, the value of such people should be obJective~ evaluated. Part I of this report gave the aeta1led organization and administration ot a stuq aesigped to test the relative merits of three types of supervisors_, name~ health

station staff working alone_, 8Z1d in conJunction wi.th either voluat;ar;y workers or ~home visitors, sel.ected aDd. trained as indicated.

•

^•

•

..

•

J

•

e

•

•

•

- 13-

It was not o~ desirable, but essential that the groups of patients to be treated should be statistical.ly homogeneous ₁ so that .

cOIQP&rtso~ could be effected. In principle it was hoped that by taltillg' areas served by "average" health statiollS this ^would be achieved, but; ill practice the additional safeguard was introduced as described, whereby ill

allY one county or city a ^B811!Ple of three cOJJ;)arable health statiOilS was chosen, and to a sector of each was allocated, as randomly as possible, oue of the t;ypes of superv.l.sion. Thua ₁ allY systematic influence exerted by health bureaux wouJ.Q. a.f'f'ect equal II.UIIIbers of areas under allY oue regt.men

e~; and by arrang1Dg for each tuberculosis control ceutre to cOI:Xtribute equal numbers of study areas ₁ the same effect would prevail. - i.e •₁ no oue systalatic influence would exert an 'UDdue weight~ (Tables 2-9 and ll).

Evaluation of results b;y type of supervision eventual..l.y bore out the e:rtectiveness of these precautions ill planning: 'Whatever small d11'ferences ill nuribers or percentages

arose

between areas under d11'fereut supervision, these wre show to be atatisticall.y not significant;. ill particular this was truear the following:

}.1 3.1.1

(a) total numbersof patieuts and cb1Jdren to be treated (as fractiOilS or sazll)les of the parent populations) ; (b) numbers of patieuts ^and children ^dying or moving out ^of

the study areas

dur:lDs

the trial;

(c) classification of patients by severity Qr type of les1011.Si (d) classification of patieuts by age and sex;

(e) classification according to previous anti-tuberculosis treatmeut;

(f) proportion of bacteriological.ly positive cases •

Drug collection Adults

The average of the ^month~ proportions of patients who collected drugs was 88.~ (over the year of the trial) 1 but in the case of lay home visitor (LHV)-supervised patients the average was 93.5%, and it was

86.9i

in the health station worker (BSW) groups and 85.~ in the voluntary worker

(vw)

group. Using the equivalent measure of mori; hs of treatment the values were 10.7 months (whole group), 11.2 (LHV group), 10.4 (HSW), 10.3

(vw)

(Tables 17 and 191 Figs.l and 3). The superioriq

ar

the IBV group over the others is significant at the

5'/J

:1eve1₁ while the difference betweet;t the other two groups is not significant •

II

II

II

II

- 14 -

The proportion of patients 'Who atteDded eveey month tor the f'irst six months to collect treatment ws 8o.8j tor the whole group. For the different tol'IIIS of supervision the results were: 90.-rJ, (IBV) ₁ 15.9'/. {HSW) ₁ 75.1'/. {VW) (Tables 21 and 22₁ Fig. 4). ^After one year of treatment, the

proportions 'Who had attended eveey month had dropped to 73.4'/. {whole series}, 87. "» {IBV) ₁ 65.<J1, (HSW) ₁ 66.9'/. (VW) (Tables 23 and

24).

The superiority of the IBV group over the other two is sigpif'icant at the ~'/. level.

3.1.2 Children

The average (over the 'Whole year) of the montbl.y proportions ot

children 'Who collected

:om

vas 85.~; tor the IBV group it vas

98.4'/.;

tor HSW

80.5'/.

and tor VW

77 • .,;,.

In tel'IIIS ot equivalent months ot treatment, the Yalues are 10.3 (total group), 11.8 (IBV)₁ 9.7 (HSW) and 9.3 (VW).

The superiority of the IBV group over the other two is sigpif'icant at the 1'/. level (Tables

l8

and 20, Figa. 2 ^and

3).

The porportioas of cb1 J dren 'Who came to collect their cfrugs eveey month for the first six months were as follows:

78.5'/.

tor ^the whole series, 97 .(JI, for IBV group, 72.(1/, {HSW) and 65.

'1'/.

(VW) (Tables 2l and 22). Taken over the 'Whole year ₁ the proportioas of children 'Who collected their drug

eveey month dropped to ($ .1'/. (whole group) ₁ 95.6j {IBV) ₁ 55.1'/. {HSW) and

56.2'/.

{VW) (Tables 23 and

24).

The superiority o:t the IBV group over the other two is sigrl1.1'icant at the

1'/.

^level, both at six and at the twelve months.

:Bef'ore leaving this section, it is worth pointing out that in general, the HSW group gave slightly better results than the VW group ₁ though the d1t:terences were DOt statistically sigpif'icaut.

J:t will be recalled from Part I that results in this section are based on the data collected by the assessment officers on their surprise v.Lsits made in accordance with random sampling determined by the central statistical office.

3.2.1 Urimtests

3.2.1.1

Adults

The general proportion of tests positive for

:om

^ws

68.0'/.

^over

the twelve months. In the IBV group the proportion was 72.1'/.₁ 67 • .,;, in

the HSW group and 63.9'/. (VW) (Tables 25 and 28). UriDe tests :tor PAS

wre

positive in 61.5'/. o:t the total series, and the Yalues tor the three supervi- sion groups were 64

.TJ,

(IBV), 63.9'/. (HSW) and 57."»

(vw).

These d1t:terences turned out not to be statistically sigrl1.1'1cant (Tables 26 and

29,

F1p.

5

and

6). . .

3.2.1.2

Children

For the series as a whole, and over the twelve months, the proportion of tests positive for

:om

^{vas 51.$; the} proportion in the LHV group vas 57 .9'/., in the HSW it vas 44.8'/., and 51.6'/. in the

vw

group

•

•

·-

... -

•

c

•

-

~5-

(Tables

27

^and

?IJ,

Fig.

6).

The d.1fi'erence between resul.ts obtained with

~ supervision as against HSW supervision turned out sipif'icaut at the

Jill leve~.

Tab~et co\Dlts

It will be re~ that when, at the time of the surprise visit actual stocks of drugs were compared with the quantities e:x;pected to be ¹ tO\Dld, but allowing a ~(1/, tolerance margin either way, only a reatively small proportion of instances ^lBB fO\Dld to satisfy this test (Tables 3]. and

~ .. Fig. ~0).

3.2.2.~ Adults

A totU of ~0.71

ot

patients visited had falled to collect their I1'IH tor a month or more. The proportion in the UN group was

6.2$,

in the HSW ~.(jj. ^and ~3.;4 in the VW group; ~. 7'J, of the relll8.inder of the whol.e

series teld.ng INH was found to be in possession

ot

the riB).lt n1,1111ber of tablets • ~(1/,; in the UN group the proportion was

47.?fl.,

^{in the} HSW group

29.ryf., iii

the VW group 26.~ (Table ~~ Figs

1

^and ll). For PAS takers, the

gene~ proportion was 20.~~ .. but the aeries was rather too small to permit rellabl.e coq>arison between supervision subgroups (Ta~e 35, Figs 1 and 12).

Turning to the proportion with a surp~us of tablets exceed.1ng 2~ of the e:x;pected number, it was f'ound to be ~-~~ of the general se.ries, 23.?fl, of' the UN series,

36.9'/>

of the HSW series and 36.$ of the VW group (Fig.

8).

The d.1fi'erences between results obtained With UN and those in the other two groups -were significant (usually at the ~~ leve~) ₁ indicating that in the IBV group a truly smeJJer proportion failed to collect tablets, a truly greater proportion appeared to ba consuming tablets at the (approximate) upected rate, and a truly smaller proportion agged in its consumption, thus accumulating excessive stocks.

3.2.2.2 Children

A totu of ~o."' of cases visited were fo\Dld not to have collected their INJ:t tor over a month, but the percentages tor the supervision groups -were l l . $ (UN), 23.&/> (HSW) and 24.~~ (VW) (Tab~es 33 and 36, Figs.

8

^and

13).

o:r

the remainder, 26.~· were found to be in possession of the e:x;pected number of tablets ( + l~) ₁ or

33·

'71in the IBV group, 23."' in the HSW group and 20.?fl, in the

vw-

group. Those with stocks exceeding the anticipated number by more than 2(1/, were

36.7'/»

of the totU series, or }4.?fl, of the IBV group, 36. ?fl. of' the HSW group and 40.(1/, ot the VW group (Fig.

9).

Again, signif'icance tests show that the LHV group fared definitely better than the other two ₁ at least as f'ar as collection of' tablets 'Went and as regards

having the risbt number of tablets ₁ but there -were no sipif'icant ditf'erences among proportions lett Vith a arge surplus of the drug.

3·3

SUpervision as measured by the extent of home visiting

It ^will be recUJ.ed that all three types of super.visors were

eJC;PeCted to trace treatlllent defaulters promptly, and that LHV were in add1-

\. tion expected to visit all persons UDder treatment twice a month at least, while HSW and VW' s were asked to do their best in the way of home visiting •

•

I I

II

I I

I I

II

I I

I I

! !

II

- 16 - .

Over the twelve months ('When twenty-four visits might be expecte.d per person under treatment) the LHV's actua.J.:cy visited adlllt patients 21.1 times on the average and chhciren 19.6 times; by compartson the corr.spond.Oo ing figures for BSW's were 4.1 and 3.4, and for VW's 6.1 arod 4.6 (Tables

31

and

38,

Figs. 14-16) •

.

3.4 Radiological changes \mder treatment

The main results as picked ollt fran the relevant Tabl.es (41-48, 53-56 and 59-62, Figs. 17-19) were olltl.ined 1D Part I. Withollt going .into detail it can be stated here that there were no significant differences 1D results between the groups under different supervision. This is true when the main trends are CO!Iilared (improvement, no ^change, deterioration) and also when the rates of cavity closure are caqpared. The only minor exeeption relates to the rates of new cavity formation, which

are

significantly higher

•

(at the 5'1> level) in the LHV group than 1D the other two. •

3.5

Changes 1D bacteriol.ogical. status under treatment

Again the reader is referr.d tor the general treDd of results to Part I (Tables 49-52, 57₁

.58

^and 6:;, Figs. 20 and 21) • Caqparison of results

ob'M.1ned under the three methods of supervision shows that, after six months positiw-to-neptiw conversion rates were higher in the LHV group (79.&)) than in the other two (75.71>), b1%t at the eDd of the year, the HSW group had

the best rate (78.~) ₁ followed by the VW group (75-~) and the LHV group

(73.5j):

the differences howewr were DOt fo\md to be signifieaut statist- ically. Negative-to-positiw rewrsions at six months were 2.Sj tor LHV, . 2.-, for HSW, and .1. ~ for VW ₁ bllt after one year the figures were :;. '(1, for the VW ^group,

3.5'/>

for the LBV ^grorq> and l.Sj for the BSW group. This latter result alone is significantly {P <0.01) 1Di1cative of superiority of the HSW group over the other tvo.

4.

CONCWSION

A ~ of patients vith actiw pulli.:>nary tuberculosis and a group of children under

5

years of age, spont&Deously reacting to tuber- culiD, were divided. into three statistically ~le series and treated . tor twelve months, the regimen largely depending on domicil.iary admin~stra­

tion of oral t!lerapy. ODe ot the series vas supervised by health station staff worke~s alone (HSW), another by these plus voluntary -workers (VW), and the third by the health station staff plus lay home visitors (UlV) • The same basic training vas given to all these supervisors.

Results of the trial, for both adults and children, are shown as follows:

(a) The LHV's provided the most assiduous domicil.iary cover and f'ollaw-up; Dext came the VW's followed. by the HSW's.

(b) Cases 1D the

mv

group collected tablets .more regularly and for a larger proportion of time during the twelve months than those in the other two groups.

•

•

•

"-

-

• ^{- 17 -}

(c) Self'..atJm1n1stration (or parental ai!m1n:lstration) of drugs was significantly more complete and regular in the mv-supervised group than in the others, Judpd by (independent) assessment .of urinary excretion and by residual tablet counts.

(d) In general, the BSW group showed slightly better resul.ts under (b) and (c) than the group supervised by HSW + VW ₁ though the dift'erence

was not significant.

(e) Radiol.ogl.cal changes in the three groups ₁ after six and t-welve months of treatment ₁ shoved s1mil.ar patterns in the three groups, w:l.th insignificant differences betveen them. This applies both to general progress and to cavity cl.osure.

(f') Bacteriological status changes after twelve months showed no significant differences betveen the three groups ₁ but the HSW had the best record for conversions from positive to negative sputum.

• (g) It is hard to separate the effects of the patients ¹ own co-

•

operation from the additional results of supervision (as there was, strictly speaking, no true control, i.e., totally unsupervised-group), and factors possibly obscuring real differences in therapeutic achievements between the groups are discussed (including the effect of' health station treatment of' the severer cases for the first six months) • Finally ₁ the case f'or mv ¹s rests on the fact that BSW supervision ~ be adequate vhen only 2(1/, or less of selected health stations ¹ territory is covered, but could hardly extend to the whole province at this level of thoroughness for an indefinite period •