Ptoc,fi¢el GaicfeUbes; fort)a"

Control and MQ.."ag~nl'ent ,of ,Tuberculosis

2nd edition

Ministry of Health Malaysia

Academy of Medicine of Malaysia

Contents

Page

List of contents

iii

Foreword

vii

Ackn owl edge me nts

viii

List of committee members

ix

1. Introduction

2. Epidemiology

3. Diagnosis of Tuberculosis 3:1 Pu lrnonary Tuberculosis

3.2 E'xtra, pulmonary Tuberculosis 3.3 Screeninq of high risk, groups 3.4 Notification of Tuberculosis 3.5 Tuberculosls Classification 3.6 Definition of terms

3.7 Radioloqical Classification

3 3 5 6' 7 7 9

10

A. Treatment Of Tuberculosis 4.1 Treatment cateqories

12 12

4.2 Chemoth era p.Y 12

4..2.1 Druqs 13

4.2.2 Treatment regir'hens 13

4.2.3 Anti-tuberculosis drugs & the 15

recommended doses

4.2.4· F I ow cha rt fo r rece rnrnend ad treatrn 8nt16 regime

iii

Page

5. Patient monitoring

5.1 Treatment response 5.2 P.atient compliance

17

6. 0 f"l1g tdxi c.Ity monltorl ngano m~n,a.g em e nt 6:.1 Monitorinqfor qrug toxicity

6.2 Management of drug toxicity

19

7. Management of tuberculosis in special situations 23

7.1 Tuberculosis in .ehildren 23

7.2 Tuberculasiadurlrrqpreqrtarrcy & lactation 25

7.3 Tuberculosis treatment for Women takin:g OCP'26

7.4 Tuberculosis in pattents with ltver impairment 26

1.5 Tuberculosis in patients with renal Impairment 27

7.6 Extra pulmonary tuberculosis. 27

7.7 T u berc ulosis 1 n p atlents with H IV infection 27

8. Fixed-dose combinations (FOG) of antituberculosis drugs

a.1 Advantages

8.2 0 isadva ntages

29

9. OOTS-O,irectly Observed Treatment, short-course .31; 9.1 Advantage.S'of DOTS

9.2 DOTS? in Malaysia

32

10. Defaulter tracing and retrieval 10.1 Detinitionof defaulter 1,0.2 Contact management

11, Outcome analysis

34

lV

Page

1 Z. Management of Resistant Tuberculosis 12,1 Definilion

12.2 Manaqernent of resistant tuberculosis

12.2.1 Pha rrnaeo I ogica ltreatmertt 12.3 BeG vaccination in Malaysia

12.4 Tuberculosis in forei,gn workers 12.5 Cherno prophylaxis

35 35 35

37

13. Prevention of Tuberculosis among Health Care 38

.\ . .., ..

WorkeT~ (H'cW)

References 41

Appendix 43

Foreword

The World Health Organization (WHO) has a,6know:ledged the fad that Tuberculosis (TB) is re-emerging in many parts of the world with a vengeance. This led to WHO declaring TB as a global emergency in 19KL Amongst others,the HIV pandemic ClS weJl as glQb~1 complacency and rreqlect towards the dis;ease_wSrEl identified as the principal factors causing the resurgence.

Although the situation in M~J9ys_ia_ is not as alarming as in many other parts otthe world, the latest statistics appear to show that TB as. a health probl.em i,s on the increase. HIV infected population afflicted with TB is, increasing and they form the major killer among this populaJion grou p.

Therefore it is timely that our doctors are armed with the. latest knowledge and strateqies to combat this scourge. This booklet, prepared by doctors and paramedics from the Min·i5try of Health and the Unlversities is to fulfill this aim. In particular; it ls hoped that with theeffe::etive implementation of 'the DOTSstrateg.y and appltcatlon, TBas a health problem would be- greatly reduced, if

not e_Uminated in the not too distant future. -

This booklet will certainly be of benefit to all primary care doctors andalso everyone else who manages patients with TB.

I also wish to conqratulate the committee for coming out with this valuable booklet.

TAN SRI DATU DR HJ MOHA DIRECTOR GENERAL OF HEA· MALAYSIA

vii

Acknowledgements

We would llke to thank the tollowinq for providing greeH support in produCing this booklet .

• :. Tan Sri Data' (Qr.) Abu Bakar bin Date' Suletman Director General of Health {retired)

(. Datu' Dr Moharnad Taha bin Arif Director General of Health

.:. Data' Dr. Kew Siang Tong

Head of Department (Medical Unit), Hospital Kuala Lumpur

.) Dr. Lee Cheow Pang

Director of Disease Control Divistcn jretlred)

VIII

Committee members:

1. Dr Hasan Abd Rahman

2. Dr Fadzllah KClmaludln

3. Dr Zalnab Ramll

4. Dr I. Kuppusam'y

5. Dr Aziah Ahmad Mahaylddin

6. Dr George Simon

7. Dr Hpoi Lai Ngo.b

B. Data' or Abd Razak Multalif

9. Professor Liaril Chong' i{iti

10. Dr Jeffrey Abu Hassan

11. Dr Tan Eng Keong

12. Dr Ashari Yunus

13. Dr Norhaya Mohd Razaf

14. Dr Norzita Mohamed Zainudin '15. Dr Wan Manser Harnzah

16. Dr Karnallah Mohd Noh

'17. Dr Fariza Mohd Yusof

18. Dr Jenarun Jelip

19. Or Norhizan Ismail

20. Dr Aishah Senin

21. Dr Yeo Peng HWi

22. N.ursing Sister Puan Christi Philips

23. Health Inspector Encik S. Thruqnasarnbather

IX

INTRODUCTION

1. Introduction

Tuberculosis (TB) as a health problem has been with us from time immemorial. Ever since the' early 50's, the Malaysian G.overnment has realised its magnitude in terms of human suffering and mortality. Hence enormous resources were injected, in terms of finance and manpower to 'achieve a situation where if becemejto lonqer a public health problem. However, in recent years tuberculosls has re-ernerqed .as a major threat in terms of rnorbidity-and mortality qlobally, ~ore recent statistics testify that tuberculosis cases areeltheron the, rise or stagnating.

Today, 50 years after the tntroduction of chemotherapy for tuberculosis, there are, still eight mlllion nE!W iafectious cases detected allover the world. Mycobaetwium,tub'erculosis probably kills more adults (three million) each year than any other single infectious pathoqen'. Since tuberculosis primarily affects those in their most productive years" the isocic-econcmic implications of the disease are tremen-dous. The rnaln reasons for this are attributed to the followihg:

(I) The rising incidence Of HIV/AIOS worldwide and the' close interaction b_etween tuberculosis and HIV/AIDS.

(ii) lncreasinq international migration.

(iii) The rerrtetqerrce of mUlti-drug resistant tuberculosls (MDR TB).

(iv) Economic: strife, war, tarnlneand natural disasters which disrupted exlstinq Tuberculosis Control Proqrarnrnes.

(v) Decr-eased awareness about tuberculosis amongst rned 1(5al personnel including doctors.

(vi) The low priority given to tuberculosis control in terms of resource allocation and training.

(vii) Changes In global population demography.

In Malaysia OVer the past 10 yean~ there has been a steady increase in yearly notlfication of flew cases of tuberculosis (infectleus cases and allformsl.!

fl EPIDEMIOLOGY _--

Mycob9ctf3r:ium tubereutosi» infects a. third of the world's population. There were, eight rt1illicmneW cases per year (1995)2, Ninety-flvepereertt of fuberculosis cases arid 98% dftuberculosis· deaths are in developinq countries, Seventy-Five percent of tuberculosis cases in developing countries are In the eco nom i ca Ily prod u ctive Eigegroup (15~ 50 years), Sin oe the early 19905 mostcountrie,s have reported either lncreased notification or stagnation in number of eases,

2_ Epidemiology

In Malaysia-for-the year 1999; 14908 new oases ottuberculests were reported. Majority 'of the-cases were in tM1S-50 years age group. There were 603 cases of H lvand tuberculosis coinfections notified for the same year. The total number of deaths 9U!3 to tubereulosis reported was 853. This makes tu be rcu I osis th e si ngle most important kill era m:an 9 st notifiabl e ihfeQiious. diseases in Malaysia.

2

3. Diagnosis of Tuberculosis

Diagnosis of tuberculosis is based on clinical. radiological and/or bacteriological evidence'.

3.1 Pulmonary tuberculosis

The commonest form of tuberculosis in adults is postprimary pulmonary tuberculosis. It is the only form of tuberculosis which is infectious and thus has qreat epidemioloqlcal "sig n'ifica nee .

3.1.1 Symptoms & Signs

Symptoms which suqqest pulmonary tuberculosis include:

- Cough persisting for more than two weeks

- Cough with sputum which is occasionally

bloodstained' ,

- Loss ofa_ppetite and loss of wei_ght

- Fever

- Dyspnoea. night sweats, chest pain and

hoa rseness of voice ,aH of wh lch a re not common

P:atiehts with the above symptoms should be: screened for tuberculosis.

Signs can be-subtle espeoially in minimal cases, or may be obvious including those ',of cortsolldatlorr, nbrosls or stony .dullness caused by pleural effusion.

3.1,.2 Investigations

The laboratory investigations Include sputum directsmears for acid-fast bacilli, which are usually positive in cavitary disease. Three, specimens, preferably including one early morning specimen, should be collected - for diagnosis. Culture using egg-based media takes

3

up to 8 weeks fora final result. There are radiometric methods such.as the BACTEC, which can give results within 2 weeks. These can be used when there 'is a need for early diagnosis and in smear-neqatlvecases. Sensitivity tests us-ing radiometric methods, which yield equally rapid results" can be performed il1 situations wh ere d fU@ res i sta nee is sus pectadand urge rrt results are required. SpeGimensobtained via bronchoscopy can be used for the above tests.

Chest x-rays often reveal lesions Inthe apical and posterior segments of the upper lobes. Lesions are often soft in active pul mcnary tuberculosis and there is usually little or no fibrosis or ealcifieation. These latter findings would sl,Jggest healed tuberculosis. Cavitles sugqest the diagnosis of active disease unless the- patient has been previously treated. Apart from the typical sites at the apices, other sites such as the apical segment of the lower lobes may also be involved.

the tuberculin or Mantoux test has some rqlein the ,diagno$'is oftuberculosts especially in pediatric cases and cases of extra pulmonary tuberculosts. The Mantol,lx test is carried out in government hospitals in Malaysia using 2 tuberculin units (T.U.) in 0.1 ml of prepared solution. The result is read after 72 hours. A diameter of indurations of less than f Omrn is grad_ed as negative but this does not exclude Cl. diagnosis of tuberculosis. A reading of1 Ornm or more in a child or adult is considered positive. A diameter of 16'mm or more ina child is considered significant and may indicate recent lnfection. A positive Mantoux test merely indicates tuberculosis infe-ction and not necessarilyactlve disease.

The erythrocyte sedimentation rate (ESR) has little role and cannot be recommended for routtrre use in the diagnosis ahd follow-up of patients with tuberculosis.

4

Recently developed diagnostic tests utilizJng nucleic acid amplification by polymerase chain reaction (peR) can give rapid results but are expensive, sincethese tests candetect small numbers of orqanisrns, talse-posltlve reactions may result from cross-contamination in busy clinicallaboratories;fa[se-negatives may result from the' presence of inhibitors or lack of target gene sequences in the causative strain. However it must be remembered that =cn can give a positive result in patients who are already on anti-tuberculosis treatment who are excretlnq small number of non-viable bacilli, thus this test is not 0.1 Value fbr follow-up of patients on treatment."

The value of serological tests. for tuberculosis should be studied in various operational: situations before theyare widely applied. Newer serodtaqnostlc tests' using purified antigens have good specificity but lower sensitivity than culture for tubercle bacilli."

3.2 Extra pulmonary Tuberculosis

ThiS IS mainly due to lyrnpho-haematogenous dissemination during' pri mary tubercu lesis i ntectlon.

Symptoms are often non-specific, Including lassitude, anorexia, fever and weight loss. The specific features relate to the organ involved.

Tuberculous .lymphadenitis can be diaqnosed by fine needle aspiration (FNA)of qlands which are accessible especially in the neck. The specimen should be sent tor direct smear, culture for tubercle bacilli and cytological examination. Biopsy may be needed in cases in where res-ults from fine needle. aspiration are negative.

Tuberculous pleural effusion is diagnosed from pleurocentesis and pleural biOP$Y. The pleural aspirate

5

on-en reveals straw-coloured fluid with protein> 30 gil, low glucose « 30 mg/dl)_, and with cells (mainly Iymphooytes). Direct smears and cultures of the pleural fluid should be requested for.

The diagnosis of genito-urinary tuberculosis can be made from radiolcqlcal tnvestlqations CIVU)ahd culture of urihe for Mxcobaclerium tubercutosie. Genital ftlberculos';s requires tissue biopsy for confirmation.

Tuberculosis of bones and joints is often diagnosed from x-rqys and tissue biopsy. The diaqnosis of tuberculosis of intestines and peritoneum would require tissue biopsy and bariumstudies. Diagnosis of cutaneous tuberculosls may be" made. by skin biopsy,

MilIary tuberculosis is often diagnosed on plain chest x-ray althouqh liver biopsy Is sometimes done and may reveal granuloma.s in I.JP to 88°/'; of the cases.! Dlaqnosis of tuberculous meningitis requires cerebrospinal fllJid for microscopic, biochemical and bacteriological examination; h.owever the patient is often iii and there is a role for a therapeutic trial of anti-tuberculosis treatment in these cases. CT scans of brain can help by showing features of basal meningitis, tuberculoma or obstructive hydrocephalus,

3.3 Screeninq of high rlsk groups

The following constitute high-risk groups which should be screened for a, ctive tuberculosis:

(I), Contacts of sputum positive tubereuloels cases. (ii) Persons with HIV tnfeetlon.

(iii) Immigrants from eountrles with high tuberculosis prevalence,

(i·v), Persons in institutions such as prisons, and drug

rehabilitation centers. '

(v) Persons with other medical risk factors such as diabete~ mellitus, 'silico$i~, renal failure, those on prolonqed corticesteroid or other irnmunesuppressive therapy and haernatoloqlcal malignancies.

6

3.4 Notification of Tuberculosis

All confirmed tuberculosis CE!S'~:S (bacteriological and/or radicloqical and lor cl ihleal)inust be jtotified to the nearest District Health Office using "Boranq Notis" within 1 week of diagnosis. This is required under the Infectious Diseases Act 342,1988"

3.5 Tuberculosis Classification

The following is a suggested system for classification of cases. of tuharculoais (9cl9pte,d from WHO treatment g\.Ji,delines).13

CLASSIFICATION

Pulmonary tuberculosls

Pulmonary tube rc u los is" srnear-posltlve

Tuberculosis involving the lung parenchyma.

(i) Tuberculosis In a patient with at least two initial sputum smear examinations (direclsrnear microscopy) positive for acid fast

bacilli (AFB,).

(Ii) Tuberculosis in a patient with orrasputurnsrrrear examination positive for AFB and radiographic abnormalities consistent with activepul mori<:lry tuberculostsas determined by the treating doctor.

(iii) Tuberculosis in a patient with at- least one sputum smear examination positive for AFB and sputum culture positive for M. tuberculosis.

7

Pulmonary

tu berculosis, smear-neqatlve

Extra pulmonary tuberculosis

Pulmonary with Extra pulmonarytuberculosis-

(f) Tuberculosis in a patient

with at least three sputum smear examinations negative for AFB, and with radiographlc almotrrtatlties consistent with pulmonary tuberculosis', determined by

a doctor followed by a decision to treat thip patient with a full course of anti-

tu berculosls therapy.

(li) Tuberculosis in a patient whose lnltial sputum smears were negafive, who had sputum sent for culture initially,?n¢ whose subsequent sputum culture resu It' is: pdsitive for

M. tuberculosis.

Tuberculosls of organs other than the lung parenchyma. Diagnosis should be based on at least one culture positive specimen, from an extra pulmonary site, or histoloqlca] or str,Orig clinical evidence, eonststent with active extra-

pu Imonary tuberculosis followed by a decision by a doctor to treat with a full course Of anti-tubercufosis therapy.

Tuberculosis involving the IUhg parenchyma as weJl as, any other part of the body ..

-SOURCE: VVHO TREATMENT GUIDELlNE$.

8

3.6 Definition of terms

TERMS

NeW case

Relapse case-

Chronic case

Treatment, failure

A patient who has never had treatment for tuberculosis or has taken anti-tuberculosis druqs for leS$ Ulan 4 weeks' duration in the past.

(i) Sputum positive relapse

A patient who has been declared cured of any form of tuberculosis in the: past by a 'doctor, after one full

course of chemotherapy, and has become sputum smearpositive.

(ii) sputum negative relapse

. A patient who has been declaretlcuredof any form of tuberculosis in the past by a doctor, after one full

course otchernotherapy, and has deVeloped active

disease based on bacteriological, histoldgical

OJ Clinical and radloloqioal assessment.

A patient Who remained or becomes smear-positive agaih after completing a fully supervised re-treatment regimen.

A patient who, while on treatment, remained (X became again smear-positive 5 months or -later after cornrnenelnq treatment. It is also a patient who was initially smearn'e'gattve before starting

9

treatment and became .srnearpositive after thesecond month of treatment.

Treatment after interrupti on

A patient who ihter(Upt$ antttuberculosis treatment for 2 rnonthsor mote, and then returns to the health service With smear-positive-sputum.

(89metimes smear-negative but still .withacttve tuberculosis as jUdged on clinical and

rad i 0 log lea lassessrn en t).

Transferred in case lJ:. patient transferred from another centre for continuation of treatment of tuberculosis. A transfer implies that the center to whieh the patient is transferred undertakes the respon si bi lityof conti nul ng to treat the patientand

supervisinq progress. A patient is not considered to have been transferred if he/she presents at another treatment centre merely to obtain treatment.

3.7 Radiological classlfleatton

Classification of radioloqical extent of disease in the.initial chest x-ray for cases of pulmonary tuberculosis may be standardized using the fiJUOVliing criterta:"

RADIOLOGICAL GLASSI FICATION

Minimal

Slight lesions. without demons-trable cavitations confined toa small part of one or both lungs. The total extent

of the leslons should not ~xcee9 the volurne .of lung on one side which ILe:s9bove the second chcrrdrosternal junctlonand the spine of the fourth or the body of the' fifth th oracle vertebra.

ModerC!te1y advanced

One or both Iwngs may be lnvolved but the totalextent of the lesions should not exceedthe following limits:

(t) Disserninatedlesiena of sl1.ght to moderate density not excaedinpthe total volume of one lung' or the equivalent in both lungs.

(ii) Denseund confluent lesions bot exceeding on's third the volume of one lung.

(iii) Total diameter of cavitations, if present, must be less than 4 ern,

Far advanced

Lesions sire more extensive than rnoderatety advanced.

For extra pu Imonary tuberculosis" involvement Of an anatomical site.results in classiflcation as severe disease if there is ei~her a ,significant acute threat to life (:e.g. pericardial tuberculosis) or risk ,ofsWb§equent 'severe hand leap (13, g. sp i nal tubercu 105.1.5) or b.oth (6':g: men irigea I tu be rcu losi s). Th'Edo llowi n 9 formsof e xtta. pulmonary tuberculosis are classified as severe: meningitis. mil ia ry. perica rd itls,p~ riton itis, bi lateral or extensive pi eu ral effusion" spinal, intestinal, genito-urinary. The following torrnsof extra' pulmonary tuberculosisare' ciassified as less severe: lymph libde, pleural effusion (unilateral),

bone '(exCiudingspirie"), peripheral joint, skin. '

I]

4. Treatment of Tuberculosis

4.1 Treatment eateqories [modified from WHO)~

4.2 Chemotherapy

Treatment categories

• Relapse

Treatment Failure

Treatment

after

lnterruptton

Modern chemotherapy should cure almost all newly diagnosed patients if an effective reqlrnen is prescrlbed for an adequate periad af time and if the patient inqests the prescribed medications veqularty. A six months course of chemotherapy has proven highly effective and reliable.a.s

The aims of treatment are: .. ,

(i) To reduce morbidity (ii) To prevent mortality

(iii) To prevent relapse of fuberculoela (iv) To decrease transmission

(Ii) To prevent the emergence of MDR T8

12

4.2.1 Drugs

Five drugs .are considered essential (1 st lin-e) for the treatment 91 tuberculosls. These are isqnlazld (Hl,. rlfarnplcin (RJ ; pyrazinarnide (Z); streptornyci titS)

Essential 1st line drugs

4.2.2 Treatment reg'irnens

Treatment regimens are divided into:

(i) Initial or Intensive phase

(ii) Continuation or maintenance phase,

DUFi'rig tlie intensive phase, three or four drugs are given daily. This leads to rapid sputum conversion andamelioratlen of clinical symptoms. During the oonttnuattonphass, two or three drugs are us ua n yg]ve n i nterm tttently. Th esteri I iz! rig effect of the therapyettmlnates remaining_ bacilll

, - .. .

a,n·d reduces drastically the chances of subsequent re+apse ..

13,

c....,c ... a ... t ... e ... 9 ... o""'""'rY_' .... ......l1.H Mew C.,.se.

(I) Intensive phase;

2SHRZor 2EHRi or 2HRZ

(2 months of 'daily dose-s)

(ii) Continuation phase: 4H~R"'2 or 4S;'H2R2 or 4HRQf 4H3R~ Qr 4S~H3R:l

{Duration may be, 'extended for severe forms of extra pulmonary tuberculosis arid trnrnuno compromised patients).

* The number preceding the treatment regimen refers to the treatment duration in months.

** The subscript below the drug symbol refers to the 'frequency of doses per week.

Category II

Relapse" Treatment failure, '!"rea'lnierit, attar jilterruptio'n.

(i) Send Mycobacterium tuberculosis culture and sensitivity (MTB O&S) (Rapid culture method if available)

(ii) Do not initiate standard therapy

(iii) Refer to chest physician or physician in charge of chest clinic

(iv) Subsequent dn.)g re:gimen based on serrsitivity results and cllnisal response.

L4

Category III H ChroflicCa::;e J

(i) Send MycobacterilJm tuberculosis culture and sensitivity (MTB C'&S) (Rapid culture rnethee if available)

(iI) Refer to chest physician or physician in charge Of chest clinic,

4.2.3 Anti.tuberculosi.s drugs and the recommended dosa.gesfD

4.2.3-.1 1"\ Ii ne antl-tuberculosts drugs

Isoniazid (H) Rtfampidn~i'{}'

Pyrazin;i"rrii'de(Z)

Streptomycin (8")

15 • 2,0

1000

15 . 20

101)0

Note: For patients more /(lan 65:years ot age, the do_si;; of iitreptomjlCin sli6t!Jd -riot exceeit 7$Omg -

1.5

4.2.4 Flow chart for recommended 24 weeks(w)f 6 months(m) treatment regimen (adult)

,visit oUl'a.tlon

1.

Ow (0 m)

/nvestigat1on

,.' - 1'.,-

Basellrie investigation fBC, RFT, LFt RBS, HIV, Sputum AfB DIS; culture

2. B w (2 m) 4SHR2 4HR' sputum AFB DIS
1 1 sputum MTB C&S
il smear positive
CXR
3, 8 w(·Z m) C9ntinue contlnue sputum MB DIS
Rx Rx CXR
1
4:. .Bw'tZ m) s~~tum A:f~:,Dl~
OXR 5.

24. W (6 m)

sputum MB DIS CXR

.Ethambutol Isoniazid' ~i~~melCJu; Str-eptomyc'lp

RF.F= DlS ,= Q~re:c(sme'a'r:

Pyrl!~~-Miif~ .

'Rxc ~ i17rea;'tlll~nt'

-a&s = jjJjlflJ"~;.ahd

, ~eiJ~itI"vi(Y';,!~~t

Note: C') Recommended to be done where facilities are-avallabte

16

5. Patient monitoring

5.1 Treatment .response

In order to monltoruputum conversion and treatment outcome it is recommended that all patients who are initially sputumsmear-positive have repeat sputum smears performed at the end of the second month of treatment. To verify treatment success, addltlonal sputum smear", should be taken at the fourth month and a! the end of therapy for the 6 rna-nth regimens. Sputum cultures should be obtained at the start of treatrnent.. Sensitivity tests for allavailable druqs if possible should be performed for new patients still positive at the end of the intensive, phase of treatment

5.2 Patient compliance

Patient non-compltance is the main cause of treatment failure;tho',se who do not take. prescribed medications witn sufficient regularity and duration to achieve cure are most likely to fall.

Historically: long term institutional care was employed to overcome patient non-compliance. In certain settings .today, hospitafisation has been one of the critical elements in achieving nearly 100% patientcornptlanee tothe intensive phase. A very high treatment completion tate can be achieved by adeq.uate patient education.

Indications for hospita I isationinclude: (I) Gravely ill patients

(Ii) Cases of acute disseminated tuberculosis

(ii i) T8 involving CNS, pertcardi u m, adrenal andspi ne, (iV) MOR TB

(v) Patients who default frequently or whose compliance is'suspect.

17

(vi) Complications such as haemoptysis, pneumothorax and empyema.

(vii) Associated diseases such as uncontrolled diabetes and renal failure.

(viii) Severe side-effects such as. severe skin reactions or Jaundice.

(ix) Patients who need de sensf ttsatlon to antituberculosis drugs.

(x) Social reasons ego Homeless patients, patients with poor family support

1 l

Dire'clly observed treatment, short-course {DOTS), has been shown to be feasible arid hi,ghlysuccessful towards achieving the objective ofa 95%; cure rate ..

,I I

18

DRUG TOXICITY MONITORING AND MANAGEMENT

6. Drug toxicity monitoring and management

6~ 1 Monitoring for drug toxicity

Where facilities are available, atl patients should have baseline measurements of liver enzymes, serum bilirubin, serum creatinine, blood urea and a full blood count Serum uric acid can 13150 b13 measured if pyrazinamide isuse'd and a baseline examinanon of visual acuifyshculd be obtained for patients to be treated with ethambutol. The purpose of these baseline tests is to detect-any abnormality that would necessitate modification of the: treatment regimen. IA addition, these baseline tests allow fOJ comparison wi1h later measurements- in the event of an adverse: reaction. Patients with pre-existing liver disease, or conditions such as alcoholism known to potentiate hepatotoxicity of tuberculosis drugs,and children with severe forms of tu bercu los is she u Id have reg u la r mo n itorin_g of'Iiverfurtction especially durIng the first few months of therapy.

All patients should be monitored clinically tor adverse reactions during the period of chemotherapy. They should be instructed to reports symptoms posslbly caused by adverse reactrons to the medications theyare receiving. Patients should be seen by a doctor-at least two monthly during therapy and should be specifically asked about such symptoms. Routine· laboratory rnonltorinq tor asymptomatic; patients is: not necessary. If symptoms suggesting dnJg toxicity occur, appropriate laboratory testing should be performed to confirm such toxicity.

6.2 Management of drug toxicity

Minor side effects, such as gastroihtestinal intolerance, are best managed by reassurance and symptomatic treatment a nd the patient shou Id be encouraged to contln ue

19

anti-tuberculosis treatment. Treatment with non-steroidal anti-inflammatory 'drugs (NSArOs) provide symptomatic

relief for pyrazlharnlde related arthralgia. '

The most common serious drug toxicity .seen with short course.therapy is hepatitis. Patients who develop symptoms of liverdystunctlon 'such asnausea, vorniting,anorexia and abdomlna] pain during therapy should have their treatment stopped irnrnediately. Many patients with drugirtduced hepatotoxicity may be successfully restarted on the same drugs, when liver function returns to normal. This is best done in a $etting, where, liver function can he careful,ly. monitored", hence patients with this problem should be sent to a referral centre for further management.

Patients who develop hypersensitwlty reactions, such as rash, to the two' most potent drugs i.e. isoniazid and rlfarnpicin, may be. desehsitised if a suitable regimen cannot be provided with the other druqs wh ich the patient can 'tolerete. This is done by careful administration of tncreasinq doses of the druq under close supervision. Desensitisation should not be attempted for patients With HIV infection.

The developmerttofthe following conditions contralndlcate thefurther use of the causative drug: thrombocytopenia, shock and/or renal failure due, to rifampicin, visual impairment due to ethambutol and eight cranial nerve damage from ,streptomycin.

6.2.1 Challenge dose for hypersensitivity reactions

Generally 1/10 of the therapeutic dose is used on the first day. The initial dose will depend on the severity of the hypers_ensitivity reaction. Hence the day 1 challenge' dose may need to be adjusted.

If rash occur after 1 sr challenge dose, do not p recs ed, Wa it for rea cUo n to su bs i'de, a nd the ng,o oh to the next drug. Challenge should be done for one drug at a time.

20

Table 1 Drug cl1aJlenge dose regime (modified from Gi rl'ingll)

Isoniazid (INH) Rifampicin (RFP) Pyrazinamide. (PZA) EthambutOl (ETM) Streptomycin (SM)

6.2.2 Desensltisatlon

5.0 300 300

75 360 450
250 1000 2000
100 500 1000
125 5.00 1000 Desensitlsation is only done lfone I~ unable to devise a suitable regimen of treatment without theoffendihg'drugs. If an alternative and suitable drug cornbmation is avallableit is not necessary tosta rot deserts i fisa ti 6 h. Dese n sitisation is done by dailyadrninistration of increasing doses until the therapeutic dose is reached. During desensitisatien it is necessary tq pOy!?f the patient with at least two other drugS, which the patient can tolerate.

The initial dose depends on the severity .of the hypersensitivity rea'Gtion.Generally begin with 1 h 0 - 1/100 of the therapeuticdose and then the dose are doubled each time.

6.2.3 Gastrointestinal- upset

Treat symptoilTstically first; and If still not relieved, theoffendirig drugs can be withdrawn.

21

6.2.4 Drug Interactions"

6.2.4..1 Isoniazid

lsonlaz id lends to raise plasma concentrations of anti-epiteptic drugs such as phenytoin and carbamazepine by Inhibiting .thelr metabcllsrn In the liver, The, absorption of isorriazid is impaired by aluminium hydroxide,

6.2.4.2 Rifamplclh

Rifampicin induces liver enzymes, and may increase the dosage r-equirements of drugs metabclised in the liver. These include protease inhibitors, cyclosporin, corti O.Q stero I ds, oralcontraceptlve pill, d ra I h Y pog rycaem i C .8g e nts, 0 ra I anticoaq u la n Is', phenytoin , cimetidine, theophylline and digitalis glycosides.

Biliaryexcretion of nadiocontrast media am:l Sulphobromephthaletn sodium may be reduced and rnierobinloqlcalassays fOf folieacid and vitamin 812 disturbed.

6.2.4.3 Streptomycin

Other ototoxic or nephrotoxic drugs {ihould not be administrated to patients r,eceiving 'streptomycin. These include vother aminoglycoside antibiotics, arnphoterictn B, cephalcsporins. ethacrynic acid, cyclosporln, eisplatln, frusernide and vancomycin. streptomycin may potentiate the effect of neuromuscular blocking agents administrated during anaesthesia.

22

MANAGEMENT OF TUBERCULOSIS IN PEel L SITUATION

7. Management of tuberculosls in special situations

7'.1 Tuberculosis in children U.22

7.1.1. Pulmonary' tuberculosis

• Diagnosis In children is Llsually difficult to make.

Most children with pulmonary tuberculosis are sputum direct smear-negative, therefore a high index of suspicion Is. needed to make the

diagnosis. .

• Features indicative of tuberculosis are:

(i) Recent contact with a person (usuatty adult) with active tuberculosis. This constitutes one of the strongest evidence of tubereutosls I ri a child who has symptoms and x-ravebnorrna I ities suggestive of tuberculosls,

(ii) Symptoms and signs (a) Low grage fever (b) Cough

(e) Weight loss

(ei) Failure to thrive (6") Wh~ezing

(f) Tachypnoea

(9) Occasionally frank respiratory distress

(h) ReduceIl breath sound

(Iii) Unresolving pneumonia

(tv) Posttive Mantoux test:

A Mantoux test of ;2: 10 mm induration-at 72 hours constitutes "1. positive test.

23

(v) Chest X-ray:

(a) enlarqe d hllar lymph nodes .± loca I tsed ob stru ctivaern p h yserna

(b) Per slstant segmental cotlapse consolidation not responding to conventional antibiotic.

(c) Pleural e-ffusion

(d) Calciflcation ln lymph nodes, this, usually develops more than 6 months after infection

(vi) Gastric lavage for direct smear and culture

(vii) Bronchoscopy may be necessary to o bta i n rspecimen s tor rn icrob: 01 og leal tests

7.1.2 Antl-tuberculoals chemotherapy In children

• Intenslve phase (2 months)

Daily HRZ fer 2 months, (56 dos€!s).Syrup preparations should generally be provided on a: fortn ig htly basis.

• Maintenance phase (4 months)

There are 2 regimens:

(0 Daily RH regimen

This: Is preferred for younger children because biweekly regimen may result in omission of doses b'y the mother 'and the larger doses that need to be given with biweekly regimen may not be acceptable to the child.

24

(ii) Biweekly RHfully supervised regimen

May occasionally be used tor older children iespectalty those who liv.e relatively near to the health facility:

Ethambutol is best avoided because Cit the difficulty in detecting visual impairment

7.1.3 Extra pulmonary tu berculosis

7.1.3.1 Tuberculous meningitis:

The total duration of treatment is at least 12 months, Steroids are usually recommended in the acute stage,

7.1.3.2 Other extra pulmonary tubareulosis:

The regimen and duration of treatment is the same as for pulmonary tuberculosis but may be extended depending on the clinical and/or radiological response,

7.2 Tuberculosis during pregnancy and lactation 23,24

Untreated tuberculosis presents a much greater risk to a pregnant woman and her foetus than does the treatment of the disease. Standard treatment usihq isoniazid, rifampicin, pyraztnarnlde and ethambutol is used. Doses of anti-tuberculosis druqs given in pregnancy are similar 'to that in 'a non-pregnant patient. 8,treptomycin is best avoided because of the risk of ototoxtcity to the foetus. Normal recommended desaqes of rifampicin are safe in pregnant patients.

Tuberculosis treatment In lactatin .. g mothers is safe as the amount of drug ingested by nursing infant 'IS minimal. If the mother at the time of delivery is smear-posltlve, the newborn should be separated from the mother at least for a p,eriod of two weeks.

25

Brea:st-feeding is best avoided dl,lring these two weeks and expressed milk should be given to the child. BCG should be given as-scheduled and is"Ohi~zid prophylaxls should be given for 6 months followed by Mantoux test' at the end of 6 months. In the event of absence of scar, BCG vaccination should be repeated. When there is doubt about the presence of-active tuberculosls, the child should be treated.

Congenital tuberculosis, although rare should be suspected ifan.infant born to a tuberculous mother fails. to thrive, has non-specific symptoms such as fever, respiratory distress, poor feeding and vornitinq, or has suggestive signs sueh as hepatosplenotneqaly.

7.3 Tuberculosis treatment for women taking the oral contraceptive pill

Rifampicin interacts with thecralcoritraceptive pill, with' a risk of decreased protective efficacy against pregrYan'cy. A woman who usually takes the oral contraceptive pill may choose between an oral contraceptive pili containing a higher dose of' oestrogen (50mcg) or use another form of contrace-ption after consultation with a- doctor.

7.4 Tuberculos.is in patients with liver impairment

Tile patlents with no evidence of ,Chronic liver disease. (e.g. hepatitis virus.carrier, past history of acute hepatitis and alcoholics) can receive the usual short-course che-motherapy reqimens but therapy should b€ modified in patients with established chronic liver disease and acute hepatitis. These cases are best-referred to specialists for management.

7.4.1 Est-ablished 'chronic liver disease

The following regimens are recommended: (i.) 2SHRE/TWR2

(ii) 2SH E/1 OHE

(iii) 2SH/12S2H2

26

7.4.2 Acute hepat_ifis (e.g. acute viral hepatitis)

ltisa ra re' sventu a lity that a patient has tu bersulosls and also at the same time acute hepatitis unrelated to, tuberculosrs or anti-tuberculosis treatment. Cliriical judqernant Is necessary, In some cases it is possible to defer tuberculosis treatment until the acute hepatitis has resolved. Inother cases when it is necessary to treat tuberculosis during acute hepatitis; the 'safest r~gimf2m is $SE/6HR,

lsoniazid, rifampiCih and pyrazinamide.are either elirninated almost enfirely by biliary excretion or metabolised into non-toxlo compounds. These drugs can, therefore'; be given in normal .dosaqe to patients with renal failure, Streptomycin and ethambutol areexcreled by kidney. Wh,ere facilities are available' to monitor renal function :closely ltma-Y be possible to- give streptortryctn-and' ethambutol in reduced dose's. The .satest regimen to be 'administered in patients with renal failure is 2HRZI6HR.

7.5 Tuberculosts ih patients with renal lmpalrment

7.6 Extra pulmonary tuberculosis

The: regimen of treatment is sirrrilarnsfor pulmonary tubereulosis but the duration may be extended and it varies frOrfi 6mdnths td12 monthsor longer deperrdlnq on theclinica,1 response of the individual patient, for example in tuberculosis.rneninqitis, it is advisable to treat the patient for at least 12 months.

Steroids shou Id be given in tube rcutous me n i n;giti s, gen I tourinary tract tuberculosisand rnay alsr; be conslderedln mil[ary tuberculosis.

7.7 Tuberculosis in patients with HIV infection.

Recommended treatment regimens for patients who, have tuberculosis, with HIV infections (The recommendations are based on those of th~ COC,nOavidsQn'4and The American Thoracic S.ociety'5-modified)

27

Table 2: Clinical presentation of TB in HIV/AIDS (from chemotherapyg uideli ne, 1994)

Glihicaj ~ituat!Qh,'

Initial therapy

• No suspicion of drug resistance

• possible drug resistance

Long-term therapy

• Druq-susceptlble Organisms

• Isoniazid resistance or intolerance

• Rifampicin resistance or intelerance

1're:atime:nt

Isoniazid, rifampicin, pyrazinamide daily

lson i az id, rifarrtp lei n, pyrazinamide, Etambutbldaily

Isoniazid, rifampicin, pyrazinamide for 2 months daily followed by isoniazid, rifampicin for 7 months biweekly or for 6 months after cultures are negative, whichever is longer. Avoid protease ln hibitor if regimen contains rifampicin.

RifampiCin,etha,mbutol and Pyrazinamide dailY for 2 months followed by rifampicin arid ethambutol daily fOf 12-16 months or 12 months after cultures are neqative, whichever is longer.

Isoniazid, pyrazinamide, ethambutol

Daily for 18 months to 24 month's, Of tor 12 months after culture's .are negative whichever is, longer.

FIXED .. DOSE COMBINATIONS (F'OC) OF ANTI .. TUBERCULOSIS DRUGSB

8. Fixed-d o s e combinations (FOC) ofanti~ tuberculosis dtugsii

Fixed-dose comblnatlons (FDe)

F ixed-d ose co m bin-at io n (F D G) tab lets in co rporate two or rno re drug,s within the same tablets (tsoniaatd, Rifampicin and

." . . - .

Pyrazinamide). The fplloWi'ng preparatlonsare available in the

private sector:

1. Rifinah I Rimactazld / Rifamate (combinations of ritamplein and isonlaaid),

2. Rifater (cbmbihatibn -of rifampicin, isoniazid and pyraz! narriide).

3. Myrin (ethambutol, rifamplein and isoniazid),

4. Myrin P (ethambutol, rifampicin, isoniazid and pyrazinamide).

8.1 Advantages

0) reduced risk of emergence of drug-resistant Qrganisms

(i,i) an 'effectiVe ri:!gi·men is ·rr'l$relikely to lYe prescribed (i i i) oppo rtu n ltyfo r ina dye rtent med i ca tion errors is' decreased

(iv) many oJ the Ipgi:stic problems which cause shortage of individual drugs are" limited

(v) promotes patient campi lance

(vi) decre.as ed usag:eof ritampimn for .other infectiQn$

29

8.2 Disadvantages

(i) Btoavailabllity: WHO and IUATLD recommend the use of only FOGs for which in vivQstU!;lies have dem 0 nstrated satisfactory bloava i la bi I ity of ritarn plcin.

(il) Cost: Prices may· fall as use becomes more widespread.

(Iii) May b'E:! necessary to adjust the dcsaqe: programmes us.ing FDGs still require limited amounts of single drugs.

3Q

DOlS·OIRE,CTLY OBSERVED TREATMENT. SHORTiiCOURSEG

9. DOTS- DirectlyObserved Treatment, Sha:rt-course6

DOTS

Theaeronym stands for Directly Observed Treatment, Short.course. The DOTS strategy comprises the following five elements tor its success:

1. Government commitment' to. a National Tuberculosis Control Programme ..

2 'Caae detection through sp uturn-srnaa! microscopy examination of tuberculosls suspects in gene'tal health services.

~. Asta n dard i se ds hart -cou rse tune rc u I Q sis~re:a tmen t regimen of six months Linder directobservatien by a tratned supervlsor to. ensure the patient takes every dose of trredication.

4. A regular, uninterrupted ,supply of quality anti-tuberculosis drugs.

5. A monitortru) arid re,portitig system to evaluate treatment outcome. for each and every patlent with proper documentafion

9.1 Advantages of OafS

(i) DOTS can produce cure rates of up to. 9'5'% even in the poorest countries.

(ii) This slrat'e'gy can be iritegrateds"Ucc'essfully withih exisfing primary health care services to achieve widespread coverage.

(iii) Case detection by sputum rnlcroscopy is cheap, simple and reliable.

(iv) Trained health care workers or even community volunteer? can supervise the treatment.

11

(v) DOTS does not require hospitalisation OJ isolation; patients can remain with their families and return to work in a few-days.

(vi) DOTS helps to prevent drug resistance which is often fatal and up to 100 times more expensive to. treat than drug susceptible cases'"

(vii) The DOTS recording and monItoring system follows each patient through the en fire course Of treatment to ensure a cure.

(viii) DOTS is a sound economic investment for any: government Each healthy year of life brought about by using DOTS costs as little as US $.1116.

9.2 DOTS In Malaysia

Malaysia is ccrnrnitted to adopting the OOTS:.strategy. All druqs should be administered under supervision i.e. directly observed by health personnel or tralneu person. Ea.ch dose of medication taken by the patient under supervision should be recorded. Supervision of treatment need not necessarily be confined to health care facilities,

32.

10. D,efaulter tracing and retrieval

10.1 Definition of 'defau Iter'

A patient who has: missed more than 25%) of the treatment doses in one month ie., more than 6 dose-s of daily treatmentor mere than 2,doses of biweekly treatment.

10.1.1 Steps to be taken by treatment centre when patient misses a dose:

1. Send first reminder letter or phone call on the same day

2. Second reminder Jetter or phone Gall if patient does not- turn up the next day

3. If patient does not turn up 'on 3rd day" home visit must be done to retrieve patient.

All treatinent centres must report tuberculosis patients who default treatment for 1 week to the nearest district heaith office.

10.2 Contact management

All persons staying in the same house or have been in ,dose contact 'with the presenttnq index case should be investigated (see appendix 1 and 2)

III OUTCOME ANALYSIS

11. Outcome analysis,

Outcome analysis

• Form 1;:.1 to be completedfor svery patient 'On initiation of treatment.

• Form 1 b to be completed at the end of treatment I disposal

Analysis of form 1a and form 1 b is to De done (or every hew smear-positive case after 1 year of follow-up. Cure rate, treatment completion rate, treatment failure rate, treatment interrupted rate and death' rate during treatment should be calculated based on form 1 a and form rl b.

11.1 Cure

Patient who is smear-negative at, or one month prior to, the completion of treatment and on at least one previous occasion

11.2 Treatment completed

RaUenl who has completed treatment but Without proof of cure

11.3 Treatment fai lure

Patient who remains or becomes aqainsmear-positive at five months Of later during treatment

11.4 OJ,ed

Patient 'Who dies for any reason during the Course of treatment

11.5 Treatment Interrupted

Patient whose treatment was interrupted for 2' months or more

34

MANAGEMENT OF RESISTANT TUBERCULOSIS

12. Management of resistant tuberculosIs

12.1 Defin lti on s

(i) Drug~resh;;tailt tuberculosis _

This is a case Of tuberculosis (us-ually pulmonary) excreting bacilli reststant to one or more antituberculosis drugs'.

(ii)Mu Itidrug-resistant tuberculosis

This is a case of tuberculosis which is resistant to at least" lseniazid and rifampicin.

12.2 Managemeiltof resistant tuberculasis'"

12.2.1 Pharmacoloqlcal treatment_:

The most irrtportant line of management is prevention by initiating~treatment of all cases of confirmed tuberculosis on eftectlvartruq re.gimen followed by dire:C:tly observed treatrnentfellow-up. All cases of resistant tuberculosis should be referred to and the treatrn eritshou I d be in itiatad by trained physleians.

12.2.1.1 Second line drugs

2n<:l nne anti-tuberculosis drugs

• No! used in Malaysia ..

'Re.G:6mrnenflell d·osa_gij. 15mgfkgId<lY 5x/week :4dOI--"liO'Qllfg/aa¥

750 • 15.00mg/day ~'5,[!)~kPHI_~y' .

5mg/kg/day 5x/week 15mglkg/day 5x/week 500mg bd

~tlOilTi"' -aaU''l:

"- .f;!'¥:.

2 • 16gm/day

fs.· • '~O:ffi'if,k1l1iJ ay; 100-300mgfday" 15:0,n:!91tt~M

Basic principles

Assume thatatl patient With apparent drug, resistant tuberculosis will have bacllli resistant to isoniazid.

It Is advisable to m(3na9E1 patient with MDR TB as in-patient until sputum 'conver::;ion is achieved.

In de~igning. a regimen. do not aim to keep drugs

In reserve. - - '

Prescribe drugs which the patient has not had p rev j 0 usly,

The initial regimen should consist of at least three drugs, preferably four or five, to which the bacilli are IIk,ely to be fully sensitive,

Among these drugs, it is desirable to use in combination .an injectable arnincqlycoslde and pyrazlnamldeveven if previously used because resistance tsusually unlikely. This cornelnation has good bactericidal activity.

On sputum .ccnverston to negative, one or more druqs may be' withdrawn, preferably a weaker drug which is causlnq side-effects.

The treatment with the weaker regimen should be continued for at least 18 months after sputum conversicn to prevent relapse.

In any regimen chosen especially when weaker drug:s are used the treatment should be qiven daily and should be directly observed. It is also mandatory to monitor bacteriological results i.e smear and culture monthly from the second month until the sixth month, and then quarterly till the end of treatment.

12.2.2 Surgical Intervention

Surgery should be considered for a patient with ba-cilli resistant not responding to medical treatment. Unfortunately manysuch patients will have too extensive disease and/or too poor lUng function for surgery. Operation should be done when 'the bacillary population is likely

36

to be lowest. After surgery the same drug regimen should be continued for at least 18 months.

12.3 BeG vacc"ination in Malaysia

BCG vaccination ts given to ~II newborns -, vacctnation for children with no scar is done at primary school entry or earlier.

12.4 Tubercu losis in Foreign workers

All foreign workers found to have CXR .abnorrnalities. should be fully investigated fortuberculoais and IffOund to have active tuberculosis, should receive treatment (including those ih detention camps) until furtheraction by the relevant authorities.

12.5 Chemoprophylaxis

(i) Chemoprophylaxis is indicated in H IV posttive. patients who have Mantoux reading of :;" 5mh1 regardless of age or prior skin testing results. Chemoprophylaxis With isoniazid should also be conslderedfor anergic HIV infected patients who are known contacts of persons with lnfectlcus tuberculosis. They should be.evaluatedcarefully for active tuberculosis before' preventive therapy is started. The reoernrnende d duration of chemoprophylaxis with isoniazid in HIV infected patients i$12 months. Compliance-to chemotherapy with isoniazid should be considered carefully when chemoprophylaxis is to be instituted. In the event of suspected isoniazid resistanceva combination of two drugs eg., isoniazid and rlfarnpicin, may be required for 6 months.

(In Asymptomatic children under 5 years old who are contacts of infectious tuberculosis cases, with Mantoux reading ~ 'lOrnrn should receive Isoniazid 5iTJg/kg once daily for a minimum of

6 months. .

37

PREVENTION OF TUBERCULOSIS

- . '.- - - . - ---. - . .- .

AMONG HEALTH CA.RE WORKERS, Hew

13. Preventi.on.of tuberculosis arnonq health care workers (HeW)

Tuberculosisisa very infectious disease, sprElaq by droplets from asputurn positive source vi'acou_ghln,g, srieeztnq, talking andsiriging. Tuberculosis organisms may remelnafrbcrne after beihg coughed out, The probabillty that a person who is exposed to M. tubeteulosl« will become infected depends primarily on the concentration of the infectious droplet nuclei in the airend the duration of exposure.

The risk of spread of tuberculesls from a given source case 1$ re::1at:ed to several fa:cto rsro rga n i srn load. venti lafio n of Workin9 environment, protective measures taken by 1heHCW and duration of exposure to the organism. The size of the risk varies accordlnq to the type otheattbcare setting, the prevalence of tuberculosis in the community; the patient population served, the area of the health-care facility in which the HeW works and the effectiveness of tuberculosis infecti 0 n con tro I lnterventions.

The riskof infection is hig her i ria reas where patients with tu bercu losls.a re provi defd ca re before d fagn osi s a rid i ri itiatio n of tuberculosis treatment or where diagnostic or treatment procedures that stimulate coughing; are performed. In hospitals where there were more than 200 sputum smear positive admlsslons.annualty; infectioneceurred in 1 10 10 percent of workerseaoh yeCj(11. The prevalence' of infection is directly proportienal to the duration of emplbyment in the hospital.

There is no. perrntsslble levelofexposure to tubercle bacill i '9:

Studies in guinea pigs showed that inhalation otasrnq!e droplet nucleus containing no more than three tubercle-bacilli can result In conversi:onon tuberculin testing and the development of rnacroscoplc granulorna,2o.

39

The transmissi_on of tuberculosis- to HeWs is dependent on the following factors,

1. the number .of patients with active tuberculosis in

contact with the HeW,

2,. the infectiousness of the index case.

3. the ventilation rate of the worker,

4. the duration of exposure, and

"5. the air-exchange rate in the interior space.

High index of su spielo n for tu bereu I osi s wi th pro mpt diagnosis and treatment can limit its spread to Hews. All HCWsaii'dsupportiVestaff should be periodically trained to recoqntse the symptoms 'arid signs of tuberculosis and to i niti a teprotsctlo ii protocols.

13.1 TB infection control

Effective infection control 'efforts are essantia! ! n preventing nesoeomtal trarrsmlsslon of tuberculosis. A hrerarchy of control measures ls recommendedto prevent tuberculosis transmtsslon in health care facilities.

1. Administrative controls: Administration controts are most important in preventing nosocomial 'transmission of tuberculosis: This measure is primarily intended to reduce the risk for exposing the uninfected HeW to tuberculosis. Measure-s ihdudedeveloping arid implementing effective protocol's to ensure rapid- identification, isolation and treatment. Effective_ work practices among Hew should be implemented and th-ere -should be ed u catio n,trai n i n 9 a ndcb.un sal i ngabo ut tuberculosi-s, FiMlly Hews should be screened for tubercul osi s.

2. Engineering' controls: This measure Will prevent the spread and reducethe concentration pf infectious droplet nuclei. These controls include I.ocal exhaust ventilati on, un id i rectional airflow, gene ra I ventil ation and air Gleaning via filtration or ultravleletqermicidal irradiation CUVGI). Bioloqicelaafety cabinets Class II should be used by laboratory personnel handling: infectious material.

3. Personal Respirator Protectlorn Appropriafe respirator masks should be worn by HeWs when performing high risk procedures such as cough induction and bronchoscopy

13.2 Surveillance of HeWs for latent tubercu lcsts

All HeWs should have chest x-ray upon employment. Those working in high risk areas should have chest xray at intervals of orrce every 2 years. Any worker who develops symptoms of tuberculosis .should be.evaluated promptly. HC:Ws with active tuberculosis shouto be treated promptly and be given leave from duties until sputum AFBs are. negative and th'e HeW has completed treatment.

The risk of nosocomial transmission of tuberculosis varies considerably among and within health care setting. The complete elimination of risk among HeWs is an un realisti e goa I. A more rati ona] 0 bJectiv:e is the red ueti on of risk to a level similar tothat in the general population. There is evidence that Hews workirig in high risk areas such ias chest clinic, wards treating active' tubereulosls and laboratory staff are among the risk group. Several control measures as mentioned earlier need to be implemented to reducetransmlssiorrof the bacilli totne HeWs.

NOTE: For furtheririfOrmation please refer guidelines.

40

References

1. World Health Organization (1998). The Global toll of tuberculosis in 1997.

2. Annual Report of Tuberculosis, Ministry' of Health Malaysia (1999).

3. Barnes PF. Rapid Diagnostic Test for Tuberculosis. AM J Respir Crit Care Med. 1997; V 155: 1497 -149,8

4. Iseman MD, A clinician's Guide To Tuberculosis. Biology and Laboratory Diagnosis of Tuberculosis 2000 :21-45

5 Alvamz S 8t at Extra pulmonary tuberculosis revisited : a review of the experience at the Boston City Hospital and other Hospitals. Medicine (Baltimore) 1984; V6.3:25 -55.

6. 'World Health Organization. Treatment of Tuberculosis: Gu!dellnes for National Programmes, 1997 (Second Edition).

7. National Tuberculosis and Respiratory Disease Association, New York. Diagnostic stanoardsand classification of tuberculosls, 1969.

8. East African/Briti$h Medical Research Councils :Cbntrolled clinical trial of four 'snort-course (6-mmlth) regimens of chemotherapy for treatment. of pulmonary tuberculosis. Second report. Lancet 1973/1,1331.

9. East AfricqnfS,ritis.h Medical Research Councrls : Controlled clinical trial of four short-bourse (6-mohth) regimens of chemotherapy for treatment of pulmonary tuberculosis. Third report. Lancet 1973/11,13'31.

10. Crofton J et aLWorld Health Organ lsation. Gulqellnes for the management of drug-resists nt tuberculosls, 19tH.

11. Girling OG.Adyerse effects' of anti-tuberculosis drug. Bulletin of the Intemational Union Ag,ainst Tuberculosis 1984; V 59: 152 - 162

12, Paediatric Tuberculosis. P,Soileimam, L Refabert, C. Delacourt, M. Le Bourqeois, European Respiratory MotlQgraph 4, JulY 1997, pg 144-174.

4L

13. Centers 'for Disease Control: Nosocomial transmission of multidrug reslstant ti.Jberculosisaniollg H lv-irifected persons - Florida and New York. 1988-1991.

14. Davidson PT. Drug resistance and the selection of therapy for tubereutosis. AM Rev Respir Di§ 1987; 136::?55 -257

15. American Thoracic Society Treatment of tuberculcsl sand tuberculosls infection iii adults andchildren. Am Rev Respir Dis 19,86; 134:355 - 36,3

16. World He-alth Organisation. Stop TB crisis in the Western Pacific Region from risk to opportunity 1999.

17. Crofton J, Chaulet P, Maher D, et al; Guidelines for the rnanaqernentof drug resistant tubereulosis. WHO ITS 196.210 (Rev. 1 ); 19,97: 26-35.

18. CDC. Guideline,s for the preventing the transmission of mycobacteriu rn tu bercu I osl sin Hea Ith Care fa ci I itie s., 1994, MMWR 43 (RR13); 1-132

19. Guidelines for Infection control In Healthcare Personnel, 1998 I nfection Control and Hospital Epidemiology Vol. 19-no. 6; 407- 462

20. Arnerlcan C-ollegeof Occupational and Envlronmental Medicine, guidelines for Protecting Health CareWorkers,agaihst tubarculosis. J Occupational and Environmental Medicine 1998. vol 40 no, 9; 1-7

21. Tuberculosis among Health Care Workers. NEJM vol 3,32, no. 2; 92-98

22. Tuberculosts, clinical manaqernentand newchalienges , chapter 9pg 145,155.

23. Rosenfeld E A .Haqernan JR, YogenR" Tuberculosis in infancy in the 1990s, Paed cltn N .Am 1993; 4-0: 10-87-1103.

24. American Thoracic Society and the center for Disease Control i:\.n.d Prevention, Treatment of tuberculosis and tuberculosis I nfeGtion in adults and children. Arn.J Resp. Critcare Med 1994; 149: 1359- 1374.

42

Appendix 1

Flow chart for' contact investigation (Adults)

Chest X-ray I

Asymptomatic review at 3, 6 months & 1 year

43

Appendix 2

Flow Chart for Managelllent of Tuberculosis contacts (Children)

'DHIL[J J (Gbnta@t)

Investigate further

Treathigh. lisj(,'

I .

~ I~Ollow-1

~ ~up

44