CLINICAL MANAGEMENT OF TUBERCULOSIS OF ADULT, CHILDREN AND SPEACIAL GROUP

Dr. Noor Aliza Bt. Md. TarekhChest Physician, HSAJB

History

• One of the oldest diseases known to affect humans - tuberculous spinal disease found in Egyptian mummies.

• First recognised in 4000 B.C• “White plague”/ “consumption”

in Europe 16th century.

• Spread worldwide 17th century.

GLOBAL PERSPECTIVE

• TB is leading cause of death due to an infectious disease in adults

• TB kills 2 million people every year

• Declared global emergency by WHO in 1993

Introduction

• Caused by bacteria belonging to M. tuberculosis complex

• Usually affects lungs (80-85%) but other organs may be involved

• Curable in all cases if properly treated

Aetiologic Agent• M. tuberculosis – most

frequent agent of human disease

• M. bovis – once an important cause of tuberculosis transmitted by unpasteurised milk

• M. africanum – West Africa

• M. microti – does not cause disease in humans

Pathogenesis

CMI + tubercle CMI + tubercle formationformation

droplets droplets nucleinuclei

organismorganismreplicationreplication

macrophage macrophage lysislysis

lymphatic and blood lymphatic and blood spreadspread

miliarymiliary

further multiplicationfurther multiplication

latent (LTBI)latent (LTBI)

Not controlNot control

Ghon focus/ ranke complexGhon focus/ ranke complex

Person at risk

Specific immunity is usually adequate to limit further multiplication of the bacilli; the host remains asymptomatic, and the lesions heal.

Host defences weakening

A droplet nucleus, passes down the bronchial tree and implants in a respiratory bronchiole / alveolus beyond the mucociliary system.

DepositionDeposition

Tubercle bacilli multiply in the alveoli.

Within 2-10 weeks, the immune system produces special immune cells called macrophages that surround the tubercle bacilli. The cells form a hard shell that keeps the bacilli contained and under control. ( TB Infection ).

If the immune system cannot keep the bacilli under control, the bacilli begin to multiply rapidly (TB disease).

This process can occur in different places in the body, such as the lungs, kidneys, brain, or bone

Droplet nuclei containing tubercle bacilli are inhaled, enter the lungs.

Through lymph nodes and lymphatics

BLOOD STREAM

Acute spread

Chronic spread

Miliary tuberculosis

Tuberculous meningitis

Bones

Joints

Kidneys

Etc

Direct from lung lesion

TB Infection Vs TB Disease

TB Infection ( Latent TB Infection )

TB Disease

M. Tuberculosis in the bodyTuberculin skin test reaction usually positive

No symptoms Symptoms such as cough, fever, weight loss

CXR usually normal CXR usually abnormalSputum smears & cultures -ve

Sputum smears & cultures tve

Not Infectious & not a case of TB

Often Infectious before treatment & a case of TB

Infectivity

sputum smear positive

very infectious

sputum smear negative/culture positive

less infectious

sputum smear negative/culture negative

non-infectious

extra pulmonary

non-infectious

Primary Pulmonary Tuberculosis

Tubercle bacilli are transmitted from a patient with pulmonary TB to other persons by droplets during coughing, sneezing, speaking and singing.

Cough > 10 days

Fever

Haemoptysis

Pleuritic Chest Pain

Weight lostNight Sweat

Physical Findings

• Limited use

• May not have any abnormalities during auscultation

• May have crackles or signs of consolidation

Diagnosis of TB• High index of suspicion needed

• Symptoms and signs depend on organs involved

• For pulmonary TB:• Sputum AFB D/S x 3

• Chest radiograph

• Mantoux test

• Sputum MTB C & S or BACTEC

Diagnostic Procedures

• Bronchochoscopy ( BAL )

• Gastric lavage

• Lumbar puncture ( PCR )

• Pleural, pericardial, peritoneal biopsy

• Bone marrow and liver biopsy

Indications for AFB Culture

• For bacteriological confirmation of TB

• When we suspect a h/o being treated for TB before

• Any foreigners where we are not certain of previous history

• Any history of irregularities in treatment

• Treatment failures• Relapse TB

Aims of Treatment

• To cure patients and render them non- infectious

• To reduce morbility and PREVENT mortality

• To prevent relapse and emergence of resistant of tubercle bacilli (MDR TB).

PRINCIPLES OF TB TREATMENT

CORRECT COMBINATION

CORRECT DOSAGES

CORRECT DURATION

APPROPRIATENESS TO PATIENT

Deciding To Initiate Treatment

Should be based on clinical, pathological, and radiographic findings; and the results of microscopic examination of acid-fast bacilli (AFB)--stained sputum (smears) (as well as other appropriately collected diagnostic

specimens and cultures for mycobacteria.

ISONIAZIDETHIONAMIDETHIACETAZONERIFAMPICINRIFABUTINRIFAPENTINEKRM-1648PYRAZINAMIDESTREPTOMYCINKANAMYCIN

SPARFLOXACINGATIFLOXACINCLOFAZIMINECLARITHROMYCINAZITHROMYCINERYTHROMYCINCEFIXITINCEFMETAZOLEIMIPENEMSULPFAMETHOXAZOLESULFISOXAZOLE

AMIKACINCAPREOMYCINGENTAMYCINTOBRAMYCINETHAMBUTOLPASD-CYCLOSERINEOFLOXACINLEVOFLOXACINCIPROFLOXACIN

ANTI-MYCOBACTERIAL DRUGS

PRINCIPAL PREREQUISITE FOR AN EFFICACIOUS ANTI TB DRUG

Early bactericidal activity

Sterilizing activity

Ability to prevent emergence of resistance to the companion drug.

GRADING OF ACTIVITIES OF ANTITB DRUGS

Extent of activity Prevention Early Sterilizing of resistance bactericidal

High Isoniazid isoniazid rifampicin Rifampicin pyrazinamide ethambutol ethambutol rifampicin Isoniazid streptomycin streptomycin streptomycin pyrazinamide pyrazinamide thioacetazone Low thioacetazone thioacetazone ethambutol

Recommended Regimen

• 2SHRZ /4S2H2R2• 2EHRZ /4R2H2• 2HRZ / 4H2R2

– Streptomycin 0.5 -0.75 mgm.– Rifampicin 10 mgm/kg/bw– Pyrazinamide 25-35 mgm /kgm/bw– Isonizide 5-10 mgm /kgm /bw– Ethambutol 25 mgm/kgm/bw

2 HRZ / 4 HR DAILY ( Paediatric)

Intensive Phase

• Inj. Streptomycin ( S ) • T. Isoniazid ( H ) • CAP .Rifampicin ( R )

• T. Pyrazinamide ( Z ) • T. Pyridoxine ( VIT.B6 )• T. Ethambutol ( E)

Daily for two months

Intermittent Phase

• Inj. Streptomycin 3/4 - 1 g

• T. Isoniazid ( 13 - 17 mg /Kg body wt)

• C. Rifampicin 600 mg.• T. Pyridoxin ( Vit B6 ) 10

mg.

Biweekly for four months.

WHO RECOMMENDATION(According to treatment categories)

From the public health perspective the highest TB control programme priority is the identification and cure of the infectious cases i.e those patients with sputum smear positive PTB.

In settings of resource constraint, it is necessary for rational resource allocation to prioritize TB treatment categories according to the cost- effective of treatment of each categories.

Treatment categories are therefore ranked from 1 (highest priority ) to IV (lowest priority).

CATEGORY I NEW SMEAR POSITIVE PTB 2EHRZ(SHRZ) 6HENEW SMEAR NEGATIVE WITH 2EHRZ(SHRZ) 4HREXTENSIVE LESION 2EHRZ(SHRZ) 4H3R3

CATEGORY IISPUTUM SMEAR POSITIVE

RELAPSE 2SHRZE/1EHRZ 5H3R3E3RX. FAILURE 2SHRZE/ 1EHRZ 5HRERX.INTERRUPTION

CATEGORY IIINEW SMEAR NEGATIVE PTB 2HRZ 6HENEW LESS SEVERE FORMS 2HRZ 4HR

EXTRA PTB 2HRZ 4H3R3CATEGORY IV

CHRONIC CASES(sputum positive after supervised rx) NOT APPLICABLE

ALTERNATIVE TB RXINITIAL PHASE CONT.PHASE

DAILY OR 3X/WEEK

TREATMENT BY CATEGORY (WHO guidelines)

Notes:

• Initiate treatment with 4 drugs on high index of suspicion

• Repeat smear and culture at 2 months

• Lengthened if culture still positive at 2 months/ cavitations to 9 months

• EMB is discontinued when drug testing showed no resistance

• PZA is discontinued after 56 doses

Treatment Flow ChartINITIATION OF TREATMENT

56 DOSES DAILY (8 WEEKS/2 MONTHS)* baseline investigations

BIWEEKLY TREATMENT16 DOSES (8WEEKS/2MONTHS)

*sputum D/S ,CXR

BIWEEKLY TREATMENT16 DOSES(8 WEEKS/2 MONTHS)

*sputum D/S, CXR

FOLLOW UP 3/12, 6/12 AND 9/12

*sputum D/S X3,sputum culture AFB, liver function test, renal profile blood sugar, pregnancy test, sr. uric acid,visual test and HIV if indicated.

DOT (Directly Observed Treatment)

COMPLICATIONS OF DRUG THERAPY

ADVERSE REACTION TO TB DRUGS

DRUG RESISTANCE

MODIFICATION TO SUIT PATIENT’S NEEDS

RELAPSE

IMMUNOLOGICAL REBOUND

OUTCOME OF TREATMENT

• CURE ( SPUTUM CONVERSION RATE )• COMPLETED TREATMENT• INTERUPTTED TREATMENT• RELAPSED• DEATH• LOST TO FOLLOW UP• TREATMENT FAILURE

– NON COMPLIANCE– RESISTANT TB

TREATMENT FAILURE

Patient who remains or becomes again smear-positive at five months or later during treatment.

– POOR COMPLIANCE– INAPROPRIATE TREATMENT– DRUG RESISTANCE

Side effects of Anti TB Drugs

MECHANISMS OF TOXICITY

• DOSE RELATED OR HYPERSENSITIVITY

• HIGH DUE TO MULTIPLE DRUGS USE• MAJOR DETERMINANTS ARE :

- DOSE - MODE OF ADMINISTRATION - AGE - GENETIC STATUS

- NUTRITIONAL STATUS - CONCOMITANT THERAPY - HEPATIC/RENAL FUNCTION

STREPTOMYCIN

• Is not absorbed by GIT• Bactericidal• Plasma half life 2-3 hrs, prolonged in

new-born,elderly ,renal patients• Given by deep I/m injection• Contraindication:

-Hypersensitivity -Auditory nerve impairment -Myasthenia gravis

• Dosage : 15mg/kg.

STREPTOMYCIN Adverse reactions

• Hypersensitivity reactions• Auditory nerve damage• Dose related renal damage• Sterile abscesses• Headache,vomitting, vertigo and

tinnitus• Haemolytic anaemia• Aplastic anaemia• Lupoid reactions

ETHAMBUTOL

• Bactericidal• Readily absorbed from GIT• Plasma half life 3-4 hours• Dosage: Adults- 15/kg daily - 45mg/kg biweekly

Children : max.15mg/kg

• Contraindications: - known hypersensitivity ,

- pre-existing optic neuritis - inability to report visual impairment , - CC < 50ml/min.

ETHAMBUTOLAdverse reactions

• Dose dependent optic neuritis

• Peripheral neuritis• Preferred to streptomycin in

pregnancy

RIFAMPICIN Adverse reactions

• Gastrointestinal intolerance• skin rashes ,exfoliative

dermatitis• fever• influenza-like illness• Thrombocytopenia / haemolysis• dose related hepatitis• immunological reactions

-renal impairment.

PYRAZINAMIDE

• Weakly bactericidal• Potent sterilizing activity• Readily absorbed • Metabolized mainly in the liver• Plasma half life 10 hours• Dosage : 25mg/kg daily, 50 mg/kg

biweekly• Contraindications:

-Known hypersensitivity -severe hepatic impairment

PYRAZINAMIDE: Adverse reaction

• Flushing of skin• Hepatotoxicity - rare• Hyperuriceamia• Arthralgia• Labile blood glucose

concentrations

ISONIAZID Adverse reactions

Precautions : -measurement of serum transminases.

Adverse effects -cutaneous hypersensitivity - peripheral neuropathy - optic neuritis - psychosis - generalized convulsions - hepatitis

Approach to Mx of A/E of TB drugs

1. Monitoring • Before treatment ° clinical features – drug history: OCP, PI warfarin - liver & renal disease ° baseline Ix – LFT, RFT, FBC, visual acquity

• During treatment monitored for adverse effects of anti TB

2. Management

• minor adverse effects adverse effects management GIT upset give drug last thing at anorexia/nausea night Joint pain aspirin/NSAID Burning sensation pyridoxine 100mg daily in the feet orange/red urine reassurance

Mild skin rash reassurance and and pruritis symptomatic Rx

• major adverse effects

° hypersensitivity reaction ° drug induced hepatitis

° renal impairment

° reversible visual impairment – ETH

° irreversible eight CN damage – SM

° thrombocytopenia, shock - RFP

Skin Rash

Exanthematous Eruptions

Urticarial Drug Eruptions

Pustular Drug Eruptions

Steven Johnson Syndrome (SJS)

Hypersensitivity reaction Skin rash Steven-Johnson syndrome

Hypersensitivity Drug

least likely Isoniazid Rifampicin Pyrazinamide Ethambutol most likely Streptomycin

Management

• stop all anti TB drugs until the reaction has subsided

• symptomatic Rx

• once the reaction has subsided the drug or drugs responsible for the reaction must be identified:

a challenge dose for hypersensitivity

A challenge dose for hypersensitivity anti TB regimen

skin rash

a challenge dose of each drug of the regimen ° dose: 1/10 of the therapeutic dose daily ° start with the drug that are least likely to cause the reaction ° challenge should be done for one drug at a time

rash after 1st yes no

do not proceed continued in full dosage desensitization

Drug Challenge Dose(mg) D1 D2 D3 INH 50 300 300

RFP 75 300 full dose

PZA 250 1000 full dose

ETM 100 500 full dose

SM 125 500 full dose

Desensitization

Reaction occurs with the 1st dose desensitizing

• only done if one is unable to devise a suitable regimen of treatment without the offending drugs

• do not start desensitization doses when other alternative and suitable drug combinations are

available

• done by giving initially small and slowly increasing dosage of the offending drug

• the patient should observed for T and pruritis

Rapid desensitization

• dosage can be given by giving the drug more frequent • generally begin with 1/10 – 1/100 of the therapeutic dose

and then doubled each time • example: rapid desensitization for INH Day suggested time dose(mg) 1 6 am 1 12 noon 2 6 pm 4 12 mn 8 2 6 am 15 12 noon 30 6 pm 60 12 mn 100 3 6 am 200 12 noon 200 4 & beyond 6 am 300

• same procedure with other drugs: SM, Rifam, PZA & EMB

Drug-induced hepatitis

• Predisposing factors

° pre-existing liver disease - HBV, alcoholic

° old age ° malnourish

• Common drug: PZA > RFP > INH

• Management - rule out other possible causes Drug induced hepatitis

LFT ( AST, ALT and ALP ) >3x 2-3x <2x

Pt well pt unwell monitor LFT repeat LFT after Non-infec infec weeklyx2/52 after 2/52 then 3 weeks Stop all Rx: SM,EMB,Qua continue Rx with

till LFT till LFT N continue Rx all drugs with all drugs LFT N abN suggested Rx: 2SHE/10HE(S) A challenge dose

Renal impairment

• INH, RFP, PZA ° eliminated by non renal routes ( hepatic / bile )

° can be given in normal dose to patient with renal failure

° several reports RFP renal toxicity – tubulo-interstitial nephritis - interstitial fibrosis - tubular necrosis dramatic response after – stop RFP - corticosteroid ° severe RF - INH 200mg daily to avoid peripheral nephropathy

Management of Extrapulmonary

Tuberculosis

Extrapulmonary TB

Virtually any organ may be affected

• Lymph node• Pleura• Genitourinary tract• Bones and joints• Brain• Peritoneum• Skin

In order of decreasing frequency

Extrapulmonary Tuberculosis

DIFFERENT TREATMENT

DURATION !!!

TB Lymphadenitis

• Painless swelling of lymph nodes

• Commonly affects cervical and supraclavicular lymph nodes

• Lymph nodes may have sinuses discharging caseous material

Tuberculous Lymphadenitis

Evaluation:

Diagnosis can be established by culture of M. tb from lymph node biopsy or aspirate. Demonstration of AFB in tissue or aspirate or pathologic evidence of caseating granuloma is consistent with TB.

Treatment:

Treatment follows pulmonary TB regimen. Prolong treatment for a total of nine (9) months. Even if lymph node excision is complete, chemotherapy is indicated.

TB Lymphadenitis

TB Lymphadenitis

TB Lymphadenitis

TB Pleura• Penetration by tubercle

bacilli into pleural space

• Feature – pleural effusion, empyema

• Tuberculous empyema – AFB direct smear often positive and usually requires surgical drainage

Pleural Tuberculosis

Evaluation:

In pleurocentesis, AFB stain of the fluid sediment is seldom positive; culture is positive in a quarter to third of cases.

Treatment:

Treatment follows pulmonary TB regimen. A total of 9 months treatment.

Right pleural effusion

Genitourinary TBSymptoms – frequency, dysuria, haematuria, loin pain, may be asymptomatic, discovered only after severe renal destruction.

Evaluation:

Urinalysis has been reported to be abnormal in 90% of cases (mostly gross or microscopic hematuria and/or pyuria). AFB culture of three morning urine specimens will show M. tb in 90% of patients.

Treatment:

Treatment follows pulmonary TB regimen, and is usually highly successful. Surgery is indicated only for intractable pain, persistence of non-tuberculous infection from obstruction or serious, persisting hematuria. Treatment should be continued for nine to twelve months.

Genital TB• Female – affects fallopian tubes

and endometrium - may cause infertility, pelvic pain, menstrual

abnormalities

• Male – affects epididymis, testes and prostate

                                      Testicular tuberculosis. Computed tomographic scan of the pelvis showing a large, irregular, mixed solid and cystic left testicular mass (arrow).

Tuberculosis of the Bones and Joints

Skeletal TB occurs most commonly in the weight-bearing joints. The spine is the most frequent site (also known as Pott's disease), followed by the hip and knee. The most common presenting symptoms are pain and difficulty with locomotion.

Evaluation:

For skeletal TB should be X-ray films of the involved joint, followed by specimen collection and culture. Biopsy will be necessary to obtain tissue for confirmation of diagnosis.

Treatment:

Treatment follows the regimen for TB meningitis, treatment for twelve (12) months for all individuals, regardless of immune status.

Osteoarticular tuberculosis. Radiograph of the right knee showing a large effusion, osteopenia, joint space narrowing, and lucencies in the distal femur.

Spinal tuberculosis. Magnetic resonance imaging of the spine revealing osteomyelitis involving T10 and T11 vertebral bodies and disc space (A; arrow) and an adjacent multiloculated paravertebral abscess (B; arrow).

Gastrointestinal TB• Any part of GI tract may be

involved

• Spread via swallowing of sputum, blood-borne or ingestion of unpasteurised cow’s milk

• Terminal ileum and caecum most common

• Features – abdominal pain, diarrhoea, obstruction, palpable mass

Tuberculous Peritonitis

The disease presents with one of two manifestations: 1) ascites that leads to abdominal pain and distention with or

without gastrointestinal symptoms; 2) abdominal pain, with or without symptoms suggesting

intestinal obstruction.

Evaluate :

Culture of the ascitic fluid or peritoneal or open biopsy; the diagnosis of "dry" tuberculous peritonitis is made, usually, by laparotomy and biopsy that reveals caseating granulomas with or without tissue stains positive for AFB.

Treatment:

Treatment is comparable to that for pulmonary tuberculosis

( nine to twelve months ).

Ascites

Miliary Tuberculosis

• Due to haematogeneous spread of tubercle bacilli

• Either 1° or reactivation of old disseminated foci

• Symptoms – fever, night sweat, anorexia, weakness

• Signs – hepatosplenomegaly,

lymphadenopathy

• Cryptic form – elderly characterised by mild intermittent fever, anaemia and meningeal involvement

Miliary Tuberculosis

Evaluation:

The diagnosis of disseminated TB is usually suspected because of the presence of miliary infiltrates on chest x-ray. Transbronchial biopsy is the most high-yield procedure to obtain tissue. In other instances, hematogenous dissemination is evidenced by tissue biopsy from other organs such as lymph nodes, liver, or bone marrow.

Treatment:

Treatment follows the regimen for TB meningitis.

Use of corticosteroids:

Fulminant miliary TB may be associated with the Adult Respiratory Distress Syndrome (ARDS) and disseminated intravascular coagulation (DIC). In such cases, corticosteroid treatment (prednisone 60-80 mg/day) is indicated.

Miliary Pulmonary Tuberculosis

TB Meningitis / Tuberculoma

• Features – headache, confusion, altered sensorium, neck stiffness, cranial nerve palsy

• Hydrocephalus is common

• Tuberculoma presents as space-occupying lesion, seizures and focal signs

Tuberculous Meningitis

Evaluation: Examination of the cerebral spinal

fluid (CSF).

CSF - pleocytosis (65% of cases have white blood cell counts between 100-500) with lymphocytic predominance, elevated protein and low glucose are usual. Acid fast bacilli (AFB) have been

seen in up to 37%..

Tuberculous Meningitis

Treatment:

TB meningitis can be treated with isoniazid, rifampicin, pyrazinamide and ethambutol in doses comparable to those use in pulmonary TB for the first two (2) months, followed by isoniazid and rifampicin in the continuation phase for 7 (in non-immunocompromised individuals) to 10 additional months

(in children and immunocompromised individuals ).

Use of corticosteroids:

The use of corticosteroids in patients who are initially confused, stuporous, or have focal neurologic deficits, dense paraplegia or hemiplegia, or "CNS block". Cerebral edema evidenced by CT scan is considered an indication for corticosteroid therapy by some.

Prednisone is started at 40-60 mg daily. The dose is gradually reduced after one or two weeks, using the patient's symptoms as a guide. If the patient has responded to treatment, steroids can usually be discontinued entirely after 4-6 weeks.

Pericardial Tuberculosis

Pericardial TB is much more common in HIV-infected individuals. Onset may be either subtle (dominated by cardiovascular consequences of effusion) or abrupt (fever and precordial pain).

Examination:

Fluid from pericardiocentesis will be similar to fluid from tuberculous pleural effusion. A positive acid-fast bacilli (AFB) smear is uncommon; a culture will be positive in only 25-50% of cases. issues of immediate treatment. Some physicians advocate primary surgical intervention with a pericardial "window" and biopsy in every case of suspected TB pericarditis.

Pericardial Tuberculosis

Treatment:

Treatment follows pulmonary TB regimen.

Use of corticosteroids:

Corticosteroid use is generally recommended. If used, begin prednisone 60-80 mg daily, and

gradually decrease the dosage over a period of several weeks as the effusion subsides.

Use of corticosteroids is not necessary if pericardiectomy has been performed.

Pericardiectomy:

This procedure is indicated if there is constriction.

TB Skin

TB Skin

Treatment Regimens in special situations

TB with HIV co-infection

In early stages the presentations of TB in TB-HIV co-infection is the same as HIV negative but in late stages extra pulmonary and dissemination are common.

Diagnostic problems arise as other respiratory diseases occur frequently and tuberculin test may be negative.

WHO recommends standard short course chemotherapy (DOTS or FDC) similar to that recommended for HIV negative cases.

After initiating ATT or anti retroviral therapy (ART) worsening of preexisting lesions or appearance of new lesions is more commonly seen than in HIV sero negative individuals due to a marked improvement in immunity. This is called “paradoxical response” or “immune reconstitution phenomenon”.

TB with HIV co-infection

Effect of TB on HIV

TB causes release of TNF and stimulates multiplication of virus inside T cells. TB helps in destruction of CD4 cells Helps release of new virions from HIV infected

cells

Effect of HIV on TB Decrease macrophage activating lymphokines. Increase in number of CD8 cells. Increase tissue destruction. T4 lymphopenia. HIV promotes T4 destruction and CD4 cells impairment.

TB with HIV co-infection

Multidrug resistant TB can occur due to poor compliance to ATT due to behavioural pattern and increased incidence of side effects.

Malabsorption of drugs is common due to associated diarrhoea, which can contribute to the selection of drug resistant mutants.

ART for HIV, containing protease inhibitors (PI) and Non nucleoside reverse transcriptase inhibitors (NNRTI) cannot be used along with R, as R induces metabolism of PI and reduces the efficacy.

TB with HIV co-infection

The various options are :     To postpone anti retroviral therapy.   To use no PI or NNRTI containing anti retroviral combinations (NRTI based regimens).   To use certain PI/ and/or NNRTIs with modification in doses  Efavirenz or Saquinavir with Ritonavir, without the need to adjust the doses.   To use non R regimens ( 2SHEZ+10HE )

Regimens which are compatible with simultaneous use of rifampicin are

2NRTI+ Abacavir (ABC) 2 NRTI+ Efavirenz (EFZ) 2 NRTI + Saquinavir (SQV)/Ritonavir (RTV)

The NRTIs can be either Zidovudine (ZDV)+ Lamivudine (3TC) or Stavudine (d4T) + Lamivudine (3TC)

TB and pregnancy

Tuberculosis during pregnancy is rarely, if ever, an indication for a therapeutic abortion. An exception might be if a pregnant woman has multidrug-resistant tuberculosis. A pregnant woman with culture-proven MDRTB, should be offered abortion counseling, because almost all of the medications used to treat MDRTB are known to cause fetal abnormalities.

No increase in morbidity or mortality from TB has been noted during pregnancy if treatment is adequate.

All drugs, that is, rifampicin, isoniazid, ethambutol, and pyrazinamide can be used during pregnancy. Streptomycin is not given due to ototoxicity to the fetus. Prophylactic pyridoxine in the dose of 10mg/day is recommended along with ATT.

Breast-feeding is safe during anti-TB therapy.

Breast feeding and Maternal Tuberculosis

( Summary Management ) According to the time of diagnosis and bacteriological status of the

mother.Active pulmonary TB before delivery Active pulmonary TB after

delivery> 2 months before < 2 months

before< 2

months after

> 2 months after

Smear negative just before delivery

Smear posative just before delivery - - -

Treat motherBreastfeedNo preventive chemotherapy for infant

BCG at birth

Treat motherBreastfeedGive isoniazid to infant for 6 months

BCG after stopping isoniazid

Treat motherBreastfeedGive isoniazid to infant for 6 months

BCG after stopping isoniazid

Treat motherBreastfeedGive isoniazid to infant for 6 monthsBCG after stopping isoniazid

Treat motherBreastfeedGive isoniazid to infant for 6 months

BCG after stopping isoniazidMonitor all infants for weight gain and health

Do not give BCG to infants who are symptomatic for yellow fever or HIV infection.Division of Child Health and Development Update Feb. 1998

Liver disorders.

Isoniazid, rifampicin, pyrazinamide are all associated with hepatitis. Of these 3 agents, pyrazinamide is the most hepatotoxic.

Patients with liver disease should not receive pyrazinamide. Isoniazid plus rifampicin plus one or two non-hepatoxic drug such as streptomycin and ethambutol can be used for a total treatment duration of 9 months. ( 2 SHRE / 7 HR )

Alternative regimens are SHE in the initial phase followed by HE in the continuation phase, with a total treatment duration of 12 months. ( 2 SHE/10 HE ).

Renal failure

Isoniazid, rifampicin, pyrazinamide can be given in normal dose to patients with renal failure.

Streptomycin and ethambutol may be given in reduced doses as both drugs are excreted by the kidney.

The safest regimenfor the patient with renal failure is 2HRZ / 4RH

In post renal transplant patients: Rifampicin-containing regimens are

avoided as rifampicin causes increased clearance of cyclosporin.

TB in Children

TB in Children

A child usually gets TB infection from being exposed to a sputum-positive adult.

Young children below ten years of age are at risk of becoming infected with TB bacilli because the immune system of young children is less developed. 

In HIV infected children the risk of developing TB meningitis is very high and often result in deafness, blindness, paralysis and mental retardation.  

TB in Children

o The diagnosis is thus largely based on the clinical features of cough, weight loss, with a history of close contact with an infectious adult TB patient.

o With increasing coverage of BCG vaccination, the tuberculin skin test is no longer considered a confirmatory test.

o Chest X-rays of children are difficult to interpret as the typical shadow is rarely seen.   

TB in Children

WHO guidelines for diagnosisSuspect TB in a child -      Who is ill, with a history of contact with a

suspect or confirmed case of pulmonary TB;

Who does not return to normal health after measles or whooping cough;

With loss of weight, cough, fever who does not respond to antibiotic therapy for acute respiratory disease;

With abdominal swelling, hard painless mass and free fluid;

With painless firm or soft swelling in a group of superficial lymph nodes;

With signs suggesting meningitis or disease in the central nervous system.

TB in Children•  Preventing TB disease in children Early diagnosis and successful treatment of an infectious

adult patient is the best way to protect children from becoming infected with TB.

BCG immunization of babies soon after birth up to 2 years of

age will protect them mainly against the development of TB meningitis.

 Treating TB in children The management of TB in children is similar to those in adults.

Some important differences are:

      Dosages in children per kilogram body weight should be higher as they have a higher metabolism. They can tolerate higher doses with fewer side-effects.

      Children usually have fewer microorganisms and are less likely to develop secondary resistance

      Extra-pulmonary TB is more common in children and therefore the drugs used should be able to penetrate and achieve the required concentration in specific body fluids and tissues.

PROPHYLACTIC TREATMENT

Def : Treatment to prevent acquisition of infection with MTB in a person exposed to tubercle bacilli.

WHO ? Children under the age of 5 years at risk

of being infected from a person with sputum smear-positive TB living in the same household.

MANAGEMENT OF RESISTANT TB

Definitions :a) Drug-resistant tuberculosis : This is a case of tuberculosis (usually pulmonary ) excreting bacilli resistant to one or more anti-tuberculosis drugs.

b) Multidrug-resistant tuberculosis :

This is a case of tuberculosis which is resistant to

Isoniazid and Rifampicin.

MANAGEMENT OF RESISTANT TB

Prevention Adequate treatment Full supervision High suspicion on high risk group. Previously treated patients Immigrants from high resistant areas Contacts of patients Immuno-suppressed patients

PRINCIPLE OF THERAPY

TREATMENT OF MDR TB

• DEF : Resistant to both H & R• Overall response 56%

• BASIC PRINCIPLES:

- - At least 3 drugs ( preferably four or five ) if possible one injectable aminoglycoside.

- continued for 18 - 24 mths after culture -ve

- if fail, 2 new drugs must be added simultaneously. - Advisable to manage patient with MDR TB as in-patient until sputum conversion is achieved. - must be DOT

- manage by expert

SECOND LINE DRUGS

• OLDER DRUGS: - Ethionamide 750 mgm daily

- Cycloserine 250 mg tds - P.A.Salicylic acid 12-16 mgm/kg - Capreomycin 10-15 mgm /kg - Kanamycin/Amikacin 10-15 mgm/kg

• NEWER DRUGS:

– Quinolones -ciprofloxacin and ofloxacin– Microlides- Clarithromycin and Azithromycin– Augmentin– Clofazimine.

MONITORING MDR TB

• At least once a month• Complete physical and

laboratory evaluation• Monthly monitoring of

sputum direct smear and culture

• Discontinued isolation once sputum negative three times

• Surgical intervention if possible.

Surgical Intervention

• As adjunct to medical treatment, cure with medical therapy 56%.

• With surgery, cure rate may increase to 85-90 %.

• May be hazardous but may be life saving.

• After surgery, the same drug regimen should be continued for at least 18 mths.

“ EVERYONE WHO BREATHES AIR, FROM WALL STREET TO THE GREAT WALL OF CHINA, NEEDS TO WORRY ABOUT THE RISK OF TUBERCULOSIS”

(World Health Organization)

Role of PPD

• A purified protein derivative (PPD)-tuberculin skin test may be done at the time of initial evaluation, but a negative PPD-tuberculin skin test does not exclude the diagnosis of active tuberculosis.

• However, a positive PPD-tuberculin skin test supports the diagnosis of 1) culture-negative pulmonary tuberculosis, 2) latent tuberculosis infection in persons with stable abnormal chest radiographs consistent with inactive tuberculosis.