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Flow chart II
Treatment and follow up of Re-treatment cases (CAT 2)(Send sputum for pre-treatment culture and ABST)
2 HRZES
1 HRZE
Examine sputum (end of the 3rd
month)
Positive Negative
Continue 1 HRZE Start continuation phase5 HRE
Examine sputum
(end of the 4th
month) Examine sputum
end of the 5th
month and
end of treatment)
Positive Negative
Further treatment
determined by result Start continuation phase
of pre-treatment 5 HRE Positive Negative
culture & ABST
Examine sputum
(end of the 5th month and end of treatment) Do a CXR**
and stop ATT
(Cured)
Positive Negative
Do a CXR** and stop ATT
(Cured)
Chronic Case
Refer to a Chest Physician
**Optional
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Flow chart III
Treatment and follow up of smear-negative PTB cases
Smear-negative PTB
(Send sputum for pre-treatment culture)
2 HRZE(S)
CXR after 1 month
Examine sputum (end of the 2nd
month).
Negative Positive
Start Continuation Phase Treatment Failure
4 HR
Examine sputum Stop ATT
* Do a CXR Re-registerStop ATT Start CAT 2
(Completed Rx)
* If no improvement in the abnormality found in the original CXR, refer the patient to a
Chest Physician.
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Directly Observed Treatment
Directly Observed Treatment (DOT) is one of the important elements of the
internationally recommended strategy for TB control. Directly Observed Treatment
means that an observer watches the patient swallow their tablets. This ensures that a TB
patient takes the right anti-tuberculosis drugs, in the right doses at the right intervals
without interruption and ensures that the patient completes the full course of treatment.
Why is Directly Observed Treatment necessary?
Patient compliance is a key factor in treatment success. Many patients who receive self-
administered treatment often take drugs irregularly and a significant proportion of
patients stop treatment before completion due to various reasons. It is impossible to
predict who will or will not comply. Therefore directly observed treatment is required to
ensure treatment adherence and it also helps to motivate the patient to continue treatment.
It is recommended in the intensive phase of treatment at least for all sputum positive
cases. A patient who misses one attendance for DOT can be traced immediately,
counseled and returned to treatment.
Patient compliance should be promoted through a patient centered approach by:
- Facilitating easy access to treatment, by organizing directly observed
treatment as close to patients home (or the work place) as possible
- Providing anti-tuberculosis drugs free of charge- Providing polite and rapid attention.
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National policy for the implementation of Directly Observed
Treatment (DOT)
Patients who will be given DOT
New Pulmonary TB (sputum positive and negative) casesIntensive phase:
All new Pulmonary TB (sputum positive and negative) patients should be given
directly observed treatment daily during the intensive phase. This should be
arranged as far as possible community based, or hospital based wherever
necessary as in the case of very ill patients or those patients who are unable to
come daily for supervised treatment
Continuation phase:
Since the continuation phase also contains Rifampicin, every effort should be
made to give each dose under observation. Wherever this is not possible patients
will be advised to attend the chest clinic once a week, and the first dose will be
given under direct observation and the remaining six doses will be supplied for
self-administration at home. DTCO will make arrangements for supervisory visits
to check drug intake (including pill counts).
Extra pulmonary TBIntensive Phase:
Drugs will be given under direct observation
Continuation phase:
Since the continuation phase also contains Rifampicin, every effort should be
made to give each dose under observation. Wherever this is not possible patients
will be advised to attend the chest clinic once a week and the first dose will begiven under direct observation and the remaining six doses will be supplied for
self-administration at home. The DTCO will make arrangements for supervisory
visits to check drug intake (including pill counts).
All Re-treatment casesDirectly Observed treatment should be given throughout the entire period of
treatment daily, both in the intensive and continuation phase of treatment.
Admission to hospital is recommended whenever possible.
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DOT Providers
The following categories will provide Direct Observation of Treatment.
Health workers at state health care facilities Field health care workers General practitioners Trained volunteers Community leaders
Trained community volunteers or community leaders need regular support, motivation
and supervision by the NTP staff to ensure that quality is maintained.
Provision of drugs for the DOT Centres -
Drugs for each patient will be delivered to the DOT centres from the District Chest Clinic
by the PHI or any other staff assigned by the DTCO.
Interruption of treatment (default)
Directly Observed Treatment adapted to the needs of the patient is the best method of
avoiding treatment interruption. However, even with directly observed treatment and
during the continuation phase of treatment, which may be self-administered, there may be
treatment interruption.
Measures to minimize treatment interruption
At the time of registration of a TB patient, the staff must educate the patient and the
family regarding the duration of treatment and the importance of adherence to treatment.
It is vital to record the patients address and other relevant addresses e.g. parents or workplace etc. in order to help locate the patients who interrupt treatment. As far as possible,
the address should be verified at the beginning of treatment.
Management of patients who interrupt treatment
It is important to take action on defaulters immediately. Patients should be contacted the
day after missing a dose during the intensive phase and as soon as possible during the
continuation phase. It is important to find out the reason for the patients absence in order
to take appropriate action and continue treatment.
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Table 3 Actions in interruption of TB treatment
Interruption for less than 1 month
Trace patient Solve the cause of interruption Continue treatment and prolong it to compensate for missed dosesInterruption for 1-2 months
Action 1 Action 2
Continue treatment and prolong it to
compensate for missed doses
Treatment Continue treatment and
received: prolong it to compensate
for
< 5 months missed doses
Trace the patientSolve the cause of
interruption
Do 3 sputum smears.Continue treatment
while waiting
If smears negative
or EPTB
If one or more
smears positive
do culture &
ABST
> 5 months Category 1: Start Cat 2
Category 2: refer for advice
(may evolve to Chronic)
Interruption for 2 months or more (defaulter)
Action 1 Action 2
Do 3 sputum smearsSolve the cause of
interruption, if possible
No treatment while
waiting for results
Send culture & ABST
Negative smears
or EPTB
One or more
smears positive
Clinical decision on individual basis
whether to restart or continue treatment,
or no further treatment
If on Category 1 Start Category 2
If on Category2 Refer for advice (may
evolve to Chronic)
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ESSENTIAL (FIRST LINE) ANTI-TB DRUGS5Isoniazid (INAH)
Isoniazid is highly bactericidal against replicating tubercle bacilli. It is rapidly absorbed
and diffuses readily into all fluids and tissues. The plasma half-life, which is genetically
determined, varies from less than one hour in fast acetylators to more than three hours in
slow acetylators. It is largely excreted in the urine within 24 hours, mostly as inactive
metabolites.
Uses
Isoniazid is a component of all TB chemotherapeutic regimens currentlyrecommended by WHO.
Isoniazid alone is occasionally used in chemoprophylaxisAdministration
Isoniazid is normally given orally.
Dosages
For treatment-
Adults and children: 5mg/kg (4-6mg/kg) daily, maximum 300mg.
10 mg/kg 3 times weekly
Preventive therapy:
Adults: 300mg daily for at least 6 months
Children: 5mg/kg daily (maximum 300mg) for at least 6 months
Side-effects
Isoniazid is generally well tolerated at recommended doses.
Systemic or cutaneous hypersensitivity reactions occasionally occur during the firstweeks of treatment.
Peripheral neuropathy may occur in persons with malnutrition, chronic alcoholics, andpregnant women or in diabetics. This can be prevented or minimized by giving,
supplementary pyridoxine 10 mg daily to those at risk.
Other less common forms of neurological disturbances including optic neuritis, toxicpsychosis, and generalized convulsions can develop in susceptible individuals,
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particularly in the later stages of treatment, which occasionally may necessitate
withdrawal of Isoniazid.
Hepatitis is an uncommon but potentially serious reaction that can usually be avertedby prompt withdrawal of the treatment. Monitoring of hepatic transaminases should
be done in patients with pre-existing chronic liver disease.
Isoniazid tends to raise plasma concentrations of phenytoin and carbamazapine byinhibiting their metabolism in the liver. Therefore it may be necessary to reduce the
dosages of these drugs during treatment with Isoniazid.
Patients on treatment with Isoniazid should be cautioned against eating Red fishsuch as skipjack and tuna, which contain high concentrations of histamine. Isoniazid
is an inhibitor of histaminase, which is normally present in the tissues and is
responsible for the inactivation of ingested histamine. As a result, the histamine level
in the tissues of the patient tends to rise shortly after a meal containing these varieties
of fish, and the patient may experience symptoms of histamine intoxication like
erythema, severe headache, red eyes, palpitation, diarrohoea, vomiting and wheezing.
Isoniazid is not teratogenic and can be used during pregnancy.
Rifampicin
Rifampicin has a potent bactericidal and sterilizing effect against tubercle bacilli in both
cellular and extra-cellular locations. Following oral administration, it is rapidly absorbed
and distributed throughout the cellular tissues and body fluids.
Since resistance develops rapidly, Rifampicin must always be administered in
combination with other effective anti-mycobacterial agents.
Uses
It is a component of all 6 months and 8 months TB chemotherapeutic regimens currently
recommended by WHO.
Administration and dosage:
Rifampicin is administered orally and should preferably be given at least 30 minutes
before meals, since absorption is reduced when it is taken with food.
This however may not be clinically significant and food can reduce intolerance to the
drugs.
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Adults and children: 10 mg/kg (8-12 mg/kg) daily, maximum 600mg daily.
10mg/kg 3 times weekly
Side-effects
Rifampicin is well tolerated by most patients at currently recommended doses
Side-effects include:
Gastro-intestinal - nausea, anorexia, vomiting and abdominal pain Hepatitis is a major side effect although it is rare. Alcoholics and pre existing liver
disease may increase the risk and it may be advisable to monitor the liver function
tests in these high-risk groups.
The following reactions are more likely to occur with intermittent therapy:
Flu syndrome - consisting of attacks of fever, chills, malaise headache, bonepain
Cutaneous reaction consisting of flushing, and pruritus with or without a rash *Thrombocytopenia and purpura *Heamolytic aneamia and acute renal failure may occur *Respiratory shock syndrome consisting of shortness of breath and rarely
associated with collapse and shock. may occur
* If these reactions occur Rifampicin must be stopped immediately and admitted to
hospital for management. It should not be given again.
Drug interactions
Rifampicin induces hepatic enzymes and may accelerate clearance of drugs metabolized
by the liver, and patients may need higher dosages of these drugs. These include
corticosteroids, oral contraceptives, oral hypoglyceamic agents, oral anticoagualants,
anticonvulsants, and cimetidine, cyclosporin and digitalis glycosides.
Since Rifampicin reduces the effectiveness of oral contraceptives, women should be
advised to use an alternative method of contraception.
Rifampicin is excreted in urine, tears, sweat and other body fluids and may colour them
red or orange. Patients should be warned of discoloration of urine and other body fluids.
Rifampicin may be used safely in pregnancy. Vitamin K should be administered at birth
to an infant of a mother taking Rifampicin because of the risk of postnatal haemorrhage.
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Pyrazinamide
Pyrazinamide is bactericidal and particularly effective against bacilli in an acid
environment inside macrophages. It is highly effective during the first two months of
treatment by destroying the intracellular bacilli and reduces the risk of relapse.Uses:
It is a component of all 6 month and 8 month TB chemotherapeutic regimens currently
recommended by WHO.
Administration and dosage:
It is administered orally and is rapidly absorbed from the gastro-intestinal tract and
rapidly distributed throughout all tissues and fluids.
Adults and children: (for the first 2 or 3 months)
25mg/kg daily (20-30 mg/kg)
35 mg/kg (30-40mg/kg) 3 times weekly
Side-effects
Gastro intestinal symptoms- nausea, anorexia Hypersensitivity reactions are rare, but some patients may complain of flushing of
the skin
Hepatitis is the most important adverse effect, though it is rare. Hyperuriceamia may occur due to diminished excretion of uric acid in urine, but
this is often asymptomatic. Arthralgia may occur and treatment with simple
analgesics is often sufficient. Attacks of acute gout are uncommon.
Ethambutol
Ethambutol has a bacteriostatic effect. It is used in combination with other ant-TB drugs
to prevent the emergence of drug resistant strains.
It is given orally and absorbed readily from the gastro intestinal tract.
Administration and dosage:
Ethambutol is given orally
Adults: 15mg/kg (15-20 mg/kg) daily
30mg/kg (25-35mg/kg) 3 times weekly.
Children: Maximum 15mg/kg daily
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Ethambutol is not recommended in children who are too young for assessment of visual
acuity and red- green colour discrimination (generally under 6 years of age).
Side-effects
Dose dependant optic neuritis is the most important side effect and can result in
impairment of visual acuity and colour vision. Early changes are usually reversible, but
blindness can occur if treatment is not discontinued promptly. Therefore patients should
be advised to report immediately to a clinician if their vision deteriorates.
Streptomycin
Streptomycin is bactericidal in action. It is not absorbed from the gastrointestinal tract and
must be given by intra-muscular injection
Streptomycin is excreted entirely through the kidneys and therefore drug should be used
in reduced dosage and with extreme caution in patients with renal insufficiency and in the
elderly.
Administration and dosage:
Streptomycin must be administered by deep intra-muscular injection. Syringes and
needles should be sterilized properly. Whenever possible use disposable syringes andneedles.
Adults and children: 15mg/kg (12-18mg/kg) daily or 3 times weekly.
Patients over the age of 60 years may not be able to tolerate more than 500mg daily.
Side-effects
Hypersensitivity reactions are rare.If they do occur (usually during the first fewweeks of treatment), streptomycin should be withdrawn immediately. Once fever
and skin rash have resolved, desensitization may be attempted.
Auditory nerve damage can occur resulting in deafness and is more common inelderly and in patients with renal impairment.
Vestibular damage is uncommon, with the recommended doses, but if headache,vomiting, vertigo, dizziness and nystagmus occur, doses should be reduced.
Nephrotoxicity can occur
Streptomycin should not be used in pregnancy. It crosses the placenta and can causeauditory nerve impairment and nephrotoxicity in the foetus.
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Fixed Dose Combination (FDC) tablets
Tablets containing a combination of four drugs (RHZE), three drugs (RHE) and two
drugs (RH) will be used in identified districts in Sri- Lanka from 2005.
Table 4 Number of tablets of FDC used in CAT 1 and CAT 2
Weight (Kg)
Category
70
CATEGORY 1
Duration of
treatment
Intensive phase-daily
RHZE (tab)
150+75+400+275mg
2 3 4 52 months
Continuation phase-daily
RH (tab)
150+75
2 3 4 54 months
CATEGORY 2
Intensive phase-daily
RHZE (tab)
150+75+400+275mg
&
Streptomycin
2
0.5g
3
0.75g
4
1g
5
1g
2 months
RHZE (tab)
150+75+400+275mg
2 3 4 5
1 month
Continuation phase-daily
RHE (tab)
150+75+275mg
2 3 4 55 months
*Patients over 60 years, the dose of streptomycin 0.5g, irrespective of the weight
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Management of Side-effects of First-line Anti-TB drugs
Side-effects of anti-tuberculosis drugs are of two types.
Major side-effects are those, which causes serious health hazards. In this case, the anti-
tuberculosis drugs should be stopped and the patient referred to hospital for management.
Minor side-effects cause only relatively little discomfort. They often respond to
symptomatic treatment. In general, a patient who develops minor side-effects should
continue the anti-TB treatment.
Table 5 Adverse effects of first-line anti-TB drugs
Drug Common side-effects Rare side-effects
Isoniazid Peripheral neuropathy Hepatitis Histamine Reaction after
ingestion of red fish e.g., bala,
kelawalla
Convulsions, pellagra.
Joint pains,
Agranulocytosis, lupoid
reaction, skin rash
Rifampicin Gastro-intestinal-nausea,anorexia, abdominal pain
Hepatitis Reduced effect of oral
contraceptives, antiepileptic
drugs, oral hypoglyceamic
drugs and theophyllines
Acute renal failure, shock,
thrombocytopenia, skin rash,Flu syndrome (with
intermittent doses) pseudo
membranous colitis, pseudo
adrenal crisis.
Pyrazinamide Joint pains Hepatitis Gastrointestinal symptoms, skinrashes, sideroblastic aneamia.
Streptomycin Auditory and vestibulardamage (also to the foetus)
Renal damageSkin rash
Ethambutol Optic neuritis Skin rash, joint pains,peripheral neuropathy.
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Table 6 Symptom based management of side-effects of Anti-TB drugs
Side-effects Drug(s) responsible Management
MINOR CONTINUE DRUGS
1.Anorexia, nausea,
abdominal pain
2.Joint pain
3.Burning sensation in feet
4.Orange/red urine
5.Histamine reaction
Rifampicin or bulk of
the drugs
Pyrazinamide
Isoniazid
Rifampicin
Isoniazid
Give drugs with small
meals or last thing at night
Give Asprin/NSAIDs
Pyridoxine 100 mg daily
Reassurance
Advice not to eat Red fish
MAJOR STOP DRUGS RESPONSIBLE
REFER FOR EVALUATION
1. Itching of skin, skin rash
2. Deafness
3. Dizziness, vertigo,nystagmus
4. Jaundice (other causes
excluded)
5. Vomiting and confusion
6. Visual impairment
7. Shock, purpura, acute renal
failure, haemolytic anaemia
Streptomycin
Streptomycin
Streptomycin
Most anti-TB drugs
especially INAH,
Rifampicin and
Pyrazinamide
Most anti-TB drugs
Ethambutol
Rifampicin
Stop anti-TB drugs
(See page 40)
Stop Streptomycin
Stop Streptomycin
Stop anti-TB drugs
(see page 39)
Stop anti-TB drugs
Stop Ethambutol
Stop Rifampicin
(Never give again)
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Management of severe drug reactions
Hepatitis
Most anti-TB drugs can damage the liver. Isoniazid, pyrazinamide and rifampicinare the drugs most commonly responsible and ethambutol rarely.
When a patient develops hepatitis during anti-TB treatment, it is important to ruleout other possible causes of hepatitis before deciding that the hepatitis is drug-
induced.
Mild transient increases in serum transaminases may occur during the initialtreatment. This rise is not more than 2-3 folds of the normal. This subsequently
falls to normal despite continuation of anti-TB drugs. This is not an indication to
stop anti-TB drugs provided serum bilirubin level remains normal.
Ideally, pre-treatment base-line Liver Function Tests (LFTs) should be done in allpatients. Since this may not be practical, it should be done at least on those who
are at a higher risk of developing drug-induced hepatitis e.g. known chronic
alcoholics, pre-existing liver disease, pregnant mothers and the elderly.
Liver function tests should be performed when patient is having symptoms &signs suggestive of hepatitis. i.e. nausea, vomiting with or without icterus or
hepatomegaly.
If drug-induced hepatitis is diagnosed, all anti-TB drugs should be stopped andpatient may need admission to hospital.
Repeat the Liver Function Tests after 1-2 weeks. Sometimes tuberculous disease is so severe that all anti TB drugs cannot be
withdrawn. In such situations, patient should be treated with two of the least
hepatotoxic drugs streptomycin and ethambutol (provided the patient is not
allergic to the latter two drugs) until the LFTs come back to normal.
Once LFTs return to normal, challenge doses of original drugs can bereintroduced sequentially in the order of isoniazid, rifampicin and pyrazinamide
with daily monitoring of the patients clinical condition and at least weekly
monitoring of LFTs. If symptoms recur early, LFTs should be repeated before one
week. Isoniazid should be introduced initially at 50 mg/day increasing
sequentially to 300 mg/day after 2-3 days if no reaction occurs, and then
continued. After a further 2-3 days without reaction, rifampicin should be added at
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a dose of 75 mg/day increasing sequentially to full dose after 2-3 days and then
continued. The final drug to add is pyrazinamide starting with a dose of
250mg/day increasing to the full dose after 2-3 days.
If there is no further reaction, standard chemotherapy can be continued, and anyalternative drugs introduced temporarily can then be withdrawn.
During this procedure if the patient complains of a recurrence of symptomssuggestive of hepatitis, LFTs should be repeated, and if found abnormal the drug
added last should be withdrawn and attempts should not be made to reintroduce it.
A suitable alternative drug regimen should be used on the advice of and under the
supervision of a chest physician e.g. 2 SHE / 10 HE,
2 HRE / 7 HR,
2 H3R3Z3E3/ 4 H3R3.
Generally, all previously used first-line anti TB drugs can be recommenced onmost patients who develop anti-TB drug induced hepatitis, without a recurrence of
the liver impairment.
N.B. Ideally it is better to get advice from a chest physician for the management
of drug induced hepatitis
Table 7 Re introduction of anti- TB drugs following drug induced hepatitis after
LFTs return to normal
Isoniazid 50mg, increase to full dose over 2-3 days and continue at full dose for
another 2-3 days
No symptoms
LFTs normal
Rifampicin 75mg, increase to full dose over 2-3 days and continue at full dose for
another 2-3 days
No symptoms
LFTs normal
Pyrazinamide 250mg, increase to full dose over 2-3 days and continue at full dose for
another 2-3 days
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Severe cutaneous reactions
If the reaction is only pruritus and no rash, (and there is no obvious cause e.g.scabies) give symptomatic treatment with anti-histamines, reassure and continue
anti-TB treatment and observe the patient closely.
However, if a skin rash develops, stop all anti-TB drugs. Wait till the rash resolves. Sometimes the patient may need steroids. Once the reaction has resolved, the anti-TB drugs should be re-introduced. The
drug, which was responsible for the reaction, should be identified.
The idea of drug challenging is to identify the drug responsible for the reaction.Drug challenge starts with the anti-TB drug least likely to be responsible for the
reaction (i.e. isoniazid). The idea of starting with a small challenge dose (e.g. 50mg of isoniazid) is that if a reaction occurs to a small challenge dose, it will be
less severe than the reaction to a full dose. The dose is gradually increased to the
full dose over a period of three days. The procedure is repeated, adding in one
drug at a time. A reaction after adding in a particular drug identifies that drug as
the one responsible for the reaction. There is no evidence that this challenge
process gives rise to drug resistance.
If the drug responsible for the reaction is pyrazinamide, ethambutol orstreptomycin, anti-TB treatment should be resumed without the offending drug. If
possible, the offending drug should be replaced with another drug. It may be
necessary to extend the duration of the treatment regimen. This prolongs the total
time of TB treatment, but decreases the risk of relapse.
Rarely, the patients develop hypersensitivity reactions to the two most powerfulanti-TB drugs- isoniazid and rifampicin. These drugs form the cornerstone of
Short Course Chemotherapy.
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Table 8 Re introduction of anti-TB drugs following sever cutaneous drug
reaction
Likelihood of
causing a reaction
Challenge doses
Drug Day 1 Day 2 Day 3
Isoniazid 50 mg 300 mg 300mg
Rifampicin 75 mg 300 mg Full dose
Pyrazinamide 250 mg 1 gm Full dose
Ethambutol 100 mg 500 mg Full dose
Streptomycin
Least Likely
Most Likely 125 mg 500 mg Full dose
Adverse reactions to FDCs
Adverse reactions to drugs are not more common if FDCs are used. Nevertheless,
whenever side-effects to one or more components in a FDC are suspected, there will be a
need to switch to single-drug formulations. Reactions to FDCs which warrant withdrawal
of drugs generally occur in only 3-6% of patients on TB treatment.
Role of steroids
Indications for treatment with steroids:
TB meningitis with altered level of consciousness and focal neurological signs TB pericarditis TB pleural effusion- when large and with severe symptoms and not responding
satisfactorily with anti-TB drugs alone.
TB peritonitis
Hypo-adrenalism TB laryngitis (with life threatening airway obstruction) Severe hypersensitivity reactions to anti-TB drugs Renal tract TB (to prevent ureteric scarring) Massive lymph gland enlargement with pressure effects Spinal TB with neurological involvement (e.g. paraplegia).
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MONITORING OF TREATMENT
Monitoring of treatment
There are two ways to monitor tuberculosis patients on treatment.
6
Bacteriological monitoring is done for sputum smear positive pulmonary TB casesby examination of sputum smears at regular intervals during treatment.
Monitoring the drug intake during intensive phase and drug collectionduring the continuation phase by reviewing the treatment cards.
Monitoring of sputum smear-positive pulmonary TB patients
Response to treatment should be monitored by sputum smear examination. Generally two
sputum samples should be collected for smear examination at each follow up sputum
check.
Sputum smear examinations should be performed at the end of the intensive phase of
treatment, during the fifth month and at the end of treatment. Negative sputum smears
indicate good treatment progress.
The best way to monitor the sputum smear-positive patients is to check for sputum
conversion from smear positive to negative. Conversion from smear positive to negative
is the best indicator that the intensive phase of chemotherapy has been regular and is
effective.
After two months of chemotherapy, more than 80% of new smear positive PTB cases
should be smear negative and after 3 months, the rate should be more than 90%.
Pulmonary smear positive relapse cases should have approximately the same rates of
sputum conversion as new pulmonary smear positive cases. Other smear positive re-treatment cases such as treatment failures may have sputum conversion rates of more than
75% after three months of receiving the re-treatment regimen
Sputum smears are again checked at the end of the 5th
month and at the end of treatment.
In a new smear-positive PTB case if the sputum smear is positive at the end of 5 months
or later, these cases are considered as treatment failures, re-registered and given CAT 2
regimen
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Sputum smear-negative PTB patients
Sputum smear negative patients should be monitored clinically. It is important to check
the sputum smear at the end of two months. If the sputum is positive, there are two
possibilities:
- An error at the time of initial diagnosis- i.e., a true smear positive patientincorrectly diagnosed as smear negative at the beginning of treatment
- Progress of the disease due to non- adherence to treatment
In such a situation the intensive phase with all four drugs should be continued for a
further one month under direct observation.
Extrapulmonary TB patients
These patients are monitored by assessing the clinical response to treatment.
Table 9 Schedule for follow up sputum examination
Category of patients When to do sputum smear
CAT 1 (smear-positive PTB) End of the 2nd month(End of the3
rdmonth if smear- positive
at the end of the 2nd
month)
End of the 5th month End of treatment
CAT 1 (smear-negative PTB) End of the 2nd month End of treatment
CAT 2
Relapse
Treatment after failure
Treatment after default
(smear-positive)
End of the 3rd month(End of the 4
thmonth if smear-positive
at the end of the 3rd
month)
End of the 5th month End of treatment
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Treatment Outcome
At the end of treatment course for each patient, the treatment outcome is recorded in the
District Tuberculosis Register.
There are six possible treatment outcomes.
1. CuredA patient who was initially sputum smear-positive and has completed treatment
and is sputum smear-negative in the last month of treatment and on at least one
previous occasion.
2.
Treatment completedA smear-positive patient who has completed treatment, but who does not meet the
criteria to be classified as cure or failure (e.g. follow up sputum examination not
done or results not available).
OR
A smear-negative PTB or Extrapulmonary TB Patient who has completed
treatment.
3. Treatment FailureA patient who is sputum smear-positive at 5 months or later during treatment
4. DiedA patient who dies for any reason during the course of treatment.
5. DefaultPatient whose treatment was interrupted for two consecutive months or more
before the completion of treatment.
6. Transfer outPatient who has been transferred to another district for continuation of treatment
and whose treatment outcome is not known at the initial treatment unit
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TUBERCULOSIS AND HIV
The Human Immunodeficiency Virus (HIV) destroys the immune system of an individual
and increases his susceptibility to many infections including TB.
HIV is the most potent factor known to increase the risk of progression of latent
tuberculous infection to tuberculous disease. In a HIV negative patient who is infected
withM. tuberculosis, the lifetime risk of developing tuberculosis is only 10%, whereas in
person dually infected with TB and HIV, it is 50%
Tuberculosis is the most important life threatening opportunistic infection associated with
HIV infection. It is the leading cause of death among people who are HIV positive and
accounts for more than one third of AIDS deaths worldwide.
Features of HIV related TB
TB usually occurs earlier in the course of HIV infection than other opportunistic
infections seen in HIV, but it may occur at any stage of HIV infection as a result of rapid
progression of a recently acquired new or re-infection. As a result of TB infection in a
HIV infected person there is a transient drop in CD4 count and progression of the HIV
infection.
As HIV infection progresses the CD4 lymphocyte count declines and the immune system
is less efficient in preventing the growth and spread of M. tuberculosis, As a result,
disseminated and extrapulmonary disease is more common in HIV positive patients than
in HIV negative patients. Nevertheless, pulmonary TB is still the most common form of
TB seen, in HIV infected patients, with or without concomitant extrapulmonary TB.
Pulmonary TB
The presentation of pulmonary TB in HIV infected individuals depends on the stage of
the degree of immunosuppression. The clinical picture, sputum result, and chest X-ray
appearance often differ in early and late HIV infection. (Table 9)
Diagnosis
The diagnosis of TB in HIV infected patients is often difficult because:
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- The sputum smear examinations tend to be more frequently negative,particularly in the late stages of HIV infection
- X-ray abnormalities are often atypical- The Tuberculin skin test is often negative due to immunosuppression.
Table 10 How PTB differs in early and late HIV infection
Features of PTB Stages of HIV infection
Early Late
Clinical picture Often resembles post primary
PTB
Often resembles primary
TB
Sputum smear result Often positive Often negative
Chest X-ray - Often cavities
- Lymphadenopathy usually
absent
- Pleural effusions rare
- Often infiltrates,
- No cavities
- Lymphadenopathy and
pleural effusions often
present
Treatment of HIV associated TB
Generally anti-TB treatment in HIV positive patients is the same as for HIVnegative TB patients.
It is important that these patients should receive Directly Observed Treatment.(DOT). Effective treatment using DOTS can cure TB, prevent the spread of the
disease and prolong the life of HIV patients.
Adverse reactions to anti-TB drugs are more common in HIV positive patients. The rate of recurrence of TB after completion of treatment is higher in HIV
positive patients than in HIV negative TB patients. For patients known to have
HIV co-infection, secondary prophylaxis with isoniazid 300mg daily may be
given for 9 months after cessation of anti-TB treatment.
The Case Fatality Rate is higher in HIV +ve TB patients than in HIV ve TBpatients. The excess deaths in TB/HIV patients are partly due to the tuberculosis
itself and partly due to other HIV related problems.
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Primary prophylaxis
HIV positive patients with a positive Mantoux test above 5 mm should be screened for
active TB. If there is no active disease they should be given INAH prophylaxis for 9
months.
Screening of TB patients for HIV
TB patients in the high-risk group (IV drug users, commercial sex workers, homosexuals,
people having multiple sexual partners, institutionalized individuals) need Voluntary
Counseling and Testing (VCT). Patients with atypical presentations and disseminated TB
also need VCT.
TB treatment and anti-retroviral therapy
Rifampicin stimulates the activity of cytochrome P450 that metabolizes protease
inhibitors (PIs e.g. saquinavir, ritonavir, indinavir, nelfinavir, amprenavir) and
nonnucleoside reverse transcriptase inhibitors (NNRTIs, e.g. nevirapine, delavirdine). PIs
and NNRTIs also enhance or inhibit the same enzyme system and this may result in
decreased blood levels of rifampicin and the anti-retrovirals resulting in ineffectiveness of
both.
In patients with HIV and TB, the priority is to treat TB, especially the smear positive TB
patients.
Possible options for antiretroviral therapy in TB patients include:
Defer antiretroviral therapy until TB treatment is completed Defer antiretrovirals until the end of intensive phase and use ethambutol and
isoniazid for 6 months in the continuation phase
Treat TB with a rifampicin containing regimen and use efavirenz + 2 nucleosidereverse transriptase inhibitors (NRTIs).
Treat TB with rifampicin containing regimen and use 2 NRTIs; then change tomaximally suppressive highly active antiretroviral therapy (HAART) regimen on
completion of TB treatment.
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PREGNANCY AND TUBERCULOSIS
Diagnosis
In pregnancy, chest X-rays should be avoided as far as possible, especially during the first
trimester, because of the adverse effects of x-rays on the foetus.
Therefore, diagnosis will depend more on sputum examination when a pregnant mother
presents with symptoms suggestive of tuberculosis. However, if an X-ray is absolutely
necessary, this may be done with the abdomen covered with a lead apron.
Treatment during Pregnancy
Anti-TB treatment should be started as soon as the diagnosis is made, and the full course
of treatment given.
The basic principles of treatment are the same in pregnancy. Most anti-TB drugs are safe
for use during pregnancy except streptomycin.
Streptomycin should not be given because it can cause oto-toxicity in the foetus.
Pregnant mothers should be given pyridoxine 10mg daily along with INAH.
Vitamin K should be administered at birth to the infant of a mother taking rifampicin
because of the risk of post-natal haemorrhage.
Treatment during breast-feeding
A patient who has TB and is breast-feeding should receive the full course of anti-TB
treatment. Properly taken treatment is the best way of preventing transmission of TB to
her baby. All anti-TB drugs are compatible with breast-feeding. A patient taking anti-TB
treatment can continue to breastfeed her baby in the normal way.
Breastfeeding should be avoided only in cases where the mother has dual TB/HIV
infection.
Management of a newborn child of a mother with active TB
8
Do not separate the child from the mother unless she is acutely ill. If the mother is sputum smear negative, and if the infant has no evidence of
congenital TB, BCG is given to the infant.
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If the mother is sputum smear-positive at the time of delivery, infant should becarefully examined for evidence of active disease.
- If the infant is ill at birth and congenital TB is suspected, a full course ofanti-TB treatment should be given.
- If the child is well, give prophylactic treatment with INAH 5mg/ kg bodyweight, daily for three months. BCG is withheld.
The Mantoux skin test is done after three months.- If the Mantoux test is negative and the child is well, prophylactic treatment
with INAH is stopped and child is given BCG.
- If the Mantoux test is positive, careful examination of the child for activeTB is done including a chest X-ray.
- If active disease is diagnosed, a full course of anti-TB treatment should becommenced.
- If the physical examination and the chest X-ray are normal, INAHchemoprophylaxis is continued up to six months and BCG is given.
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ROLE OF BCG VACCINATION
BCG (Bacillus Calmette Guerin) is a live attenuated vaccine derived fromM. bovis. It is a
freeze-dried vaccine. It can be stored at room temperature up to one month and in a
refrigerator at 4C up to one year.
It is easily killed by direct sunlight. Once reconstituted, it should be used within four
hours and any remaining solution should be discarded.
Dose- 0.05 ml of vaccine is administered to newborn infants aged less than one year
and 0.1 ml for children aged over one year. It should be administered intradermally to
the upper lateral aspect of the left arm.
The National Policy of Sri Lanka is to give BCG vaccination to all newborn babies
immediately after birth. BCG vaccination is carried out under the Expanded Programme
of Immunisation (EPI)
BCG protects the young children against serious disseminated forms of TB, like TB
meningitis and military TB.
It does not decrease the spread of TB in the community
Complications of BCG vaccination
Complications after BCG vaccination are uncommon. It includes the following:
9
Subcutaneous abscess at the site of injection due to secondary infection Ulceration at the site of injection Swelling with or without abscess formation of the regional lymph glands(BCG
adenitis)
Disseminated TB (which is extremely rare and occurs only in severelyimmunosuppressed patients).
Some of the complications are due to faulty immunization technique.
Most complications resolve on their own. In the case of suppurative lymphadenitis or
progressive adenitis surgical removal of affected nodes may be required. INAH may be
given for 3- 6-months for non healing ulcers or sinuses.
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Contraindications for BCG vaccination
Contraindications for vaccination are extremely uncommon. The only two known
conditions where children should not be vaccinated are:
Congenital or acquired immunodeficiency
Children with clinical signs of AIDSBCG should be withheld in the presence of skin sepsis, and systemic infections until these
conditions resolve.
If the mother is sputum smear positive at the time of delivery, the baby is commenced on
chemoprophylaxis and BCG administered at the end of the period of chemoprophylaxis.
(Refer page 49- 50).
BCG in HIV positive infants
The WHO recommended policy is to give BCG vaccination to HIV positive babies who
do not have any evidence of HIV disease. But it should not be given to children with
symptoms of HIV/AIDS.
Absent BCG scar
This is a common occurrence. If the mother is certain that there was no reaction to BCG
vaccination, or if there is no BCG scar, revaccination may be done. In children under 5
years revaccination may be done without Mantoux test.
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PREVENTION OF TUBERCULOSIS
From the public health point of view, the best way to prevent TB is to identify the
infectious cases as early as possible and provide effective treatment to cure them. This
interrupts the chain of transmission.
BCG vaccination
This protects young children against serious disseminated forms of TB, but does not have
an impact on the spread of the disease in the community, and does not protect the child
from developing post-primary tuberculosis in later life.
Contact screening
Household contacts of infectious TB patients (adults and children >5 years) should be
screened for symptoms of TB. Those who have symptoms suggestive of TB should be
investigated with sputum smears irrespective of the duration of the symptoms.
Children under the age of 5 years should be screened with chest X-ray and Mantoux test.
Preventive treatment
The aim of preventive treatment is to prevent progression ofM. tuberculosis infection to
disease.
Primary chemoprophylaxis
When a person is exposed to TB bacilli, but not yet infected eg. newborn breastfed baby
of a sputum smear-positive mother
Secondary chemoprophylaxisA person who is infected, but not yet developed clinical disease e.g. tuberculin positive
close contacts of sputum smear-positive patients.
In Sri Lanka, chemoprophylaxis is given for the following groups:
10
Breast fed infants of sputum smear-positive mothers. Household contacts below 5 years of age of sputum smear-positive patients, who
do not have evidence of active disease.
Prophylactic treatment in Sri Lanka is INAH 5mg/ kg body weight for 6 months.
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Health Education
Health education is a critical component of tuberculosis control. The target groups, which
need to be addressed, are the patients and their families, health personnel, and the
community.The health staff should educate the patients and their families regarding the disease, how
it is spread, and the duration of treatment. It must be emphasized that TB is curable if the
treatment is taken fully and to stress the importance of directly observed treatment.
Patients should be made aware of the risks of irregular and incomplete treatment. Health
workers should also teach them simple ways of decreasing the risk of transmitting the
disease, like covering the mouth with the hand when coughing and to use a sputum pot
with a lid and disposing of the sputum by burning.
The general public should be educated regarding the disease and the symptoms and the
importance of seeking medical advice early if they have any symptoms suggestive of TB.
They should be made aware of the locations and the facilities available for the
management of TB. Also, education should be aimed at removing the social stigma
attached to TB, so that symptomatic patients will seek treatment early.
Health personnel should also be made aware of the importance of identifying TB suspects
early and referring them for investigation.