Key points:-
- Active TB disease and other contraindications must be ruled out before starting TPT
- Testing for TBI is not required in (1)PLHIV and (2) household contacts less than 5 years of age
- Pregnancy is not a contraindication for TPT
- The efficacy of TPT is greatest if at least 80% of the doses are taken within 133% of the duration of the regimen
- overall there are only four TPT regimens in India to date:
- 6H, 3HP, 6Lfx, 4R
India has the highest burden of TB infection (TBI) in the World. Around 35-40 crore (350 -400 million) people in India have latent TB. Around 26 lacks (2.6 million) people develop Tuberculosis annually.
Eligible people are provided Tuberculosis Preventive treatment (TPT) to prevent developing Tuberculosis Diseases from latent TB.
Table of Contents
TPT Schedule and regimens
There are many regimens devised globally to fight Latent TB. In India TPT regimens used to date are:
TPT for contacts of Pulmonary DS-TB patients and other high-risk groups:-
- 3HP [Isoniazid (H) and Rifapentine (P), Weekly for 3 months]
- 6H (Isoniazid, daily for 6 months)
*Selection of treatment regimens is done depending on various factors like Age, drug sensitivity, co-morbidities etc.
*H- Isoniazid, P- Rifapentine, (R is used for Rifampicin)
Disclaimer:– In the box given below ‘interpretation’ part (written in italic style) is not given as such in guidelines issued by the Central TB division, Ministry of Govt of India.
| Sr.No. | Target population | TPT Treatment regimens Options (Selected depending on various factors like Age, drug sensitivity, co-morbidities etc.) | Interpretation |
|---|---|---|---|
| 1 | People living with HIV:- -All Adults -Children above 1 year of age | -3HP (not given in person below 2 years) -6H | All persons living with HIV above 1 year of age shall be provided TPT (After ruling out Active TB) irrespective of any history of contact with Active TB and without any testing for TBI, All Children living with HIV below 1 year are only treated for TBI if they are a household contact with pulmonary TB |
| 2 | All Household contacts of Pulmonary TB below 5 years of age | -3HP -6H | All Household contacts of Pulmonary TB below 5 years of age are offered TPT without testing for TBI (After ruling out Active TB) |
| 3 | All Household contacts of Pulmonary TB above 5 years of age After testing for TBI (using TST or IGRA) | -3HP -6H | All Household contacts of Pulmonary TB Above 5 years of age are offered TPT After testing for TBI ( After ruling out Active TB) |
| 4 | Other high-risk groups After testing for TBI:- – Children /adults on Immunosuppressive therapy – Silicosis – Anti-TNF treatment – Dialysis – preparing for Transplant –Cancer patients (included in Himachal Pradesh) | -3HP -6H | Other High-risk groups can be tested for Latent TB (After ruling out Active TB) and offered TPT only after being positive for TBI (After ruling out Active TB) |
Dosage of TPT medicines
Dosage of commonly used TPT- 6H and 3HP are given in the pdf below:-
TPT in contacts of Pulmonary DR-TB patients:
- 4R [Rifampicin (R) given daily for 4 months]
- 6Lfx [Levofloxacin (Lfx) given daily for 6 months]
- Even 6H can be used (in the case of RR-TB with FQ and H-sensitive reports)
| type of index DR-TB patient | regimen | taken as | Dose |
|---|---|---|---|
| R-resistant and FQ-sensitive | 6Lfx | Levofloxacin (Lfx) given daily for 6 months | Age >14 years: weight:dose(mg/day) <45 kg 750 >45 kg, 1000 Age <15 years : weight:Dose(mg/day) 5-9kg 200-300 10-15kg 300-400 16-23kg 500-750 |
| H- resistant and R- sensitive | 4R | Rifampicin (R) given daily for 4 months | Age 10 yrs & Above: 10mg/kg/day (max-600mg/day) Age Below 10 yrs: 15 mg/kg/day |
*Please note that Active TB is Always ruled out first, before testing for latent TB (For TPT initiation)
*in household contacts with pulmonary TB aged above 5 years, all efforts should be made to ensure that TBI and X-ray are done. however, TPT must not be deferred in their absence.
Contraindications for TPT
- Active TB disease– An absolute contraindication
- Regular and Heavy Alcohol users
- Acute or chronic Hepatitis
- Concurrent use of other hepatotoxic drugs (such as Nevirapine)
- Signs and symptoms of Peripheral Neuropathy
- Allergy or known hypersensitivity to any drugs being considered for TPT
Please note that the following are Not Contraindications for TPT:-
- Pregnancy
- The previous history of TB (H/O ATT intake in the past)
- Contact with DR-TB
Algorithm for Initiation of TPT in India
Target Population for TPT
As we already discussed target population for TB includes:-
- People living with HIV (Adults, Adolescents and children)
- All Household contacts of Pulmonary TB
- Other high-risk groups (list may vary from state to state in India). in Himachal:-
- Children /adults on Immunosuppressive therapy
- Silicosis patients
- People on Anti-TNF treatment
- People on Dialysis
- People being prepared for organ Transplant
- Cancer patients
WHO includes- Health care workers, migrants, the people living with diabetes mellitus as the target group.
Diagnosis of Tuberculosis Infection (TBI)
We provide TPT to those who hve the Tuberculosis infection (Mycobacterium)in their body but have not developed active TB yet. it is also known as Latent Tuberculosis.
Though the chances of developing Tuberculosis disease from the TBI are only 5-10% over the course of their lives (maximum chances during initial 2 years of infection), the risk of developing the disease remains there (>25 times among contacts of TB as compared to the general population)
testing strategies available include:-
Adherence and Follow-up
- If less than 80% of doses expected in the regimen (6H, 6Lfx or 4R) were taken, and the treatment course cannot be completed within the extended time for completion, consider restarting the full TPT course.
- If 4 or more weekly doses of 3HP are missed, consider restarting the full TPT course
- if pregnancy is detected in a woman on a 3HP regimen, 3HP is discontinued and put on an alternate regimen like- 6H [isoniazid and Rifampicin are considered safe for use in pregnancy) [safety data lacking with Rifapentine (P)]
- Persons on TPT should be monitored by a Medical officer at least once a month and should be evaluated for any adverse effect, the emergence of an active TB
- Post-TPT person should be monitored on a long-term basis at 6, 12, 18 and 24th months for the emergence of active TB (similar to post-treatment for active TB)
ADRs Associated and Management
Though most Adverse Drug Reactions (ADRs) are mild and self-limiting, in cases of severe ADRs, TPT should be stopped immediately.
For mild-moderate ADRs conservative management with TPT under close observation is recommended.
A detailed table is given in the pdf below:-
Drug-Drug interaction
Rifampicin can increase and Isoniazid can inhibit or lower the metabolism of some drugs. therefore drug-drug interaction should be kept in mind and detailed history be taken to avoid them.
- Reduction in contraceptive efficacy of oral hormonal contraceptive with TPT containing – R and P (3HP, 4R)
- TPT containing R/P should not be given with PI or Nevirapine (as we discussed in contraindications)
- R containing TPT can make HCV drugs ineffective (Sub- therapeutic levels)
Treatment Outcomes of TPT
Every person on TPT is assigned an outcome of intervention as:-
“Treatment completion”
A person initiated on TPT who completed at least:
- 80% of the recommended dose (144 doses out of 180) consumed within 239 days (133% time) for 6H or 6Lfx
- 90% of the recommended dose (11 doses out of 12) consumed within 120 days (133% time) for 3HP.
- 80% of the recommended dose (96 doses out of 120) consumed within 160 days (133% time) for 4R
Note:- time is same for all regimens- 133%, doses target is also same foe all- 80%, except for 3HP (90%)
“Treatment failed”
A person who develops active Tuberculosis at any time while on the TPT course. depending upon various practical scenarios the outcome is assigned-
“Died”
A person who died for any reason while on the TPT course
“Lost to follow-up”
- TPT interrupted by a person for 8 consecutive weeks or more for 6H or 6Lfx
- TPT interrupted by a person for 4 consecutive weeks or more for 3HP or 4R.
“TPT discontinuation due to toxicity”
A person whose TPT is permanently discontinued due to ADRs or the drug-drug interactions
“Not evaluated”
In conditions where records are lost like during transfer to another health facility without any record of TPT completion.
Role of Pyridoxine inTPT
Although deficiency of pyridoxine (Vit-B6) is uncommon with standard doses of TPT drugs but some people remain at higher risk than others.
At risk
- Malnutrition
- Chronic alcohol dependence
- Diabetes
- Renal failure patients
- HIV infection
- Pregnant or Breastfeeding women.
these at-risk people are provided with the prophylactic dose of pyridoxine to protect them from developing Pyridoxine deficiency
Prevention from Pryridoxine Deficiency
Those at higher risk of developing pyridoxine deficiency are provided with a Prophylactic dose of Pyridoxine :
- 10 mg/day in Children
- 25 mg/day in Adults
- 50 mg/day in adults with HIV
Treatment of Established Pyridoxine Deficiency
Those who develop the deficiency of Pyridoxine can be easily recognized as having:-
- Symmetrical numbness of extremities
- Tingling of extremities
They are treated with a therapeutic dose of Pyridoxine (100-200 mg/day).
References:-
- Guidelines for Programmatic Management of Tuberculosis Preventive Treatment in India, July-2021, NTEP, Central TB division, Ministry of Health & family welfare, Govt of India, New Delhi.
