RNTCP ( Revised National Tuberculosis Control Programme) is an application of WHO recommended strategy of DOTS in India. It is largely based on the research done at National Tuberculosis Institute, Bangalore and Tuberculosis Research Centre, Chennai.
1- Detecting at least 70% of sputum positive tuberculosis patients in the community.
2- Curing at least 85% of the newly detected sputum positive cases.
Components of DOTS (Directly observed treatment strategy)
1- Political and administrative commitment at all levels.
2- Diagnosis through sputum microscopy
3- Uninterrupted supply of short course chemotherapy drugs.
4- Direct observation of drug intake ( DOTS)
5- Systematic monitoring, evaluation and supervision at all levels.
*Newly diagnosed sputum positive pulmonary tuberculosis
*Sputum negative pulmonary tuberculosis with extensive
*Severe form of extrapulmonary tuberculosis
*Treatment failure cases
* Relapse cases
* Return after interruption
* sputum negative pulmonary tuberculosis with minimal involvement
* Less severe form of extrapulmonary tuberculosis
Category- 1: 2(H3 R3 Z3 E3) 4 ( H3 R3 )
Category- 2: 2( S3 H3 R3 Z3 E3)+ 1( H3 R3 Z3 E3 ) 5 ( H3 R3 E3)
Category- 3: 2( H3 R3 Z3 ) 4 ( H3 R3 )
H= INH 600mg, R= Rifampicin 450mg, Z= Pyrazinamide 1500mg,
E= Ethambutol 1200mg, S= Streptomycin 750 mg
Cat 2(H3 R3 Z3 E3) 4 ( H3 R3 ) means initial two months of therapy with INH, Rifampicin,Pyrazinamide and Ethambutol in a thrice weekly schedule followed by INH and rifampicin for a period of 4 months in a thrice weekly schedule
SOURCE OF TEXT that Follows
National Guidelines for Treatment of TB in HIV Infected Individuals
Early diagnosis and effective treatment of Tuberculosis among HIV-infected patients are critical for controlling the disease, minimizing the negative effects of TB on the course of HIV, and interrupting the transmission of tuberculosis to other persons in the community. In the absence of highly active anti-retroviral therapy, proper case management of TB can significantly prolong the lives of HIV positive people with active tuberculosis.
Treatment of active, susceptible tuberculosis with first line drugs is as effective at curing TB in people infected with HIV as in those not infected. Standard RNTCP regimens, particularly if supervised properly are as effective in HIV positive as in HIV negative patients. However, mortality under the TB treatment will be higher for people living with HIV, mainly due to other opportunistic infections. Delays in the diagnosis of TB have been associated with worse outcomes, so initiation of treatment as soon as TB is suspected is very important. Case fatality is lower in HIV-infected TB patients treated with short-course treatment than with the standard 12-month treatment regimens that do not include rifampicin.
This is partly because short-course treatment is more effective, but may also be related to the fact that rifampicin has broad-spectrum antibacterial activity. This may decrease deaths due to HIV-related bacterial infections during anti-TB treatment. Direct observation of treatment is even more important for HIV-infected TB patients. Self-administration of treatment is associated with higher case fatality rates. Hence DOT strategy that promotes adherence to therapy should be used for all patients with HIV-related TB. Relapse rate of TB is low in HIV-infected TB patients who complete a full course of directly observed rifampicin containing short-course treatment regimen.
The use of non-rifampicin containing regimens and treatment interruptions due to drug reactions and inter-current opportunistic infections are associated with an increased risk of relapse of TB. The relapse rates tend to be higher if they are treated with conventional regimens or a short-course treatment regimen that uses isoniazid and ethambutol during the continuation phase or if the treatment has not been directly observed.DOTS can prevent emergence of MDR -TB and also will reverse the trend of MDR-TB.Failure to use DOTS in the face of HIV can lead to explosive spread of TB with cases tripling and drug resistance increasing rapidly.
TREATMENT OF TUBERCULOSIS
Treatment in the RNTCP (Revised National TB Control Programme) consists of 2 phases – an initial intensive phase and a second continuation phase. The total duration of treatment is 6-9 months. Sputum microscopy is done regularly to monitor the response to treatment.
The intensive phase lasts for 2-4 months. In this phase, a health worker or some other trained person watches as the patient swallows the drugs in his presence. Treatment is given thrice a week on alternate days and every dose is directly observed.The continuation phase lasts for 4-5 months depending on the patient’s response to treatment. In this phase, the first dose of the medicine every week is taken by the patient under direct observation, while the other doses are taken by the patient himself. The patient is requested to bring the previous week’s blister pack when coming to collect the next week’s blister pack. It is extremely important that the patient takes regular and complete treatment in order to ensure complete cure and prevent development of drug-resistant TB.
Treatment of multi-drug resistant TB is extremely difficult, expensive and often unsuccessful. Once the patient is diagnosed as having TB, the next step is to classify the patient, determine the type of case and the severity of illness to decide the correct combination of drugs and duration of treatment.
A) CLASSIFICATION OF TUBERCULOSIS CASES
TB patients are classified as sputum positive pulmonary TB, sputum negative pulmonary TB or extra-pulmonary TB. Pulmonary Tuberculosis, smear positive Two or Three sputum smears positive for Acid Fast Bacilli (AFB) One sputum smear positive for AFB, with radiographic abnormalities consistent with active TB as determined by the Medical Officer One sputum smear positive for AFB, with culture positive for AFB Pulmonary tuberculosis, smear negative Three sputum smears negative for AFB, but showing radiographic abnormalities consistent with active pulmonary TB after 2 weeks of antibiotic treatment. Three sputum smears negative for AFB, but positive on culture Extra-pulmonary tuberculosis TB of any organ other than lungs such as pleura, lymph nodes, intestines, meninges, skin, joints and bones, genital system etc. Diagnosis should be based on one culture positive specimen from the extra-pulmonary site or histological evidence or strong clinical evidence consistent with active extra-pulmonary TB.
B) TYPES OF CASES
New case: A patient who has never had treatment for TB or has taken anti-tuberculosis drugs for less than one month.
Relapse case: A patient declared cured of TB by a physician but who reports back to the health service and is found to be bacteriologically positive.
Transferred in case: A patient who has been received into a Tuberculosis Unit/District after starting treatment in another unit where he has been recorded.
Treatment after default case: A patient who has received anti-tuberculosis treatment for one month or more from any source and who has interrupted treatment for more than two months.
Failure case: An initial smear positive patient who remains smear positive at five months or more after starting treatment OR an initial smear negative patient who becomes smear positive during the course of treatment.
Chronic case: A patient who remains smear positive after completing a re-treatment regimen
Other: A patient who does not fit into any of the above categories. e.g., a relapse patient may be smear negative or an extra-pulmonary TB patient who has not responded to treatment. Such patients are categorized as others and receive category two treatment.
C) SEVERITY OF ILLNESS
Seriously ill smear negative pulmonary TB Smear negative pulmonary TB cases should be clinically ascertained for the severity of illness. Seriously ill extra-pulmonary TB Seriously ill extra-pulmonary TB includes meningitis, disseminated TB, tuberculosis pericarditis, peritonitis, bilateral or extensive pleurisy, spinal disease with neurological complications, intestinal and genitourinary TB.
Depending on the classification of TB, type of TB, severity of illness, history of treatment in the past, history of interruption in treatment, the patient will receive category one, category two or category three treatment. The drugs are to be taken on alternate days under direct observation (DOTS-Directly Observed Treatment, Short-course)
TREATMENT REGIMENS FOR TUBERCULOSIS
TYPE OF TB PATIENT
Intensive phase Continuation phase
I New smear positive pulmonary TBNew smear negative, pulmonary TB, seriously illNew extra-pulmonary TB, seriously ill 2 (EHRZ)3 (24doses) 4(HR)3 (54 doses)
II Sputum smear positive relapsesSputum smear positive treatment failure casesSputum smear positive cases, treatment after default 2 (SEHRZ)3 +1 (EHRZ)3(24+12 doses) 5(HRE)3 (66 doses)
III New smear negative, pulmonary TB, not seriously illNew smear negative, extra-pulmonary TB, not seriously ill 2 (HRZ)3 (24 doses) 4(HR)3(54 doses)
Note: Prefix is number of months and suffix is number of doses in a week
The drugs are available in patient wise boxes containing the full course of treatment for the individual patient. Each box contains two pouches – one for intensive phase and the other for continuation phase. Drugs are packed in a blister pack; one blister pack for intensive phase contains drugs for a single day whereas for continuation phase, each blister pack contains drugs for one week.
All the drugs are to be taken on alternate days. During the intensive phase all the doses are to be swallowed under direct observation (DOTS) whereas in continuation phase the patient takes the first weekly dose under direct observation and the remaining drugs for the week are to be consumed at home. Follow Up Sputum Examination is done at the end of the intensive phase to decide on the further course of treatment. If the sputum remains positive for AFB, the intensive phase drugs are continued for another one month before starting the continuation phase.Duration of therapy
Treatment regimens recommended under RNTCP are the same irrespective of patient’s HIV-status. The duration of therapy will be as per the treatment regimen and category. If required, the duration of therapy may be extended within the current RNTCP guidelines. Special Situations Hospitalization: Generally, patients with TB do not need hospitalization. Those who are extremely ill can be hospitalized during the initial phase of treatment. In addition, all patients with significant haemoptysis, pneumothorax or large accumulation of pleural fluid leading to breathlessness should be referred to the hospital.
Extrapulmonary TB: The basic principles that support the treatment of extrapulmonary TB in HIV uninfected individuals also apply to HIV infected patients. Most extrapulmonary forms of TB (including TB meningitis, TB lymphadenitis, pericardial TB, pleural TB, and disseminated or miliary TB) are more common among persons with advanced stage HIV disease than among patients with asymptomatic HIV infection. The drug regimens and treatment durations that are recommended for treating extrapulmonary TB in HIV negative persons are also recommended for treating HIV positive patients. But if the clinical or bacteriologic response is slow, treatment may be prolonged as mentioned previously. Also, in TB meningitis longer duration of treatment is recommended as discussed next. Tuberculous meningitis: Tuberculous meningitis is fatal if untreated. Patients should generally be referred to the hospital. Treatment should be started as soon as possible. The continuation phase should be given for 6–7 months (total treatment 8–9 months). Steroids should be given initially to reduce meningeal inflammation and reduced gradually.
Treatment of tuberculosis during pregnancy: HIV-infected pregnant women who have tuberculosis or are suspected of having TB disease should be treated without delay. Streptomycin should not be given during pregnancy because of potential adverse effects on the foetus. Other drugs used in the RNTCP are safe during pregnancy.
ANTI TUBERCULOSIS THERAPY AND ANTIRETROVIRAL THERAPY
Till date no cure is available for HIV/AIDS. It is only the opportunistic infections in HIV/AIDS, which can be treated. The antiretroviral drugs, which are used in HIV positive patients, are effective in slowing down the action of the virus and prolonging life. These drugs are the protease inhibitors, nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors. Nucleoside reverse transcriptase inhibitors like Zidovudine, Didanosine, Zalcitabine, Stavudine, Lamivudine and Abacavir can be safely co-administered with antituberculosis drugs. Co-administration of Rifampicin with any of the protease inhibitors (Ritonavir, Indinavir, Nelfinavir) or non-nucleoside reverse transcriptase inhibitor (Nevirapine, Delavirdine, Thioben) is contraindicated.Protease Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors may inhibit or induce cytochrome P-450 isoenzymes and thus these drugs may alter the serum concentration of rifamycins. Rifamycins induce Cytochrome P-450 and may substantially decrease blood levels of the antiretroviral drugs resulting in the potential development of resistance.Rifabutin is a less potent Cytochrome-450 inducer than rifampicin and thus can be used concurrently with the NNRTIs (eg nevirapine, efavirenz) or with certain protease inhibitors (eg indinavir, nelfinavir). Rifabutin is at present not available in India . Isoniazid, Ethambutol, Pyrazinamide and Streptomycin can be concurrently used with protease inhibitors or non-nucleoside reverse transcriptase inhibitors. If protease inhibitor or non-nucleoside reverse transcriptase inhibitor is to be started after giving Rifampicin, then at least two weeks should elapse after the last dose of Rifampicin. This time gap is necessary for reduction of the enzyme inducing activity of Rifampicin prior to commencement of antiretroviral drugs.
Recent WHO Recommendations: WHO recommends that people with TB/HIV complete their TB therapy prior to beginning ARV treatment unless there is a high risk of HIV disease progression and death during the period of TB treatment (i.e., a CD4 count 200/mm3 or total lymphocyte count >1000-1200/mm3 Treat TB. Monitor CD4 counts if available. Start ART