European Society of Mycobacteriology - Instituto Nacional de Saúde ...

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THE BRAZILIAN EXPERIENCE CONTROLING TB MULTI-DRUG RESISTANCE
Fernando Augusto Fiuza de Melo
• Médico, Diretor do Instituto Clemente Ferreira – Coordenadoria de Controle de Doenças da Secretaria de Estado
da Saúde de São Paulo – ICF/CCD/SP
• Doutorado em Medicina, área de pneumologia, pela Escola Paulista de Medicina da Universidade Federal de São
Paulo - EPM/UNIFESP
• Membro do Comitê de Assessoria Técnico-Científico do Programa Nacional de Controle da Tuberculose do
Ministério da Saúde - PNCT/MS
Correspondence:
Rua Santo Estácio, 248 – Cidade Vargas, CEP. 04319-010 - Brasil - São Paulo,SP
Tele-fax: 0055 11 3218 8653 - Telemóvel 0055 11 8469 4330 - e-mail: fernandofiuza@terra.com.br
Brazil was the first developing country using the short duration regimen of rifampin (R) and isoniazid (H) combined in
one capsule for six months, plus pyrazinamide (Z) during the first two months after reorganizing the Brazilian National
Tuberculosis Control Program of (BNTBCP, Programa Nacional de Controle da Tuberculose, PNCT) in 1980. At that
moment Brazil adopted the anti-TB regimen named E-1 (2RHZ/4RH) for all forms of TB with no known previous treatment.
A similar regimen was adopted for Meningitis TB, named E-2, adding corticoids in the intensive phase with the
recommendation to lengthen the continuation phase of treatment to 7 months (2RHZCort/7RH). For those TB cases of
relapsing (RC) or re-treatment after defaulting (RA) the anti-TB regimen adopted was E-1R with ethambutol (E) during
the intensive phase (2RHZE/4RH). The recommended regimen for failure (F-1) cases was named E-3 and included Z and
E, associated with streptomycin (S) and the ethionamida (Et) during at least 12 months (3SZEEt/9EEt)¹
The E-1 was evaluated under pragmatic clinical “non-study” conditions during decades 1980/90 and also during half of the
first decade of the new millennium and shown an efficacy of 94.6 and 93.9%, an effectiveness of 77.8 and 77.1%, a default
rate of 13.7 and 13.1%13%, a failure rate of 1.5 and 1.7%%, a serious adverse events rate of 3.1 and 3.3% and a mortality
rate of 3.9 and 4.8%, respectively. ( ²,³ ) . The small worsening on mortality rate might be related to high rates of defaulting and
the HIV co-infection. The good quality of the National Aids Program Control and the increasing rate of TB treatment under
direct supervision in Brazil are possible reasons for Brazil rates of resistance were not too high. On the other hand, results
of E-3 were not nice with efficacy and effectiveness varying between 57,5% - 85,2 and 66,7 - 84.7%, respectively (4) .
4% of 80,000 cases of TB notified in Brazil were resistant to R+H or were unable to be treated with these drugs for any
other reason and were defined as F-1 case. These patients were treated with E-3 (3SZEEt/9EEt) and are considered in
Brazil as a case of MDR-TB. Brazil estimates a rate between 0,3 and 0,4% of cases of F-1 not responding to E-3. These
cases are defined in Brazil as a Multiresistant TB (MRTB) and there is no well established anti-TB regimen for these patients
in the BNTBCP 5 .
In 1995 an anti-TB regimen including amicacin (AM), ofloxacin (OFX), terizidona (TRZ), clofazimine (CFZ) and E was
evaluated in some TB Centers in Brazil with reasonable results (6) .
In 2000 the Monitoring Program for MRTB was created, centralizing the notification of all cases of TBMR in Brazil and
creating a work group including health professionals involved with MRTB in order to define and organize a way to control
MRTB in Brazil. In 2007, Guidelines for MRTB were published presenting the knowledge about TBMR and establishing
rules for diagnosis, treatment, prevention and biosafety; providing orientation on epidemiologic surveillance, building human
and material resources, and implementing a specific National Notification System for these patients. The current
alternative regimen for MRTB cases is defined by the sensitivity tests and administered under supervision, including: AM
(or S if sensible) for 12 months, OFX, TRZ and E for 18 months and Z (if sensible) for 6 months 7 . Metronidazole (MTZ)
replacing Z, especially in cases of intolerance or resistance, is used in some clinics.
TBMR rates were evaluated in Brazil between 2000 and 2005, showing the following results:
Between 323 and 334 cases had been annually notified from 2000 to 2004, with an increase in 2005 to 383 cases notified
among a total of 80.000 TB cases.
Increasing cure rates over time (40 to 62%), with some organized units showing better rates (75 to 85%).
26 ESM 2009