Transmission and prevalence of Mycobacterium tuberculosis resistance after DOTS Implementation, in the municipality of Guarulhos from 2007 to 2011

Abstract

Tuberculosis (TB) is an infectious disease of worldwide distribution and up to half of the twentieth century was considered
the leading cause of death from infectious diseases worldwide. Directly Observed Treatment (DOT) is an important
component of Directly Observed Treatment, Short Course (DOTS). DOT strategy has been an effective tool to improve
the adherence to the treatment, to reduce the dropout, to increase the cure and prevent the drug resistance. The city of
Guarulhos (SP), Brazil, had an estimated population of 1.244.518 inhabitants and it is located 17 Km from the city of São
Paulo. In 2012, Guarulhos had a TB incidence rate of 31/100,000 inhabitants. DOT was implemented in 1998 and was
intensified in 2004, with support from USAID (U.S. Agency for International Development). The aim of this study was
to describe the epidemiological characteristics of pulmonary TB (PTB) patients treated under DOT and self-administered
treatment (SAT), the prevalence of resistance to first-line drugs, and the transmission of resistant strains among PTB
patients residing in Guarulhos. PTB patients residents and treated in Guarulhos who were confirmed by culture and
started treatment between October 2007 and October 2011 were included in the study. For the transmission analysis,
patients who were residents but treated in Sao Paulo City, identified at the IS6110-RFLP database of São Paulo State,
were also included. We retrospectively analyzed, data obtained at the Instituto Adolfo Lutz, TB Surveillance System of
Sao Paulo State (CVE-TB-SP), and at the Guarulhos Municipal Public Health Laboratory (LMSPG). Mycobacterium
tuberculosis isolates were subjected to drug susceptibility testing by MGIT 960 (DST) and typed by IS6110-RFLP. In the
study period, 1.302 TBP patients were notified at the CVE-TB-SP. Of these, 408 patients had positive culture and were
submitted to the DST. Two hundred and thirty-nine (58.6%) patients received DOT (DOT Group). In comparison with
the TAA group, patients in the DOT group were lower number males (69.9%), HIV negative (95.2%) and had a higher
cure rate (92.5%). On the other hand, the number of patients in the TAA group who abandoned the treatment was higher
(21.9%) (p<0.001). Of the 408 M. tuberculosis isolates which were submitted to the DST, 361 (88.5%) were susceptive
to all drugs, 47 (11.5%) were resistant to at least one drug and 17 (4.2%) were multidrug-resistant (MR). Of the 40
resistant M. tuberculosis isolates underwent to molecular typing by RFLP-IS6110, 14 (35.0%) were clustered into four
clusters (SP5, SP5W, SP1a, 4a). Considering the inclusion of the nine patients residing in Guarulhos and treated in São
Paulo city, the number of patients belonging to a cluster pattern increased to 23 (46.9%). The SP5 pattern was the most
frequent one, with 15 (65.2%) patients. Epidemiological relationships were identified for 13 (56.5%) patients infected
with M. tuberculosis strains belonging to one of four RFLP patterns (SP5, SP5w, SP1a and 4a). These results showed that
the DOT was an important strategy for reducing dropouts and increasing cure rates. However other strategies are needed
to control the transmission of resistant strains in the municipality of Guarulhos.