Regional Prospective Observational Research for Tuberculosis

Study Sites

RePORT-Brazil Study Sites

Collaborating Institutions in Rio de Janeiro, Brazil

Rio de Janeiro has a population of 6 million people, and the highest incidence of TB in Brazil (74/100,000). However, within the lowest-income areas the incidence rate can be as high as 400/100,000. The city is sub-divided into ten major administrative areas, each of which is sub-divided into administrative regions. Each of these has at least one municipal primary care health clinic at which TB patients receive free medical assistance and treatment.

The four centers and their related clinics and hospitals are located in the eastern part of the city within 10 km of each other, and near major expressways (see map – UFRJ (red), INI (yellow), Rocinha (blue) and Duque de Caxias (green)). Each site is described below.

Instituto Nacional de Infectologia (INI) Evandro Chagas – Fundacao Oswaldo Cruz (Fiocruz)
Rio de Janeiro, Brazil
Instituto Nacional de Infectologia Evandro Chagas (INI) Hospital
The Instituto Nacional de Infectologia (INI) Hospital is a reference hospital within the Oswaldo Cruz Foundation (Fiocruz). INI has an inpatient unit with 20 beds, including 4 beds fitted for respiratory isolation and an Intensive Care Unit with 4 beds, including 1 for respiratory isolation. The outpatient unit consists of a 24/7 Emergency Room and on a daily basis provides care to patients referred for acute febrile diseases, HIV/AIDS, Chagas disease, HTLV, leishmaniasis, and sporotrichosis, among others.

INI has extensive laboratory capabilities for infectious diseases, including TB. The laboratory unit is comprised of hematology, biochemistry, mycology, virology, immunology, and microbiology laboratories. There is also an area for diagnostic imaging (digital radiography, ultrasonography and computed tomography). Information regarding patient clinical data, diagnosis and exams are available in a network system called CECLIN.

INI Mycobacterial Clinical Research Laboratory (LAPCLIN-TB)
LAPCLIN -TB was created after years serving as a TB program. Since the year 2000 a template of visit was created to standardize the information to be collected and care for TB-HIV patients. Later, non-HIV infected individuals were increasing in numbers and were included in the cohort. In the years 2010 LAPCLIN-TB increased the spectrum of the assistance, including care for TB contacts and agreed with the State of Rio de Janeiro to be a referral center for MDR-TB.

LAPCLIN-TB is a benchmark for the treatment of drug-susceptible TB and multi-drug resistant (MDR) TB and TB contacts, located in the ground floor of the INI Hospital, and provides care to patients referred from the INI Hospital outpatient unit and from the public healthcare network. LAPCLIN-TB diagnoses and treats 250 TB cases per year, of whom 50% are HIV-seropositive. In 2011, there were 350 AIDS cases reported to the National Reporting System (SINAN) among patients in care at INI.

Bacteriology and Bioassay Laboratory – INI
The laboratory conducts about 4,000 tests for tuberculosis per year. It performs Ziehl Neelsen and Auramine staining, solid medium culture and automated liquid medium culture (MGIT). Mycobacterial identification is performed by conventional and molecular methods, for both M. tuberculosis complex and for the MOTT (Mycobacteria Other Than Tuberculosis), including sequencing, where applicable. Drug susceptibility tests are performed by automation and convention for first and second line drugs, in addition to determining the minimum inhibitory concentration (MIC) to MOTT and M. tuberculosis.

The lab’s research is mainly focused on drug resistance, cost-effectiveness studies, and molecular epidemiology. In addition to providing support for other groups and research laboratories, this lab has participated for the past six years as the main laboratory in Brazil for the U.S. National Institutes of Health (NIH) and the AIDS Clinical Trials Group (ACTG); the lab is certified by the NIH.

Interdisciplinary Laboratory of Medical Research (LIPMED) of Oswaldo Cruz Institute, FIOCRUZ
Created in 2009, the LIPMED structure is highly qualified to conduct parasitology and immunology research projects by contributing to the understanding of immunopathogenic and immunoprotection processes associated with infectious disease. The staff includes 10 researchers with diverse backgrounds (physicians, pharmacists, biologists, biomedical) that coordinate post doctors, PhD, master and undergraduate students.

Universidade Federal do Rio de Janeiro (UFRJ)
Rio de Janeiro, Brasil
The Academic Tuberculosis Program (ATP) from Medical School (MS) at the Universidade Federal do Rio de Janeiro (UFRJ) has been located at the Hospital complex comprised by Hospital Universitario Clementino Fraga Filho (HUCFF) and Instituto Doenças do Tórax (IDT) at the Universidade Federal do Rio de Janeiro (UFRJ) since 1998. ATP-MS-UFRJ is affiliated with the Brazilian Tuberculosis Research Network (REDE-TB) since 2001. Currently, HUCFF/IDT-UFRJ is a referral center for complex cases in different areas such as pulmonoly, tisiology, cardiology, nephrology, hematology, endocrinology, tropical medicine and infectious diseases, video laparoscopy surgery and transplant programs, among others. Since 2004, working in collaboration with funds received from the Ministry of Health (MoH), National Development Bank (BNDES), the Ministry of Research Technology and Innovation (MCTI) and State Research Foundation of Rio de Janeiro State (FAPERJ) have been used to implement a Tuberculosis Research Center (TBRC) affiliated with ATP-MS-UFRJ. Applied basic research, Phase II/III clinical trials, and pragmatic clinical trials have been conducted for tuberculosis and other diseases. The installation of the TB Research Center in the hospital complex has improved interactions among the basic and clinical research groups, making development of new interventions possible. This has improved the partnership between the university, the health system, and industry, which has facilitated the development of innovative drugs, medical devices and procedures to reduce the burden of the most prevalent diseases of the country. The hospital has 226 residents, 1451 undergraduate students, 346 Master of Science and 184 PhD Medicine students in training programs.

Multidisciplinary Research Laboratory (LMP) of the Clementino Fraga Filho University Hospital, of Federal University of Rio de Janeiro
The LMP was founded in 1993 by Dr. Lapa e Silva and colleagues to conduct research and research training activities in pathogenesis of inflammatory and infectious diseases affecting different systems. In its 200 sq. m of laboratory and academic spaces, it hosts 10 full time researchers, 5 full time technicians and 10 graduate students, including 2 post-docs. Research is conducted in the areas of immunology, immunopathology, and immunogenetics of tuberculosis. It contains facilities for cell culture, immunocytochemistry, immunohistochemistry, image analysis, and molecular biology, including a state-of-the-art Real Time PCR and two ELISA readers. All investigators have their own space fully equipped with new computers and a shared conference room with capabilities for multimedia presentation and web conference.

Centro Municipal de Saude Duque de Caxias – Duque de Caxias
Rio de Janeiro, Brasil
Tuberculosis Control Program – Duque de Caxias
This center initially began in 1971 as a State Health Unit, but due to the high patient demand, it is now dedicated solely to the city of Duque de Caxias. This TB center accepts patients and referrals from other hospitals (primarily the Moacyr do Carmo Municipal Hospital and Adam Pereira Nunes Hospital), Emergency Care Units, Family Health Programs, and primary units of the municipality.

Secretaria Municipal de Saude do Rio de Janeiro – Rocinha
Rio de Janeiro, Brasil
Rocinha is a low-income ‘favela’ of 70,000 inhabitants located in southern Rio de Janeiro, where TB incidence rates have reached levels four times higher than those recorded in the municipality. Since 2010, the primary health care model, the Family Health Program was implemented in Rocinha. Currently there are 3 primary health care clinics in Rocinha with 25 Family Health Program teams working in these three units, accounting for 25 general practitioners, 25 nurses, 25 nursing technicians, 150 community health workers as well as managers and administrative assistants. Rocinha population is 100% covered by the primary health care program and have access to TB care in their own community. The TB research site is able to receive patients from the 3 clinics to participate in the study.

The Rio de Janeiro Municipal Health Secretariat site for tuberculosis research in RePORT-Brazil is located in a building that hosts a Primary Health Care clinic for the “favela” of Rocinha named Clínica da Família Rinaldo Delamare. This research site has housed tuberculosis and HIV-related tuberculosis research for the last 8 years and will be used for the current study. There are many other departments and services of the City Hall in the same building.

Collaborating Institutions in Salvador, Brazil

Instituto Brasileiro de Investigacao da Tuberculose (IBIT) and Instituto Bahiano de Reabilitacao (IBR), Fundacao Jose Silveira (FJS)
Salvador, Bahia, Brasil
FJS/IBIT is a non-profit organization that was founded as Instituto Brasileiro de Investigação da Tuberculose – IBIT in February of 1937 in the State of Bahia/Brazil accredited by the government as a TB treatment center. IBIT founder Dr. Silveira built up a tuberculosis research program that has included participation in the research of the main drugs and drug-schemes against tuberculosis. Currently, FJS/IBIT serves as a reference center for TB primary care and annually treats 10—15% TB cases of the city of Salvador. This institute is part of the Brazilian National TB control program and follows all guidelines and recommendations of the Brazilian Society of Pulmonology and Tisiology, which are similar to the WHO recommendations. All patients are reported to the national TB Program. In addition, IBIT provides free Lowenstein-Jansen culture analysis to patients. LJ cultures are taken from all patients with respiratory symptoms or suspected extra-pulmonary tuberculosis, and about 10% of the treated patients are AFB negative/culture positive. The last 5 year cohort study indicate cure rate over 85% and abandonment less than 5%. Recently, the institute started implementing GeneXpert® MTB/RIF technology for screening of TB patients.

IMU-LIMI-CPqGM-FIOCRUZ Salvador
The Investigative Medicine Unit (IMU) is an advanced laboratory facility within the Laboratório Integrado de Microbiologia e Imunorregulação (LIMI) at the Centro de Pesquisas Gonçalo Moniz (CPqGM), Fundação Oswaldo Cruz (FIOCRUZ), located in Salvador. CPqGM has been the leading scientific institution in immunology of infectious diseases in Bahia and one of the most respected research centers of FIOCRUZ. The IMU is a newly established research unit that performs advanced translational research in the field of immunology of human tuberculosis and HIV infection. IMU is integrated to an initiative named Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER), which includes basic science laboratories, clinical research institutions, and biostatistics facilities in Brazil (FIOCRUZ and FJS/IBIT), South Africa (University of Cape Town), United States (NIH, JHU), and India (National Institute for Research in Tuberculosis).

 

Collaborating Institutions in Manaus, Brazil

Fundacao de Medicina Tropical (FMT)
Manaus, Amazonas, Brasil
Laboratory facilities: FMT is the leading institution of Tropical Diseases in the Amazonas State, with more than 40 years of experience in Public Health. There are 10 specialized laboratories dedicated to routine diagnosis and research in infectious and parasitic diseases at the FMT-HVD, including a level III-biosafety laboratory.

FMT is a referral center for the diagnosis and treatment of infectious, parasitic and dermatological diseases, admitting in their facilities patients referred by the health network of Manaus and from the countryside of the Amazonas State, as well as from neighboring states and countries. The FMT-HVD Outpatient Clinics has 40 medical offices and held more than 285,000 health consultations in 2014. The Clinical Research Inpatient Unit is open 24 hours a day, seven days a week, including holidays. The hospital has 143 beds, including 7 beds in the Intensive Care Unit (ICU), with a demand of approximately 156 admissions per month. Fourteen beds are dedicated exclusively to clinical research. All the medical information is routinely available in electronic clinical charts (iDoctor®), allowing faster monitoring in clinical trials. FMT has a Clinical Analysis Laboratory, including Hematology, Biochemistry, Parasitology, Bacteriology and Immunology sections. FMT was responsible for the diagnosis and treatment of 2,118 cases of malaria and 451 cases of TB in 2014.

 

Coordinating Center

Vanderbilt Tuberculosis Center (VTC)
The Vanderbilt Tuberculosis Center was established in 2012 to expand the Vanderbilt global research portfolio in tuberculosis (TB) and HIV-related TB, with a focus on epidemiology, clinical trials, and translational research. The Vanderbilt Tuberculosis Center includes investigators from across the university, as well as local, regional, and global collaborators. The Center focuses on four broad areas of research:
1. TB/HIV Co-Infection
2. TB Drug Resistance
3. TB Treatment and Prevention
4. M. tuberculosis transmission and Pathogenesis
The Center has an emphasis on developing and mentoring junior faculty members, fellows, and students from Vanderbilt University, Meharry Medical College, and collaborating health departments and international institutions, particularly RePORT-Brazil institutions. The Center also provides technical assistance to the Vanderbilt-linked global and local service programs engaged in TB control: the Metro Nashville Public Health Department, the Tennessee Department of Health, and PEPFAR/Global Health Initiatives in Africa, Asia, and the Americas.

Contact

For comments or questions, please contact:

Marina Cruvinel Figueiredo, Program Manager
Vanderbilt University Medical Center
marina.cruvinel.figueiredo@vanderbilt.edu

Funders

RePORT-Brazil acknowledges funding from the National Institutes of Health (NIH) (the National Institute of Allergy and Infectious Diseases (NIAID)), CRDF Global, Departamento de Ciencia e Tecnologia (DECIT)- Secretaria de Ciencia e Tecnologia (SCTIE) of the Ministry of Health of Brazil.