SUMMARY OF TUBERCULOSIS RESEARCH PROGRAM AT UT-SPH BROWNSVILLE
Tuberculosis in the Texas-Mexico border. In the United States (US) TB has declined consistently since 1992 to its lowest rate in US history (4.6 cases/100,000 in the year 2006), and the distribution of the infection has become limited to well-defined populations. Our Brownsville campus is located in the Texas-Mexican border, where the TB prevalence is more than twice the national rate (13.6 cases/100,000 in 2005). Reactivation of LTBI and spread of MTB is facilitated in this population made vulnerable by health disparity, poverty, stress of migration, crowding and lack of access to health care. This population also has one of the highest rates of DM in the US (19.4% in Cameron county; Preliminary Data), associated with an increased risk for TB of up to 8-fold.
Our first step: Formation of a binational TB consortium: Initiation of the TB program at UT-SPH through formation of a consortium of TB researchers and public health workers in the Texas-Mexico border. Our TB program is young. The program begun in 2002, when, we (UTSPH-B researchers) created a working tuberculosis consortium. In 2003 we obtained R21 funds from the National Institutes of Allergy and Infectious Disease (NIAID 1 R21 AI056207-01) to formalize the consortium and initiate its scientific and public health program. The consortium consists of all key public health officials and tuberculosis researchers on both sides of the Tamaulipas/Texas border (figure 1). Mexican members include the directors of the tuberculosis programs of all 3 Sanitary Jurisdictions (Matamoros, Reynosa and Nuevo Laredo) the director of the tuberculosis program in the State of Tamaulipas, Ciudad Victoria, and heads of the Laboratorio Estatal de Tamaulipas. US members include all directors of county tuberculosis control programs (Cameron, Hidalgo and Webb), the Texas Department of State and Health Services (DSHS), and tuberculosis researchers from other regions of Texas. The consortium provided the environment for a binational collaboration. One of the major accomplishments has been the ability to access data from all the TB patients reported to both sides of the border. We have concluded an analysis of more than 5,000 patients reported from 1996-2002 (Texas) and 1998-2003 (Mexico). The chief observation was the strong association between diabetes and tuberculosis, including MDR-TB.
Since 2006 we have enrolled an average of 126 TB suspects/year who present sequentially at the Texas (~30% of our enrolled patients) and Mexico (~70% of our enrolled patients) TB clinics. Final TB diagnosis is established by the TB control program in 86% (63% confirmed by microbiology and 23% by clinical criteria).
RESEARCH STUDIES
Our TB research program has three lines of research:
• Epidemiology of the association between TB and diabetes
• Biological basis of the association between TB and diabetes
• Development of improved approaches for TB diagnosis
Our field site: Prospective enrollment of tb patients and their contacts.Our study population lives in Starr, Hidalgo, Webb and Cameron Counties in Texas and the city of Matamoros, located in the Sanitary Jurisdiction 3, State of Tamaulipas in Mexico (Fig 3). TB and DM are endemic in this region. TB is a reportable disease in the US and Mexico, and all individuals with suspected TB identified by public or private health providers are referred to the local health department clinics. In Texas, Hidalgo County Health Department is the reference center for Hidalgo and Starr counties, and Cameron County Health Department for Cameron County. In the State of Tamaulipas, Mexico, patients identified at the Sanitary Jurisdiction 3 are referred to the reference clinic in Matamoros (Fig 3). We refer to our study sites as ‘Texas’ and ‘Mexico’. These clinics manage TB patients from diagnosis to end of treatment. Clinical evaluation is made by the local physicians. Microbiological confirmation is by smear microscopy and culture at the local state laboratory in Texas, and by smear microscopy in Mexico. Selected specimens from Mexican patients (usually not responding to treatment and who are MDR-TB suspects) are cultured at the same Texas State laboratory with the support of a binational program (Grupo Juntos; funded and operated by Texas state and CDC). We have recently begun culturing the sputum from all participants lacking culture confirmation. Final diagnosis is based on the combination of clinical and microbiological findings. HIV status is conducted on all patients. We have been enrolling TB patients at the Hidalgo, Cameron and Matamoros clinics since 2006. For our current prospective studies we identify patients at these clinics, where we have trained phlebotomists and interviewers and a basic laboratory for immediate specimen processing. Specimens are transported daily to Brownsville for further downstream analysis.
PUBLICATIONS
• Mirza S, Restrepo BI, McCormick JB, Fisher-Hoch SP. (2003) Diagnosis of tuberculous lymphadenitis using a polymerase chain reaction on peripheral blood mononuclear cells. American Journal for Tropical Medicine and Hygiene; 69:461-5.
• Perez AP, Brown HS, Restrepo BI. (2006) The association between tuberculosis and diabetes in South Texas. American Journal for Tropical Medicine and Hygiene; 74:604-611.
• Restrepo BI, Gomez DI, Shipley, G, McCormick JB, Fisher-Hoch SP. (2006) Selective enrichment Selective enrichment and detection of mycobacterial DNA in paucibacillary specimens. Journal of Microbiological Methods; 67:220-229.
• Restrepo BI, Fisher-Hoch SP, Crespo JG, Whitney E, Perez AP, Smith B, McCormick JB for the Nuevo Sanatander Tuberculosis Trackers. (2006) Impact of the Type 2 diabetes epidemic on tuberculosis in people of Mexican descent. Epidemiology and Infection (epub ahead of print, July 25, p 1-9)
• Supplemental material link:
Figure 1. Map of study site in the
Texas (United States) and Tamaulipas (Mexico) border. All tuberculosis cases reported to Texas Department of State and Health Services Region 11 (PHR-11) between 1996-2002 and to the Secretaría de Salud de Tamaulipas Sanitary Jurisdictions 3 (Jur-3), 4 (Jur-4) and 5 (Jur-5) were studied.
• Restrepo BI. Convergence of the tuberculosis and diabetes epidemics: renewal of old acquaintances. (Invited Editorial) Clinical Infectious Diseases. 2007 Aug 15;45(4):436-8.
• Restrepo BI, PA Pino, M Volcy, AF Franco, GV Kanaujia, J Robledo. (2008) Interpretation of anti-mycobacterial antibodies in the cerebrospinal fluid of adults with tuberculous meningitis. Tropical Medicine and International Health; May 13(5):653-8.
• Fisher-Hoch SP, Whitney E, Crespo JG, Perez AP, Smith B, McCormick JB, Restrepo BI for the Nuevo Santander Tuberculosis Trackers. (2008) Multi-drug resistance in tuberculosis driven by Type 2 diabetes. Scandinavian Journal of Immunology (in press).
• Restrepo, BI, Fisher-Hoch SF, Smith B, Joen S, Rahbar MH, McCormick JB. (2008) Mycobacterial clearance from sputum is delayed during the first phase of treatment in patients with diabetes. American Journal for Tropical Medicine and Hygiene (in press).
• Restrepo BI, SP Fisher-Hoch, PA Pino, A Salinas, MH Rahbar, F Mora, N Cortes-Penfield, JB McCormick. (2008) Tuberculosis in poorly controlled type 2 diabetes: altered cytokine expression in peripheral white blood cells. Clinical Infectious Diseases (in press)
FACILITIES
The University of Texas School of Public Health at Brownsville (UTSPH-B) campus. The school occupies a purpose-built building constructed in January 2002, situated on the UT Brownsville campus. With additions and updating in 2008 it now comprises 31,000 square feet of teaching, office and laboratory space, with an additional community outreach center. It has classrooms and meeting rooms equipped with state-of-the-art projection and communication equipment, including Smartboards for computer projection and ITV facilities.
State-of-the-art research laboratory near our field sites. The University of Texas School of Public Health at Brownsville laboratory has a 6000 square foot wet-laboratory completed in 2008 This custom-built space has two suites of specialized dedicated rooms and an open laboratory offering bench space for field programs and students. The first suite includes i) a fully equipped BSL3 laboratory and an anteroom ii) a dark room designed for a FACS Canto II and other imaging equipment, iii) a PCR room for real time PCR (ABI7900), a positive pressure tissue culture room with 1 6ft Class IIA hood, and a chemistry room for liquid and mass spectrometry (Agilent LC/MS) with fume hood and chemical storage and piped gases.
NIH-sponsored Clinical Research Unit (CRU). Our UT-SPH-B campus has an NIH-funded CRU which is staffed by a Medical Director and two nurses, and is part of the University of Texas Houston Health Science Center Translational Research Award (CCTS-CTSA (1U54RR023417-01). This units is the coordinating center for the cohort studies conducted by the Hispanic Health Research Center (www.hhrc.info), including the HHRC cohort for studies on diabetes and vaccine testing.
CONTACT US:
Blanca I. Restrepo, Ph.D., TB Program Director at Blanca.I.Restrepo@uth.tmc.edu
