Innovations in Tuberculosis Diagnostics in Peru
Infectious Disease Research Center Becomes a Resource for Peru, Hopkins and the World
For over 20 years, Professor Robert Gilman, International Health, has conducted infectious disease research and training based at the Universidad Peruana Cayetano Heredia in Peru. Over the years, a unique relationship has developed between Hopkins and Cayetano University that has strengthened local research capacity in Peru. It has also created a research network and infrastructure that offer many opportunities for Hopkins faculty and students. Moreover, Gilman’s team’s ground-breaking work in the development of MODS–a rapid TB diagnostic technique—has made them an internationally known training resource with projects based in Asia, Africa and the Americas.
MODS: Microscopic-Observation Drug-Susceptibility
Microscopic-Observation Drug-Susceptibility, better known as MODS, is a faster, cheaper, and more sensitive test for multidrug-resistant tuberculosis (MDR-TB). In the early 2000s, IH MHS Grad Luz Caviedes, working under the supervision of Professor Gilman in Peru, discovered that the morphology of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) could be detected under the microscope. In collaboration with industry and academic experts, they refined and validated the method, culminating in the publication of a seminal article in the New England Journal of Medicine in 2006 (“Microscopic-observation drug-susceptibility assay for the diagnosis of TB”).
Diagnosing MDR-TB quickly and at a low cost is especially important in poor regions where co-infection with HIV is also prevalent. Before MODS, diagnosing MDR-TB could take up to 2 months.
“While HIV infection is not extremely high in Peru, 40 percent of HIV patients develop TB and in the past up to 40 percent of those cases were drug resistant. Many patients were dying from TB before a reliable diagnosis was made,” explains Professor Gilman. Since its development, research faculty based in Peru and Hopkins have been awarded several grants to conduct trainings in MODS across the globe.
Recently, a private firm called Hardy Diagnostics, working with global TB experts including Gilman, developed a low-cost, pre-assembled MODS test kit. The kit is currently in production and will be available on the market soon. The kit will enable MODS to be simpler for lab technicians since all the reagents will be present in one kit.
Other TB work
Diagnosis of TB in children is especially challenging. Diagnosing and treating it quickly among HIV-infected children is crucial. Gilman’s group has recently begun work testing several methods, including MODS, in Ethiopia where TB rates are high and where co-infection with HIV results in very high mortality rates.
Gilman’s lab is also conducting basic science research on pyrazinamide-resistant TB. Direct observation therapy, short-course (DOTS) for TB requires the use of pyrazinamide. But determining resistance to the drug still is a lengthy process. Scientists based at Cayetano are currently conducting research into the mechanics of the drug with active TB to develop more rapid diagnostic tests.
Infectious Diseases Training Grant
In addition to the many tuberculosis-related projects, Gilman administers a training grant funded by Fogarty International Center and NIH. The existing infrastructure Gilman’s team has helped build in Peru is being utilized to expand the infectious disease research capabilities of scientists and health professionals from developing countries. The program trains students at both the master’s, doctoral and postdoctoral levels. To date 45 Peruvians and over 300 students from other nations have completed the program.
Cysticercosis has also been a major research focus of Gilman’s team for over 20 years. Cysticercosis, a parasitic disease, is responsible for more cases of epilepsy in the world than any other condition. Dr. Hugo Garcia, a PhD training grant graduate, is now one of the leading experts in the field. He is currently based at Cayetano University and his work there has resulted in articles on the benefits of treatment to reduce seizures. (A trial of antiparasitic treatment to reduce the rate of seizures due to cerebral cysticercosis. N Engl J Med. 2004 Jan 15;350(3):249-58).
Recent PhD Dissertations by Training Grant Students in Peru
Cesar Gavidia: Cystic Echinococcosis in Peru: Human prevalence study and chemotherapy evaluation in sheep, 2009.
Andres Lescano: Taenia solium cysticercosis hotspots surrounding tapeworm carriers, 2008.
Holger Mayta: Cloning and characterization of two novel Taenia solium antigenic proteins and applicability to the diagnosis and control of taeniasis/cysticercosis, 2009.
Patricia Sheen: Molecular diagnosis of pyrazinamide resistance and molecular understanding of the pyrazinamidase functionality in Mycobacterium tuberculosis, 2008.
Manuela Verastegui: Studies on the mechanisms of Teania soluim larval stage adherence to host tissue, 2010.
Mirko Zimic: Taenia solium proteases: Novel antigens for cysticercosis immunodiagnosis and potential vaccine targets, 2008.
Current Training Grant Students
Department Faculty and Students
Broadening the Scope of Work in Peru
The quality of Cayetano’s facilities and its longstanding relationship with Hopkins have opened up a variety of opportunities for Hopkins students and faculty. Currently, Senior Associate Elli Leontsini and Hopkins alumna Angela Bayer are teaching a course in Peru on qualitative research. MHS graduate Gabrielle Hunter, who interned in Peru for her master’s degree, continued to work on several projects based in Peru after graduation. She is now analyzing data from projects on water and sanitation and Chagas disease that she worked on while in the country.
In addition, Assistant Scientist Margaret Kosek, Assistant Professor Bill Pan, and recent PhD grad Gwenyth Lee are working on various diarrhea and malaria projects across Peru and the Amazon. Their projects are headquartered in Iquitos, where they have developed a significant research laboratory that collaborates closely with the laboratory in Lima. And, Assistant Professor William Checkley from IH and the School of Medicine, along with Hopkins MHS grad Lauren Baumann, recently published data from their project based in Peru on road side pollution and asthma. The project was funded by NIH and the Fogarty foundation and operated in two major cities in Peru: Lima and Tumbes. More information can be found about the study from recent news articles.
Years of steady growth have established a world-class infectious disease center in Peru. With a broad scope of work, from training to cutting-edge research, the capacity provides opportunities for Peruvians, Hopkins faculty, students, and public health professionals from across the world.
Select Publications from Peru-based Research
Rapid, efficient detection and drug susceptibility testing of Mycobacterium tuberculosis in sputum by microscopic observation of broth cultures. The Tuberculosis Working Group in Peru. Caviedes L, Lee TS, Gilman RH, Sheen P, Spellman E, Lee EH, Berg DE, Montenegro-James S. J Clin Microbiol. 2000 Mar;38(3):1203-8.
Microscopic-observation drug-susceptibility assay for the diagnosis of TB. Moore DA, Evans CA, Gilman RH, Caviedes L, Coronel J, Vivar A, Sanchez E, Piñedo Y, Saravia JC, Salazar C, Oberhelman R, Hollm-Delgado MG, LaChira D, Escombe AR, Friedland JS. N Engl J Med. 2006 Oct 12;355(15):1539-50.
Sputum PCR-single-strand conformational polymorphism test for same-day detection of pyrazinamide resistance in tuberculosis patients. Sheen P, Méndez M, Gilman RH, Peña L, Caviedes L, Zimic MJ, Zhang Y, Moore DA, Evans CA. J Clin Microbiol. 2009 Sep;47(9):2937-43. Epub 2009 Jun 17.
Effects of distance from a heavily transited avenue on asthma and atopy in a periurban shantytown in Lima, Peru. Baumann LM, Robinson CL, Combe JM, Gomez A, Romero K, Gilman RH, Cabrera L, Hansel NN, Wise RA, Breysse PN, Barnes K, Hernandez JE, Checkley W. J Allergy Clin Immunol. 2011 Jan 13.
A trial of antiparasitic treatment to reduce the rate of seizures due to cerebral cysticercosis. Garcia HH, Pretell EJ, Gilman RH, Martinez SM, Moulton LH, Del Brutto OH, Herrera G, Evans CA, Gonzalez AE; Cysticercosis Working Group in Peru. N Engl J Med. 2004 Jan 15;350(3):249-58.
--Brandon Howard, February 2011