Skip to main content
Public Health Reports logoLink to Public Health Reports
. 1998 Mar-Apr;113(2):128–136.

The tuberculosis epidemic. Scientific challenges and opportunities.

A M Ginsberg 1
PMCID: PMC1308651  PMID: 9719813

Abstract

One in every three people on Earth is believed to be infected with Mycobacterium tuberculosis, leading to seven to eight million cases of active tuberculosis (TB) per year and approximately three million deaths annually. this epidemic, like those of most infectious diseases, creates scientific challenges and opportunities as it raises the demand for public health solutions. The currently available weapons for fighting TB are inadequate. The ultimate goal of biomedical TB research is to lessen the public health burden of this disease by developing improved diagnostic, therapeutic, and intervention strategies. Achieving this goal requires a base of knowledge about the biology of M. tuberculosis and related mycobacteria, their interactions with human and animal hosts, and the nature of an effective host-protective immune response. TB researchers are applying this accumulating base of knowledge to developing rapid, easy-to-use diagnostic assays appropriate for low-as well as high-income countries, improving the current complicated therapeutic regimen, identifying potential new drugs to combat multidrug-resistant TB, and creating more effective vaccines.

Full text

PDF
133

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arain T. M., Resconi A. E., Singh D. C., Stover C. K. Reporter gene technology to assess activity of antimycobacterial agents in macrophages. Antimicrob Agents Chemother. 1996 Jun;40(6):1542–1544. doi: 10.1128/aac.40.6.1542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bange F. C., Brown A. M., Jacobs W. R., Jr Leucine auxotrophy restricts growth of Mycobacterium bovis BCG in macrophages. Infect Immun. 1996 May;64(5):1794–1799. doi: 10.1128/iai.64.5.1794-1799.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bardarov S., Kriakov J., Carriere C., Yu S., Vaamonde C., McAdam R. A., Bloom B. R., Hatfull G. F., Jacobs W. R., Jr Conditionally replicating mycobacteriophages: a system for transposon delivery to Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10961–10966. doi: 10.1073/pnas.94.20.10961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barry M. A., Lai W. C., Johnston S. A. Protection against mycoplasma infection using expression-library immunization. Nature. 1995 Oct 19;377(6550):632–635. doi: 10.1038/377632a0. [DOI] [PubMed] [Google Scholar]
  5. Beckman E. M., Porcelli S. A., Morita C. T., Behar S. M., Furlong S. T., Brenner M. B. Recognition of a lipid antigen by CD1-restricted alpha beta+ T cells. Nature. 1994 Dec 15;372(6507):691–694. doi: 10.1038/372691a0. [DOI] [PubMed] [Google Scholar]
  6. Behr M. A., Small P. M. Has BCG attenuated to impotence? Nature. 1997 Sep 11;389(6647):133–134. doi: 10.1038/38151. [DOI] [PubMed] [Google Scholar]
  7. Belisle J. T., Vissa V. D., Sievert T., Takayama K., Brennan P. J., Besra G. S. Role of the major antigen of Mycobacterium tuberculosis in cell wall biogenesis. Science. 1997 May 30;276(5317):1420–1422. doi: 10.1126/science.276.5317.1420. [DOI] [PubMed] [Google Scholar]
  8. Bifani P. J., Plikaytis B. B., Kapur V., Stockbauer K., Pan X., Lutfey M. L., Moghazeh S. L., Eisner W., Daniel T. M., Kaplan M. H. Origin and interstate spread of a New York City multidrug-resistant Mycobacterium tuberculosis clone family. JAMA. 1996 Feb 14;275(6):452–457. [PubMed] [Google Scholar]
  9. Bradford W. Z., Martin J. N., Reingold A. L., Schecter G. F., Hopewell P. C., Small P. M. The changing epidemiology of acquired drug-resistant tuberculosis in San Francisco, USA. Lancet. 1996 Oct 5;348(9032):928–931. doi: 10.1016/S0140-6736(96)03027-9. [DOI] [PubMed] [Google Scholar]
  10. Carrière C., Riska P. F., Zimhony O., Kriakov J., Bardarov S., Burns J., Chan J., Jacobs W. R., Jr Conditionally replicating luciferase reporter phages: improved sensitivity for rapid detection and assessment of drug susceptibility of Mycobacterium tuberculosis. J Clin Microbiol. 1997 Dec;35(12):3232–3239. doi: 10.1128/jcm.35.12.3232-3239.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Casper C., Singh S. P., Rave S., Daley C. L., Schecter G. S., Riley L. W., Kreiswirth B. N., Small P. M. The transcontinental transmission of tuberculosis: A molecular epidemiological assessment. Am J Public Health. 1996 Apr;86(4):551–553. doi: 10.2105/ajph.86.4.551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Colditz G. A., Brewer T. F., Berkey C. S., Wilson M. E., Burdick E., Fineberg H. V., Mosteller F. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA. 1994 Mar 2;271(9):698–702. [PubMed] [Google Scholar]
  13. Collins D. M., Kawakami R. P., de Lisle G. W., Pascopella L., Bloom B. R., Jacobs W. R., Jr Mutation of the principal sigma factor causes loss of virulence in a strain of the Mycobacterium tuberculosis complex. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):8036–8040. doi: 10.1073/pnas.92.17.8036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Collins L., Franzblau S. G. Microplate alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium. Antimicrob Agents Chemother. 1997 May;41(5):1004–1009. doi: 10.1128/aac.41.5.1004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Comstock G. W. Field trials of tuberculosis vaccines: how could we have done them better? Control Clin Trials. 1994 Aug;15(4):247–276. doi: 10.1016/0197-2456(94)90042-6. [DOI] [PubMed] [Google Scholar]
  16. Dessen A., Quémard A., Blanchard J. S., Jacobs W. R., Jr, Sacchettini J. C. Crystal structure and function of the isoniazid target of Mycobacterium tuberculosis. Science. 1995 Mar 17;267(5204):1638–1641. doi: 10.1126/science.7886450. [DOI] [PubMed] [Google Scholar]
  17. Donnelly J. J., Ulmer J. B., Liu M. A. Immunization with DNA. J Immunol Methods. 1994 Dec 2;176(2):145–152. doi: 10.1016/0022-1759(94)90308-5. [DOI] [PubMed] [Google Scholar]
  18. Fine P. E. Variation in protection by BCG: implications of and for heterologous immunity. Lancet. 1995 Nov 18;346(8986):1339–1345. doi: 10.1016/s0140-6736(95)92348-9. [DOI] [PubMed] [Google Scholar]
  19. Fodor S. P., Rava R. P., Huang X. C., Pease A. C., Holmes C. P., Adams C. L. Multiplexed biochemical assays with biological chips. Nature. 1993 Aug 5;364(6437):555–556. doi: 10.1038/364555a0. [DOI] [PubMed] [Google Scholar]
  20. Guleria I., Teitelbaum R., McAdam R. A., Kalpana G., Jacobs W. R., Jr, Bloom B. R. Auxotrophic vaccines for tuberculosis. Nat Med. 1996 Mar;2(3):334–337. doi: 10.1038/nm0396-334. [DOI] [PubMed] [Google Scholar]
  21. Gupta H. P., Singh N. B., Mathur I. S., Gupta S. K. Mycobacterium habana, a new immunogenic strain in experimental tuberculosis of mice. Indian J Exp Biol. 1979 Nov;17(11):1190–1193. [PubMed] [Google Scholar]
  22. Harth G., Lee B. Y., Horwitz M. A. High-level heterologous expression and secretion in rapidly growing nonpathogenic mycobacteria of four major Mycobacterium tuberculosis extracellular proteins considered to be leading vaccine candidates and drug targets. Infect Immun. 1997 Jun;65(6):2321–2328. doi: 10.1128/iai.65.6.2321-2328.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Huygen K., Content J., Denis O., Montgomery D. L., Yawman A. M., Deck R. R., DeWitt C. M., Orme I. M., Baldwin S., D'Souza C. Immunogenicity and protective efficacy of a tuberculosis DNA vaccine. Nat Med. 1996 Aug;2(8):893–898. doi: 10.1038/nm0896-893. [DOI] [PubMed] [Google Scholar]
  24. Kelly B. P., Furney S. K., Jessen M. T., Orme I. M. Low-dose aerosol infection model for testing drugs for efficacy against Mycobacterium tuberculosis. Antimicrob Agents Chemother. 1996 Dec;40(12):2809–2812. doi: 10.1128/aac.40.12.2809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Laal S., Samanich K. M., Sonnenberg M. G., Belisle J. T., O'Leary J., Simberkoff M. S., Zolla-Pazner S. Surrogate marker of preclinical tuberculosis in human immunodeficiency virus infection: antibodies to an 88-kDa secreted antigen of Mycobacterium tuberculosis. J Infect Dis. 1997 Jul;176(1):133–143. doi: 10.1086/514015. [DOI] [PubMed] [Google Scholar]
  26. Mahairas G. G., Sabo P. J., Hickey M. J., Singh D. C., Stover C. K. Molecular analysis of genetic differences between Mycobacterium bovis BCG and virulent M. bovis. J Bacteriol. 1996 Mar;178(5):1274–1282. doi: 10.1128/jb.178.5.1274-1282.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. McAdam R. A., Weisbrod T. R., Martin J., Scuderi J. D., Brown A. M., Cirillo J. D., Bloom B. R., Jacobs W. R., Jr In vivo growth characteristics of leucine and methionine auxotrophic mutants of Mycobacterium bovis BCG generated by transposon mutagenesis. Infect Immun. 1995 Mar;63(3):1004–1012. doi: 10.1128/iai.63.3.1004-1012.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Moore M., Onorato I. M., McCray E., Castro K. G. Trends in drug-resistant tuberculosis in the United States, 1993-1996. JAMA. 1997 Sep 10;278(10):833–837. [PubMed] [Google Scholar]
  29. Murray P. J., Aldovini A., Young R. A. Manipulation and potentiation of antimycobacterial immunity using recombinant bacille Calmette-Guérin strains that secrete cytokines. Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):934–939. doi: 10.1073/pnas.93.2.934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. O'Donnell M. A., Aldovini A., Duda R. B., Yang H., Szilvasi A., Young R. A., DeWolf W. C. Recombinant Mycobacterium bovis BCG secreting functional interleukin-2 enhances gamma interferon production by splenocytes. Infect Immun. 1994 Jun;62(6):2508–2514. doi: 10.1128/iai.62.6.2508-2514.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Orme I. M. Progress in the development of new vaccines against tuberculosis. Int J Tuberc Lung Dis. 1997 Apr;1(2):95–100. [PubMed] [Google Scholar]
  32. Pelicic V., Jackson M., Reyrat J. M., Jacobs W. R., Jr, Gicquel B., Guilhot C. Efficient allelic exchange and transposon mutagenesis in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10955–10960. doi: 10.1073/pnas.94.20.10955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Raviglione M. C., Dye C., Schmidt S., Kochi A. Assessment of worldwide tuberculosis control. WHO Global Surveillance and Monitoring Project. Lancet. 1997 Aug 30;350(9078):624–629. doi: 10.1016/s0140-6736(97)04146-9. [DOI] [PubMed] [Google Scholar]
  34. Reichman L. B. Tuberculosis elimination--what's to stop us? Int J Tuberc Lung Dis. 1997 Feb;1(1):3–11. [PubMed] [Google Scholar]
  35. Robbins J. B., Schneerson R., Anderson P., Smith D. H. The 1996 Albert Lasker Medical Research Awards. Prevention of systemic infections, especially meningitis, caused by Haemophilus influenzae type b. Impact on public health and implications for other polysaccharide-based vaccines. JAMA. 1996 Oct 9;276(14):1181–1185. doi: 10.1001/jama.276.14.1181. [DOI] [PubMed] [Google Scholar]
  36. Rodrigues L. C., Diwan V. K., Wheeler J. G. Protective effect of BCG against tuberculous meningitis and miliary tuberculosis: a meta-analysis. Int J Epidemiol. 1993 Dec;22(6):1154–1158. doi: 10.1093/ije/22.6.1154. [DOI] [PubMed] [Google Scholar]
  37. Schena M., Shalon D., Davis R. W., Brown P. O. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science. 1995 Oct 20;270(5235):467–470. doi: 10.1126/science.270.5235.467. [DOI] [PubMed] [Google Scholar]
  38. Silva C. L., Lowrie D. B. A single mycobacterial protein (hsp 65) expressed by a transgenic antigen-presenting cell vaccinates mice against tuberculosis. Immunology. 1994 Jun;82(2):244–248. [PMC free article] [PubMed] [Google Scholar]
  39. Stanford J. L., Rook G. A., Bahr G. M., Dowlati Y., Ganapati R., Ghazi Saidi K., Lucas S., Ramu G., Torres P., Minh Ly H. Mycobacterium vaccae in immunoprophylaxis and immunotherapy of leprosy and tuberculosis. Vaccine. 1990 Dec;8(6):525–530. doi: 10.1016/0264-410x(90)90002-4. [DOI] [PubMed] [Google Scholar]
  40. Tascon R. E., Colston M. J., Ragno S., Stavropoulos E., Gregory D., Lowrie D. B. Vaccination against tuberculosis by DNA injection. Nat Med. 1996 Aug;2(8):888–892. doi: 10.1038/nm0896-888. [DOI] [PubMed] [Google Scholar]
  41. Velculescu V. E., Zhang L., Vogelstein B., Kinzler K. W. Serial analysis of gene expression. Science. 1995 Oct 20;270(5235):484–487. doi: 10.1126/science.270.5235.484. [DOI] [PubMed] [Google Scholar]
  42. Yuan Y., Crane D. C., Musser J. M., Sreevatsan S., Barry C. E., 3rd MMAS-1, the branch point between cis- and trans-cyclopropane-containing oxygenated mycolates in Mycobacterium tuberculosis. J Biol Chem. 1997 Apr 11;272(15):10041–10049. doi: 10.1074/jbc.272.15.10041. [DOI] [PubMed] [Google Scholar]

Articles from Public Health Reports are provided here courtesy of SAGE Publications

RESOURCES