The Coming Plague

by Laurie Garrett

  133 U.S. Department of Health, Education, and Welfare, “The Project Years 1961–69,” Tuberculosis Program Reports (December 1970).

  134 Centers for Disease Control, “Tuberculosis in the United States: 1981–84,” U.S. Department of Health and Human Services, Washington, D.C., 1986.

  135 See Chapter 9 of this book for further discussion of tuberculosis in urban centers of the Western world prior to 1981.

  136 M. A. Barry, C. Wall, L. Shirley, et al., “Tuberculosis Screening in Boston’s Homeless Shelters,” Public Health Reports 101 (1986): 487–94; P. W. Brickner, B. Scanlan, A. Conan, et al., “Homeless Persons and Health Care,” Annals of Internal Medicine 101 (1986): 405–9; Centers for Disease Control, “Drug Resistant Tuberculosis Among the Homeless,” Morbidity and Mortality Weekly Report 34 (1985): 429–32; R. Glickman, “Tuberculosis Screening and Treatment of New York City Homeless People,” Annals of the New York Academy of Science 435 (1984): 19–21; E. B. Narde, B. Mclnnis, B. Thomas, and S. Weidhass, “Exogenous Reinfection with Tuberculosis in a Shelter for the Homeless,” New England Journal of Medicine 315 (1986): 1570–75; and A. Pablos-Mendez, M. C. Raviglione, R. Battan, and R. Ramos-Zuñiga, “Drug Resistant Tuberculosis Among the Homeless in New York City,” New York State Journal of Medicine 90 (1990): 351–55.

  137 M. N. Sherman, “Tuberculosis in Single-Room-Occupancy Hotel Residents: A Persisting Focus of Disease,” New York Medical Quarterly 1 (1980): 39–41.

  138 Centers for Disease Control, “Tuberculosis, Final Data—United States, 1986.” Morbidity and Mortality Weekly Report 36 (1988): 817–19; and Centers for Disease Control, “Tuberculosis—United States, 1985—and the Possible Impact of Human T-Lymphotropic Virus Type III/Lymphadenopathy-Associated Virus Infection,” Morbidity and Mortality Weekly Report 33 (1986): 74–79.

  139 Global Programme on AIDS and Tuberculosis Programme, “Statement on AIDS and Tuberculosis,” World Health Organization, WHO/GPA, INF/89.4, March 1989; and A. D. Harries, “Tuberculosis and Human Immunodeficiency Virus Infection in Developing Countries,” Lancet 335 (1990): 387–90.

  140 C. L. Daley, “Tuberculosis Recurrence in Africa: True Relapse or Re-Infection?” Lancet 342 (1993): 756–57; and J. D. Klausner, R. W. Ryder, E. Baende, et al., “Mycobacterium tuberculosis in Household Contacts of Human Immunodeficiency Virus Type-1-Seropositive Patients with Active Pulmonary Tuberculosis in Kinshasa, Zaire,” Journal of Infectious Diseases 168 (1993): 106–11.

  141 K. M. DeCock, “Tuberculosis and HIV Infection in Sub-Saharan Africa,” Journal of the American Medical Association 268 (1992): 1581–87.

  142 M. Hawken, P. Nunn, S. Gathua, et al., “Increased Recurrence of Tuberculosis in HIV-1-Infected Patients in Kenya,” Lancet 342 (1993): 332–37; and A. L. Pozniak, “The Influence of HIV Status on Single and Multiple Drug Reactions to Antituberculosis Therapy in Africa,” AIDS 6 (1992): 809–14.

  143 Y. Mukadi, J. H. Perriens, M. E. St. Louis, et al., “Spectrum of Immunodeficiency in HIV-1-Infected Patients with Pulmonary Tuberculosis in Zaire,” Lancet 342 (1993): 143–46; and Centers for Disease Control, “Tuberculin Reactions in Apparently Healthy HIV-Seropositive and HIV-Seronegative Women in Uganda,” Morbidity and Mortality Weekly Report 39 (1990): 638–46.

  144 D. S. Shepard, R. N. Bail, and A. Bucyendore, “Costs of AIDS Care in Rwanda,” Report to the Bigel Institute for Health Policy, Brandeis University, Waltham, MA, 1992; and K. B. Noble, “AIDS Linked to TB Outbreak in Africa,” New York Times, April 29, 1990: A14.

  145 H. L. Rieder, G. M. Cauthen, G. W. Comstock, and D. E. Snider, “Epidemiology of Tuberculosis in the United States,” Epidemiologic Reviews 11 (1989): 79–96.

  146 Centers for Disease Control, “Tuberculosis Morbidity in the United States: Final Data, 1990,” Morbidity and Mortality Weekly Report 40 (1991): SS23–SS27.

  147 J. J. Ellner, A. R. Hinman, S. W. Dooley, et al., “Tuberculosis Symposium: Emerging Problems and Promise.” Journal of Infectious Diseases 168 (1993): 537–51.

  148 G. Sunderam, R. J. McDonald, T. Maniatis, et al., “Tuberculosis as a Manifestation of the Acquired Immunodeficiency Syndrome (AIDS),” Journal of the American Medical Association 256 (1986): 362–66; Centers for Disease Control, “Tuberculosis and Acquired Immunodeficiency Syndrome—Florida,” Morbidity and Mortality Weekly Report 35 (1986): 587–90; J. Garrison, “AIDS Fuels Sharp Rise in TB Cases,” San Francisco Sunday Examiner and Chronicle, December 27, 1987: Al; Centers for Disease Control, “Tuberculosis and Acquired Immunodeficiency Syndrome—New York City,” Morbidity and Mortality Weekly Report 36 (1987): 785–95; and Centers for Disease Control, “Tuberculosis and AIDS—Connecticut,” Morbidity and Mortality Weekly Report 36 (1987): 133–35.

  149 Tuberculosis rates in Harlem had always been exceptionally high.

  NEW YORK CITY TUBERCULOSIS (cases per 100,000):

  150 K. Brudney and J. Dobkin, “Resurgent Tuberculosis in New York City,” American Review of Respiratory Disease 144 (1991): 745–49.

  151 C. Woodard, “TB in New York,” New York Newsday, March 8, 1992: 1; C. Woodard, “Bitter Medicine to Swallow,” New York Newsday, March 8, 1992: 38; M. Gelman, “A Prison Breeding Ground,” New York Newsday, March 11, 1992: 23; M. Gelman, “City Races to Finish ‘Cutting Edge’ TB Jail,” New York Newsday, March 11, 1992: 87; L. Garrett and C. Woodard, “New Risk in Hospitals,” New York Newsday, March 10, 1992: 6; L. Garrett, “HIV/TB—Tandem Epidemics Breed a Contradiction in Control,” New York Newsday, March 31, 1992: 57; L. Garrett, “Jobs That Carry a High Risk of TB,” New York Newsday, March 31, 1992: 61; L. Garrett, “Tackling the TB Puzzle,” New York Newsday, March 12, 1992: 8; and G. Cowley, E. A. Leonard, and M. Hager, “A Deadly Return,” Newsweek, March 16, 1992: 53–57.

  152

  Source: Centers for Disease Control.

  153 D. E. Snider and W. L. Roper, “The New Tuberculosis,” New England Journal of Medicine 325 (1992): 703–5; F. Gordin, “Tuberculosis Control—Back to the Future?” Journal of the American Medical Association 267 (1992): 2649–50; P. F. Barnes, A. B. Bloch, P. T. Davidson, and D. E. Snider, “Tuberculosis in Patients with Human Immunodeficiency Virus Infection,” New England Journal of Medicine 324 (1991): 1644–50; and M. A. Fischl, G. L. Daikos, R. B. Uttamchandani, et al., “Clinical Presentation and Outcome of Patients with HIV Infection and Tuberculosis Caused by Multiply-Drug-Resistant Bacilli,” Annals of Internal Medicine 117 (1992): 184–90.

  154 Centers for Disease Control, “Drug-Resistant Tuberculosis Among the Homeless—Boston,” Morbidity and Mortality Weekly Report 34 (1985): 429–31.

  155 Centers for Disease Control, “Multi-Drug-Resistant Tuberculosis—North Carolina,” Morbidity and Mortality Weekly Report 35 (1987): 785–87.

  156 For these and other chilling findings, see a lengthy memo from the CDC to the Department of Health and Human Services, Washington, D.C., dated December 31, 1991; and T. R. Frieden, M. L. Pearson, and J. A. Jereb, “Drug Resistant and Nosocomial Tuberculosis, New York City, 1991,” EPI-AID (1991): EPI-91-42–2.

  157 There were many outbreaks of MDR-TB in the United States and Puerto Rico during the epidemic, which appears to have begun sometime in the mid-1980s and continues at this writing.

  MDR-TB OUTBREAKS REPORTED IN THE UNITED STATES AND PUERTO RICO, 1985–92

  158 R. E. Brown, C. S. Palmer, and K. Simpson, “Estimate of Identifiable Costs of Tuberculosis in the United States in 1991,” Battelle Medi
cal Technology Assessment and Policy Research Center, Washington, D.C., 1993.

  159 New York State Assembly Committee on Health, “Tuberculosis in New York: The Return of an Epidemic,” Report to the Legislature, Albany, 1991.

  160 The actual allocation approved by the White House was for $40 million in 1992. CDC director Roper “found” another $14.9 million in funds designated for AIDS education efforts. Of the total $54.9 million, $6.5 million went to the National Institutes of Health for basic TB research and $46.5 million went to CDC tuberculosis control. Of its share, the CDC sent a good portion to New York City.

  Already facing a budget crisis, New York City spent more than $40 million on TB control in 1992 alone.

  The NIH’s TB spending climbed from $3.5 million in 1991 to $46 million in 1994.

  161 The cities surveyed were Atlanta, Baltimore, Boston, Chicago, Cleveland, Dallas, Detroit, Honolulu, Jacksonville, Los Angeles, Memphis, Miami, Milwaukee, Nashville, Newark, New Orleans, New York, Philadelphia, Phoenix, San Antonio, San Diego, San Francisco, Seattle, Tampa, and Washington, D.C. See D. R. Leff and A. R. Leff, “Tuberculosis Control Policies in Major Metropolitan Health Departments in the United States: V. Standard of Practice in 1992,” American Reviews of Respiratory Disease 148 (1993): 1530–36.

  162 Tuberculosis Task Force, “Nassau County Policy Plan for Responding to the Metropolitan New York Tuberculosis Epidemic,” Report to the Nassau County Health Department, November 1993.

  163 M. Goble, M. D. Iseman, L. A. Madsen, et al., “Treatment of 171 Patients with Pulmonary Tuberculosis Resistant to Isoniazid and Rifampin,” New England Journal of Medicine 328 (1993): 527–32.

  164 D. E. Snider, “Shortages of Antituberculosis Drugs, Outbreaks of Multidrug-Resistant Disease and New Drug Development in the U.S.,” presentation to the World Health Organization, November 22, 1991.

  165 New York City Task Force on Tuberculosis in the Criminal Justice System, “Final Report to Mayor David N. Dinkins and Margaret A. Hamburg, M.D., Commissioner, Department of Health,” June 1992.

  166 Among the questions TB scientists at the February 10, 1992, meeting identified as most pressing were the following:

  Epidemiology

  • How long do the bacteria survive in an enclosed airspace, potentially infecting a person?

  • How many bacteria does a human need to be exposed to in order to be infected?

  • What, precisely, are the relationships between HIV, injecting drug use, poverty, poor housing, and tuberculosis?

  Treatment

  • How can laboratories shorten the amount of time required to diagnose MDR-TB to some clinically useful period?

  • What are the optimal ways to use antitubercular drugs to avoid development of resistance?

  • What are the risks for patient reinfection?

  • What steps should hospitals and individual health providers take to avoid catching TB from their patients? To prevent patient-to-patient transmission?

  • How can surfaces be sterilized for TB?

  • Are there any other drugs out there for TB?

  • Can anything be done to save HIV-positive people who become infected with MDR-TB?

  Pathogenesis/Immunology

  • How does the bacteria use complement receptors to gain entry into human cells?

  • Why do the bacteria have strong iron-binding capabilities?

  • What is the nature of the cell-mediated immune response to the microbe? Do antibodies play any significant role?

  • How much of the disease is due to macrophages’ release of cytokines and other chemicals following M. tuberculosis invasion?

  • Why does the human lung self-destruct when infected?

  • How do the bacterial colonies form the protective encasements that allow them to hide from the immune system? And what, exactly, causes the liquefaction process that melts those casings and floods the bloodstream with the bacteria?

  • Are any of the bovine-based BCG vaccines against TB useful? How useful? For whom? Resistance

  • What is the molecular/genetic basis of drug resistance? Does it always vary from drug to drug, or are there universal resistance mechanisms?

  • Is there any way to design a drug that the mycobacteria can’t resist?

  167 Y. Zhang, B. Heym, B. Allen, et al., “The Catalase-Peroxidase Gene and Isoniazid Resistance of Mycobacterium tuberculosis,” Nature 358 (1992): 591–92; and A. Banerjee, E. Dubnau, A. Quemard, et al., “InhA, a Gene Encoding a Target for Isoniazid and Ethionamide in Mycobacterium tuberculosis,” Science 263 (1993): 227–30.

  168 B. J. Culliton, “Drug-Resistant TB May Bring Epidemic,” Nature 356 (1992): 473.

  169 W. R. Jacobs, R. G. Barletta, R. Udani, et al., “Rapid Assessment of Drug Susceptibilities of Mycobacterium tuberculosis by Means of Luciferase Reporter Phages,” Science 260 (1993): 819–22.

  170 P. Pancholi, A. Mirza, N. Bhardwaj, and R. M. Steinman, “Sequestration from Immune CD4+ T Cells of Mycobacteria Growing in Human Macrophages,” Science 260 (1993): 984–86; and S. Arruda, G. Bomfim, R. Knights, et al., “Cloning of a Mycobacterium tuberculosis DNA Fragment Associated with Entry and Survival Inside Cells,” Science 261 (1993): 1454–58.

  171 Somewhat after the emergence of MDR-TB in the United States, European communities of poverty witnessed identical chains of social and biological events. In Switzerland, the Netherlands, Italy, Denmark—all over Europe—HIV, poverty, and injecting drug use drove tuberculosis rates upward. According to WHO, Western Europe’s increases were as follows:

  Country Time Period Percent Increase in TB

  Switzerland 1986–90 33

  Denmark 1984–90 31

  Italy 1988–90 28

  Norway 1988–91 21

  Ireland 1988–90 18

  Austria 1988–90 17

  Finland 1988–90 17

  Netherlands 1987–90 9.5

  Sweden 1988–90 4.6

  United Kingdom 1987–90 2.0

  France, Germany, Belgium 1987–91 stable

  Source: World Health Organization, Press Release, June 17, 1992.

  See also A. Genewein, A. Telenti, C. Bernasconi, et al., “Molecular Approach to Identifying Route of Transmission of Tuberculosis in the Community,” Lancet 342 (1993): 841–44; and E. Drucker, “Molecular Epidemiology Meets the Fourth World,” Lancet 342 (1993): 817–18.

  172 K. Brudney and J. Dobkin, “A Tale of Two Cities: Tuberculosis Control in Nicaragua and New York City,” unpublished, 1992.

  173 D. Wilkinson, “High-Compliance Tuberculosis Treatment Programme in a Rural Community,” Lancet 173 (1994): 647–48.

  174 E. P. Y. Muhondwa, “The Role and Impact of Foreign Aid in Tanzania’s Health Development,” in M. R. Reich and E. Marvi, eds., International Cooperation for Health: Problems, Prospects, and Priorities (Dover, MA: Auburn House, 1989).

  175 C. Murray, K. Styblo, and A. Rouillon, “Tuberculosis,” in D. T. Jamison and W. H. Mosley, eds., Disease Control Priorities in Developing Countries (New York: Oxford University Press, 1991).

  176 Sadly, the U.S. Agency for International Development cut its entire overseas tuberculosis budget—all $3 million—the day after Christmas 1993. That represented a third of all funds for the World Health Organization’s TB program.

  177 Some countries had no tuberculosis control program at all. There, of course, the TB situation could have been worse than in the United States. The World Bank chose to limit comparisons to countries with TB programs and prevalence data.

  178 In 1994, the CDC and the New York City Department of Health cautiously announced some success in DOT control of TB, but repeatedly warned physicians
and the general public not to misinterpret their findings as indicating that the epidemic was under control. See A. B. Bloch, G. M. Cauthen, I. Onorato, et al., “Nationwide Survey of Drug-Resistant Tuberculosis in the United States,” Journal of the American Medical Association 271 (1994): 665–71; and S. E. Weis, P. C. Slocum, F. X. Blais, et al., “The Effect of Directly Observed Therapy on the Rates of Drug Resistance and Relapse in Tuberculosis,” New England Journal of Medicine 330 (1994): 1179–84.

  179 National MDR-TB Task Force, “National Action Plan to Combat Multidrug-Resistant Tuberculosis,” U.S. Department of Health and Human Services, Washington, D.C., April 1992.

  15. All in Good Haste

  1 Early accounts of the investigation appear in the CDC’s Morbidity and Mortality Weekly Report. See Vol. 42: 421–24, 441–43, 477–78, 495–96, 517–19, 570–71, and 612–13. In addition, the CDC published a special MMWR: “Hantavirus Infection—Southwestern United States: Interim Recommendations for Risk Reduction,” Vol. 42 (No. RR–11), 1993.