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The Next Great Plague

This essay by Shaunak Kishore ‘12 won an Asia Society and Goldman Sachs Foundation Prize for Excellence in International Education in the youth category in November 2008.

In the past fifty years, massive worldwide efforts have eliminated diseases that were once at pandemic proportions. During the 1950s, the World Health Organization began a program to end malaria by killing off mosquitoes, the disease’s primary vectors [4]. The widespread use of vaccines has wiped out smallpox entirely and will soon eradicate the polio virus. However, there are several infectious diseases - notably tuberculosis and malaria - that have been controlled in the developed world, but still affect millions in parts of Asia and sub-Saharan Africa, despite the availability of relatively cheap treatments [5]. Though it is almost forgotten in the United States, tuberculosis remains a grave danger, one that must be fought in hospitals and clinics in developing countries around the world.
Today, tuberculosis (TB) is far harder to control than it was 40 years ago. TB is caused by Mycobacterium tuberculosis, a bacterium that primarily attacks the lungs, causing victims to cough up blood and destroying parts of the lung tissue. The disease is deadly and highly contagious, spread through coughing, but it is curable with a cocktail of several antibiotics [9]. Tuberculosis is treated with a mixture of isoniazid and rifampin, a treatment which has curbed the spread of TB in the US and Britain since the 1970s. But this program has not worked so well in Africa and Asia. A growing obstacle to treating TB is the evolution of multi-drug resistant strains, or MDR-TB, which are invulnerable to both of the first-line drugs. The second-line antibiotics needed to treat MDR-TB are expensive and not widely available in developing countries [10].

While tuberculosis is often overlooked in the US, it remains a significant public health problem. In most areas of the country, the disease is controlled, with only a few cases per hundred thousand [8]. But a closer look at current trends reveals that TB still poses a danger. In the late 1980s, the incidence of tuberculosis actually grew, mainly because of an increased prevalence of multi-drug resistant TB in infected patients [7]. Many hospitals throughout the country did not have treatments for MDR-TB immediately available, because most tuberculosis cases in the US were still drug-susceptible. It took seven years - 1985-1992 - to bring TB incidence levels back down [7]. The problem facing our communities is that we are still unprepared to combat a highly drug-resistant strain of tuberculosis.

The United States has largely managed to prevent drug resistant TB from entering its borders, but it will be difficult to keep up this success. As of 2006, only 1.1% of infections in the US were multi-drug resistant [8]. The situation worldwide is much worse. By 2004, 60% of tuberculosis cases in Asia and 39% worldwide were MDR-TB [3]. The global spread of drug resistance has grave implications for the US. Almost nine in ten cases of resistant tuberculosis in 2006 affected foreign-born Americans, which is a strong indication that the high prevalence of MDR-TB in other countries is causing more cases here [8]. Further, this means that tuberculosis disproportionately affects ethnic minorities, even more than other diseases - TB hits already disadvantaged groups the hardest. A WHO report found that blacks, Hispanics, and Asians were almost ten times as likely to have tuberculosis as an average American [8]. This pattern worsens inequalities in US towns and cities. It also makes controlling TB more difficult, because as long as certain segments of the population have a high prevalence of the disease, it will continue to spread.

While doctors in the US fight to prevent a resurgence of infectious disease, healthcare providers in India, and throughout Asia, face a TB epidemic. Tuberculosis treatment in the developing world poses unique challenges. I learned about these difficulties firsthand, when I worked in a pathology lab in Bihar, a state in northern India, two summers ago. A major problem there is the duration of the treatment. Even a cocktail of isoniazid and rifampin, the most effective TB medication, must be administered for six months to completely wipe out the infection [2]. Unfortunately, many patients stopped taking their medication after a few weeks, when tuberculosis symptoms disappeared. As the doctors in the lab explained, this is mostly because people wanted avoid the side effects associated with their medication and the comparatively high-cost of a sustained treatment. To encourage patients to take their antibiotics consistently, doctors offered them a free meal each day they came for treatment, and they made sure the treatment was administered during these meetings.

Unfortunately, this directly observed treatment (DOTS) program was still not entirely effective. Further, while the hospital I worked in was relatively well-equipped, many other hospitals in the area did not have the funds to feed their patients. When patients stop their treatment prematurely, TB bacteria that are resistant to drugs in the cocktail proliferate, and the more drugs that are added to a failing treatment, the greater the resistance is built up [2]. Aborted treatments are a major cause of the other challenge doctors in India face: a very high prevalence of MDR-TB. The secondary drugs used against this strain can require up to two years to be effective, and many clinics in the country simply don’t have them in stock [9]. The result is a vicious cycle: more aborted treatments leads to a higher incidence of resistant mycobacteria, which makes treatment even more difficult.

The evolution of multi-drug resistant and extensively drug resistant bacteria in Asia poses a grave danger in the United States and Europe. The CDC is clearly cognizant of this threat, as shown by its actions in the Andrew Speaker case, last year [6]. After Speaker was told he had contracted XDR-TB in Greece, he illegally flew back into the US, where the CDC put him under federal quarantine. This measure had not been used since 1963 [6].

As resistance continues to develop in India and in other countries, it will be increasingly difficult to resolve situations like Andrew Speaker’s. The TB epidemic in different countries is linked by travel and immigration. What doctors and epidemiologists are beginning to realize is that there are important spatial components to the spread of tuberculosis on smaller levels, as well. The new DOTS-Plus treatment program, proposed by several Indian doctors, would use this knowledge to better treat the disease [1]. The DOTS-Plus strategy is to treat MDR-TB in several large cities with a strong cocktail of six second-line antibiotics. The plan takes into account the unfortunate reality that secondary drugs are often unavailable in small towns or rural areas.

To test the effectiveness of this plan, I developed a mathematical model of TB, which simulated the epidemic on a graph, or network, of cities. What I found is that if treatment were aggressively applied to larger cities, it could shield smaller towns from the epidemic. The doctors who proposed DOTS-Plus had guessed that an effect like this would take place [1]. Because treatment in one city has consequences in nearby towns, this plan would be an effective and practical way to stem the spread of drug resistant infections.

If there is one thing the tuberculosis epidemic shows, it is that the incidence of disease in one continent, country, or city has an enormous impact throughout the world. While this fact contributes to the ease of the disease’s spread, it can also be used to devise a more effective worldwide treatment strategy. The best way to prevent MDR- and XDR-TB from taking hold in the United States is to combat it in India and other parts of Asia, where the bacteria is evolving quickly. TB, as the WHO notes, is not just a problem for the people of Bihar or the US; it is a “global health emergency.”

Works Cited

  1. Arora, V.K., et al. “DOTS-Plus for Patients with Multidrug-resistant Tuberculosis in India: Early Results After Three Years.” October 2006. The Indian Journal of Chest Diseases & Allied Sciences.
  2. Davies, Peter D. O. “Multi-Drug Resistant Tuberculosis.” March 1999. Priory Lodge Education. 30 May 2007.
  3. Emergence of Mycobacterium tuberculosis with Extensive Resistance to Second-Line Drugs - Worldwide, 2000-2004.” MMWR Weekly. March 24, 2006.
  4. The History of Malaria, an Ancient Disease.” Malaria. April 2004. Centers for Disease Control and Prevention. 31 May 2007.
  5. Kent, Mary M. “Controlling Infectious Diseases.” Population Bulletin. June 2006.
  6. McPhee, Mike, and Karen Auge. “Patient’s In-Law a TB Expert.” Denver Post. 31 May 2007.
  7. Trends In Tuberculosis - United States, 2004.” MMWR Weekly. March 18, 2005.
  8. Trends In Tuberculosis - United States, 2007.” MMWR Weekly. March 21, 2008.
  9. Tuberculosis Fact Sheet.” March 2007. World Health Organization. 30 May 2007.
  10. Tuberculosis in Developing Countries.” MMWR Weekly. August 24, 1990.

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