After her conversation with Dr. Sanjari, Aisha began to think about the children of the immigrants. So often the specific needs of children are overlooked, and with TB it was no different. There were many public health specialists and physicians advocating for a more effective vaccine and more appropriate diagnostics for children, who often are unable to cough up a sufficient amount of sputum. Some of Aisha’s friends had been vaccinated as children in other countries since the vaccine can reduce symptoms, but in the U.S., TB vaccination is not promoted.
Aisha reflected on the fact that an effective vaccine had not yet been developed. Despite the number of studies that demonstrated variable effectiveness of the current Bacillus Calmette-Guerin (BCG) vaccine, the vaccine had been used around the world in childhood vaccination programs. The vaccine appeared to reduce the symptoms of TB disease and, thus, its spread. Because rates of TB infection in the U.S. are relatively low and because vaccination can result in inaccurate readings of the Mantoux PPD skin test during TB screening, most U.S. born are not vaccinated. Work on a new vaccine was underway, but it would be some time before it would be available.
New diagnostics had also been approved and implemented in the last few years in Europe. The QuantiFERON-TB-Gold (QFT) detection system is more sensitive and specific than the Mantoux skin test. But since the test was only just approved by the FDA in 2005, it is not yet in wide use in the U.S. Just the other day, Aisha had attended a meeting where researchers were discussing the difference in positive diagnoses of infection using these two tests. If the same isolates were tested, QFT-Gold detected a lower number of positives as compared to the Mantoux test, suggesting that each test might target a different stage of infection. Aisha had asked if QFT-Gold might be detecting recent infection and not latent infection, and she was pleased to learn that research was underway to determine if this was the case. Since the QFT-Gold uses blood samples to detect the presence of IFN-γ, an immune protein, it might not be an effective means to conduct mass screening as it would involve needles and more equipment for analysis.
Aisha was concerned about the latent TB infections that might be MDR but which would not be detected by these two diagnostics. Both the Mantoux skin test and the QFT-Gold detect a generic immune response to tuberculin proteins, but don’t provide unique genetic or molecular information about the M. tuberculosis. Drug susceptibility tests require a sputum sample and are performed only on those with active disease and not latent infection. The testing involves culturing the bacteria and subjecting it to genetic analysis, or alternatively the bacteria could be grown in the presence of antibiotics that would reveal the drug resistance profile. The lengthy process could take months. A few companies were joining forces with the Foundation for Innovative Diagnostics (FIND) to develop tests that could shorten the testing time and use technologies appropriate for the developing world. “So what happens if we treat latent tuberculosis infection with antibiotics that don’t work on that person’s strain of M. tuberculosis?” Aisha thought to herself. “There must be some way to test the latent infections for drug resistance.” She decided to go to the library to see what she could find.
While conducting a literature search, Aisha came across a book titled Ending Neglect: The Elimination of Tuberculosis in the United States published by the Institute of Medicine in 2000. In the appendix, there was a proposal to prevent TB in newly arrived immigrants from countries with a high rate of TB. The proposal referred to studies that administered isoniazid for nine months to individuals who tested positive for latent tuberculosis infection (LTBI) and reported a 75% completion rate. This was part of a shift in policy, as many public health professionals were debating the pros and cons of prophylactic treatment of LTBI.
Aisha thought about TB screening and treatment protocols as they applied to immigrants applying for citizenship. Skin tests were not used in this setting; an X-ray and subsequent sputum test were analyzed in those over the age of 15, since children have difficulty producing a sufficient sputum sample. Immigrant parents who were not infectious, but tested positive for LTBI, would not receive treatment and gain entry. But the children of these individuals could later become infected with TB, should the parent’s latent infection develop into active disease. “Wouldn’t it be great if the Senate bill incorporated treatment for LTBI,” she thought. “Then the children of these immigrants would not be at risk for developing infection. But I suppose the screening alone will place a heavy burden on the states most affected by this bill.”
With a little more hunting, Aisha discovered more recent studies that were conducted on adolescent Latinos in the California high school system. These students were screened for TB using the Mantoux skin test. Anyone who tested positive for LTBI was treated for three months with rifampin and isoniazid to prevent development of TB. These students were targeted because they came from high risk countries, and childhood LTBI is more likely to progress to TB than in adults. In general, LTBI can develop into TB later in life when the immune system might be compromised by old age, smoking, or secondary infections such as HIV. Some of the studies involved coaching and DOTS-like methods of antibiotic delivery.
Though Aisha was relieved to see that something was being done to help the children, she couldn’t help but wonder if these children might suffer any negative consequences from these approaches. She also kept coming back to the risks involved in prophylactic treatment. “Could prophylactic treatment of LTBI in this recent immigrant population promote the development of XDR TB?” she wondered.
Skim the articles that Aisha collected and answer the questions below.
Originally published at http://www.sciencecases.org/mdr_tb/mdr_tb3.asp
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