TB Notes Newsletter

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No. 2, 2009

Highlights From State and Local Programs

Diabetes and TB

The following article originally appeared in the spring 2009 edition of the Curry National TB Center (CNTC) newsletter and is reprinted here with the author’s permission.

Recent research sheds new light on the impact of diabetes on TB, as well as how TB treatment can affect diabetes control. Gisela Schecter, MD, MPH, a CNTC Warmline consultant and MDR TB consultant with the California TB Control Branch, has shared a summary of recent studies that increase our understanding of the complexities of co-managing TB and diabetes. A few highlights of her review are as follows:

• Patients with diabetes have increased risk of progression to active TB. A Harvard meta-analysis (Jeon and Murray, 2008) looked at 13 observational studies that included over 1.7 million participants and found that the relative risk (of active TB) was 3-fold higher among those with diabetes.


• In presentation and diagnosis of TB among diabetics, there is an increased likelihood of lung lesions confined to the lower lobes. In one study (Alisjahbana et al., 2007), this difference ranged from 2.4% without diabetes to 23.5% with diabetes. Diagnosis may be delayed because the radiologist and treating physician may not "think TB" without upper-lobe abnormalities present.


• Response to treatment: The old dogma used to be that despite the increased risk of latent TB Infection (LTBI) progressing to active TB among diabetics, these patients did just as well on treatment. A Texas study (Restrepo et al., 2008) found that on average, diabetics achieved sputum culture conversion 5 days later than non-diabetics. A study in Taiwan (Wang et al., 2008) showed significantly higher mortality among diabetics. Of note, about one third of their TB patients had diabetes.
  


• Effect of TB treatment on diabetes: It is widely known that rifampin affects the levels of antiretroviral therapy used to treat HIV, through its effect on the CyP450 enzyme system. Both sulfonorylureas (such as glipizide) and thiozolidinediones (such as Avandia or Actos) are metabolized by this same system, so blood levels of these drugs may be lower when rifampin is being used, and therefore diabetes control may suffer. Careful monitoring is required.


• Diabetics also have a higher incidence of peripheral neuropathy while taking isoniazid (INH) for active TB or LTBI. To protect against this complication, routinely give vitamin B6 at a daily dose of 25 to 50 mg to diabetics whenever INH is prescribed.

—Reported by Gisela Schecter, MD, MPH
Physician Liaison, TB Control Branch
California Department of Public Health

Smoking as a Risk Factor for Tuberculosis

Note: Lynelle Phillips, a former CDC Public Health Advisor, teaches at the University of Missouri Sinclair School of Nursing. One of her students (pictured here) wrote his final paper for community health on smoking and TB.  The idea for this paper occurred to him while he was involved in a TB investigation in a Kansas City homeless shelter, where he observed many smokers. The assignment required the paper to be persuasive, thus the author takes a somewhat editorial tone. We reprint it here, with his permission, as an interesting and thoughtful opinion piece.

Although the incidence and prevalence of tuberculosis (TB) are much lower in America than in other areas of the world, globally the mycobacterium is still alive and kicking, and the U.S. may experience another resurgence of TB if diligent care is not taken by doctors, nurses, and public health workers. Of course, credit must be given for the achievements that have been made in recent years, but the low rates we enjoy in the United States do not exclude Americans from susceptibility.  This is why the U.S. strategy for battling the disease must be monitored and updated continuously in accordance with new findings from the research realm.

Smoking tobacco has been suspected to be a contributing risk factor for TB for decades, and some recent research seems to substantiate this claim. It is hoped that smoking will be added to the official list of risk factors for TB. The list of risk factors for TB was established for the purpose of education and prevention.  These goals can be enhanced by the addition of smoking to the list.  Smoking tobacco products leads to higher rates of TB transmission and disease, and such should be known by a greater audience (Bates et al, 2007).

Current Risk Factors
There are a number of risk factors that lead to increased TB morbidity and mortality.  Some of the most significant include recent TB infection, crowded living conditions, as well as a diagnosis of HIV or another condition that suppresses the immune system (CDC, 2000).  These carry some of the highest relative risks, but other risk factors can contribute to one’s risk as well, such as low socioeconomic status, poor nutrition, injection drug use, alcohol consumption, and living or working in high-risk settings (CDC, 2000; Bates et al, 2007; Altet-Gomez et al., 2005).

These risk factors give us a great deal of information about the disease.  They allow us to see TB’s main avenues of transmission and prevalence. This ultimately leads to increased awareness, which is hopefully followed by enhanced prevention measures taken against the disease. This is especially important, considering that TB is one of the more tenacious infectious diseases, one that requires long treatment regimens, patience, and perseverance among those being treated. CDC recommends that preventive measures be given a high priority in combating the disease. The currently recognized risk factors play a huge part in this preventive role. It is my belief that CDC could further enhance the list of risk factors by adding smoking to it.

Evidence Supporting Smoking as a TB Risk Factor
There are several reasons for smoking to be on the list of TB risk factors.  The connection between the two seems obvious: one pulmonary insult must certainly compound another. Smoking’s harmful effects on immunity have been long known (Arcavi & Benowitz, 2004).  Decreased ciliary function and immunity can lead to increased risk for acquiring other respiratory infections, such as pneumococcal pneumonia, Legionnaire’s disease, and influenza (Arcavi & Benowitz, 2004; Bothamley, 2005).

Recent research demonstrates a direct connection between smoking and TB.  According to Bates et al. (2007), smoking increases one’s risk of latent TB infection by nearly two times, as well as increasing one’s risk of developing active TB by around two and a half times. The basis of these findings was a large-scale meta-analysis, in which studies from 14 different countries were assessed, ranging from first-world to third-world settings.  Confounding variables were scrupulously assessed.  Other research has produced similar results, with smokers having the relative risk of around twice that of nonsmokers for acquiring TB (Arcavi & Benowitz, 2004; Bothamley, 2005; Hussain, Akhtar, & Nannan, 2003).  Smoking has also been found to lead to increased severity of the disease, longer hospital stays, and decreased survival rates (Altet-Gomez et al., 2005; Wang et al., 2007).  While some extraneous variables may play into this research, the striking similarity among findings should be more than convincing regarding the relationship between smoking and TB.

Assessing other factors that play into the relationship is important in making sound decisions about causation and correlation.  However, this particular relationship seems to hold regardless of age, gender, or smoking amount and duration (Arcavi & Benowitz, 2004; Bates et al., 2007).  Second-hand exposure to tobacco smoke has also been found to lead to increased risk for TB (Chiang, Slama, & Enarson, 2007; Lin, Ezzati, & Murray, 2007). Although lower socioeconomic groups are generally more susceptible to TB through a combination of multiple risk factors (Lin, Ezzati, & Murray, 2007), the risk spans all socioeconomic groups.

Global Impacts and Solutions
Governmental and societal perceptions of tobacco use are in need of overhaul if we are to beat TB disease.  According to Slama (2004), “Tobacco is the world’s biggest preventable killer.” The problem is huge, and is possibly perceived as too big to tackle by many.  In the 1940s and 1950s, smoking was “hip”; it was also profitable and created jobs (Slama, 2004).  Prevalence rates in the 1950s were as high as 70% in North American and Western European men (Slama, 2004).  The seed was sewn, and the tree of death and disease began to grow.  Sadly, it continues to grow, despite knowledge that smoking causes multiple forms of cancer, cardiovascular diseases, negative reproductive effects, and of course respiratory diseases such as TB, among other things (Slama, 2004).

Prevalence rates may decline in some populations, but in general, the trend is still growing, taking into consideration the higher rates of smoking among lower socioeconomic groups (Slama, 2004).  This is truly frightening, as those most susceptible to TB infection and disease are those who are smoking more and more. Where is the intervention?  How can the government step in?  Aid programs to the poor generally do not include education on the ill effects of smoking (Slama, 2004).  Massive international cooperation, legislation, and a push towards abstinence from smoking is a must. This can be accomplished by increasing awareness and education efforts, and by making smoking cessation tools more available (Slama, 2004).  The governmental advocacy of smoking cessation has not kept up with the spread of the pandemic; this will inevitably lead to increased rates of TB, and deaths associated with its spread.

One suggestion is to put a certain amount of pressure or expectation on health care providers to take the lead on this issue. Physicians and nurses are at the forefront of patient care, and need better direction and stronger conviction in promoting abstinence from smoking.  This drive should occur in every patient contact with smokers. American health authorities can contribute to this cause through unanimous agreement that smoking is truly a risk factor for TB. Many countries look to American medicine as a leader, since U.S. technology and research have led to better health outcomes historically.  Taking the step of actively pushing the anti-smoking campaign could help in the battle against TB and would improve world health in general. 

Conclusion
The supporting evidence shows that smoking increases one’s risk for TB.  The implications of this increased risk are significant, since there are currently over one billion smokers in the world today, and around two million deaths attributable to TB every year (Lin, Ezzati, & Murray, 2007).  Given TB’s tenacity and length of treatment, and the lack of an effective vaccine against the disease for adults, prevention methods must be optimized as the first line of defense.  Part of this optimization should involve the addition of smoking tobacco as a risk factor for TB.  Taking this measure could mean increased awareness among both health care providers and the general public, hopefully leading to decreased morbidity and mortality from TB disease.

—Written by Nicholas Robert
Univ. of Missouri Sinclair School of Nursing
Submitted to Lynelle Phillips
Former CDC Public Health Advisor

References

Altet-Gomez M et al. Clinical and epidemiological aspects of smoking and tuberculosis: a study of 13,038 cases. International Journal of Tuberculosis and Lung Disease 2005; 9(4): 430-436.

Arcavi L and Benowitz N. Cigarette smoking and infection. Archives of Internal Medicine 2004; 164: 2206-2216.

Bates M et al. Risk of tuberculosis from exposure to tobacco smoke: a systematic review and meta-analysis. Archives of Internal Medicine 2007; 167: 335-342.

Bothamley G. Smoking and tuberculosis: a chance or causal association? Thorax 2005; 60: 527-528.

Chiang C, Slama K, and Enarson D. Associations between tobacco and tuberculosis. International Journal of Tuberculosis and Lung Disease 2007; 11(3):258-262.

CDC. Targeted Testing and the Diagnosis of Latent Tuberculosis Infection and Tuberculosis Disease. Self Study Modules on Tuberculosis No. 3. Atlanta, Ga; 2008: 6-7.

CDC. CDC’s Response to Ending Neglect: The Elimination of Tuberculosis in the United States. 2002. Retrieved from http://www.cdc.gov/tb/pubs/iom/iomresponse/default.htm on Nov. 8, 2008.

CDC. Targeted tuberculin testing and treatment of latent tuberculosis infection. Morbidity and Mortality Weekly Report 2000; 49: 16-17.

Den Boon S et al. Association between smoking and tuberculosis infection: a population survey in a high tuberculosis incidence area. Thorax 2005; 60: 555-557.

Hussain H, Akhtar S, and Nanan D. Prevalence of and risk factors associated with Mycobacterium tuberculosis infection in prisoners, North West Frontier Province, Pakistan. International Journal of Epidemiology 2003; 32: 794-799.

Lin H, Ezzati M, and Murray M. Tobacco smoke, indoor pollution, and tuberculosis: a systematic review and meta-analysis. PLoS Med 2007; 4(1): 173-189.

Slama K. Current challenges in tobacco control. International Journal of Tuberculosis and Lung Disease 2004; 8(10): 1160-1172.

Wang J et al. The effect of smoking on tuberculosis: different patterns and poorer outcomes. International Journal of Tuberculosis and Lung Disease 2007; 11(2): 143-149.