http://www.nccn.net/~wwithin/TBtest.doc
(nice formatted Word Doc)

The Rationale for TB Screening of Healthcare Workers (HCWs) and Other Low-risk Populations:

A Critical Review of CDC Policy
or
The Emperor Has No Clothes, Cough or Fever

Summary:
1) Healthcare workers(HCWs) are identified by the CDC as a high risk group
for development of TB; however, no current clinical data exists that
supports that contention. The overwhelming majority of TB, as with most
infectious diseases, occur in individuals with compromised immune systems.

2) Targeted TB testing in HCWs is only recommended by the CDC; however,
local facilities have often initiated mandatory testing policies amongst
employees, subject to employment termination for refusal.

3) According to the CDC, initiation of chemoprophylaxis in the TB positive
HCW is not mandatory in circumstances of negative health exam, negative
chest radiograph and absence of additional risk factors. The overwhelming
majority of HCWs who test positive have normal clinical exams and radiographs.

4) Current randomized studies of chemoprophylaxis in the TB skin test
positive, healthy HCWs do not exist. Some randomized studies in AIDS
patients show TB disease occurs with higher incidence in those receiving
therapy for latent TB compared with those receiving no therapy.

5) One analysis showed no benefit to treatment of LTBI in all non disease
states despite risk factors. Risks associated with chemoprophylaxis for TB
may outweigh potential benefits.

6) TB skin test is inaccurate but yet is considered the gold standard to
diagnose infection. Because there is no better method to diagnose
infection, its actual test accuracy is unknown.

7) Phenol, a component of Tubersol, is a highly toxic industrial chemical
with numerous known health risks yet this is a component of Tubersol.

8) The CDC claims that the TB skin test is safe, yet the manufacturer
states that NO known carcinogenicity studies have been performed. In fact,
phenol, when injected intradermally, is associated with skin cancer
development in test animals.

9) The CDC states that TB skin testing is safe in pregnant women yet
manufacturers have NOT performed mutagenicity testing. This is alarming in
consideration that phenol, a component of Tubersol, is a known mutagen.


Summary: TB skin testing should not be required of otherwise healthy HCWs
unless safety and efficacy studies have proven a benefit in this low risk
population. The FDA should halt the use of Tubersol pending the standard
and usual safety testing has been performed, including carcinogenicity and
mutagenicity testing.


INTRODUCTION
The following document is a review of current TB screening policies for
HCWs. This includes an analysis of two published documents. First, "The
Core Curriculum on Tuberculosis" (4th edition, 2000), published by the U.S.
Department of Health and Human Services and The Centers for Disease
Control. The second, a joint statement published in the MMWR, June 2000,
represents the works of the American Thoracic Society and the CDC.

After anti-TB medications became available in the 1940's, a gradual decline
of the number of TB cases were reported from 1953 until about the mid
1980's when there was a 20% increase from 1985 through 1992 (1, p. 16).
According to the CDC, the major factors for this rise were 1) a
deterioration of TB public health infrastructure, 2) HIV/AIDS epidemic, 3)
immigration and 4) transmissions in congregate settings. (It would seem
most logical that, since HIV increases the risk of TB by as much as
100-fold, and AIDS was an entirely new disease entity coinciding with this
period of TB resurgence, that HIV would be the most likely contributing
factor for rising cases of TB.) The CDC  claims that the deterioration of
the TB public health infrastructure was a major factor for TB resurgence,
yet, the CDC publication offers no supportive evidence of this conclusion.
If this were true, there would be an increase in the incidence of TB
amongst healthy HCWs. Data to this effect is absent. In fact, I have not
discovered any published data that proves the hypothesis that the neglect
in screening programs resulted in more cases of TB during this era.

It is interesting to note that the incidence of TB in the US has declined
steadily since the 1900's. This decline was noted in spite of the fact that
pharmaceutical therapies were unavailable for nearly five decades. How did
the incidence of TB decline in the absence of TB screening programs and
chemoprophylaxis? The CDC's contention that the small TB spike occurring in
the late 1980's was the result of deteriorating TB control infrastructure
seems very questionable.

The unrealistic goals of the CDC
In 1989, the CDC announced the goal of eliminating tuberculosis from the US
by 2010. Plans and task forces were then established to accomplish this
goal. To apparently help achieve this goal, the CDC now concludes that
healthcare workers are part of a "targeted" population of individuals who
are at high risk for developing the infection  (TB skin tested positive)
and developing subsequent clinical disease of tuberculosis. Institutional
TB skin testing is recommended for the staff of healthcare facilities (1,
p. 25;90-91).

Elimination of TB is unachievable and unrealistic. First, our government's
open door immigration policy allows countless high risk individuals into
the US undetected on a daily basis. How can those individuals be screened
when our government refuses to identify illegal aliens and allows them
access to the healthcare system? Secondly, since the majority of TB occurs
in the immune compromised host, how will the disease be irradicated unless
the coexisting conditions are eliminated. AIDS, cancer and chemotherapy
populations grow each year. Thirdly, false negative skin testing alone will
bypass significant numbers of infected individuals (even one case missed in
screening is significant when the goals are 100% eradication and the CDC
claims a 23% transmission rate!) .



CURRENT POLICIES

Risk analysis for TB and the rationale to screen HCWs
There are an alleged 10-15 million infected (skin test positive) persons in
the US (1, p20:no source given).  Of these, if not detected and no
preventative treatment is initiated, the CDC states that 10% will develop
TB at some point, 5% within the first 1-2 years, in spite of normal immune
system (1, page 7; (2) page 8). The  primary source of this data is not
referenced in the CDC publications. Accurate natural historical data is
critically important in order to support screening of asymptomatic HCWs. A
study recently published in JAMA (3) challenges the CDC report and showed
that of the estimated worldwide TB infection (TB test positive) rate of
32%, only 7.96 million cases of disease were reported in 1997, or a TB
disease incidence of less than  0.2% amongst infected individuals (assuming
a 6 billion world population). This is far less than the 5-10% rates quoted
in the CDC publications and are consistent with the general concept that TB
is a disease of opportunity, generally harmless to the immune competent
host. This data alone should challenge the wisdom in screening otherwise
healthy populations.

In addition, the CDC quotes a transmission rate of 21-23% (ref 1, page 6):
this seems alarmingly high (referenced from "CDC Program Management
Report"-unavailable). This implies that 21-23% of all contacts with a TB
patient will develop the infection or disease! Demographic data simply does
not support this alarmingly high rate.

Summary of CDC's High Risk Groups for Developing TB (modified from 1, p 8)


HIV/AIDS
Silicosis
Substance abuse
Hematological and reticuloendothelial disease 
Chronic malabsorption and malnutrition
Diabetes Mellitus
Prolonged steroid therapy
Solid organ transplantation
Cancer of head and neck
Chronic renal failure
Low body weight
Healthcare workers









Table 3 in Ref 2 (p 9) assigns relative risk values for many of these
groups; however, missing in this table are relative risk data of HCWs with
healthy immune systems! 


DISEASE Relative Risk
Silicosis  30
Diabetes mellitus 2-4.1
Chronic renal failure/hemodialysis 10-25.3
Gastrectomy 2-5
Jejunoileal bypass 27-63
Solid organ transplant
 renal 37
 cardiac 20-74
Carcinoma of head or neck 16



The HCWs receiving mandatory yearly testing should be informed of his
relative risk to develop TB disease. With the sole exception of the HCWs,
all individuals designated  in the CDC publications as high risk are those
with abnormal systemic or pulmonary immune defenses. But is this proven? Is
it possible that, as with many other diseases, the integrity of the host
immune response system is of far greater importance than the presence of
mere exposure to microorganisms?  In fact, if HCWs were not at higher risk
than the general population, unless they had additional medical risk
factors, screening of HCWs would be no more valid than screening 100% of
the population.

Although historical studies showed higher infection and disease rates in
HCWs in an era when the prevalence of TB was higher, modern era data
suggests this is no longer the case. McKenna, et al (4) concluded that the
"overall case rate of tuberculosis in healthcare workers was slightly lower
than the natural rate....most healthcare workers do not appear to have a
risk of clinically active tuberculosis greater than the general
population".  This conclusion has been confirmed in other recent studies (5).


TESTING AND THERAPY

The TB skin test
Tubersol, manufactured  by Aventis, is comprised of a purified protein
derivative of the organism M. tuberculosis. Its efficacy as a screening
test is derived from the delayed hypersensitivity response in the infected
host after intradermal injection. The exact number of doses sold in the US
annually is apparently a guarded secret (personal communication, Aventis
Pasteur, Sept 12, 2003).

False negatives are thought to occur frequently. Listed causes (6) include
anergy, recency of exposure, viral infections, various vaccinations,
overwhelming infection, various drugs(steroids) and malignancies and any
condition that can impair the cell mediated immune response (sarcoid,
malnutrition) . False positives include nontuberculous infections and BCG
vaccine state. In spite of these inaccuracies, the CDC states that for
persons with latent TB infection who have a normal immune system, test
sensitivity approaches 100% ( 2, p 11). This statement is ridiculous for
several reasons. First, the TB skin test is the gold standard, so it is not
possible to accurately gauge the incidence of false negative exams. The
sensitivity of this test , in actuality, remains unknown. Secondly, false
negative exams occur in the groups who are at the very highest risk for
disease in the first place, meaning that the false negative tests weigh
heavily against the efficacy of screening in the most important risk
groups-the one's most likely to develop disease in the first place!

Compounding the inaccuracies of the TB skin test is the revelation that
only one in three positive reactions are correctly classified as positive
by screen test interpreters (7).

Serious untoward reactions to the Tuberculin substance have been reported.
Adverse reactions include local skin reactions (vesicles, ulcers, necrosis,
scarring), rashes, and  anaphylaxis.

Shockingly, in spite of its widespread use, the manufacturer's insert 6)
states that Tubersol has not been evaluated for its carcinogenic or
mutagenic potentials or influence on fertility. This is surprising
considering the widespread use and frequent repetition intervals of
administration, particularly to the long term HCWs employee. It is also
irresponsible for the CDC to  state that tuberculin is safe and reliable
throughout the course of pregnancy (1, p. 29). This is in direct opposition
with the manufacturers statement that Tubersol is NOT tested for
mutagenicity. It is a fact that a declaration of safety without testing is
a declaration of assumed safety, not a proven scientific fact.

What can we gather from the toxicology of its components? Tubersol contains
0.28% phenol(5), which is known to be highly toxic to humans (8). The 1969
American Heritage Dictionary defines phenol as a "caustic, poisonous,
white, crystalline compound...derived from benzene and used in various
resins, plastics, disinfectants, and pharmaceuticals. Phenol is also known
as 'carbolic acid.'" Amongst the known adverse reactions to phenol are:

-irritating to skin, eyes, mucous membranes in humans
-ingestion in humans may cause death, paralysis, weakness, seizures, coma,
respiratory collapse
-animal testing has shown severe toxicity
-limited data available on the chronic effects in humans, but in humans has
caused dermal inflammation and necrosis, arrhythmia's, hepatic enlargement
and dysfunction.
-animal studies have shown chronic exposure effects the CNS, respiratory,
renal and cardiovascular systems
-no human development and reproduction studies have been performed BUT...
-animal studies have shown reduced weight, growth retardation, abnormal
development, increased maternal mortality and decreased maternal weight gain.
-no studies have been done in humans with regards to carcinogenicity BUT...
- animal studies show phenol applied to skin is a skin carcinogen in mice!

These findings should be embarrassing to the FDA and shocking to recipients
of the TB skin test. The CDC has no supportive data to state unequivocally
that this test  agent "is both safe and reliable throughout the course of
pregnancy" (1, p 29) when animal studies exist to the contrary and
demonstrate that one of its constituents is a skin carcinogen! How did the
FDA approve this agent for use in the tuberculin skin test? Without
testing, no conclusions can be made as to the safety of Tubersol,
regardless of what comments critics might offer such as, for example,
"....but it is such a small dose". Has Aventis proven that Tubersol is
safe? The FDA, CDC and Aventis simply cannot answer that question with
available scientific data.


The myth of screening and prophylactic therapy for the skin test positive
HCWs- is there any proof of benefit?

With regards HCWs, a 1992 survey of 210 hospitals in the U.S. calculates
the tuberculin reactivity rate of only 0.64% (9). This rate would even be
expected to be  lower today with falling prevalence of TB. Is it really
worth screening 156 health HCWs in order to discover one positive
convertor? In turn that convertor invariably will have a negative clinical
exam and radiograph.

Cost benefit analysis was studied at a time when the tuberculin agent was
$10. The costs of screening was $4,500 per person eligible for treatment
and and $350,000 per case of TB prevented (10).  The current cost of
tuberculin is $18. It is particularly disappointing that as few as 25% of
treated individuals actually are able to complete therapy.

Do local TB statistics support screening studies? Illinois Department of
Public Health Statistics (11) compiling TB disease in all counties between
1990-2001 reveals that 86% of 104 counties reported on average fewer than
two TB cases per year and 67% as few as one case annually! How can
screening healthy HCWs in those counties with such low disease prevalence
be justified? It simply cannot.

Inconsistencies within the CDC guidelines are easily found.  First, the CDC
publications do not  support blanket chemoprophylaxis for all TB skin
positive individuals with normal health exams and radiographs, yet one
wonders how the CDC could NOT suggest therapy if the CDC believes their own
statistic that 10% of these individuals really were destined to developed
disease. If a subsequent TB positive test results in a negative clinical
exam and chest radiograph and a decision NOT to treat, why not replace the
risky, inaccurate TB test with a clinical exam and an employee radiograph?
The decision to test SHOULD be a decision to treat.

Secondly, in order to justify chemoprophylaxis, outcomes studies must show
proven safety, efficacy and long term benefit. If there were no proven
benefits to the treatment group over non treated individuals, then the
screening program would be without merit. Are there studies that support
better outcomes in the treated group vs. untreated group in healthy HCWs?
This author has discovered no such literature. Other studies challenge the
supposition of beneficial chemoprophylaxis.

In Ref 2 (pg. 12), there is an allusion to seven trials in the 1950's -60's
which demonstrated reduction of TB disease in the 25-92% range with
chemoprophylaxis. Since these studies were done in the decades when TB was
significantly more prevalent, approximately 50 years ago, they are no
longer valid. Secondly, these studies almost exclusively involved non-US
participants in countries where environmental and health issues were
substantially different than in the US. This is not applicable to the
current issue of treatment outcomes in healthy US HCWs treated for LTBI.
The MMWR report  (2, p 13) also refers to the IUAT trial which indicated a
reduction of LTBI by 65-75%. Unfortunately, this trial was also performed
in non-US individuals, all of whom had abnormal chest radiographs. This is
a significantly different population than the typical US HCW who rarely
displays an abnormal radiograph (2, pg. 11, and personal experience). The
MMWR report attempts to further inflate these success statistics by quoting
a 69-93% efficacy in "compliant" participants, a statistic that has little
significance in real-life clinical outcomes. A closer look at the success
rates shows they are quoted in meaningless percentages (if i bought three
lottery tickets instead of one, does the 200% improved chance of winning
mean anything in the real world?) Where is the statistical proof (for CDC
authors, that would be the "p" values)? For the group with fibrotic lesions
< 2 cm (the group closest to the most typical HCWs), there was NO
STATISTICALLY SIGNIFICANT DIFFERENCE in placebo treatment and 12 week, 24
week and 52 week regimens. In addition, these trials were conducted from
1969-1977, over 30 years ago when TB rates were generally higher than today.

The MMWR report reviewed randomized treatment of LTBI in HIV positive
individuals in seven studies from 1980-1997, although only one was strictly
in the US (2,p  16). These results were decisively mixed, with some studies
actually demonstrating higher TB rates in groups receiving isoniazid than
nontreated groups! If benefit of prophylaxis is at best equivocal in high
risk individuals, on what basis does the CDC use to justify prophylaxis in
the healthy HCWs?

In a more recent study involving a New York area population of HIV-positive
patients with anergy, there was a no significant difference in TB rates in
those receiving anti-TB prophylaxis with INH compared with placebo (12).
Once again, if efficacy of therapy for LTBI in the highest risk group is
unproved, how can we justify prophylaxis in low risk HCWs with an intact
immune system?

In order to answer these questions more completely with regards to the low
risk HCWs, Tsetat et. al. (13)  performed a decision analysis of screening
test positive adults and concluded that "from the perspective of the
individual adult with a positive skin test for TB, we cannot make a case
for INH therapy". Furthermore these authors distinguished TB mortality
rates from individuals dying with their disease rather than because of
their disease and calculated lower TB mortality rates than earlier authors.
With this factored into the risk-benefit analysis they further concluded
that "it does not matter how high the rate of developing TB is-the
preferred strategy is always "NO INH". These authors do not recommend
therapy unless active TB disease is detected.


The FDA safety record with anti-tuberculous drugs
The 2000 MMWR report states:

"In 1965, when Isoniazid was first recommended in the United States for
treatment of LTBI , it was not thought to cause severe toxicity. However
studies in the late 1960's suggested that isoniazid did cause
hepatitis....It was not until the 1970's that when several persons
receiving isoniazid for LTBI died from hepatitis that the likelihood of
isoniazid hepatitis was understood" (2, p 15-16).

Most clinicians are now very aware of the dangers of INH therapy and the
need for careful clinical evaluation of all patients receiving therapy for
LTBI. Unfortunately, this  failure of the CDC/FDA to detect toxicity in
recommended drug therapies prior to their widespread use and acceptance was
not an isolated incidence.

The CDC manual published in 2000 (1, pg. 78) did not discuss potential
hepatotoxicity of two additional anti-TB drugs, rifampin and pyrazinamide.
In 2003, the CDC published a retraction of the recommendation of these
drugs for LTBI based on the discovery of 48 cases of severe liver injury
and 11 related deaths (14). An alarming 5% of patients who started this
therapy did not complete the regimen due to hepatic toxicity. With these
high percentages of complications it is difficult to comprehend how such
severe adverse reaction rates were not discovered in pilot studies before
the CDC issued widespread recommendations for their use in LTBI.
Understandably, the FDA's and CDC's track record in TB drug safety testing
would leave one even more concerned of their widely held opinion of the
untested but assumed safety of the phenol containing skin testing agent
Tubersol.

When recommendations become mandatory
According to the CDC, the "risk assessment should identify which HCWs have
the potential for exposure and the frequency with which the exposure may
occur. This information can then be used to determine which HCWs to include
in the skin testing program and the frequency with which they should be
tested" (1, p 91). This site or occupation-specific risk assessment of all
HCWs is a targeted testing program. It is uncertain how individual
institutions implement targeted testing. Radiology technicians currently
undergo mandatory yearly testing at Memorial Medical Center and Springfield
Clinic. It is my understanding that employment can be terminated in HCWs
refusing to be tested.

The FDA and CDC: conflicts of interest

The following was published in the Washington Free Press as the results of
an UPI investigation(15).

In the year 2000, the U.S. House of Representatives Committee on Government
Reform held hearings to examine conflicts of interest in the two official
panels that control vaccine policy in the U.S. (there is one panel at the
Centers for Disease Control and one at the FDA). Among the committee's
findings were widespread conflicts of interest among panel members in the
form of financial ties to pharmaceutical companies who manufacture vaccines
that the panels oversee. Following is a summary of the committee findings,
assembled by Dr Joseph Mercola.

    * The CDC routinely grants waivers from conflict of interest rules to
every member of its advisory committee.

    * CDC advisory committee members who are not allowed to vote on certain
recommendations due to financial conflicts of interest are allowed to
actively participate in committee deliberations and advocate specific
positions.

    * The chairman of the CDC's advisory committee until recently owned 600
shares of stock in Merck, a pharmaceutical company with an active vaccine
division.

    * Members of the CDC's advisory committee often leave key details out
of their financial disclosure statements, and are not required to provide
the missing information by CDC ethics officials.

    * Three out of the five FDA advisory committee members who voted to
approve the rotavirus vaccine in December 1997 had financial ties to the
pharmaceutical companies that were developing different versions of the
vaccine. The vaccine was recalled a few years later after numerous public
complaints of serious bowel obstruction due to the vaccine.

* Four out of the eight CDC advisory committee members who voted to approve
guidelines for the rotavirus vaccine in June 1998 had similar financial ties.

In a USA Today report of conflicts of interest on the 18 advisory
committees established by the FDA, the following was reported (16).

* 54% of the experts hired to advise the government on safety and efficacy
policies had financial relationships with the pharmaceutical companies that
would be directly affected by their opinions

* since 1988, the FDA has waived on more than 800 occasions the federal
law that would have other wise prohibited use of experts with financial
conflicts

* 92% of FDA advisory meetings had at least one member with a conflict of
interest

* 55% of FDA advisory meetings were held when at least half of the
committee members had conflicts

*  in 102 FDA advisory meetings dealing with the fate of a specific drug,
33% of the experts had a financial conflict.

The pharmaceutical industry enjoys the benefits of increased revenue when
government regulatory bodies pass favorable legislature promoting use of
its products. The influential power of this industry has been subject to
much criticism.
According to Public Citizen's report (17)

Drug industry lobbying ranks include 26 former members of Congress. All
told, 342 lobbyists (51 percent of those employed by the industry) have
"revolving door" connections between K Street and the federal government.

The Pharmaceutical Research & Manufacturers of America (PhRMA), which
represents more than 100 brand-name prescription drug companies, shelled
out $14.3 million last year, a 26 percent increase from 2001 and nearly
double what the group spent in 2000. PhRMA hired 112 lobbyists in 2002, 30
more than the year before.

Brand-name drug manufacturers spent more than 20 times as much on lobbying
as generic drug-makers - $76 million versus $3.4 million. And they employed
seven lobbyists for every one hired by their generic counterparts.
Biotechnology companies spent $12 million on lobbying.

Since Public Citizen began tracking the drug industry's lobbying activities
in 1997, the industry has spent nearly $478 million lobbying the federal
government. In that same period, the top 25 pharmaceutical companies and
trade groups gave $48.6 million to federal campaigns. Well over $100
million more went to paying for issue ads, hiring academics, funding non
profits and other activities to promote the industry's agenda in
Washington. All told, the drug industry has spent nearly $650 million on
political influence since 1997.

Drug company profits have been staggering.

*By comparison, all companies in the Fortune 500 suffered a combined loss
of 66.3 percent in profits from 2001 to 2002. The pharmaceutical industry
soared past other business sectors - raking in profits five-and-a-half
times greater than the median for all industries represented in the Fortune
500.

*17% profit (as a percent of revenue) far outpaces the 3.1% median value
for all other Fortune 500 industries.

*Profits registered by the 10 drug companies on the list were equal to more
than half the $69.6 billion in profits netted by the entire roster of
Fortune 500 companies - when all losses are subtracted from all gains.


The dollars available to the drug companies for influencing industry
agencies are staggering. There is no question that the CDC's policy of
widespread use of Tubersol for testing HCWs has widely increased the market
for their product. National advisory committees have been an essential and
necessary part of healthcare policy in this country but has been also
linked to significant conflicts of interest, as reported in JAMA (18). In a
review of of doctors involved in establishing national guidelines on
disease treatment, they found that :


85% of guideline authors have some sort of relationships with drug
companies, and they are often not disclosed

38% of respondents said they had served as employees or consultants for
drug companies; 58% received research money

59% had links with drug companies whose medications were considered in the
particular guidelines they authored, almost all cases predating the
guideline creation process


These numbers may be even greater, as only 52% of authors responded


These are disturbing revelations. Questions must be asked regarding the
establishment of national TB skin testing policies for healthy HCWs. First,
to what degree has Aventis benefited from the expansion of mandatory
testing to healthy HCWs in the United States? Secondly, did advisory
committee members who established TB skin testing policies have financial
ties with Aventis?

Conclusions

There is no clinical scientific  evidence that the healthy HCW is at higher
risk than the general population. Furthermore, even in positive TB
reactors, there is no modern scientific evidence that would support benefit
of chemoprophylaxis for LTBI in healthy HCWs. The Tubersol agent in use has
not been adequately tested for safety and its accuracy is questionable and
unproveable. The TB skin testing policy for LTBI in the typical HCW is of
doubtful efficacy and benefit and of unknown risk to the individual HCW.
Mandatory testing is unsupported. Most tragically, our government health
agencies have a tract record of errors in drug safety testing and these
same agencies have conflicts of interest that raise serious questions of
the mechanisms that healthcare policies are established.

Recommendations
Immediate suspension of mandatory TB skin testing policies of HCWs is
reasonable considering the lack of clinical efficacy of testing or
subsequent treatment of LTBI. A review of current local and state public
health records could be undertaken to determine a) the incidence of TB skin
test reactivity amongst HCWs, b) the true risk of TB disease in the skin
reactive HCWs who fails to receive prophylaxis for LTBI and c) the outcome
analysis of the HCWs placed on preventative drug therapy and finally d) the
review or performance of pertinent toxicology studies on Tubersol that
establishes this agent as  safe.

References

1) Core Curriculum on Tuberculosis. What Every Clinician Should Know.
U.S. Department of Health and Human Services, Centers for Disease Control
and Prevention, Fourth Ed. 2000

2) Targeted tuberculin testing and treatment of latent TB infection. MMWR;
49, June 9, 2000

3)JAMA 1999;282:677-686

4) McKenna, MT, et. al., The association between occupation and
tuberculosis. A population-based study. Am. J. Resp. Crit Care Med.154:
587-93, 1996.

5) Kwan, SYL, et. al., Nosocomial tuberculosis in hospital staff in a Hong
Kong chest hospital. Chinese Med J. 103, 909-914, 1990.

6) Tubersol PDR, 2003

7) Underreading of the tuberculin skin test reaction. Kendig, et.al.,
Chest,113,1175,1998

8) http://www.lakes-environmental.com/toxic/PHENOL.HTML

9) Fridkin, SK, et. al., SHEA-CDC Tuberculosis survey, Part 1. Status of
tuberculosis infection control programs at member hospitals. Infect.
Control Hosp Epidemiol. 16: 129-134, 1992

10) Raad, I. et. al., Annual tuberculin skin testing of employees at a
university hospital: a cost-benefit analysis. Inf. Control Hosp Epidemiol;
10, 465-9, 1989.

11) http://www.idph.state.il.us/health/infect/tb90-01.htm

12) F. Gordin, et. al., NEJM; 337(5), 315-320, 1997.

13) Tsevat, J, et. al., Isoniazid for the tuberculin reactor: take it or
leave it. Am Rev. Respir. Dis., 137: 215-220, 1988.  

14) Update: Adverse event data and revised American Thoracic Society/CDC
recommendations against the use of rifampin and pyrazinamide for treatment
of latent tuberculosis infection---United States, 2003. MMWR; 52(31),
735-39, 2003.

15) http://www.washingtonfreepress.org/61/conflictsOfInterest.htm

16) http://www.mercola.com/2000/oct1/fda_drug_approvals.htm

17) http://www.citizen.org/pressroom/release.cfm?ID=1469-profit margins by
drung companies

18) N.K. Choudhry, et. al. Relationships between authors of clinical
practice guidelines and the pharmaceutical industry JAMA; 287,612-617, 2002.