Side-effects of Anti-TB Chemotherapy with Isoniazid, Rifampin and Pyrazinamide with Conservative Projections of Increased Illness Among School Children Forced to Receive Skin-tests by Officials of Hawaii's "Tuberculosis Control Program"

Tuberculosis skin testing of low risk school children typically results in between 30 to 50 percent false positives. False positive test persons are highly encouraged, and often coerced by health officials and "social service" agents to endure 6 to 9 months of toxic antibiotic/chemotherapeutic poisoning. Below is a highly conservative statistical analysis and projection of students (K-12) made severely ill by this medical malpractice. This analysis is based on scientific abstracts that show the risk of this "public health" Big Pharma ruse is downright criminal, especially considering the fact that active TB cases are generally easy to diagnose during routine medical examinations, and non-active TB (Latent Tuberculosis Infection, LTBI) cases never pose a threat to anyone until these carriers become seriously immune compromised. The bottom line is worse than frightening. An estimated 3,382 students became severely ill, many suffering chronic debilitating diseases, so that Hawaii's Tuberculosis Control Program could identify merely 6 active TB cases among students in 2005. (See the NIAID article below that follows Dr. Horowitz's disturbing analysis for more details.)





Original Articles

Risk factors for side-effects of isoniazid, rifampin and pyrazinamide in patients hospitalized for pulmonary tuberculosis

T Schaberg, K Rebhan, and H Lode

The aim of this study was to determine the current incidence of side-effects severe enough to cause intolerance of standard antituberculosis therapy with isoniazid, rifampin and pyrazinamide in patients hospitalized as a result of pulmonary tuberculosis. Five hundred and nineteen patients with proven pulmonary tuberculosis, who initially received standard antituberculosis therapy, were retrospectively studied in the department of infectious diseases in a teaching chest hospital. The incidence of severe side-effects related to the therapy, which led to the definitive termination of one of the three standard drugs, was measured and the risk factors for intolerance were analysed. Final termination of either isoniazid, rifampin or pyrazinamide because of severe side-effects was necessary in 121 of the 519 patients (23%). The most severe side-effects leading to final termination of one drug were hepatotoxicity (11%), exanthema (6%), and arthralgia (2%). Pyrazinamide showed more severe side-effects (15%) than isoniazid (7%) and rifampin (1.5%). Significant risk factors for intolerance of the standard therapy following a multivariate analysis were a history of hepatitis (odds ratio (OR) 3.4; 95% confidence interval (95% CI) 1.6-7.6; p = 0.0026) and an age > or = 60 yrs (OR 1.9; 95% CI 1.2-3.2; p = 0.017). Both of these risk factors were also significantly associated with the intolerance of pyrazinamide (history of hepatitis: OR 2.5; 95% CI 1.4-4.3; p = 0.0045; age > or = 60 yrs: OR 2.1, 95% CI 1.3-3.5; p = 0.0029) but not of isoniazid and rifampin. The side-effects of standard antituberculosis therapy are frequent in hospitalized patients aged > or = 60 yrs or with a history of previous hepatitis, and are probably due to pyrazinamide rather than to isoniazid or rifampin.

Source: aEur Respir J 1996; 9: 2026-2030
Copyright © ERS Journals Ltd 1996

Original Article

American Journal of Respiratory and Critical Care Medicine Vol 167. pp. 1472-1477, (2003)
© 2003 American Thoracic Society

Incidence of Serious Side Effects from First-Line Antituberculosis Drugs among Patients Treated for Active Tuberculosis

Daphne Yee, Chantal Valiquette, Marthe Pelletier, Isabelle Parisien, Isabelle Rocher and Dick Menzies

Respiratory Epidemiology Unit, McGill University; and Montreal Chest Institute, Montreal, Quebec, Canada

Correspondence and requests for reprints should be addressed to Dick Menzies, M.D., M.Sc., Respiratory Epidemiology Unit, Montreal Chest Institute, 1110 Pine Avenue West, Room 103, Montreal, PQ, H3A 1A3 Canada. E-mail: Dick.Menzies@mcgill.ca

Major adverse reactions to antituberculosis drugs can cause significant morbidity, and compromise treatment regimens for tuberculosis (TB). Among patients treated for active TB we estimated the incidence, and risk factors, of major side effects from first-line anti-TB drugs. Side effects, resulting in modification or discontinuation of therapy, or hospitalization, were attributed on the basis of resolution after withdrawal, and/or recurrence with rechallenge. Among 430 patients treated between 1990 and 1999, the incidence of all major adverse effects was 1.48 per 100 person-months of exposure (95% confidence interval [95% CI], 1.31 to 1.61) for pyrazinamide, compared with 0.49 (95% CI, 0.42 to 0.55) for isoniazid, 0.43 (95% CI, 0.37 to 0.49) for rifampin, and 0.07 (95% CI, 0.04 to 0.10) for ethambutol. Occurrence of any major side effect was associated with female sex (adjusted hazard ratio, 2.5; 95% CI, 1.3 to 4.7), age over 60 years (adjusted hazard ratio, 2.9; 95% CI, 1.3 to 6.3), birthplace in Asia (adjusted hazard ratio, 2.5; 95% CI, 1.3 to 5.0), and human immunodeficiency virus–positive status (adjusted hazard ratio, 3.8; 95% CI, 1.05 to 13.4). Pyrazinamide-associated adverse events were associated with age over 60 years (adjusted hazard ratio, 2.6; 95% CI, 1.01 to 6.6) and birthplace in Asia (adjusted hazard ratio, 3.4; 95% CI, 1.4 to 8.3), whereas rifampin-associated adverse events were associated with age over 60 years (adjusted hazard ratio, 3.9; 95% CI, 1.02 to 14.9) and human immunodeficiency virus–positive status (adjusted hazard ratio, 8.0; 95% CI, 1.5 to 43). The incidence of pyrazinamide-induced hepatotoxicity and rash during treatment for active TB was substantially higher than with the other first-line anti-TB drugs, and higher than previously recognized.


Original Articles

TUBERCULOSIS

Adverse events and treatment interruption in tuberculosis patients with and without HIV co-infection

R A M Breen1, R F Miller2, T Gorsuch3, C J Smith2, A Schwenk3, W Holmes1, J Ballinger1, L Swaden1, M A Johnson1, I Cropley1 and M C I Lipman1

1 Department of HIV Medicine, Royal Free Hospital, London, UK
2 Department of Primary Care and Population Sciences, Royal Free and University College Medical School, London, UK
3 Department of HIV Medicine, North Middlesex Hospital, London, UK

Correspondence to:
Dr R A M Breen
Department of Thoracic and HIV Medicine, Royal Free Hospital, London NW3 2QG, UK; r.breen@medsch.ucl.ac.uk

Background: Serious treatment associated adverse events are thought to occur more frequently in individuals with tuberculosis (TB) who are co-infected with HIV. A study was undertaken to assess the frequency of serious (grade III/IV) adverse events and interruption of anti-TB treatment in the era of effective antiretroviral therapy.

Methods: The incidence of serious adverse events was retrospectively compared in 312 individuals treated for TB, 156 of whom were co-infected with HIV.

Results: 111 HIV infected individuals (71%) received highly active antiretroviral therapy at the same time as anti-TB treatment. Serious adverse events were recorded in 40% HIV infected and 26% HIV uninfected individuals (p = 0.008). Peripheral neuropathy and persistent vomiting were more common in co-infected patients (p<0.001; p = 0.006), although all cause interruption of anti-TB treatment occurred with similar frequency in the two groups (13% in HIV infected patients and 15% in HIV uninfected patients; p = 0.74). In 85% of HIV infected patients and 87% of HIV uninfected individuals this was due to hepatotoxicity, which typically presented within 2 months of starting treatment. The median delay in restarting treatment was 4 weeks, so most individuals required full TB re-treatment.

Conclusion: Despite a greater rate of serious (grade III/IV) adverse events among HIV infected individuals, discontinuation of anti-TB treatment occurred with a similar frequency in HIV infected and HIV uninfected individuals.

 

Dr. Horowitz's Conservative Analysis

From the above review of simply three scientific peer-reviewed article abstracts one can gain a great appreciation for the risk of toxic side effects from long-term (> 6 months) of chemotherapy with the aforementioned drugs. Sadly, despite these data, Big Pharma (the drug and medical industry controller) has persuaded physicians and public health professionals to prescribe these liver, nerve, and blood poisoning cocktails, even though the National Institute for Allergies and Infectious Diseases (NIAID) correctly states in a related article below that "People with TB who have been treated with the correct drugs for at least 2 weeks, . . . are no longer contagious and do not spread the bacteria to others."

So what are we looking at here in Hawaii, wherein the Tuberculosis Control Program autocrats require all students young and old, high risk or not, in public and private schools to take the TB skin test that results in at least 25% of these physical and emotional abuse victims testing falsely positive. Here is a simple and conservative analysis based on the reported data:

Approximate Number of Public School Students in Hawaii: 179,234

Approximate Number of Private School Students in Hawaii: 30,000

Total (K-12) Enrollments in Hawaii: 209,000

Approx. Number of False Positive TB tests in 2005 (Highly conservative 10%): 20,000

Approx. Severe Morbidity Cases Among These 20,000 (Highly conservative 10%): 2,000

Total TB Cases (All Ages) Identified in Hawaii in 2005: 112

Total TB Cases in Hawaii Identified in Students in 2005:

6

Is this worth the risk?

According to the Tuberculosis Control Program's epidemiological website, authorities make a big deal of this abysmally low case idenfitication rate among Hawaii's students. They claim this is a great victory for national health. Read this for yourself by clicking here. They state, "the largest group of new TB cases reported in 2005 in Hawai`i were 65 years and older; 37.5% (n=42) were in this age group. There were six new cases of TB under 18 years of age: one under 5 years of age, two from 5-14 years, and three from 15-17 years."

So all of this massive TB skin testing effort annually accounts for a relatively miniscule and arbitrary benefit compared to the number of students risked and actually harmed by this public health malpractice. Here's why . . .

The Honolulu Star Bulletin, March 24, 2006 reported that in 2005, the Department of Health alone conducted "more than 50,000 tuberculin skin tests statewide. Of those, 17.8 percent were positive," said Dr. Jesse Wing, a CDC official directing Hawaii's Tuberculosis Control Program. "Most had latent TB infection and were offered nine months of antibiotics to prevent active development of the disease," the newspaper reported.

17.8% of 50,000 = 8,900 were encouraged to drug themselves for nine months! Assuming half were dumb enough to comply, that would mean approximately 4, 450 students were severely poisoned in 2005 alone.

But that was simply the work of the Department of Health. Private clinics throughout the state likely conducted an even greater number of TB skin tests with far more falsely positive results. So we must conservatively add another 8,900 students persuaded to poison themselves last year, totaling approximately 17,800 students throughout Hawaii taking the aforementioned drugs.

Thus, using the data provided by Schaberg, et al., nine months of poisoning these Hawaiian students would be expected to yield severe hepatotoxicity (liver injury) in at least 11%, or 1,958 students, exanthema, (that is a horrible skin rash with eruptions occurring as a symptom of immunological suppression followed by acute viral or coccal infections causing diseases similar to scarlet fever or measles in 6%, that is another 1,068 students, and arthralgia, severe joint pain and stiffness in 2%, or another 356 students.

This does not account for probably equal numbers of students suffering other common side effects of these drugs including nerve damage, psychological and emotional problems, and blood diseases including one simulating hemophilia.

Nor does this account for the thousands of other non-student test recipients in various fields from food service to hair stylists who tested falsely positive and likewise sustained severe injury.

ANALYSIS RESULTS:

A Highly Conservative Estimate of Approximate Number of Hawaiian Students Severely Sickened in 2005 by Dr. Jesse Wing and Her "TB Control Program" Cohorts to Identify 112 Active TB Cases Throughout the State, with the Vast Majority of These Occurring in the Elderly and Immune Compromised--Cases that Would Have Likely Been Identified Anyway During Routine Doctors' Visits or Hospital Care--with ONLY 6 CASES FOUND AMONG STUDENTS. . . .

So Here is Your Risk to Benetif Ratio for Testing Hawaii's Low Risk Students:

6 cases identified/

3,382 students severely harmed

There you have it. . . . 3,382. . . and people call our society civilized, our knowledge advanced, and this medicine "Preventive!"

If you wish to thank Dr. Wing and company for their fine efforts on behalf of our children and the public's health, they can be reached by calling:

Phone: (808) 832-5731   Fax: (808) 832-5846
TB Info Line: (808) 832-5738.

Give them my best regards. Don't forget to give very special thanks to Judith Akamini, who ordered my daughter Alena Horowitz to be expelled from school for not taking her skin test. Judy's number is:

808-974-6025

Check out Alena's website at www.myspace.com/health_freedom_hawaii . See how she's making the best of her unplanned vacation. . . .

 

March 2006

Tuberculosis

OVERVIEW

In developed countries, such as the United States, many people think tuberculosis (TB) is a disease of the past. TB, however, is still a leading killer of young adults worldwide. Some 2 billion people-one-third of the world's population-are thought to be infected with TB bacteria, Mycobacterium tuberculosis.

TB is a chronic bacterial infection. It is spread through the air and usually infects the lungs, although other organs and parts of the body can be involved as well. Most people who are infected with M. tuberculosis harbor the bacterium without symptoms (have latent TB), but some will develop active TB disease. According to World Health Organization (WHO) estimates, each year, 8 million people worldwide develop active TB and nearly 2 million die.

One in 10 people who are infected with M. tuberculosis may develop active TB at some time in their lives. [Horowitz comment: The vast majority when they are old and/or immune compromised from risky behaviors especially drug/pharmaceutical abuse.] The risk of developing active disease is greatest in the first year after infection, but active disease often does not occur until many years later.

TB in the United States

In 2005, the Centers for Disease Control and Prevention (CDC) reported 14,093 cases of active TB. While the overall rate of new TB cases continues to decline in the United States since national reporting began in 1953, the annual decrease in TB cases has slowed from an average of 7.1 percent (1993 to 2000) to the current average of 3.8 percent (2001-2005), according to CDC. In addition to those with active TB, an estimated 10 to 15 million people in the United States have latent TB.

Minorities are affected disproportionately by TB, which occurs among foreign-born individuals nearly nine times as frequently as among people born in the United States. This is partially because they were often exposed to M. tuberculosis in their country of origin before moving to the United States. In 2004, a very high percentage of Asians (95 percent) and Hispanics (75 percent) who were born outside the United States were reported to have TB.

What caused TB cases to increase the United States?

Cases of TB dropped rapidly in the 1940s and 1950s when the first effective antibiotic treatments for TB were introduced. In 1985, however, the decline ended and the number of active TB cases in the United States began to rise again. Several factors, often interrelated, were behind TB's resurgence.

  • The HIV/AIDS epidemic- People with HIV are particularly vulnerable to moving from infection with M. tuberculosis to active TB and are also more likely to develop active TB when they are first infected with TB bacteria.
  • People from many nationalities live in the United States- Increased numbers of foreign-born nationals come from places where many cases of TB occur, such as Africa, Asia, and Latin America. TB cases among foreign-born nationals now living in the United States account for more than half of the U.S. total.
  • Increased poverty, injection drug use, and homelessness-TB transmission is rampant in crowded shelters and prisons where people weakened by poor nutrition, drug addiction, and alcoholism are exposed to M. tuberculosis.
  • Failure of patients to take all prescribed antibiotics against TB-TB patients who do not complete TB drug treatment can stay infectious for longer periods of time and therefore can spread TB to more people. In addition, treatment failures may result in M. tuberculosis strains that are resistant to one or more of the standard medicines given to TB patients, making the disease much more difficult to treat.
  • Increased numbers of residents in long-term care facilities such as nursing homes-Many elderly people whose general health has declined develop active TB from TB infection they had much earlier in life. Other elderly people, especially those with weak immune systems, become newly infected with M. tuberculosis and can develop active TB rapidly.

TRANSMISSION

TB is primarily an airborne disease. The bacteria are spread from person to person in tiny microscopic droplets when a TB sufferer coughs, sneezes, speaks, sings, or laughs. Only people with active TB can spread the disease to others. People with TB who have been treated with the correct drugs for at least 2 weeks, however, are no longer contagious and do not spread the bacteria to others. [This statement's accuracy begs the question why any sane official would consider it reasonable to recommend anti-TB drugs for any more than two weeks. Consideration must be given to the fact that the disease remains latent; most people naturally overcome it and never spread it. Those who do are easily diagnosed and can be more aggressively treated. The high risk of liver disease caused by the anti-TB drugs taken for longer than two weeks far overshadows the benefit. So why is 6-month-antibiotic therapy, pure lunacy, "public health" policy? Big $$$$ for Big Pharma! Sadly, our children and families are the primary victims of this medical malfeasance.]

DIAGNOSIS

To identify those who may have been exposed to M. tuberculosis, health care providers typically inject a substance called tuberculin under the skin of the forearm. If a red welt forms around the injection site within 72 hours, the person may have been infected. This doesn't necessarily mean he or she has active disease. People who may test positive on the tuberculin test include

  • Most people with previous exposure to M. tuberculosis
  • Some people exposed to bacteria related to M. tuberculosis
  • Some people born outside the United States who were vaccinated with the TB vaccine (see TB vaccine below) used in other countries

If people have an obvious reaction to the skin test, other tests can help to show if they have active TB. In making a diagnosis, doctors rely on symptoms and other physical signs, the person's history of exposure to TB, and X-rays that may show evidence of M. tuberculosis infection.

The health care provider also will take sputum and other samples to see if the TB bacteria will grow in the lab. If bacteria are growing, this positive culture confirms the diagnosis of TB. Because M. tuberculosis grows very slowly, it can take 4 weeks to confirm the diagnosis. An additional 2 to 3 weeks usually are needed to determine which antibiotics to use to treat the disease.

What happens when someone gets infected with M. tuberculosis?

Between 2 to 8 weeks after being infected with M. tuberculosis, a person's immune system responds to the TB germ by walling off infected cells. From then on the body maintains a standoff with the infection, sometimes for years. Most people undergo complete healing of their initial infection, and the bacteria eventually die off. A positive TB skin test, and old scars on a chest X-ray, may provide the only evidence of the infection.

If, however, the body's resistance is low because of aging, infections such as HIV, malnutrition, or other reasons, the bacteria may break out of hiding and cause active TB.

SYMPTOMS

Early symptoms of active TB can include weight loss, fever, night sweats, and loss of appetite. Symptoms may be vague, however, and go unnoticed by the affected person. For some, the disease either goes into remission (halts) or becomes chronic and more debilitating with cough, chest pain, and bloody sputum.

Symptoms of TB involving areas other than the lungs vary, depending upon the organ or area affected.

TREATMENT

With appropriate antibiotic treatment, TB can be cured in most people.

Successful treatment of TB depends on close cooperation between patient and health care provider. Treatment usually combines several different antibiotic drugs that are given for at least 6 months, sometimes for as long as 12 months.

Some people with TB do not get better with treatment because their disease is caused by a TB strain that is resistant to one or more of the standard TB drugs. If that happens, their health care providers will prescribe different drugs and increase the length of treatment.

The importance of finishing the TB medicine

People who do not take all the required medications can become sick again and spread TB to others. Additionally, when people do not take all the prescribed medicines or skip times when they are supposed to take them, the TB bacteria evolve to outwit the TB antibiotics. Soon those medicines no longer work against the disease. If this happens, the person now has drug-resistant TB.

Some people have disease that is resistant to two or more drugs. This is called multidrug-resistant TB or MDR-TB. This form of TB is much more difficult to cure.

Treatment for MDR-TB

Treatment for MDR-TB often requires the use of special TB drugs, all of which can produce serious side effects. People with MDR-TB may have to take several antibiotics, at least three to which the bacteria still respond, every day for up to 2 years. Even with this treatment, however, between four and six out of 10 patients with MDR-TB will die, which is the same rate seen with TB patients who are not treated.

PREVENTION

TB is largely a preventable disease, and adequate ventilation is the most important measure to prevent its transmission in the community.

In the United States, health care providers try to identify people infected with M. tuberculosis as early as possible, before they have developed active TB. They will give infected people a medicine called isoniazid (INH) to prevent active disease. This medicine is given every day for 6 to 12 months. INH can cause hepatitis (inflammation of the liver) in a small percentage of people, especially those older than 35 years. [Horowitz comment: I would not call 23%, according to Schaberg et al., a "small percentage of people.]

Hospitals and clinics take precautions to prevent the spread of TB, which include using ultraviolet light to sterilize the air, special filters, and special respirators and masks. In hospitals, people with TB are isolated in special rooms with controlled ventilation and airflow until they can no longer spread TB bacteria.

TB vaccine

In those parts of the world where the disease is common, WHO recommends that infants receive a vaccine called BCG (Bacille Calmette Guerin) made from a live weakened bacterium related to M. tuberculosis. BCG vaccine prevents M. tuberculosis from spreading within the body, thus preventing TB from developing.

BCG has its drawbacks, however. It does not protect adults very well against TB. In addition, BCG may interfere with the TB skin test, showing a positive skin test reaction in people who have received the vaccine. In countries where BCG vaccine is used, the ability of the skin test to identify people infected with M. tuberculosis is limited. Because of these limitations, U.S. health experts do not recommend BCG for general use in this country.

TB AND HIV INFECTION

WHO estimates 11.4 million people worldwide are infected with both M. tuberculosis and HIV (human immunodeficiency virus, which causes AIDS [acquired immunodeficiency disease]). The primary cause of death in those infected with body microbes is from TB, not AIDS. In the United States, health experts estimate about two out of ten people who have TB are also infected with HIV.

One of the first signs that a person is infected with HIV may be that he or she suddenly develops TB. This form of TB often occurs in areas outside the lungs, particularly when the person is in the later stages of AIDS.

It is much more likely for people infected with M. tuberculosis and HIV to develop active TB than it is for someone that is only infected with M. tuberculosis. Fortunately, TB disease can be prevented and cured, even in people with HIV infection.

People infected with both MDR-TB and HIV appear to have a more rapid and deadly disease course than do those with MDR-TB only. If no medicines are available, as many as eight out of ten people with both infections may die, often within months of diagnosis.

Diagnosing TB in people with HIV infection is often difficult. They frequently have disease symptoms similar to those of TB and may not react to the standard TB skin test because their immune system does not work properly. X-rays, sputum tests, and physical exams may also fail to show evidence of M. tuberculosis infection with in people infected with HIV.

RESEARCH

The National Institute of Allergy and Infectious Diseases (NIAID) leads TB research at the National Institutes of Health. NIAID supports not only studies to better understand how M. tuberculosis infects and causes disease in humans but also how the human immune system responds to it. This research will help to develop new tools to diagnose TB and to find better vaccines and new medicines against TB. Below are some important advances that have been made in TB research.

Diagnostics

  • Potential new tests may speed the diagnosis of TB from 4 weeks to 2 days
  • Differences found in the DNA of M. tuberculosis and the bacterium used in the BCG vaccine may lead to a test to tell the difference between people who really have TB and those who are merely reacting to previous BCG vaccination
  • Characterization of antibodies and other components of the immune response may potentially identify people who are infected with M. tuberculosis and are at the highest risk of developing active disease

Treatment

  • Development of promising new drug candidates, some of which are currently being tested in human clinical trials
  • Evaluation of shorter treatment regimens to make it easier for people to complete drug therapy
  • Inclusion of antibiotics that are already available for treatment of other infections and have been shown to act on M. tuberculosis may make therapy more potent and easier to tolerate

Vaccines

Three new vaccine candidates are now in clinical trials and several more are being analyzed in animal studies.

Training

NIAID offers an intensive 3-year Infectious Diseases Training Program (www.niaid.nih.gov/training/infectious.htm) for physicians to produce investigators in clinical, basic, or translational research. These programs offer exposure to and insight into the science and management of mycobacterial diseases. They will increase the cadre of investigators with medical training to help identify and answer complex questions in the area of host/pathogen interactions in TB and other mycobacterial diseases.

Recognizing that disease knows no borders, NIAID has developed a global TB research agenda. A concerted global effort will require collaborations with sister agencies and other organizations with similar goals such as the Global Alliance for TB Drug Development and the STOP TB initiative, as well as partnerships with governments and scientists from countries where the burden of tuberculosis is greatest.

 

 

 

 

Dr. Leonard G. Horowitz co-authored this legal challenge to the state's TB skin testing program. Dr. Horowitz is an internationally known authority in public health and emerging diseases. One of his three national best-sellers, Emerging Viruses: AIDS & Ebola—Nature, Accident or Intentional? is credited by federal health officials as being among the most persuasive vaccine risk awareness texts in America.

Dr. Horowitz lives with his wife and three unvaccinated children on the Big Island of Hawaii. His official website is www.drlenhorowitz.com.