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(Health) Tuberculosis: Battling Tuberculosis on Many Levels

 
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PostPosted: Wed Jan 11, 2006 4:48 pm    Post subject: (Health) Tuberculosis: Battling Tuberculosis on Many Levels Reply with quote






This topic concerns one of the top killer diseases in the world, tuberculosis. It remains one of the serious problems of the Philippines. The first link provided at the end of this article comes from the National Institutes of Health (National Library of Medicine, US) website.

http://www.nlm.nih.gov/medline.....0_no_0.htm

Like other diseases in developing countries like the Philippines, it is important that children are provided correct information on this disease, its cause, its prevention, and its cure. As in other illnesses covered in this forum, the sole purpose is education. For medical advice, it is important to see your doctor.

The organism responsible for this disease is a bacterium, mycobacterium tuberculosis and you would find more about this (includes a video) in the following website, for example.

http://www-micro.msb.le.ac.uk/.....losis.html



Battling tuberculosis on many levels
STAR SCIENCE By John Phillip L. Fadul
The Philippine STAR 01/12/2006

(First of two parts)

The problem with tuberculosis is that you may already have it. Unknowingly, you may be harboring inside your body the agent that causes it, as you go about your daily routine. Imagine it quietly waiting inside your body, patiently biding its time until it finds an opportunity to catch you when you are unaware – and when you are weakest. Do we need any more reason to learn more about it?

Everyone has heard of TB. Quite possibly, you may know someone who has it. It is an ancient, highly infectious, and persistent disease that has plagued humans for centuries. Despite the availability of a vaccine and anti-TB drugs, it remains the leading infectious disease worldwide, especially in developing countries. It is responsible for killing more humans than AIDS, malaria, leprosy, and diarrhea. In 2000, the World Health Organization (WHO) estimated that there were 249,655 new cases of TB in the Philippines. An even scarier statistic is that more than a fourth of that number is projected to die. Also in the same year, it was reported that the Philippines had the seventh highest incidence in the world and the second highest in Asia. Because of these astounding figures, the Philippine government has vigorously renewed its commitment to fight the deadly disease.

TB is most often caused by the bacterium Mycobacterium tuberculosis. It is an immobile, rod-shaped bacterium which requires sufficient levels of oxygen to survive. This is why M. tuberculosis complexes are almost always found in the well-aerated upper lobes of the lungs. The bacterium is an intracellular parasite of macrophages, a kind of blood cell that functions in ingesting and destroying large amounts of foreign material. Unfortunately, humans are the primary host and the only real or natural host of M. tuberculosis. When talking, spitting, or coughing, a person with TB releases tiny, aerosolized droplets contaminated with the bacteria. An unsuspecting, healthy individual may inhale the expelled bacteria and contract the infection (luckily, one is unlikely to become infected by just one exposure). The microbes are engulfed by macrophages present in the alveoli, and they replicate in these cells for two to three days before spreading throughout the body.

TB does not immediately manifest itself upon infection. The disease has two stages, the first one being latent infection. It is characterized by the formation of hard, grayish nodules, called tubercles, in the lungs. But for most infected people, the macrophages are able to contain the bacteria for life. (Inside the macrophages, the bacteria are not destroyed but continue to live in a dormant, spore-like state.) No apparent disease is noted; they suffer no effects and are not contagious. Since this stage is asymptomatic, no one suspects the presence of the microbe in the body. It is estimated that a whopping two billion people – one-third of the world’s population – is currently in this state.

However, in 10 percent of cases, the disease progresses into the second stage of active tuberculosis. Factors such as old age, malnutrition, or the presence of another disease – especially HIV/AIDS – enable latent infections to develop into active TB. In this stage, tubercles proceed to the air passages, blood vessels, and other parts of the body. Local tissue and cells of our immune system die, causing the formation of granulomas, sites where active microbes can survive. These granulomas expand with more destroyed lung tissue and may spread into the larger airways of the lungs. They may also liquefy as the disease worsens, allowing the bacteria to multiply and spread to create new lesions. Meanwhile, the patient experiences a plethora of symptoms, from chest pains and shortness of breath to weight loss, from fatigue and paleness to painful joints and swollen glands. TB during this stage becomes very contagious.

To address the TB problem on a worldwide scale, the Global Tuberculosis Programme of the WHO developed DOTS (Directly Observed Treatment, Short-course) in 1993. More than just prescribing drugs and ensuring that their supply is uninterrupted, DOTS underscores the importance of self-reporting to health centers and of patient compliance to the treatment. Most importantly, it enjoins governments worldwide to go all out in the fight against TB. In this program, there is a standardized recording and reporting process that allows assessment of treatment results for each patient and of the overall TB control program. With DOTS, the patient, health care workers, public health officials, governments and communities all share the responsibility of effectively treating and controlling the killer disease.

(To be concluded) * * *

John Phillip L. Fadul completed his B.S. MBB degree at the National Institute of Molecular Biology and Biology in UP Diliman in 2004. He is presently taking his Master’s at the same institute. He works at the UP Marine Science Institute, where he tests marine compounds for cytotoxicity to mammalian cells. E-mail him at john@upmsi.ph.


*************************************************************

Questions to explore further this topic:

What is tuberculosis?

http://www.nlm.nih.gov/medline.....lesson.htm
http://www.cdc.gov/nchstp/tb/f.....htm#Intro1
http://www.niaid.nih.gov/publi.....lish06.pdf
http://kidshealth.org/parent/i.....losis.html
http://www.niaid.nih.gov/factsheets/tb.htm
http://www.lungusa.org/site/pp.....5778#about

What is mycobacterium tuberculosis?

http://www-micro.msb.le.ac.uk/.....losis.html
http://www.wadsworth.org/databank/mycotubr.htm
http://www.vetmed.wisc.edu/pbs.....s/mtb.html
http://biology.kenyon.edu/Micr.....cteria.htm
http://www.ebi.ac.uk/2can/geno.....losis.html

What is the alveoli?

http://science.nhmccd.edu/biol.....lveoli.htm
http://oac.med.jhmi.edu/res_ph.....veoli.HTML

What are macrophages?

http://www.astrographics.com/G.....P2008.html
http://education.vetmed.vt.edu.....SEPTAL.HTM

Tuberculosis, macrophage, and smoking

http://www.medpagetoday.com/tb.....ealth/1290

Drugs against Tuberculosis

http://www.aidsmeds.com/OIs/TB4.htm

Why is it important to follow strictly the medication guidelines for tuberculosis?

http://www.lungusa.org/site/pp.....mp;b=35815

How does tuberculosis spread?

http://www.phac-aspc.gc.ca/pub.....stb_e.html

Prevention of Tuberculosis

http://www.factmonster.com/ce6/sci/A0861648.html

Structural and functional changes in tissues and organs caused by tuberculosis

http://www-medlib.med.utah.edu.....B/MTB.html

Tuberculosis explained at the advanced microbiology level

http://www.tuberculosis.net/gk/

GAMES

http://www.lung.ca/children/games/


Last edited by adedios on Sat Jan 27, 2007 4:46 pm; edited 5 times in total
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PostPosted: Wed Jan 18, 2006 2:24 pm    Post subject: Battling tuberculosis on many levels Reply with quote

Battling tuberculosis on many levels
STAR SCIENCE By John Phillip L. Fadul
The Philippine STAR 01/19/2006

(Conclusion)
Treatment under DOTS consists of the daily administration of four drugs, namely, isoniazid, pyrazinamide, rifampin, and ethambutol, for two months; and a follow-up, thrice-a-week treatment of isoniazid and rifampin for another four months. The drugs affect different biochemical processes in the bacterium to inhibit its growth. Interestingly, some of these drugs enter the body in their inactive form. Proteins present in the intracellular environment alter the structure of these prodrugs and, consequently, activate them. Mutations in the genes’ coding for proteins involved in the target biochemical processes and in the activation of the drugs confer drug resistance, which is one of the foremost problems in treating TB. Drug resistance also arises when the full drug therapy is not completed. Therefore, compliance of the patient is highly important.

With this increased need for drugs to combat TB and its drug-resistant variants, there is an urgent need for investment in anti-TB drug discovery. A battery of rapid, low-cost, high-throughput screening methods for selecting new drug candidates against active TB is available to researchers. For this, initially only avirulent, i.e. non-disease-causing, strains of the bacterium, are used. This is to obtain quicker results and more importantly, to protect the worker from contracting the disease. Once compound leads have been identified, virulent and drug-resistant strains of the bacterium are then tested using high-level containment facilities. Among the methods used in anti-TB testing are the Agar Diffusion Method, the Microplate Alamar Blue Assay, BACTEC, and macrophage culture. The Agar Diffusion Method is a widely used method for drug testing. In this method, bacteria are grown in culture plates. Candidate drugs are then introduced; clear zones in the "lawn" of bacterial growth indicate effective killing of the bacteria. The Microplate Alamar Blue Assay is a high-throughput method that utilizes the dye Alamar blue for assessing cell viability. The non-fluorescent dye is originally blue; in response to changes in the culture medium resulting from cellular growth, its color turns into a fluorescent pink. This color change can then be measured quantitatively. In the BACTEC system, the culture medium used contains a substance called palmitate, specially tagged with radioactive atoms. As M. tuberculosis multiplies, it breaks down the palmitate and releases radiolabeled carbon dioxide, which can easily be detected and measured.

Anti-TB testing may also be carried out in an in vitro (literally, "in glass") macrophage culture, to make testing conditions closer to the real situation in the body. In this technique, macrophages are grown in culture plates. They are then infected with M. tuberculosis, and treated with possible anti-TB drugs. After a prescribed incubation period, the macrophages are ruptured and the remaining bacteria inside them are counted. In another anti-TB test which is relatively new, compounds are tested to see if they inhibit the enzyme isocitrate lyase, since this enzyme is shown to be important in latent TB. Each method has its advantages and drawbacks; researchers have to consider factors such as the availability and cost of materials and equipment, time required until results are acquired, reproducibility of results, and biosafety concerns, before selecting which method is most suitable to their objectives. In all cases, compound leads are those that are shown to kill or inhibit the growth of the M. tuberculosis but not mammalian cells. After in vitro testing, a drug candidate is tested in vivo (in animals) to see whether the drug is effective as it circulates in the body.

The beginning of this piece was quite pessimistic; fortunately, we do not have to end on that note. The Department of Health, with the help of the WHO, has instated structural reforms and also provided a better system of technical support and drug procurement to control TB. Research interest in anti-TB drug discovery continues to grow, particularly in university-based research centers such as the UP Marine Science Institute where the research groups of Drs. Gisela P. Concepcion and Lourdes J. Cruz have published on anti-TB marine compounds. So you see, the war against TB is multi-armed. Equally as important as the availability of the anti-TB vaccine and drugs (which are imported) are government prevention and intervention through public health measures, local development and production of the BCG vaccine, rigorous research on anti-TB drug discovery, and a zealous drive to help stop TB – and stop it now. The outlook is actually quite good, especially for you who took the time to learn about this. As the saying goes, knowing is winning half the battle.

* * *
John Phillip L. Fadul completed his B.S. MBB degree at the National Institute of Molecular Biology and Biology in UP Diliman in 2004. He is presently taking his Master’s at the same institute. He works at the UP Marine Science Institute, where he tests marine compounds for cytotoxicity to mammalian cells. E-mail him at john@upmsi.ph.
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PostPosted: Sat Jan 21, 2006 12:21 pm    Post subject: JOHN PHILLIP L. FADUL-Is his roots from Paete? Reply with quote

Prof Angel,

Could you help me find out if the author of this article is related to the FADULs of Paete? He might be one of our relatives. Kanino kaya siyang anak/apo?

Maraming salamat!
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PostPosted: Sat Jan 21, 2006 12:50 pm    Post subject: Reply with quote

The email address of the author of the article is there. This may be a good place to start to know more about the author.
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PostPosted: Mon Mar 06, 2006 4:39 pm    Post subject: Studies Suggest New Targets for Tuberculosis Treatments Reply with quote

Studies Suggest New Targets for Tuberculosis Treatments
Details of protein-cleaving complex key to microbe’s survival may improve drug design
DOE/Brookhaven National Laboratory
March 6, 2006


With the hope of designing more effective treatments for tuberculosis (TB), scientists from the U.S. Department of Energy’s Brookhaven National Laboratory and collaborating institutions have published the first detailed reports on the biochemistry and structure of a protein-cleaving complex that is essential to the TB bacterium’s survival. The research is published in two papers in the March 2006 issue of Molecular Microbiology, which features a rendition of the “proteasome” structure on its cover.

“Understanding the structure and biochemistry of this proteasome, and how it is different from those found in human cells, could greatly improve prospects for developing specific proteasome-based anti-tuberculosis treatments,” said biophysicist Huilin Li, who led Brookhaven’s role in the research.

Mycobacterium tuberculosis, the bacterium that causes TB, infects one person in three worldwide. In most infected people, who remain symptom-free, the bacterium is kept in check within immune system cells known as macrophages by compounds such as nitric oxide that kill or disable most bacteria. The current hypothesis is that the compounds work by damaging or destroying proteins, and the accumulated damaged proteins kill the cells if not removed.

The current studies reveal that TB bacteria have a sophisticated way to remove the damaged proteins — a protein-cleaving complex known as a proteasome — with wide specificity for degrading protein parts. This protein cleanup mechanism allows Mycobacterium tuberculosis to remain in macrophages, and possibly go on to cause active TB infections. With details revealed, it could also serve as a target for new anti-TB drugs.

“If we could find a way to specifically inhibit the activity of this Mycobacterium tuberculosis proteasome, then we might have a new, effective treatment for TB,” said Li. “Such a treatment might even eradicate TB microbes from infected individuals who show no signs of infection.”

One complicating factor is that human cells also contain proteasomes for degrading unneeded proteins. This process is essential for human cell survival. So any drug targeting the TB proteasome would have to be extremely specific. This was one reason for conducting such detailed structural and biochemical studies, to try to identify the unique characteristics that would allow such a targeted drug design.

In addition, the scientists conducted studies to see how an analog for a newly approved anti-myeloma drug that targets human proteasomes binds to the TB proteasome. These studies revealed highly specific details of the proteasome active site and mechanism, which will be invaluable to designing TB specific inhibitors.

http://www.bnl.gov/bnlweb/puba.....me-300.jpg

Ribbon diagram (left) showing seven-fold symmetry in the top view of the cylindrical TB proteasome, as revealed by x-ray crystallography. The core looks open, however, cryo-electron microscopy images (green structure, center) reveal a closed end, suggesting the structure is gated. Side views (right) also reveal that the structure is symmetrical top to bottom. Inside the structure there is a large chamber where the denatured proteins are cleaved.

The proteasome structure was revealed by Guiqing Hu and collaborators using cryo electron microscopy in Brookhaven Lab’s Biology Department and by x-ray crystallography at the Lab’s National Synchrotron Light Source. It is a cylindrical gated structure, which suggests that it requires an activator that has yet to be investigated.

The biochemical studies were conducted at Weill Medical College of Cornell University by Gang Lin in a group led by Carl Nathan. Other collaborating institutions included the Max Planck Institute of Biochemistry, Cold Spring Harbor Laboratory, and Millennium Pharmaceuticals.

This research was funded by the Office of Biological and Environmental Research within the U.S. Department of Energy’s Office of Science, the National Institutes of Health, and Brookhaven’s Laboratory Directed Research and Development program.
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PostPosted: Tue Mar 21, 2006 11:41 am    Post subject: Researchers seek answers to combat TB epidemic Reply with quote

University of Florida
21 March 2006

Researchers seek answers to combat TB epidemic

Solution may lie in a protective protein

Most Americans think of tuberculosis as a disease of the past, but with HIV and drug-resistant strains fueling epidemics in India and Africa, TB kills someone every six seconds across the world.
Now University of Florida and Indian scientists suspect they are on the path to solving a piece of the puzzle. The researchers are studying a protective protein they believe may boost bacteria-battling defenses, protecting against TB and giving infected patients an easier recovery.

Alcohol consumption likely reduces the amount of this protective protein, called heme oxygenase 1, weakening the body's defenses against TB, said Veena Antony, M.D., a UF professor of pulmonary medicine and division chief of pulmonary and critical care medicine for the College of Medicine. The researchers hope to pinpoint the role of alcoholism in the global epidemic by studying a population of HIV- and tuberculosis-infected patients in India. The researchers are collecting data for the National Institutes of Health-funded project and hope to have answers within two to three years, Antony said.

The epidemic may be more prevalent in resource-poor countries like India right now, but with immigrants unknowingly carrying bacteria that cause TB into the United States each year, this crisis could spread to American soil if left untended, Antony warns.

"We cannot build walls high enough to keep these organisms out," she said. "In the U.S., we cannot afford to grow complacent about TB. This is a disease that appears in many forms, many guises. We will never be able to eradicate it from the U.S. unless we eradicate it from the world."

The increasing number of multidrug-resistant strains of TB makes the disease even more troublesome, Antony says. The only currently approved treatment for TB requires patients to go to a clinic every day for up to nine months, and people often do not complete the full course of therapy, breeding new bacteria that are immune to the drugs. There is currently no way to treat large populations infected with drug-resistant strains of the disease, Antony said. The drug-resistant organism is one of several the federal government lists as a potential bioterrorism threat.

But the combination of HIV and TB currently poses the biggest problem globally. Patients with HIV are more apt to develop tuberculosis after they have contracted bacteria that cause TB, said Amy Davidow, Ph.D., an associate professor of preventive medicine and community health at the University of Medicine and Dentistry of New Jersey.

"The rule of thumb is if you have been infected (with TB) and are otherwise healthy, there is a 5 to 10 percent chance you will (ever) develop active disease," Davidow said. "The immune system keeps the infection in check so it never develops. HIV depresses the immune system, so certain infections (such as TB) can become active."

Tuberculosis can affect any organ in the body but causes more problems in the lungs, resulting in painful coughing and respiratory problems. Coupled with HIV, the two diseases form a deadly one-two punch that could be just as dangerous to the public as it is to the HIV- and TB-infected patient. Because TB develops more quickly in a person with HIV, the organism is more prevalent in the body and may spread more easily to other people, other research has shown.

"In resource-poor societies there is a meeting of HIV and tuberculosis, so that one disease is fueling the other disease," Antony said. "That is true in Africa. That is true in India where the HIV epidemic is just beginning to explode.

"Because of this concern, we believe we have to find novel ways of killing the organism. We have shown that heme oxygenase 1 is effective in boosting the cell's ability to protect itself."

In India, outbreaks of HIV and TB have erupted along highways where truck drivers often solicit prostitutes, Antony said. Doctors at the Post Graduate Institute of Medical Education and Research in India treat many of these patients, which is one of the reasons why UF researchers chose to collaborate with them for this research project, Antony said.

UF researchers also hope to initiate an international training program with PGIMER, allowing Indian researchers to come to Florida to learn sophisticated techniques and giving UF trainees firsthand experience in dealing with the epidemic there.

"One single patient with tuberculosis can infect hundreds of people," Antony said. "One-third of the world's population is infected with the organism that causes tuberculosis. We're going out into the field to meet the disease head-on and try to find answers."
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PostPosted: Sun Mar 26, 2006 7:47 am    Post subject: Researchers Seek Answers To Combat TB Epidemic Reply with quote

Source: University of Florida

Posted: March 25, 2006

Researchers Seek Answers To Combat TB Epidemic; Solution May Lie In A Protective Protein

Most Americans think of tuberculosis as a disease of the past, but with HIV and drug-resistant strains fueling epidemics in India and Africa, TB kills someone every six seconds across the world.

Now University of Florida and Indian scientists suspect they are on the path to solving a piece of the puzzle. The researchers are studying a protective protein they believe may boost bacteria-battling defenses, protecting against TB and giving infected patients an easier recovery.

Alcohol consumption likely reduces the amount of this protective protein, called heme oxygenase 1, weakening the body's defenses against TB, said Veena Antony, M.D., a UF professor of pulmonary medicine and division chief of pulmonary and critical care medicine for the College of Medicine. The researchers hope to pinpoint the role of alcoholism in the global epidemic by studying a population of HIV- and tuberculosis-infected patients in India. The researchers are collecting data for the National Institutes of Health-funded project and hope to have answers within two to three years, Antony said.

The epidemic may be more prevalent in resource-poor countries like India right now, but with immigrants unknowingly carrying bacteria that cause TB into the United States each year, this crisis could spread to American soil if left untended, Antony warns.

"We cannot build walls high enough to keep these organisms out," she said. "In the U.S., we cannot afford to grow complacent about TB. This is a disease that appears in many forms, many guises. We will never be able to eradicate it from the U.S. unless we eradicate it from the world."

The increasing number of multidrug-resistant strains of TB makes the disease even more troublesome, Antony says. The only currently approved treatment for TB requires patients to go to a clinic every day for up to nine months, and people often do not complete the full course of therapy, breeding new bacteria that are immune to the drugs. There is currently no way to treat large populations infected with drug-resistant strains of the disease, Antony said. The drug-resistant organism is one of several the federal government lists as a potential bioterrorism threat.

But the combination of HIV and TB currently poses the biggest problem globally. Patients with HIV are more apt to develop tuberculosis after they have contracted bacteria that cause TB, said Amy Davidow, Ph.D., an associate professor of preventive medicine and community health at the University of Medicine and Dentistry of New Jersey.

"The rule of thumb is if you have been infected (with TB) and are otherwise healthy, there is a 5 to 10 percent chance you will (ever) develop active disease," Davidow said. "The immune system keeps the infection in check so it never develops. HIV depresses the immune system, so certain infections (such as TB) can become active."

Tuberculosis can affect any organ in the body but causes more problems in the lungs, resulting in painful coughing and respiratory problems. Coupled with HIV, the two diseases form a deadly one-two punch that could be just as dangerous to the public as it is to the HIV- and TB-infected patient. Because TB develops more quickly in a person with HIV, the organism is more prevalent in the body and may spread more easily to other people, other research has shown.

"In resource-poor societies there is a meeting of HIV and tuberculosis, so that one disease is fueling the other disease," Antony said. "That is true in Africa. That is true in India where the HIV epidemic is just beginning to explode.

"Because of this concern, we believe we have to find novel ways of killing the organism. We have shown that heme oxygenase 1 is effective in boosting the cell's ability to protect itself."

In India, outbreaks of HIV and TB have erupted along highways where truck drivers often solicit prostitutes, Antony said. Doctors at the Post Graduate Institute of Medical Education and Research in India treat many of these patients, which is one of the reasons why UF researchers chose to collaborate with them for this research project, Antony said.

UF researchers also hope to initiate an international training program with PGIMER, allowing Indian researchers to come to Florida to learn sophisticated techniques and giving UF trainees firsthand experience in dealing with the epidemic there.

"One single patient with tuberculosis can infect hundreds of people," Antony said. "One-third of the world's population is infected with the organism that causes tuberculosis. We're going out into the field to meet the disease head-on and try to find answers."
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PostPosted: Sat Jul 08, 2006 5:05 am    Post subject: Reply with quote

6 July 2006
BMJ-British Medical Journal

Tuberculosis must be tackled among socially excluded groups

Tuberculosis and social exclusion BMJ Volume 333 pp 57-8
Tuberculosis cannot be controlled unless the disease is tackled effectively among socially excluded groups, warn experts in this week's BMJ.

Tuberculosis can infect anyone, but predominantly affects the poor, write Alistair Story and colleagues. In London, where over 40% of all cases in the UK in 2004 were reported, rates of tuberculosis have more than doubled since 1987 and are now the highest among homeless people, problem drug users, people living with HIV, prisoners and new entrants, particularly those from countries experiencing chronic civil conflict.

Recently published guidance from the National Institute of Health and Clinical Excellence (NICE) recommends chest x-ray screening for homeless people and entry screening for prisoners. Mobile x-ray units targeted at high risk groups are also being evaluated in London.

The guidance also suggests hospital admission for homeless people and those with clear socioeconomic need, allocation of a named key worker for all patients, and risk assessment to identify those patients unlikely to adhere to treatment. Directly Observed Therapy (DOT – where a health worker or other responsible adult observes the patients taking their medication) is also recommended to improve adherence to treatment.

Most tuberculosis patients are not infectious, readily access health services, and complete treatment successfully without DOT, say the authors. As a result, they make only limited demands on services and pose little public health risk.

By contrast, many socially excluded patients are at risk of delayed presentation, poor adherence and loss to follow-up. A major and persistent outbreak including over 200 linked drug resistant cases disproportionately affecting homeless people, prisoners and problem drug users in London clearly illustrates the urgent need to strengthen tuberculosis control among socially excluded groups.

The occurrence of tuberculosis in England closely reflects indices of poverty and overcrowding, they add. If the major determinants of a disease are social, so must be the remedies.

Tuberculosis cannot be controlled unless the disease is tackled effectively among socially excluded groups. This demands co-ordinated action beyond established control strategies that will require significant and sustained investment, they conclude.
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PostPosted: Fri Sep 15, 2006 10:31 am    Post subject: World-wide warning of highly drug-resistant tuberculosis Reply with quote

BMJ-British Medical Journal
14 September 2006

World-wide warning of highly drug-resistant tuberculosis

Extensively drug-resistant tuberculosis
New forms of highly drug-resistant tuberculosis are emerging and action must be taken soon before they become widespread globally, says an editorial in this week's BMJ.

The authors say that urgent action is needed to implement effective tuberculosis control strategies, especially in countries where tuberculosis control practices have been inadequate.

Research is also needed to assess the extent of the spread of these highly drug resistant strains of tuberculosis worldwide and improved means of diagnosis of tuberculosis and early detection of drug resistance are urgently required, they add.

Among 536 cases of tuberculosis confirmed at a rural hospital in South Africa earlier this year, 41% were multi-drug resistant and of those, 24% met the exact definition of being extensively drug resistant tuberculosis (also referred to as XDR tuberculosis). Such tuberculosis is almost untreatable.

All patients in this outbreak who were tested were HIV positive and 52 of the 53 died after an average of 25 days.

Strains of extensively drug resistant tuberculosis have also been noted in Europe, Asia and North and South America. It appears that there are several strains of this tuberculosis.

Author Dr Stephen Lawn, senior lecturer in infectious and tropical diseases at the University of Cape Town, South Africa, says that drug resistance to tuberculosis results largely from poorly managed care and control of the disease.

Poor prescribing practices, low drug quality (or erratic supply) and poor adherence to drugs can all contribute to this resistance to drugs. Where HIV rates are high, this allows particularly rapid spread of the disease within hospital settings and the community.

Dr Lawn says several responses to this problem are required including urgent assessment of the scale of the problem and an increase in laboratory capacity.

"Detection rates for cases of tuberculosis need to be improved, highlighting the need for a new diagnostic test," he writes. "Technologies that can determine the presence of drug-resistance at the point of care are needed as are new drug treatments."
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PostPosted: Fri Sep 22, 2006 3:06 pm    Post subject: Tuberculosis Helped Bring Down Mastodons Reply with quote

Tuberculosis Helped Bring Down Mastodons

By Ker Than
LiveScience Staff Writer
posted: 22 September 2006
09:00 am ET



A tuberculosis pandemic among an ancient mammoth-like creature probably contributed to the great beasts' demise, a new study suggests.

Scientists examining mastodon skeletons found a type of bone damage in several of the animal's foot bones that is unique to sufferers of tuberculosis. The disease would have weakened and crippled the animals, making them more vulnerable to humans and climate change, two factors that scientists have long speculated were behind their extinction in North America.

Mastodons were ancient elephants that resembled mammoths, but were shorter and less hairy. Both species lived in North America and disappeared mysteriously, along with other large mammals, around the time of the last major Ice Age about 10,000 years ago.

For the full article:

http://www.livescience.com/ani.....on_tb.html
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PostPosted: Fri Sep 22, 2006 6:35 pm    Post subject: More Drug-Resistant TB Seen in U.S. Reply with quote

More Drug-Resistant TB Seen in U.S.

By Jordan Robertson
Associated Press
posted: 22 September 2006
09:57 am ET

SAN FRANCISCO (AP) — The worst forms of the killer tuberculosis bug have been gaining ground in the United States, alarming public health officials over imported drug-resistant strains of a disease that is mostly under control in this country.

Although the number of drug-resistant TB cases in the U.S. is small compared to developing nations, health officials here warn that visitors from other countries who are unaware of their infections are bringing over the deadliest mutations.

Often those with drug-resistant strains stop taking their medicine when they feel better but aren't cured.

That's what happened with Pich Chhieng, 61, a teacher who was infected in his native Cambodia and carried it with him to this country. He took medication for eight months but abruptly stopped because he ran out of money and was feeling much better.

He didn't know until he was hospitalized while visiting family in Los Angeles that by neglecting his treatment he had allowed the disease to mutate, and the drug-resistant bacteria had overwhelmed his lungs.

“I knew it wasn't cured yet, but I thought it wasn't that strong,'' said Chhieng, who has been forced to stay in California until he is cured. “I thought it was gone, and when it came back like that, I felt really bad. I wanted to kill myself.''

The majority of drug-resistant infections in the U.S. are brought in by legal visitors, and health officials argue that simply tightening immigration controls won't solve the problem.

The only visitors to the U.S. who are screened for tuberculosis and other medical conditions are immigrant and refugee visa applicants, and TB experts say there is no easy way to screen the millions of tourists, workers and others who aren't currently evaluated.

Worldwide, TB kills 2 million people each year, mostly in Africa and southeast Asia.

Of gravest concern is so-called “extensively drug-resistant'' TB, which recently killed more than 50 people in South Africa. It's been found in limited numbers in the U.S. — 74 reported cases since 1993.

The strain is nearly impossible to cure because it's immune to the best first- and second-line TB drugs. It is as easily transmitted through the air as garden variety TB.

Health officials here also have been jolted by a spike in a milder but still-lethal form called “multi-drug resistant'' TB.

That's the strain afflicting Chhieng. It responds to more treatments but can cost up to $250,000 and take two years to cure.

The number of cases of that variety are multiplying worldwide, jumping more than 50 percent from about 273,000 in 2000 to 425,000 in 2004, according to a study published in August in the Journal of Infectious Diseases.

In the U.S., 128 people were diagnosed with it in 2004, a 13 percent spike from the previous year.

Health officials say a drug-resistant outbreak like the one in South Africa is unlikely here because of stringent public health safeguards, but warned that more widespread infections are possible in the future because the disease is so easily transported.

“That's a red light flashing,'' said Dr. Charles Wallace, an infectious disease specialist with the Texas Department of State Health Services. “That's a warning sign that TB is becoming more difficult to manage when it goes untreated and undiagnosed. We always like to think that it can't happen here, but any disease that travels through the air could be on a plane flying here at any time.''

U.S. health officials believe more money is needed for prevention and treatment abroad.

“It certainly has outbreak potential if we don't get on it right away,'' said Dr. Kenneth Castro, director of the CDC's Division of Tuberculosis Elimination.

The states with the highest numbers of multi-drug resistant cases in the last decade were New York, California, Texas and Florida, according to the CDC.

In New York City, a series of deadly HIV-related drug-resistant TB outbreaks ripped through prisons and hospitals in the early 1990s, killing hundreds of people, including many who had started treatment.

But mortality rates dropped dramatically after the health department created a separate unit to target the strain, stepped up education in multiple languages and improved coordination with doctors.

Last year, overall tuberculosis rates in the city hit their lowest point since the peak of the most recent epidemic in 1992; however, drug-resistant cases jumped from 18 in 2004 to 24 cases last year.

“The threat is always there,'' said Dr. Sonal Munsiff, director of the city's tuberculosis control bureau. “And I think it's increasing in some ways because drug-resistant tuberculosis is increasing worldwide. So it doesn't take long to get a case here.''

Health officials complain that federal funding has not kept up with the increased demands of battling the disease. State and county health departments wind up paying for uninsured patients like Chhieng, who has six months left in his two-year treatment.

Chhieng praises the treatment he has received in the U.S. He says he has gained weight and is feeling better, but has not seen his wife in a year and a half. And he regrets being a burden to his daughter-in-law, who is housing him and translates for him.

“Everything's better right now,'' he said. “I'm going to have a long life to live. I really miss home. I miss my wife, I miss my country, I miss the weather over there. I just want to go home.''
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PostPosted: Tue Jan 02, 2007 7:54 am    Post subject: Change in guidelines could help eliminate TB in US Reply with quote

American Thoracic Society
2 January 2006

Change in guidelines could help eliminate TB in US

To eliminate tuberculosis (TB) in the United States, current guidelines should be changed to reclassify all foreign-born residents from high-incidence countries as "high-risk," regardless of the amount of time they have lived in the U.S.

These findings appear in the first issue for January 2007 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

Kevin P. Cain, M.D., of the Division of Tuberculosis Elimination at the Centers for Disease Control and Prevention in Atlanta, and seven associates collected data on all 2004 TB cases listed in the U.S. National TB Surveillance database. The investigators' aim was to understand why the number of annual cases of TB reported in U.S.-born persons declined by 93 percent from 1993 to 2004, while foreign-born cases increased by five-percent.

"For example, in 2004, a total of 14,517 cases of TB were reported," said Dr. Cain. "Of these, 3,444 or 24 percent were foreign-born persons who had entered the United States more than five years previously."

Present guidelines recommend only those residing in the U.S. for five years or less be targeted for tuberculin skin testing and treatment of latent TB infection.

The following countries of origin of U.S. immigrant residents had the largest number of TB cases in 2004: Mexico (1,976), Philippines (829), Vietnam (619), India (557), China (352), Haiti (248), South Korea (219), Guatemala (190), Ethiopia (169) and Peru (159).

"Twenty-five percent of all reported TB cases in the United States are among foreign-born persons who have lived in the U.S. for more than five years," said Dr. Cain. "There is no policy to test foreign-born persons for latent TB infection before entering the U.S., or to test them after they have lived here for more than five years. As such, present guidelines do not currently address the burden of latent TB infection in the foreign-born subgroup."

According to the authors, the goal of TB control efforts in the U.S. is eliminating the disease. They define elimination as less than one case reported per million in a given population. If achieved, the number of TB cases diagnosed in 2004 would have been less than 300, as contrasted to the 14,517 reported.

"Until we address the burden of latent TB infection in the foreign-born group, achieving TB elimination will not be possible," said Dr. Cain.

He noted that controlling and eliminating TB will require a comprehensive strategy, with varying approaches for immigrant populations from high-risk countries.
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PostPosted: Sun Feb 18, 2007 8:47 am    Post subject: Harvard scientists partner to develop and distribute new tub Reply with quote

Harvard University
17 February 2007

Harvard scientists partner to develop and distribute new tuberculosis vaccine

Low-cost scaleable solution could improve TB care, slow spread of HIV/AIDS in developing world
CAMBRIDGE, Mass. -- Bioengineers and public health researchers at Harvard University have developed a novel spraying method for delivering the most common tuberculosis (TB) vaccine, providing a new low-cost and scaleable technique that offers needle-free delivery and greater stability at room temperature than existing methods. The process could one day provide a better approach for vaccination against TB and help prevent the related spread of HIV/AIDS in the developing world.

Researcher David Edwards will describe the finding -- and ongoing work to encourage widespread use of the new vaccine in the developing world -- this week at the annual meeting of the American Association for the Advancement of Science in San Francisco.

Edwards, an international leader in aerosol drug and vaccine delivery, sees great promise for the advance, which he and his colleagues hope to develop in the next few years through a partnership with the international not-for-profit Medicine in Need (MEND), based in Cambridge, Mass., Paris, and Cape Town.

His research, as well as the efforts to distribute the new vaccine in conjunction with MEND, are supported by a Grand Challenge Grant from the Bill and Melinda Gates Foundation.

"With the increasing incidence of tuberculosis and drug-resistant disease in developing countries due to HIV/AIDS, there is a need for vaccines that are more effective than the present Bacillus Calmette-Guérin (BCG) vaccine," says Edwards, the Gordon McKay Professor of the Practice of Biomedical Engineering in Harvard's School of Engineering and Applied Sciences. "An optimal new vaccine would provide a safe and more consistent degree of protection by eliminating needle injection and refrigerated storage."

BCG, the most widely administered childhood vaccine in the world with 100 million infant administrations annually, is presently dried by freezing and delivered by needle injection. The commercial formulation requires refrigerated storage and has shown variable degrees of protection against tuberculosis in different parts of the world. Because of such limitations, public health experts and physicians have long seen a need for alternatives to the traditional BCG vaccine and current treatment strategies.

The spray drying process Edwards developed for the BCG vaccine is similar to the way manufacturers prepare powdered milk. In fact, Edwards's first exposure to the spray drying process occurred when he was working with a spray dryer to produce highly respirable drug aerosols in a food science lab.

While spray drying of small and large molecules is common in the food, cosmetic, and pharmaceutical industries, the method has not been commonly used for drying cellular material. Most important, the new technique enables the BCG vaccine, and potentially other bacterial and viral-based vaccines, to be dried without the traditional problems associated with standard freezing.

"Unlike traditional freezing techniques, spray drying is lower-cost, easily scaleable for manufacturing, and ideal for use in needle-free formulations, such as inhalation," Edwards says. "Its greater stability at room temperature and viability ultimately could provide a more practical approach for creating and delivering a vaccine throughout the world.”


###
Edwards's work is also funded by the National Institutes of Health.
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PostPosted: Wed Feb 21, 2007 7:47 am    Post subject: New research may overturn conventional wisdom on drug-resist Reply with quote

Infectious Diseases Society of America
20 February 2007

New research may overturn conventional wisdom on drug-resistant tuberculosis

A newly released study suggests that the majority of cases of drug-resistant tuberculosis (TB) among patients undergoing treatment for the disease may be due to new infections, not acquired resistance. If confirmed in future studies the research, in the March 15 issue of The Journal of Infectious Diseases, may drive a major shift in strategy for controlling TB.

A major difficulty in treating patients with pulmonary TB is that the organism can become progressively resistant to standard therapy. This resistance was long thought to be acquired through mutations in the infecting strain when the treatment regimen was inadequate or the patient did not comply with it. More recently, studies of the genetic make-up of Mycobacterium tuberculosis (M. tuberculosis) strains have shown that resistance can also result from re-infection with a new strain that is already drug-resistant, sometimes against multiple drugs.

The authors of the new study, Qian Gao, PhD, and coworkers in Shanghai, China and elsewhere, used molecular genetics and drug susceptibility testing to investigate patients with TB who were treated in Shanghai hospitals during 1999-2004. They focused on 38 patients from whom samples were available before and during treatment. The researchers found that the strains of TB in the samples taken before treatment were genetically different from those taken during treatment in 87 percent ( 33 out of 38 ) of patients.

To determine the relative proportion of drug resistance caused by re-infection or mutation, the authors excluded six patients who were initially infected with resistant TB and then became drug-susceptible or resistant to fewer drugs. In the remaining 32 patients, the initial sample was drug-susceptible or resistant to at least one drug and the subsequent sample resistant to one or more drugs. Of these patients, 84 percent (27 patients) had before-and-during samples with different genetic patterns and only 16 percent (5 patients) had identical patterns. Thus, there were more than 5 times as many cases caused by re-infection compared to mutation.

"It was surprising to find a high rate of primary drug-resistant strains among treated patients," said Dr.Gao. "This overturned the common belief that drug resistance among treated patients is always acquired."

The investigators also noted that two patients in the study had multidrug-resistant strains in both their first and second sample, and that 10 others had multidrug-resistant strains in their second sample; genetic testing showed that 9 of the 10 patients had a different strain in the second sample. The most serious kind of drug-resistant disease therefore accounted for about a third of patients with drug resistance.

Limitations of the study included the exclusion of many patients without sample results, reliance on previously collected data in which some patients might have been misclassified, use of computerized drug susceptibility data, and the unknown contribution of mixed infections. Nevertheless, the findings are a warning. Although better diagnostics, drugs, and effective vaccines for TB are clearly needed, the authors said, "Our findings highlight the urgency of accelerating efforts to interrupt the transmission of drug-resistant tuberculosis." The research shows improved methods of preventing TB transmission may be needed in the very facilities and communities where TB patients are treated.

Fast Facts


Tuberculosis (TB) is one of the world's top killer diseases, claiming roughly 2 million lives each year.


Drug-resistant TB is a growing problem worldwide. Most resistance is believed to derive from inefficient treatment, leading to mutations.


This study found that 33 of 38 patients had a different strain of TB during treatment than before treatment.


Improved methods of preventing TB transmission may be needed in the very facilities and communities where TB patients are treated.

###
Founded in 1904, The Journal of Infectious Diseases is the premier publication in the Western Hemisphere for original research on the pathogenesis, diagnosis, and treatment of infectious diseases; on the microbes that cause them; and on disorders of host immune mechanisms. Articles in JID include research results from microbiology, immunology, epidemiology, and related disciplines. JID is published under the auspices of the Infectious Diseases Society of America (IDSA). Based in Alexandria, Va., IDSA is a professional society representing 8,300 physicians and scientists who specialize in infectious diseases. Nested within the IDSA, the HIV Medicine Association (HIVMA) is the professional home for more than 3,500 physicians, scientists and other health care professionals dedicated to the field of HIV/AIDS. HIVMA promotes quality in HIV care and advocates policies that ensure a comprehensive and humane response to the AIDS pandemic informed by science and social justice. For more information, visit www.idsociety.org and www.hivma.org.
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PostPosted: Tue May 15, 2007 9:24 am    Post subject: Vitamin D supplements may offer cheap and effective immune s Reply with quote

Wellcome Trust
15 May 2007

Vitamin D supplements may offer cheap and effective immune system boost against TB

Scientists have shown that a single 2.5mg dose of vitamin D may be enough to boost the immune system to fight against tuberculosis (TB) and similar bacteria for at least 6 weeks. Their findings came from a study that identified an extraordinarily high incidence of vitamin D deficiency amongst those communities in London most at risk from the disease, which kills around two million people each year.

The research, funded by the Wellcome Trust, the Department of Environmental Health at Newham Council and Newham University Hospital NHS Trust Respiratory Research Fund, is published online in the American Journal of Respiratory and Critical Care Medicine.

Whilst a diet of oily fish can provide some vitamin D, the main source of the body's vitamin D comes from exposing the skin to sunlight. In Britain, however, the amount of sunlight is usually insufficient to make vitamin D in the skin between October and April, and much of the population becomes deficient during the winter and spring.

Researchers from Queen Mary's School of Medicine and Dentistry, London, and the Wellcome Trust Centre for Research in Clinical Tropical Medicine, Imperial College London, studied patients at Newham University Hospital and Northwick Park Hospital in London who had been exposed to TB. They found that over 90% of such patients had a vitamin D deficiency.

Vitamin D was used to treat TB in the pre-antibiotic era, when special sanatoria were built in sunny locations, such as the Swiss Alps. But until now, no study has evaluated the effect of vitamin D supplementation on immunity to mycobacteria, the family of bacteria that cause TB.

The researchers performed a randomised control trial on a group of volunteers who were given either a 2.5mg supplement or a placebo. Samples of the volunteers' blood were then tested in Dr Robert Wilkinson's Wellcome Trust-funded laboratory at Imperial College, to see whether the supplement affected the immune system's ability to withstand infection by mycobacteria.

"We found that a single large dose of vitamin D was sufficient to enhance a person's immunity to the bacteria," says Dr Adrian Martineau from Imperial College London, who co-ordinated the study. "This is very significant given the high levels of vitamin D deficiency in people at the highest risk of TB infection, and shows that a simple, cheap supplement could make a significant impact on the health of people most at risk from the disease."

According to the Health Protection Agency, the incidence of TB in the UK is increasing, with around 8,000 new cases a year. Cases in the UK are predominantly confined to the major cities and about 40 per cent of all cases are in London. TB is also a major global problem: an estimated one-third of the world's population – nearly two billion people – are infected. Nine million people a year develop the active disease worldwide, which kills two million each year.

"Most cases of TB in London arise from people who have already become infected with the bacteria but in whom it lies latent," says Professor Chris Griffiths from Queen Mary's School of Medicine and Dentistry. "Our results indicate that vitamin D supplementation may prevent reactivation of latent TB. Identifying people with latent TB and providing supplements could be an important strategy for tackling the disease."

Treatment is both very cheap – about 60p per dose or 10p per week – and safe. Vitamin D supplements could be prescribed for patients with or at risk of latent TB through GP surgeries.

Dr Martineau points out: "Our work adds to the growing evidence that vitamin D may have a wide range of important health benefits, including preventing falls and fractures and reducing risk of cancer and diabetes, as well as boosting the immune system against infection. Population-wide supplementation needs to be considered by public health planners."

"Milk and orange juice could be fortified with vitamin D, as in the US and Canada," he says. "At present only margarine is supplemented in the UK, and recent studies show that this is not an effective way to prevent vitamin D deficiency."
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PostPosted: Tue May 15, 2007 10:53 pm    Post subject: A Comprehensive Review on TB Updates: Kudos to the Work of A Reply with quote

I would like to commend on the work of A. de dios on this TB articles that he posted on this website. I am very happy that I am not the only one interested on TB and its potential control measures for our future generation. This is part of the health education aspect of TB control. I hope that more people will be interested to join in the effort of the government to control TB in our midst. The topics that you picked up were mostly published in February or March to highlight this disease for the commemoration of World TB Day every March 24th annually.

Indeed, control of TB requires a multi-pronged approached. Philippines is known for high endemicity of this disease. TB ranked 6th in the 10 leading causes of diseases and death among Filipinos. Philippines ranked 3rd in the Western Pacific Region and 9th in the world in terms of the high burden of TB in the country. You see, we are very famous!! (he he he)

This is the reason why a lot of foreign grants are pouring in the Philippines to help us solve the problem. However, stigma on the disease still prevails in our minds. Pag sinabing TB, takot na kaagad. If we have the symptoms, we tend to hide it because of our fear of discrimination. So the bottom line of my message is to promote that " TB is curable and preventable". Hindi ito dapat ikahiya upang magamot kaagad. DOTS if properly implemented is the cost effective way of treating the disease. Health seeking behaviour of patients, prescribing habits of physicians, commitmentof the Heallth care providers to implement DOTS and political committment from the government to support the fight against the disease should be in place plus the results of the new researches with definite impact on the different aspect of prevention and control of this disease.

In our town, Paete, TB is also one of the problems. I heard a news of Multi-Drug Resistant (MDR) cases already there because of failure to comply with the required of treatment as relayed by their relatives. They died na so you don't have to worry. But are these cases reported to the health sector to prevent the proliferation of this strain in Paete? MDR can still be treated but it is costly, the total cost of treatment is about P180,000 to P200,000 in 18-24 months of treatment in Makati Med. If the patient failed to continue the treatment, extremely resistant strains (XDR) of TB will be in our environment soon. XDR is incurable as of now.

This is just an additional info re: TB. Hope to see more TB-related topics again in August, for our lung month celebration and awareness campaign.

To A. de Dios, you have done a great job! Keep up with your good work! I've been browsing some of your works before, I really admire you for the efforts and time that you have been spending for this website.
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PostPosted: Sat May 26, 2007 2:06 pm    Post subject: Dangerous History: The genetic secrets of a savvy killer Reply with quote

Week of May 26, 2007; Vol. 171, No. 21 , p. 330

Dangerous History
The genetic secrets of a savvy killer

Emily Sohn

Throughout recorded time, tuberculosis has wrought death among the people infected and frustration among those trying to tame it. As recently as the 1950s, prescribed treatment included little more than rest, sunlight, and fresh air. Today, patients take powerful drug cocktails for months. Even so, tuberculosis kills more people each year than any infectious disease other than AIDS.

For the full article:

http://sciencenews.org/articles/20070526/bob9.asp
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PostPosted: Fri Jun 01, 2007 9:38 am    Post subject: TB test offers patients quicker and easier diagnosis Reply with quote

Imperial College London
1 June 2007

TB test offers patients quicker and easier diagnosis

A new test for diagnosing TB offers a quick and simple alternative to existing three-day methods, according to research published today in the journal Clinical Infectious Diseases.

The study shows that the test, which involves taking three sputum samples from a patient over the course of one day, is just as effective as other more invasive and complicated testing methods, which take three days.

For the new test, patients use a nebuliser to inhale salty water, or hypertonic saline, for twenty minutes. This enables them to produce sputum samples from deep inside the lungs. The samples can then be analysed for traces of mycobacterium tuberculosis, the bacterium which causes most cases of TB.

Other procedures for testing for TB are gastric washing and bronchoscopy with bronchoalveolar lavage. These invasive procedures involve placing tubes in the stomach, to collect samples of mucus swallowed during the night, or the broncial tubes, to try to wash bacteria from infected lung tissue. Patients have to be in hospital for three days to allow these samples to be collected and analysed, delaying the start of treatment.

Such tests are given where patients have symptoms or chest radiography results that suggest the patient might have TB and they are unable to cough up a sputum sample.

The new research, which was carried out by researchers from Imperial College London and Northwick Park Hospital NHS Trust, showed that the new test is just as effective, if not more so, than existing methods for diagnosing TB.

In the 140 people who were examined, use of 3 sputum specimens correctly detected TB in 39% of the patients. Gastric washing detected TB in 30% of the same patient sample. No additional cases were diagnosed in the 21 patients who underwent bronchoscopy.

Dr Robert Davidson, from the Division of Medicine at Imperial College and the Department of Infection and Tropical Medicine at Northwick Park Hospital NHS Trust, and one of the authors of the research, said: "This is a simple method of ollecting bacteria from individuals with the early stages of TB, and who are unable to cough sputum samples. By doing all the tests in one day, we can start treatment sooner and get patients home sooner. Previously we relied on bronchoscopy or gastric washings, which were uncomfortable for the patient and required a longer stay in hospital. The patient breathing nebulised hypertonic saline feels little or no unpleasant sensation, and it is a very cheap test".

According to the Health Protection Agency, the incidence of TB in the UK is increasing, with around 8,000 new cases a year. Cases in the UK are predominantly confined to the major cities and about 40 per cent of all cases are in London. TB is also a major global problem: an estimated one-third of the world's population - nearly two billion people - are infected. Nine million people a year develop the active disease worldwide, which kills two million each year.
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PostPosted: Mon Sep 24, 2007 12:54 pm    Post subject: Drug-resistant tuberculosis rises, but new treatments in the Reply with quote

Drug-resistant tuberculosis rises, but new treatments in the pipeline
24 September 2007
Chemical & Engineering News

An arsenal of promising new medications, vaccines, and diagnostic tests are moving toward the global battlefield that pits medicine against drug-resistant tuberculosis (TB), which is claiming a terrible toll, particularly in HIV-infected individuals, according to an article [ http://pubs.acs.org/cen/covers.....cover.html ] scheduled for the Sept. 24 issue of Chemical & Engineering News, ACS’ weekly newsmagazine.

In the cover feature, C&EN senior correspondent Ann Thayer and assistant editor Carmen Drahl describe far-ranging efforts underway to develop new TB diagnostic tests and treatments. For years, conventional treatments for TB had slowed the spread of the disease, but the emergence of new drug-resistant strains has reduced the effectiveness of those medications. Researchers are developing more accurate diagnostic tests, new drugs to fight multidrug resistant strains, and ones that are more compatible with individuals who are undergoing treatment for HIV. Scientists are also developing more effective vaccines, including those that might show promise for both preventing and treating the disease, Thayer notes.

“In the past five years or so, the TB drug pipeline has shifted from nearly empty to having about 30 compounds under investigation; several are in early clinical testing,” Thayer writes.

ARTICLE #5 EMBARGOED FOR 9 A.M., EASTERN TIME, Sept. 24, 2007
“Taking Down TB”

This story will be available on Sept. 24 at:
http://pubs.acs.org/cen/covers.....cover.html
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PostPosted: Thu Nov 01, 2007 11:31 am    Post subject: Tuberculosis breaches borders, but not public health Reply with quote

American Thoracic Society
1 November 2007

Tuberculosis breaches borders, but not public health

Immigrants from countries with high rates of tuberculosis who move to countries of low TB incidence do not pose a public health threat to native citizens, according to researchers in Norway, who analyzed the incidence and genetic origins of all known cases of TB in the country between 1993 and 2005.

Their results were reported in the first issue for November of the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.

After gathering all available cultures from the identified cases and eliminating samples suspected of being contaminated in the lab, the researchers examined 2,173 cases of TB in the country over 12 years. They tracked outbreaks among native-born citizens and immigrants, and analyzed the genetic strain of each confirmed case using cultures obtained through patient samples at 14 laboratories that service the entire country.

They found little evidence to support the belief that immigrants from countries with high TB incidence present a public health threat to non-immigrant natives in low-incidence countries. Instead, the researchers documented an increase in number of strains in immigrants, but a decrease in the number and incidence of native infections, suggesting that while immigrants from high-TB regions do bring with them more strains of TB, they do not significantly contribute to the spread of TB within native-born populations of low-incidence countries.

“Immigrants have been accused of spreading TB. However, the current study demonstrated that the importation of M. tuberculosis, over 12 years, did not generate significant negative effects on the transmission of TB in a country that was considered to be in the elimination phase of this disease,” wrote lead researcher, Ulf R. Dahle, Ph.D., of the Norwegian Institute of Public Health.

This finding is especially relevant in the current climate of increased public anxiety in the wake of Andrew Speaker, the American who traveled extensively while infected with multidrug-resistant TB disease, and Amado Isidro Armendariz Amaya, a Mexican businessman who is reported to have crossed the U.S. border 76 times, carrying with him construction materials and multidrug-resistant TB.

“Anyone involved in TB management or control needs no reminder of the key role played by human movement—across oceans, within rapidly industrializing countries, from war zones to refugee camps,” wrote Kevin Schwartzman, M.D., M.P.H., of McGill University, a researcher unaffiliated with the study, in an accompanying editorial in the same issue of the journal.

The investigators found that the genetic diversity of the TB strains identified remained high throughout the 12 years at about 87 percent, indicating very limited transmission to both immigrants and non-immigrants within the country. “Had there been more extensive transmission on Norwegian soil, we would have seen a greater degree of similarity between infecting strains. The lack of similarity suggests that most patients acquired TB infection abroad,” said Dr. Dahle.

Furthermore, they were unable to attribute any outbreak to the infamous Beijing family of TB, despite its presence in the country. Among all the imported strains during the 12 years, only 10 led to more than five cases of active TB within five years. “This indicates that the importation of M. tuberculosis isolates did not represent an immediate challenge to the national TB control program,” wrote Dr. Dahle.

“The low number of clustered strains could not support the statement that public health in this recipient country was hampered by immigration from high-incidence countries,” Dr. Dahle concluded. “It appeared that the TB control efforts were not overwhelmed by the challenge of imported TB… If these control strategies are well maintained, elimination of indigenous transmission of TB could be achievable, despite extensive import from high-incidence countries.”

Ultimately, the strategies used to control TB are more important to public health than immigration. “The take-home message is not one of blame or stigmatization—quite the opposite,” said Dr. Schwartzman. “By ensuring access to TB care and public health programs for all, Norwegian authorities are controlling TB and preventing transmission.”


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PostPosted: Fri Dec 07, 2007 2:49 pm    Post subject: Most ancient case of tuberculosis found in 500,000-year-old Reply with quote

University of Texas at Austin
7 December 2007

Most ancient case of tuberculosis found in 500,000-year-old human; points to modern health issues
Evidence suggests vitamin D deficiency endangers migrating populations

AUSTIN, Texas—Although most scientists believe tuberculosis emerged only several thousand years ago, new research from The University of Texas at Austin reveals the most ancient evidence of the disease has been found in a 500,000-year-old human fossil from Turkey.

The discovery of the new specimen of the human species, Homo erectus, suggests support for the theory that dark-skinned people who migrate northward from low, tropical latitudes produce less vitamin D, which can adversely affect the immune system as well as the skeleton.

John Kappelman, professor of anthropology at The University of Texas at Austin, is part of an international team of researchers from the United States, Turkey and Germany who have published their findings in the Dec. 7 issue of the American Journal of Physical Anthropology. The Leakey Foundation and the Scientific and Technical Research Council of Turkey funded the research.

Prior to this discovery in western Turkey, which helps scientists fill a temporal and geographical gap in human evolution, the oldest evidence of tuberculosis in humans was found in mummies from Egypt and Peru that date to several thousand years ago.

Paleontologists spent decades prospecting in Turkey for remains of Homo erectus, widely believed to be the first human species to migrate out of Africa. After moving north, the species had to adapt to increasingly seasonal climates.

The researchers identified this specimen of Homo erectus as a young male based on aspects of the cranial suture closure, sinus formation and the size of the ridges of the brow. They also found a series of small lesions etched into the bone of the cranium whose shape and location are characteristic of the Leptomeningitis tuberculosa, a form of tuberculosis that attacks the meninges of the brain.

After reviewing the medical literature on the disease that has reemerged as a global killer, the researchers found that some groups of people demonstrate a higher than average rate of infection, including Gujarati Indians who live in London, and Senegalese conscripts who served with the French army during World War I.

The research team identified two shared characteristics in the communities: a path of migration from low, tropical latitudes to northern temperate regions and darker skin color.

People with dark skin produce less vitamin D because the skin pigment melanin blocks ultraviolet light. And, when they live in areas with lower ultraviolet radiation such as Europe, their immune systems can be compromised.

It is likely that Homo erectus had dark skin because it evolved in the tropics, Kappelman explained. After the species moved north, it had to adapt to more seasonal climates. The researchers hypothesize the young male’s body produced less vitamin D and this deficiency weakened his immune system, opening the door to tuberculosis.

“Skin color represents one of biology’s most elegant adaptations,” Kappelman said. “The production of vitamin D in the skin serves as one of the body’s first lines of defenses against a whole host of infections and diseases. Vitamin D deficiencies are implicated in hypertension, multiple sclerosis, cardiovascular disease and cancer.”

Before antibiotics were invented, doctors typically treated tuberculosis by sending patients to sanatoria where they were prescribed plenty of sunshine and fresh air.

“No one knew why sunshine was integral to the treatment, but it worked,” Kappelman said. “Recent research suggests the flush of ultraviolet radiation jump-started the patients’ immune systems by increasing the production of vitamin D, which helped to cure the disease.”
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PostPosted: Sat Dec 15, 2007 1:42 pm    Post subject: Ancient Ailment? Early human may have carried tuberculosis Reply with quote

Week of Dec. 15, 2007; Vol. 172, No. 24 , p. 371

Ancient Ailment? Early human may have carried tuberculosis

Brian Vastag

Check your tile countertop for fossils. A consumptive Homo erectus—or at least a piece of him—might be trapped there.


While cutting coveted travertine into tiles, a saw operator in Turkey sliced through a fossilized skull and gave the pieces to his supervisor. The fragments from the 500,000-year-old rock sat on a shelf behind the supervisor's desk until a local geologist visiting the fossil-rich site claimed them.

For the full article:

http://sciencenews.org/articles/20071215/fob2.asp
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PostPosted: Tue Dec 18, 2007 3:35 pm    Post subject: Simple strategy could prevent half of deadly tuberculosis in Reply with quote

Yale University
18 December 2007

Simple strategy could prevent half of deadly tuberculosis infections

By using a combination of inexpensive infection control measures, hospitals around the world could prevent half the new cases of extensively drug resistant tuberculosis (XDR TB), according to a new study in The Lancet by researchers at Yale School of Medicine.

Dubbed “Ebola With Wings” for its ability to spread and kill rapidly, XDR TB has been reported in 37 countries and has been identified in all regions of the world, including the United States. The disease has become an epidemic among hospitalized patients in South Africa, according to researchers on the Yale study. Cases of XDR TB have been diagnosed in every province of South Africa, and are particularly concentrated in the area surrounding Tugela Ferry.

To assess the spread of XDR TB, Yale School of Medicine M.D., Ph.D. student Sanjay Basu and the research team developed a computer model of a virtual world that incorporated over two years of data from Tugela Ferry. The model was 95 percent accurate at predicting the trends in XDR and other forms of TB in the region. The Yale study provides the first estimates of the XDR TB burden in South Africa. According to the model over 1,300 cases of XDR TB could arise in the Tugela Ferry region by the end of 2012.

“It is critically important to take steps now to prevent further spread of XDR TB,” said Basu. “If we wait to act, this form of TB will spread further in the community and beyond borders. When a drug resistant strain hit New York in the 1990s, it cost over $1 billion to bring under control.”

Tuberculosis is caused by bacteria that target the lungs and is spread through the air when an infected person coughs or sneezes. HIV-positive people constitute a vast majority of the XDR TB cases, given their greater risk of infection.

The authors write that the best way to address this type of TB effectively is to change the healthcare environment. Use of masks alone would prevent fewer than 10 percent of cases in the general epidemic, though they would help many healthcare workers, say the researchers. Reducing time spent in the hospital and shifting to outpatient therapy could prevent nearly one-third of cases, they note. About half of XDR TB cases could be prevented by addressing hospital overcrowding, improving ventilation, enhancing access to HIV treatment, and providing faster diagnostic tests, say the study authors.

Basu said that the problem is compounded in South Africa where there are long waiting lists of up to 70 patients hoping to gain admission to hospitals, and crowded wards with as many as 40 people packed into one room. Some of these patients have to sleep on the floor, and many travel for days to reach the hospital.

“We can do a lot to change what is going on,” said senior author Gerald Friedland, M.D., a professor of medicine at Yale. “This is a train crash between the two epidemics of HIV and TB, and we have to address both problems together to fix this situation.”


###
Other authors on the study included Jason R. Andrews, Eric M. Poolman, Neel R. Gandhi, N. Sarita Shah, Anthony Moll, Preshnie Moodley and Alison P. Galvani.

Citation: The Lancet, Early online edition (October 27, 2007)
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PostPosted: Fri Dec 21, 2007 5:34 pm    Post subject: Seeking to create better drugs, researchers chip away at how Reply with quote

Dec. 12, 2007
Seeking to create better drugs, researchers chip away at how tuberculosis survives inside human defense cells
By Krishna Ramanujan

Cornell researchers are using advanced genetic techniques to better understand the relationship between the bacteria that cause tuberculosis and the human immune system defense cells that engulf them.


The researchers have discovered that unlike many bacterial pathogens, Mycobacterium tuberculosis does not react when immune system cells called macrophages initially make contact; but the bacterium's genes become activated minutes after the pathogen is enveloped by a macrophage and contained in one of its membrane-bound compartments called vacuoles.

David Russell, professor of molecular microbiology at Cornell's College of Veterinary Medicine, and colleagues reported in a November issue of the journal Cell Host and Microbe, that increased acidity inside the vacuoles containing the bacteria serves as the trigger for M. tuberculosis genes to express proteins.

The study also compared the responses of M. tuberculosis to a live bacterial vaccine against tuberculosis known as Bacillus Calmette-Guerin (BCG). It found that the two bacteria may each respond differently to the same stimuli and that BCG appears less capable of protecting itself once inside a macrophage. The findings are consistent with the reduced virulence of BCG, which is key to its safety as a vaccine.

The study is a small part of a larger plan to understand the processes that allow the bacteria to survive within macrophages and then to use that knowledge to develop more effective drugs to fight tuberculosis, which currently kills 2 million people worldwide each year. Existing drugs require six to nine months to treat the active disease that invades and replicates within the lungs.

"What we propose is the exploitation of the data obtained from these basic science studies to develop a comprehensive program of drug development that targets bacterial processes critical to survival inside the human host," said Russell.

Russell's lab used gene chips, or microarrays, to identify genes activated under specific environmental conditions. This allowed them to generate real-time readouts of bacterial health and their response to stress. The researchers have also created real-time readouts that measure conditions within the tuberculosis-containing vacuole at any time during the immune system's process.

"Our goal is to develop these bacterial fitness readouts to screen small molecule libraries for compounds that will kill M. tuberculosis inside the macrophage," said Russell. "Unfortunately, Cornell does not have either the instrumentation or the chemical libraries necessary to do this work, so I am trying different, private funding agencies to get the support to purchase equipment and libraries."

Kyle Rohde, a research associate in Russell's lab, is the paper's lead author. The study was funded by the National Institutes of Health.
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