A leading cause of death

By Usha Perera
Tuberculosis (TB) is the leading cause of death in the world from a bacterial infectious disease. The disease affects 1.8 billion people/year which is equal to one-third of the entire world population.
Mycobacterium tuberculosis
Mycobacterium tuberculosis is the etiologic agent of tuberculosis in humans. Humans are the only reservoir for the bacterium.
Mycobacterium bovis is the etiologic agent of TB in cows and rarely in humans. Both cows and humans can serve as reservoirs. Humans can also be infected by the consumption of unpasteurised milk. This route of transmission can lead to the development of extrapulmonary TB, exemplified in history by bone infections that led to hunched backs.
Other human pathogens belonging to the Mycobacterium genus include Mycobacterium avium which causes a TB-like disease especially prevalent in AIDS patients, and Mycobacterium leprae, the causative agent of leprosy.
Mycobacterium tuberculosis is an obligate aerobe. For this reason, in the classic case of tuberculosis, MTB complexes are always found in the well-aerated upper lobes of the lung

The disease tuberculosis
TB infection means that MTB is in the body, but the immune system is keeping the bacteria under control. The immune system does this by producing macrophages that surround the tubercle bacilli. The cells form a hard shell that keeps the bacilli contained and under control. Most people with TB infection have a positive reaction to the tuberculin skin test. People who have TB infection but not TB disease are NOT infectious, i.e., they cannot spread the infection to other people. These people usually have a normal chest x-ray. TB infection is not considered a case of TB disease. Major similarities and differences between TB infection and TB disease are given in the table below.
Predisposing factors for TB infection include
l Close contact with large populations of people, i.e., schools, nursing homes, dormitories, prisons, etc.
l Poor nutrition
l Iv drug use
l Alcoholism
l HIV infection is the 1 predisposing factor for MTB infection. 10 percent of all HIV-positive individuals harbour MTB. This is 400-times the rate associated with the general public

Tuberculosis treatment
Because administration of a single drug often leads to the development of a bacterial population resistant to that drug, effective regimens for the treatment of TB must contain multiple drugs to which the organisms are susceptible. When two or more drugs are used simultaneously, each helps prevent the emergence of tubercle bacilli resistant to the others. However, when the in vitro susceptibility of a patient’s isolate is not known, which is generally the case at the beginning of therapy, selecting two agents to which the patient’s isolate is likely to be susceptible can be difficult, and improper selection of drugs may subsequently result in the development of additional drug-resistant organisms.

A vaccine against MTB is available. It is called BCG (Bacillus of Calmette and Guerin, named after the two Frenchmen that developed it). BCG consists of a live attenuated strain derived from Mycobacterium bovis. This strain of Mycobacterium has remained avirulent for over 60 years. The vaccine is not 100% effective. Studies suggest a 60-80% effective rate in children.

Tuberculosis (MDR TB) and Extensively Drug-Resistant Tuberculosis (XDR TB)
Resistance to anti-TB drugs can occur when these drugs are misused or mismanaged. Examples include when patients do not complete their full course of treatment; when health-care providers prescribe the wrong treatment, the wrong dose, or length of time for taking the drugs; when the supply of drugs is not always available, or when the drugs are of poor quality.
Multidrug-resistant tuberculosis (MDR TB) is TB that is resistant to at least two of the best anti-TB drugs, isoniazid and rifampicin. These drugs are considered first-line drugs and are used to treat all persons with TB.
Extensively drug resistant TB (XDR TB) is a relatively rare type of MDR TB. XDR TB is defined as TB which is resistant to isoniazid and rifampin, plus resistant to any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin). Because XDR TB is resistant to first-line and second-line drugs, patients are left with less effective treatment options, and cases often have worse treatment outcomes.
Both MDR TB and XDR TB are more common in TB patients that do not take their medicines regularly or as prescribed, or who experience reactivation of TB disease after having taken TB medicine in the past.


A landmark happening in Sri Lanka

The DOTS treatment method has been successfully implemented in Sri Lanka for the past decade but it was limited to the government health sector. But as a land mark happening in Sri Lanka, two DOTS treatment centres were opened at two private hospitals in Sri Lanka, namely Asiri Medical Hospital at Narahenpita and Hemas Hospital at Wattala.
According to the officials of the National Programme for the Control of Tuberculosis and Chest Diseases, this will be expanded to the private sector hospitals in all the districts in Colombo in the future. This was a need to cater to a sector of the population who patronize the private sector health services rather than the public sector.
According to the District TB Control Medical Officers of Colombo and Gampaha, the services at both hospitals will be completely free for the patients and the centre will be open for twenty four hours of the day. This is to enable people to take their treatment after working hours.
Speaking at the opening of the DOTS centre at Asiri Hospital, Health Minister Maithripala Sirisena said that every year around 11,000 new Tuberculosis (TB) patients are discovered and 2,000 of them are from Colombo. Out of this number, 1,000 are detected from the Colombo Municipality. The Minister further mentioned the rapidly increasing population in the Colombo city, environmental pollution, and similar reasons are behind the increasing number of TB patients in the Colombo city. In the early nineties, TB was a scary disease that could not be cured. But now TB can be completely cured within six months with proper treatment.
Minister Sirisena pointed out that private and public sectors should join hands to deliver a better service to the public. President Mahinda Rajapaksa’s Government always promotes the partnership between State and private sector. A healthy society can be created with the participation of both the State and private sector.
People like to visit private hospitals when they are concerned about their privacy and the confidentiality. Therefore they like to get treatment for TB from private hospitals than State hospitals.


What is DOT

Directly Observed Treatment (DOT) and the method is that a trained health care worker or other designated individual (excluding a family member) provides the prescribed TB drugs and watches the patient swallow every dose.
Why use DOT’S?
We cannot predict who will take medications as directed, and who will not. People from all social classes, educational backgrounds, ages, genders, and ethnicities can have problems taking medications correctly.
Studies show that 86-90% of patients receiving DOT complete therapy, compared to 61% for those on self-administered therapy.
DOT helps patients finish TB therapy as quickly as possible, without unnecessary gaps.
DOT helps prevent TB from spreading to others.
DOT decreases the risk of drug-resistance resulting from erratic or incomplete treatment.
DOT decreases the chances of treatment failure and relapse.
Who can deliver DOT’S?
A nurse or supervised outreach worker from the patient’s county public health department normally provides DOT.
In some situations, it works best for clinics, home care agencies, correctional facilities, treatment centers, schools, employers, and other facilities to provide DOT, under the guidance of the local health department.
Family members should not be used for DOT. DOT providers must remain objective.
How is DOT’S administered?
DOT includes:
delivering the prescribed medication
checking for side effects
watching the patient swallow the medication
documenting the visit
answering questions
DOT should be initiated when TB treatment starts. Do not allow the patient to try self-administering medications and missing doses before providing DOT. If the patient views DOT as a punitive measure, there is less chance of successfully completing therapy.
The prescribing physician should show support for DOT by explaining to the patient that DOT is widely used and very effective. The DOT provider should reinforce this message.
DOT works best when used with a patient-centered case management approach, including such things as:
helping patients keep medical appointments
providing ongoing patient education
offering incentives and/or enablers
connecting patients with social services or transportation
Patients taking daily therapy can usually self-administer their weekend doses.
How can a DOT’S provider build rapport and trust?
1. “Start where the patient is.”
2. Protect confidentiality.
3. Communicate clearly.
4. Avoid criticizing the patient’s behavior; respectfully offer helpful suggestions for change.
5. Be on time and be consistent.
6. Adopt and reflect a nonjudgmental attitude.

Tuberculosis: Infection vs Disease

TB Infection TB disease in lungs
MTB present MTB present
Tuberculin skin test positive Tuberculin skin test positive
Chest X-ray normal Chest X-ray usually reveals lesion
Sputum smears and cultures negative Sputum smears and cultures positive
No symptoms Symptoms such as cough, fever, weight loss
Not infectious Often infectious before treatment
Not defined as a case of TB Defined as a case of TB


Drug relapse brain region found

Scientists in the US have identified an area of the brain which makes heroin-addicted rats relapse.
The study, published in Nature Neuroscience, showed that part of the medial prefrontal cortex was activated.
When the researchers blocked nerve cells in the region, there were fewer relapses.
Experts in the UK said the study was a technical ‘tour de force’; however, it did not promise new treatments in humans.
The study worked on the idea that when addicts stopped taking drugs, but then returned to the place they were taking drugs, they were likely to relapse.
Rats were trained to take drugs in one environment, where they were delivered a dose of heroin.
The rodents then “went to rehab” in another environment where the feel of the floor, lights and sounds were different and there was no access to heroin.
Once the rats were “clean” they were returned to the drug-taking environment, where they demonstrated heroin-seeking behaviour.
By examining the rats’ brains, the researchers showed increased activity in some neurons in the medial prefrontal cortex.
They then used drugs, muscimol and baclofen, to selectively inhibit this region. Heroin-seeking activity was then decreased.
Dr Jennifer Bossert, from the National Institute on Drugs Abuse in the US, told the BBC: “There are two main implications, at a research level we’ve demonstrated this cause/effect relationship in a specific set of activated neurons.
“In the clinical setting, heroin relapse is different to cocaine relapse so drug relapse is probably caused by different circuits for different drugs, which would have consequences for medication.”
She also warned about transferring the findings into humans, saying: “You have to be very careful, you can’t. Human addicts are very different to rat models, they’re often multi-drug users, they’re complex.”
Ian Stolerman, Emeritus Professor of Behavioural Pharmacology at King’s College London, said: “It’s a considerable achievement, it’s a research tour de force, which sheds new insight into the nerve cells in the brain which are important for drug-seeking behaviour in animal models.”
“It doesn’t, however, suggest a route for new treatments in the near future.”
(BBC Health)


Key breast cancer ‘driver’ gene found

Cancer experts have identified a gene which can cause a particularly aggressive form of breast cancer to develop.
ZNF703 is the first “oncogene” to be discovered in five years.
It is overactive in around one in 12 breast cancers.
Cancer Research UK, whose scientists carried out the work, said the gene was a “prime candidate” for the development of new breast cancer drugs.
An oncogene is one which would normally help instruct healthy cells to divide but if it becomes overactive, it upsets the normal checks and balances that control that process.
That damage is described as being “like a car’s accelerator becoming stuck down”, and the cell and all its daughter cells are permanently instructed to divide.
Her2 – another oncogene – is already tested for. The drug Herceptin was developed to treat Her2 positive breast cancers.
In two patients studied, ZNF703 was the only gene shown to be overactive, showing it was driving the development of the cancer.
Professor Carlos Caldas, of the Cambridge Research Institute, who led the research, said: “Scientists first discovered this region of DNA may be harbouring genes linked to the development of breast cancer 20 years ago.
“But it’s only with the technology we have today that we’ve been able to narrow down the search sufficiently to pinpoint the gene responsible.”
He added: “Crucially, testing whether this gene is overactive in a patient’s tumour could help highlight those more likely to be resistant to standard hormone therapies, helping to make sure the right drugs are matched to the right patient.”
Dr Lesley Walker, director of cancer information at Cancer Research UK, said: “This is the first gene of its kind to be discovered in breast cancer for five years.
“This is exciting because it’s a prime candidate for the development of new breast cancer drugs designed specifically to target tumours in which this gene is overactive.
“Hopefully this will lead to more effective cancer treatments in the future.”
Dr Rachel Greig, of Breakthrough Breast Cancer said the research was “a vital step in understanding the genes that drive the growth of some types of breast cancer.”
(BBC Health)