What Is Tuberculosis?

Tuberculosis or popularly known as its abbreviated form TB, is a bacterial infection caused by a bacterium called Mycobacterium tuberculosis. Lungs usually are the target of the disease but the bacterium can often attack spine, brain, and kidneys too. If not treated properly the disease can be potentially fatal.

Not everyone infected with the bacteria will show symptoms of the disease. Two common types of TB infections exist; he latent TB infection (LTBI) and the TB disease. The disease is highly communicable especially in closed quarters.

The bacteria often spread through air with the help of particulates. When a person infected with the bacteria coughs, sings, speaks: the Mycobacterium tuberculosis bacteria can travel through air which other uninfected people can breathe in, thus becoming infected.

Though highly contagious the bacteria does not spread through sharing of food or drinks, sharing tooth brushes, shaking someone’s hand, or kissing.

When a person breathes in the bacteria, it can settle in the lungs where it begins to reproduce. The organism can than spread to a person’s other body parts like spine, brain, or kidneys through his or her blood stream. The people than becomes a carrier for the bacteria and can potentially infect anyone.

Friends, family, co workers and other people dealing on day to day basis with the infected individual are at a greater risk of acquiring the bacteria and becoming sick themselves.

How the infection displays itself directly depends on where in the body the bacterium is reproducing. When the TB infection is primarily present in the lungs, symptoms like persistent cough for three or more weeks, pain in the chest, and coughing with blood and sputum which is phlegm from deep in the lungs, are often present.

Other symptoms for the TB disease include weight loss, no appetite, fever, sweating at night, chills, and weakness often accompanied by fatigue.

Patients who have the Latent Tuberculosis Infection are often asymptomatic, that is they do not show any signs of the disease. The bacteria can sometimes grow and reproduce in the body without making a person sick. Often people who get infected are able to fight of the bacteria and stop it from growing.

People with such TB infection often do not feel sick; give positive results when tested for the TB skin test or TB blood test, may develop the TB disease if not receiving treatment and most importantly cannot spread the disease to others. Sometimes the TB infection can remain latent in a person for a lifetime without morphing into a disease.

People with compromised immune systems, can have latent bacteria becoming active, multiplying and causing the disease

On the other hand the second form of the TB infection, The Tuberculosis Disease can be potentially fatal. When bacteria are actively reproducing in a person’s body, the condition is termed as the TB disease. These people often show symptoms like the ones mentioned above and are active spreaders of the disease.

Approximately one third of the world’s population is believed to be infected by the TB bacteria, Mycobacterium tuberculosis and in United States

  • 2 percent Americans (13 million people) are infected with TB bacteria
  • CDC estimates that six percent of all the cases and ten percent of the cases among people aged 25-44 occur in patients with HIV/AIDS

What Is Tuberculosis? And What Is Multi-drug Resistant Tuberculosis?

Drug resistant TB occurs when some bacteria becomes resistant to the effects of antibiotics, which can be due to multiple reasons such as people leaving the treatment halfway, using drugs of poor quality for treatment, taking drugs irregularly and coming from areas where drug resistant TB is very common.

There are two types of such infections, multidrug-resistant TB (MDR TB) and extensively drug-resistant TB (XDR TB); where former is resistant to only a few antibiotics but the latter is resistant to multiple potent TB drugs. Extensively drug-resistant TB (XDR TB) is extremely hazardous for patients with weakened immune systems such as the ones with HIV.

WHO estimates that five percent of the cases are multi drug resistant. This constitutes of almost 480 000 cases and 190 000 deaths each year. Nearly nine percent of the patients

Tuberculosis Symptoms

If Mycobacterium tuberculosis is activated in the body and their population grows, the person will develop sickness from a latent TB infection.

The TB disease manifests symptoms and may spread TB bacteria to others.
TB bacteria most commonly grow in the lungs, and can cause symptoms such as:

  • Chronic coughing for 3 weeks
  • Mild to severe chest pain
  • Blood during coughing and spitting
  • Loss of appetite
  • Loss of weight
  • Fatigue
  • Sweating
  • Cold
  • Fever

How Tuberculosis is Diagnosed?

Tuberculosis latent infection is often detected with the help of screening and diagnostic testing. Screening tests help identify potential disease indicators in a large population setting of apparently healthy individuals whereas diagnostic testing is used to confirm the presence or absence of the disease which can sometimes be invasive and expensive.

To minimize risk and make the process economically productive, the person is first screened for a disease. If the test shows a positive result, the diagnosis is confirmed through a clinical test which confirms the finding. Same is the case for the TB testing.

People identified to be exposed to potential risk factors of the TB disease are first screened using either Tuberculin Skin Test (TST) or the interferon-gamma release assay (IGRA). Those testing positive for the disease indicators along people showing suspected symptoms of the TB disease are than tested with an established clinical diagnostic test.

Tubercukin Skin Test (TST)

TST or Mantoux test works by identifying people with previous sensitization to the Mycobacterium antigens. Testing involves injecting the forearm of the person with an in dermal injection of tuberculin protein; purified protein derivative or PPD.

The protein stimulates the delayed type hypersensitivity response, which is mediated by the T- lymphocytes. The response can be seen within the 48 to 7 2hours of the injection in the form of a red bump. If a person does not have a latent infection, the skin does not react to the injection. If the person had been vaccinated for Tuberculosis, the skin might show a slight skin reaction that does not mean you have latent TB infection.

False positives and negatives in the test can be the result of nontuberculosis myobacteria infection, vaccination for the bacteria and the suppressed immune system as a result of HIV co- infection.

Interferon -Gamma Release Assays (IGRA).

The IGRA is a type of blood test which can help identify presence of latent TB infection and is becoming widely available now. It can help with diagnosing the infection if a person tests positive for a Montoux test, if someone has had the BCG vaccination or had treatment which can potentially suppress the immune system. Health care workers performing their duties in close proximity to TB infected individuals may be advised to get regularly tested by this test.

The test cannot differentiate between latent infection and the active disease and is not advised to be used to confirm the presence of TB disease. The test performed on a blood sample can present results in 24 to 48 hours.

The types of assays used are QuantiFERON-TB Gold In-Tube (QFT-GIT) assay manufactured by Cellestis Limited, Carnegie, Australia and the T-SPOT.TB assay manufactured by Oxford Immunotec, Abingdon, United Kingdom.

The QFT-GIT, an immunosorbent enzyme linked assay uses peptides from three individual TB antigens to help indicate presence of a TB infection. The result is considered positive if the antigen-specific interferon-gamma level exceeds a standard pre decided value limit, after subtracting the interferon gamma value in the negative control.

The T-SPOT.TB, an immunospot enzyme linked assay is performed on separated and counted peripheral mononuclear cells from the blood.

The number of interferon gamma producing T cells (spot forming cells) is counted. If the number of the spot forming cells exceeds a particular standard value in the TB antigen wells, the results are deemed positive.

What Is Tuberculosis? Diagnostic Test For Tuberculosis

In resource rich settings, such as high income and most middle income countries a chest x-ray is advised to diagnose the TB disease. Other methods such as sputum smear examinations, culture, appropriate molecular tests such as Xpert MTB/RIF assay by the company Cepheid Inc, United States, may be used to rule out active TB. The Xpert MTB/RIF assay is a superior diagnostic tool than sputum smear examination as it can simultaneously identify Mycobacterium Tuberculosis and rifampin resistance.

In limited resource settings such as poor income countries, WHO advises that the patients be only screened for symptoms like cough, fever, etc, before initiation of LTBI therapy in the absence of sputum culture.

Rapid testing is done through Nucleic Acid Amplification (NAA) tests which detect nucleic acid sequences unique to organisms in the M tuberculosis bacterium. Only one NAA test is currently approved in United States by the FDA, known as the Amplified Mycobacterium Tuberculosis Direct Test (MTD; Gen-Probe). The test is only used for patients who are not yet treated for TB.

Treatment Of Latent TB Infection 

Treatment of latent TB is only initiated after the possibility of TB is excluded. Treatment preference is given to the people with positive results of IGRA test or TST reaction of five millimeters or more and people with HIV, people who have had recent contact with a TB case, organ transplant recipients, people which are immune suppressed, or show fibrotic changes on chest radiographs consistent with old TB.

People with risk factors like immigrants from high prevalence countries, injection drug users, laboratory personnel, children under the age of four, and residents of congregate settings like homeless shelters, nursing homes are given priority if they have positive results of IGRA test or TST reaction of ten millimeters or more.

Even though targeted TB testing programs are advised in high risk groups. People with no risk factor exposure and positive results of IGRA test or TST reaction of fifteen millimeters or more are treated with the LTBI regiment.

Regimens For Latent TB Infection

Four kinds of treatment regimens are available for the latent TB infection and all of them use isoniazid (INH), rifapentine (RPT), or rifampin (RIF). These drugs in different combinations are used to treat Tuberculosis, else than the case of drug resistant TB disease, where consultation with a TB expert and modification of regiment is advised.

  • First regiment prescribes Isoniazid for duration of nine months. People with HIV, pregnant women, and children between 2-11 years of age are kept on a daily dose. Pregnant women can also be treated with the drug two times a week employing a DOT strategy.
  • Second regiment can be used to treat patients for only six months following the same protocols as the first regiment of daily and twice weekly schedule.
  • Third regiment prescribes Isoniazid in combination with Rifapentine, for a period of three months with drugs administered once weekly using DOTS.
  • The fourth regiment suggests use of Rifampin daily for a period of four months.

DOTS or Directly observed therapy strategy is used to ensure proper and timely administration of the medicine. A patient meets with a healthcare worker or a designated family member every time he or she has to take a dose. The patient takes the medicine as the healthcare worker watches.

New 12 Dose Regiment For Latent Tuberculosis 

A new twelve dose regiment uses rifapentine and isoniazid once a week for every twelve weeks to treat latent TB infection. The treatment course however is not recommended to be used in patients with HIV on antiretroviral therapy, children under the age of two and women already pregnant or planning to pregnant during the course of the treatment.

Treatment For Tuberculosis

It is very important for a person with TB disease to take their medication correctly. If a patient stops earlier than needed the bacteria in the body can become drug resistant and the person can fall ill again. The disease is treated with continuous therapy of 6 to 9 months with any of the ten drugs currently approved by the US FDA for the treatment which can include isoniazid (INH), rifampin (RIF), ethambutol (EMB), and pyrazinamide (PZA).

Treatment for the drug resistant TB infection is complicated. Multidrug-resistant TB (MDR TB) is often resistant to one anti TB drug and at least rifampin and isoniazid.

A new treatment course for MDR TB has recently been approved by the WHO. At less than US$ 1000 per patient the new treatment would last for only 9 -12 months. Previously, this kind of infection was treated with extensive duration of more than 2 years. The longer treatment yielded low cure rates of only fifty percent as patients do not comply with their dosage schedules.

The shorter treatment is for patients with uncomplicated MDR-TB, like patients whose infection is not resistant to the most of important drugs such as fluoroquinolones and injectables also known as “second-line drugs”.

Extensively drug-resistant TB (XDR TB) is a rare type where the bacteria is resistant to rifampin, isoniazid, any fluoroquinolone and at least one of three injectable second-line drugs such as kanamycin, amikacin, and capreomycin. In such scenarios only a TB expert is used for specifically tailored regiments of treatment for each case.

These new recommendations are not based on data from any clinical trials, but were designed by some organizations working on the disease. The protocols have been successfully tested in nearly a thousand people in different settings and are being tested in an official trial in Mongolia.

Adverse events experienced by the patients on the treatment courses, such as Persistent paresthesia, persistent weakness, fever, abdominal tenderness, and fatigue, bleeding, bruising and vision change along with anorexia, nausea and vomiting should be reported to a health worker.

WHO’s “End TB Strategy”, being utilized by all the WHO member States, aims at reducing TB deaths by 90%, TB incidence by 80%, and to eliminate any catastrophic costs for households affected by the disease till the year 2030.

Risk Factors And Prevention Of Tuberculosis

Nearly five to ten percent people infected with latent TB acquire the disease at some point in their lives. Two type people are at high risk for developing the disease; the ones recently infected with the bacteria or the ones with medical conditions that weaken their immune responses.

A person is at a greater risk of being infected with the bacteria if:

  • He has spent time with a person who has the disease
  • He has visited a country or a place where TB prevalence is very high
  • He or she has continuous interaction with people who have the disease (for example working in a homeless shelter, jail, or prison)
  • He is a healthcare worker who has continuous dealings with people who are at an increased risk of TB

Once infected with the bacteria, the chance that a person will acquire the disease increase

  • If a person has HIV
  • If the infected person is a child under the age of 5
  • If a person has recently been infected like in the last two years
  • If a person has other diseases
  • If a person has drug abuse issues or he or she smoke tobacco cigarettes
  • If the person has not been treated correctly for the infection or disease in the past

Prevention of Tuberculosis is fundamental to achieve targets set by the WHO “End TB Strategy” and prevent disease occurrence. This entails designing programs which protect people against any future infections, such as vaccination programs along with interrupting transmission cycles which ensures program safety for health workers and other community residents.

Tuberculosis Infection Control 

Infection control in health care settings is ensured through timely detection, installing safety measures and providing early treatment interventions where needed.

The first level of control, administrative, is ensured by minimizing the areas of exposure for the bacteria and includes measures like

  • Making someone responsible for infection control in the health care setting
  • Conducting routine TB risk assessments for the facility
  • Developing and implementing a plan to control TB
  • Ensuring continuous and proper working of laboratory process for quick and accurate diagnosis and testing services
  • Managing the patients who have the disease
  • Ensuring proper sterilization and disinfection procedures
  • Educating and training health care workers for better counseling of patients and visitors
  • Evaluating and testing healthcare workers at greater risk of acquiring the infection and the disease
  • Using epidemiological prevention principles to prevent infection spreading in the facility and outside
  • Using poster, signs and visual aids to remind people of the preventive measures like covering the mouth while coughing
  • Coordinating these efforts with other healthcare facilities to ensure more coverage

Second level, the environmental control, ensures reduced concentrations of the bacterium in the air.

  • Primary controls ensure the control of the source of infection. Like dilution and removal of the contaminated air with the help of general ventilation or exhaust ventilation.
  • Secondary controls are there to prevent the spreading of contaminated air to other areas, with the help of ultraviolet germicidal irradiation or high efficiency particulate air (HEPA) filtration.

The third level is the use of respiratory protective equipment in high risk scenarios.

  • Respiratory protection in the form of particulate filter respirators can be used. National Institute for Occupational Safety and Health (NIOSH) attached with the CDC, has certified several of these respirators for this particular use. Some of them include high-efficiency filters known as Powered air purifying respirators and non powered respirators with N, R, and P filters of numbers 95, 99, and 100.

NIOSH administration requires development, designing, adoption, management and periodic review of a respiratory protection program. The key elements of such a program are responsibility assignment, training and testing the efficiency of the program.

What Is Tuberculosis Vaccination With BCG?

Bacille Calmette-Guérin (BCG) is a tuberculosis vaccine. Though not efficient one hundred percent of the time, it is often given to children in countries other than United States to protect them from acquiring the TB disease.

In America the vaccine is only given to selected people who meet specific criteria with the help of TB specialist. For children the vaccine is only considered when

  • They have a negative TB test
  • They are continuously exposed to the disease
  • And cannot be separated from the adults who are untreated or ineffectively treated for the TB disease, have drug resistant TB, and the child cannot be given long term preventive treatment for tuberculosis

For healthcare workers, the cases are decided individually for administration of the vaccine usually when

  • High percentages of patients in the given facility are infected with both isoniazid and rifampin resistant strains of TB.
  • There is an ongoing transmission of drug resistant strains to the workers
  • TB infection control protocols, mentioned above, have failed.

The BCG vaccine is recommended to be given as early as possible after birth in high endemic areas but should not be given to HIV/AIDS positive babies.

The vaccine’s wholesale cost is at 0.16 USD per dose since 2014 and in United States it costs from $100-$200. Globally the vaccine is given to almost 100 million children per year.

The vaccine is administered in the form of intradermal injection, which can cause pain and scarring at the site of the infection. The vaccine is never given to an immunocompromised patient, even when they are at high risk for tuberculosis disease. It is also used in treatment of cancer sometimes, like bladder cancer.

TB And HIV Co Infection

Human Immunodeficiency Virus (HIV) is closely linked to TB. The disease is the most common opportunistic infection which affects HIV seropositive individuals worldwide and is also the most common cause of death amongst patients with AIDS.

HIV infection has increased the worldwide incidence of TB by progressively declining cell mediated immunity thus altering the pathogenesis of TB and increasing risk of TB in HIV infected individuals.

The risk of rapid progression of HIV in patients with HIV infection is much greater as HIV hinders the human immune system’s ability of containing a new TB infection.  When a person with a normal functioning immune system acquires TB, he or she has 10% lifetime risk of developing TB with half of the risk occurring in the first 1-2 years after infection. However in a patient with HIV the chances of developing TB are 20-30 times more than those who do not have HIV.

In several outbreaks it has been observed that patients with HIV, who were exposed to TB bacterium contaminated air, developed the disease with 60 to 100 days of exposure.

Tuberculosis is also affected by the extent of immunosuppression of HIV patients. In patients with CD4 cell counts below 350, the clinical presentation of TB was similar to those who did not have HIV. However in patients with advance immunosuppression, the radiograph presentation was less typical and the disseminated disease became more common.

Many people with HIV gives a false negative result in TB sputum smear test, leading to many of the cases going undiagnosed. Other tests are advised to make diagnosis in such sensitive cases.

The Stop TB Partnership’s Global Plan to Stop TB had planned to test all patients with TB for HIV infection by the end of year 2015.

Research efforts into the disease are vital, with three of them deserving of special attention.

  • TB trials consortium (TBTC)

It is a special collaboration project of international clinical investigators and North America, to conduct scientifically relevant research related to diagnosis, management, and prevention of Tb infection and disease.

  • TB epidemiologic studies consortium (TBESC)

TBESC is a special and significant project that focuses on strengthening and coordination of Tuberculosis (TB) research. It helps with building scientific research capabilities of the metropolitan and state TB control programs, with special focus on laboratories, hospitals, academic institutes, relevant organization including for profit and non profit.

  • Behavioral and Social Science Research

The research collaboration has a two prong approach 1) how behaviors of relevant parties affect the actual TB related healthcare activities like treatment, diagnosis, and prevention 2) how social influences affect health seeking behaviors and outcomes related to the disease. This type of research is fundamental to elimination efforts directed towards TB.

UN Global Fund For Tuberculosis Prevention 

The United Nations Global Fund to fight AIDS, Tuberculosis, and Malaria (GFATM) is a financing organization that provides additional support if needed to fight and treat the three diseases.

The organization started working in January 2002 and Bill Gates (founder of Microsoft) was one of the first people who provided initial investment for the project. Other key influencers of the organization are Ban Ki-Moon, Bill Clinton, Tony Blair, Jeffery Sachs, and Bono. It has provided more than 22.9 billion dollars to support more than a thousand programs to control these diseases all over the world.

The organization has provided treatment for more than 9.3 million people suffering from tuberculosis.

 

CO Author : Huda Munir

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