Finally, expensive, long-term therapy, disturbed therapeutic regimens, dosage variance and irregularity in follow up, form additional challenges for an effective TB management (Lawn and Zumla, 2011).
What are the challenges of tuberculosis (TB) control?
The continuing challenges of TB control can be distributed into 5 key areas: inadequate diagnostics and treatment; the need for expansion of the World Health Organization (WHO) Directly Observed Therapy, short course (DOTS) program; multidrug-resistant tuberculosis (MDRTB); and HIV coinfection.
What's new in TB research?
A recent new development is the whole-blood interferon γ assay, which detects interferon in response to TB challenge, and is currently being validated in the field. 2, 4 Diarylquinolone is an encouraging new treatment initiative that appears to be highly active against TB (including MDRTB) and requires shorter periods of treatment.
What is the current treatment for tuberculosis (TB)?
Current tuberculosis (TB) treatment is based on a combination of drugs that were developed mostly in the central decades of the last century. Cure rates are high for drug sensitive strains of Mycobacterium tuberculosis (M. tb) when the recommended complex and lengthy treatment protocols are adhered to.
Why is TB care so different around the world?
Even when people are able to overcome the barriers to accessing help for their TB, the quality of health systems varies widely throughout the world due to a number of challenges including: a lack of community participation in planning services.
Why is TB treatment challenging?
Tuberculosis treatment is a combination of antibiotics taken for half a year or more—a major drawback, because patients often quit therapy prematurely, increasing the risk of drug-resistant strains emerging.
What three 3 measures can be taken to control tuberculosis on a community level?
According to the CDC guidelines1,2, a TB infection control program should be based on the following three levels of hierarchy: (1) administrative control, which reduces the risk of exposure; (2) environmental control, which prevents the spread of the disease and reduces the concentration of droplet nuclei; and (3) ...
What is an emerging problem with the treatment of tuberculosis?
A major problem in the management of TB infection is the development of MDR-TB in the two most commonly used drugs: isoniazide and rifambicine. MDR-TB is characterized as a significant problem by WHO as 300.000 new MDR cases are recognized every year.
What is the most common cause of tuberculosis treatment failure?
Some of the factors associated with treatment failure include poor drug compliance, primary drug-resistant TB, lack of efficacious anti-TB drugs, and presence of comorbidities such as HIV infection and diabetes mellitus.
What is the most effective way to prevent transmission of TB in the community?
The risk of infection can be reduced by using a few simple precautions:good ventilation: as TB can remain suspended in the air for several hours with no ventilation.natural light: UV light kills off TB bacteria.good hygiene: covering the mouth and nose when coughing or sneezing reduces the spread of TB bacteria.
What are the complications of TB?
Without treatment, tuberculosis can be fatal. Untreated active disease typically affects your lungs, but it can affect other parts of your body, as well....Tuberculosis complications include:Spinal pain. ... Joint damage. ... Swelling of the membranes that cover your brain (meningitis). ... Liver or kidney problems. ... Heart disorders.
What are the 3 stages of TB?
There are 3 stages of TB—exposure, latent, and active disease. A TB skin test or a TB blood test can diagnose the disease. Treatment exactly as recommended is necessary to cure the disease and prevent its spread to other people.
What method monitors the effectiveness of the treatment regimen for TB?
The use of sputum smear microscopy and culture rather than sputum smear microscopy alone is recommended for the monitoring of patients with multidrug-resistant TB (MDR-TB) during treatment (conditional recommendation/very low quality evidence) (2).
What are the 3 types of tuberculosis?
Tuberculosis: TypesActive TB Disease. Active TB is an illness in which the TB bacteria are rapidly multiplying and invading different organs of the body. ... Miliary TB. Miliary TB is a rare form of active disease that occurs when TB bacteria find their way into the bloodstream. ... Latent TB Infection.
When does TB treatment fail?
Treatment failure of TB, which is defined as a patient who is sputum smear or sputum culture positive at 5 months or later after the initiation of anti TB treatment, 3 is one of the threats to the control of TB.
How do you know if TB treatment is not working?
Testing to Monitor Tuberculosis Treatment Examining the sputum at regular intervals lets your doctor know the condition of your lungs — to confirm that the active tuberculosis disease is regressing and treatment is progressing the way that it should.
What causes TB to relapse?
TB recurrence can be due to either reactivation of the same strain, i.e., relapse, or reinfection with a new strain. Recurrence due to reinfection has become an area of intense study due to its perceived significance in TB endemic settings with high rates of human immunodeficiency virus (HIV) coinfection.
Is TB increasing in Africa?
Rates of tuberculosis (TB) are also increasing rapidly in Africa , in parallel with the HIV/AIDS epidemic. The continuing challenges of TB control can be distributed into 5 key areas: inadequate diagnostics and treatment; the need for expansion of the World Health Organization (WHO) Directly Observed Therapy, short course (DOTS) program;
Does sputum smear detect TB?
Sputum-smear microscopy, which was developed in 1882, does not detect extrapulmonary or smear-negative TB, and is less effective in children and people infected with HIV, whose smear results are often negative. 1 Most laboratories also lack the facilities to identify MDRTB. 2.
Why can't I seek treatment for TB?
Delaying treatment. People may not seek treatment for a range of reasons including: stigma can make them reluctant to seek help for unexplained symptoms, for fear of receiving a diagnosis of TB.
How many people can get TB every year?
This has implications for both their own health and the health of others, as someone with untreated infectious TB can pass it on to 10-15 people every year.
Why do people not seek treatment?
People may not seek treatment for a range of reasons including: 1 stigma can make them reluctant to seek help for unexplained symptoms, for fear of receiving a diagnosis of TB 2 poverty can make it difficult for people, particularly women, to prioritise their health over other demands on resources: the threat of lost income and the costs of travel can stop people seeking appropriate help even where treatment is free 3 many people simply do not know about tuberculosis or recognise their symptoms as TB 4 people from the marginalised communities that are most often affected by TB may distrust health services, be unaware of their rights to treatment or lead chaotic lifestyles that prevent them from accessing care; others may favour the traditional healers and private practitioners they are familiar with, who may know little about TB.
Why is TB treatment so long?
As previously stated, the primary reason why current TB therapy requires a long treatment duration is that some of the bacteria in the infection can enter what is defined as a “persistent” state and become phenotypically, although not genetically, resistant to the treating drugs [5]. The development of drugs that target proteins essential for persistence should enable more rapid clearance of the infection. It has been very difficult to identify these drug targets and validate them as being essential to the persistent bacteria. In M. tb, persistence appears to involve a switch of metabolism to the glyoxylate shunt, and therefore a shift in carbon source to acetyl CoA generated by -oxidation of fatty acids [35]. The best characterized mycobacterial enzyme in this metabolic pathway is isocitrate lyase, encoded in fact by two genes in the M. tb genome – icl1 and icl2. Inhibition of both appears to be required for complete inhibition of M. tb growth in the persistent state [36]. Icl1 and icl2 have been the object of intensive high-throughput screening (HTS), however, due to the need to inhibit both enzymes and the fact that the isocitrate lyase active site is very small and hydrophilic, this effort has not been successful to date and the target is considered not easily “druggable”. As a result, effort has now focused on the next enzyme in the glyoxylate shunt, malate synthase, which appears to be a more promising target based on its larger, hydrophobic active site. It is currently the focus of joint efforts by researchers in academia (Texas A&M University and Rockefeller University), the pharmaceutical industry (GSK), and the TB Alliance to complete target validation and identify specific inhibitors. To provide direct evidence of this target’s relevance, the first step will be the demonstration that inhibition of malate synthase in vivo kills persistent M tb. Compounds that show good potency will undergo further characterization and will be examined in whole cell and animal models of acute and persistent infections. If successful, a lead malate synthase inhibitor could be entered into preclinical development within the next two to three years and would represent a completely novel class for the treatment of TB. Such an agent could potentially shorten TB treatment through potent killing of persistent bacteria, and provide a novel treatment in the armamentarium against drug-resistant as well as drug-sensitive disease.
How long does it take to treat TB?
The regimens currently recommended for treatment of drug-sensitive TB are considerably simpler than the initial TB treatment regimens, having been shortened from two years to six months ; however they are still far from optimal. A major focus of current efforts in TB drug development therefore is the identification and registration of shorter, simpler treatments. The development of a two to three month regimen with once weekly dosing of three to four drugs would result in decreasing the duration of treatment from the currently recommended twenty-eight weeks to eight to twelve weeks, and from approximately one hundred and thirty doses of a combination regimen to ten. Such a change should have a significant positive impact on control of the disease by improving patient adherence, and on inhibiting development of drug resistance by improving treatment completion rates. However, reaching this objective of a two month regimen will likely require a substantially new therapeutic armamentarium. As previously stated, one of the key challenges in the field of TB drug development is that the therapeutic unit is a combination regimen, not a single drug. It has been estimated that the clinical testing of a TB combination regimen containing a single new compound requires a minimum of six years. Assuming that the adoption of a new combination would be immediate, and that one could move from one new combination to the next one with no idle time, a simple mathematical operation allows one to conclude that in order to go from an existing and accepted combination of four drugs to a totally new four-drug combination by substituting the four components serially would require a minimum of twenty-four years. This is clearly not an acceptable timeframe given the severity of the TB epidemic globally, and therefore alternative development approaches must be found. A new paradigm is needed for the rational selection and development of new drug combinations. Pre-clinical combination testing is an essential step in the search for a combination that will allow shortening treatment duration to two months, have no interactions with ARVs and be effective against MDR-TB. Preclinical combination testing should proceed in parallel with testing individual new drugs in standard Phase I and early proof of concept studies, followed by testing optimized combinations as the developmental unit in human studies to evaluate their PK interactions, safety, tolerability, early bactericidal and sterilizing activity. An extensive effort of this kind should lead to the identification of a very small number of drug combinations deserving further pre-clinical and clinical development. This approach will require a new cooperation amongst sponsors and a true paradigm shift, both among researchers and regulators. Finally, this approach should ideally be accompanied by the availability of surrogate markers to streamline development timelines, and by the build-up of clinical trial site capacity for the conduct of modern, registration-standard clinical trials.
What are the main inhibitors of TB?
Based on mechanism of action, TB drugs can be classified as inhibitors of: bacterial protein synthesis (aminoglycosides), electron transport across the bacterial membrane (a proposed mechanism of action for pyrazinamide), nucleic acid synthesis (rifampin, quinolones) and cell wall synthesis (isoniazid, ethambutol, ethionamide and cycloserine). See Fig. (1). Perhaps the greatest hurdle to optimal TB therapy with the current drugs is the long treatment time necessary to achieve cure. The requirement for this long duration of treatment is generally attributed to physiologic heterogeneity of TB bacteria -
How long does it take to treat TB?
TB disease can be treated by taking several drugs for 6 to 9 months. There are 10 drugs currently approved by the U.S. Food and Drug Administration (FDA) for treating TB. Of the approved drugs, the first-line anti-TB agents that form the core of treatment regimens are: isoniazid (INH) rifampin (RIF)
What is it called when TB bacteria multiply?
When TB bacteria become active (multiplying in the body) and the immune system can’t stop the bacteria from growing, this is called TB disease. TB disease will make a person sick. People with TB disease may spread the bacteria to people with whom they spend many hours.
What is XDR TB?
Extensively drug-resistant TB (XDR TB) is a rare type of MDR TB that is resistant to isoniazid and rifampin, plus any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin). Treating and curing drug-resistant TB is complicated.
Can TB be treated?
It is very important that people who have TB disease are treated, finish the medicine, and take the drugs exactly as prescribed. If they stop taking the drugs too soon, they can become sick again; if they do not take the drugs correctly, the TB bacteria that are still alive may become resistant to those drugs.