Evidence-Based Pharmacology: Diagnosis and Treatment of Tuberculosis

Pathophysiology of TB

Tuberculosis (TB) is a contagious bacterial airborne disease, the causative agent of which is Mycobacterium tuberculosis (Nahid et al. 2016). TB’s prevalence is high in people living with the Human Immunodeficiency Virus (HIV). Getahun et al. (2011) state that, in the end of 2009, nearly thirty-three million people worldwide were infected with HIV. Most of them were in Asia and Sub-Saharan Africa (p.2). Tuberculosis (TB) is the most common death among the people infected with HIV (Getahun et al., 2011). It means that TB’s prevalence is higher in HIV positive people than their uninfected counterparts. The researchers also explain that Tuberculosis can occur at any stage of HIV (Getahun et al., 2011). The risk of death among the HIV infected patients, who suffer from this disease, also increases depending on whether or not they are under the Anti-Retroviral Treatment (ART). According to Getahun et al. (2011), “Up to 50% of people living with HIV infection (without ART), who are diagnosed with TB, die during the 6-8 months of TB treatment,” (p. 2). However, the risk of death increases to within 72% and 98% among people being diagnosed with Multidrug Resistant (MDR) or Extensively Drug Resistant (XDR) tuberculosis (Getahun et al., 2011). TB is a disease with serious health implications, including the risk of death. Its diagnosis is through screening; while the treatment approaches (options) include the use of first-line or second-line anti-TB drugs.

This paper is an evidence-based pharmacology essay focusing on the diagnosis and treatment of TB. It derives its data from peer-reviewed research articles with some information on its flow and one published clinical guideline from CDC. The paper restricts its information to the sources published within seven years. The process of locating the researches entails searching professional online sites such as PLoS Medicine and PubMed. These are the credible online sources with the peer reviewed study on TB. Only these research articles being relevant to the diagnosis and treatment of TB and the publication of which falls under the criterion of seven years qualify for inclusion. The keywords for the search are: Tuberculosis, diagnosis, treatment, and pharmacology.

Implications of the Age Continuum

The research on the pathophysiology of the disease reveals that TB affects the respiratory system. However, its symptoms are manifested on other parts of body as well as the breathing system. Some of the observable manifestations include weight-loss (anorexia), frequent coughs, fever, and sweating at night (Getahun et al., 2011). Additional symptoms of the illness are body-fatigue and pain in the chest (Getahun et al., 2011). Although the common assumption is that TB is widespread among adults, the incidences of its prevalence in children below 15 years are also common. The CDC’s clinical guideline by Nahid et al. (2016) explains the following fact. Pediatric tuberculosis, which is the disease that affects children under 15 years, has become a significant public health problem as the indication of recent TB transmission (Nahid et al., 2016). The CDC guideline states that infants and children below the age of five years face a greater risk of contracting this illness than adolescents and adults (Nahid et al., 2016). In children, tuberculosis is significantly common for the kids below 5 years. For adolescents, their age is above 10 years (Nahid et al., 2016). The current literature does not provide the prevalence information about any specific range of age for adults. Therefore, the disease commonly impacts the kids under 5, adolescents above 10, and the general grown population.

Genomic Issue of TB

The genomic issue of TB that is known is the disease’s resistance to drugs being linked to genetics. The systematic review that Maruri et al. (2012) have performed focuses on the problem of gyrase mutations during the treatment of tuberculosis using fluoroquinolone. The reviewers explain that the issue of resistance to fluoroquinolone has become important (Maruri et al., 2012). Therefore, it is necessary to study the mutations that occur in the gene gyrase when treating tuberculosis with this medicine. The reviewers have sampled 42 studies in total with 1220 incidences of treatment of this disease using fluoroquinolone. The participants underwent the sequencing of the “quinolone resistance determining region” (QRDR). As a result, the outcome was that 64% (780 participants) suffered gene mutations that was the cause of resistance to the drug (Maruri et al., 2012, p. 821). The article concludes that it necessary to use a consensus numbering system as a way to detect gene mutations in the process of fluoroquinolone resistance. However, the precise reasons of this phenomenon is not yet known. The reason is that not all patients, who had used the drug in the review by Maruri et al. (2012), developed mutations. It is necessary for scientists to investigate the exact reasons for the occurrence of such issue so that the better generation of fluoroquinolone can be developed to reduce such resistance.

Another common knowledge about TB is its prevalence that is being higher in crowded places than in non-crowded environments. The systematic review by Baussano et al. (2010) has studied the incidence level of tuberculosis within the prison setting. In the introduction of their study, the scholars (2010) discuss that the occurrence of this disease in prisons is usually higher than among the general population. They list some of the contributing factors for the high level of the illness there as: the inmates coming from population groups that are predisposed (high-risk) to TB. Such groups include the users of alcohol and drugs, mentally ill persons, ex-prisoners, and immigrants from high-prone TB areas (Baussano et al., 2010). The researchers also explain that the criterion for segregating the criminals in jail is according to the nature of a crime. However, it does not consider the concerns for public health (Baussano et al., 2010). Other factors that facilitate the quick spreading of tuberculosis in prison include overcrowding, the delayed detection of incidences of TB (the lack of timely screening), and the improper implementation of the measures to control the spread of infection (Baussano et al., 2010). The effect of the findings is that they explain the relationship between the population level and the transmission of the disease. However, the other factors besides overcrowding also account for the high incidence level of tuberculosis in prisons.

Literature Review

The current literature explains the diagnosis and treatment of tuberculosis. Getahun et al. (2011) is the article that explains the standardized screening method for HIV positive people living in resource-constrained environments. The researchers have identified 12 studies that performed the TB diagnosis through collecting sputum cells for screening (Getahun et al., 2011). The average age of 9,626 participants diagnosed with TB was 34; and they were all HIV positive (Getahun et al., 2011). The standard for inclusion was the presence of the common symptoms of tuberculosis, such as frequent coughs, sweating at night, fever or weight-loss (Getahun et al., 2011). Nearly 557 of 9,626 participants were diagnosed with TB. The researchers have concluded that the simplified rule of testing (screening) people for this disease could be used in the areas with inadequate resources (Getahun et al., 2011). The guideline depends on the presence of any of the symptoms, which lead to the suspicion that an individual suffers from this illness. Therefore, it helps in its early detection and treatment.

There are the particular tests that may be conducted during diagnosing TB. The two popular methods of screening the disease are Mantoux tuberculin method that conducts a test of skin and the in-vitro test that uses blood as specimen (Nahid et al. 2016). When a patient is suspected to be TB-positive, e.g. after observing one of the symptoms, a series of lab checks can form a part of the diagnosis. They include Acid-Fast Bacilli smear (AFB) that uses the human sputum as specimen and HIV serology, which follows the following assumption. The people who are infected with HIV are at a high risk of contracting TB (Nahid et al. 2016). The other diagnostic tests are blood culture and ELISpot (Nahid et al. 2016). When the diagnosis confirms that the patient has TB, the requirement is follows. The person undergoes the check for drug susceptibility. The reason for taking the patient through the final diagnosis is that the initial methods do not differentiate among those individuals, who are fully susceptible to drugs and those with multidrug resistant (MDR) tuberculosis (Nahid et al. 2016). The drug susceptibility test can use the approach of analyzing DNA sequencing directly or molecular testing. Other checks in this category are the ligase chain reaction test and BACTEC-460 (Nahid et al. 2016). At the end of these assessments, it is possible to determine if the patient has MDR-TB or the tuberculosis that is fully susceptible to drugs.

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Diagnosis of TB

The diagnosis for TB also requires the performance of radiography on the chest. This test is restricted to people who have been tested positively for this disease during the laboratory checks (Nahid et al., 2016). The radiograph enables the medical team to detect the level of infection. For example, the presence of cavity formation is the indication that the person is at the advanced level of TB infection because the availability of cavities means a high load of bacteria (Nahid et al., 2016).

Getahun et al. (2011) derive the standardized rule that guides the tuberculosis’ diagnosis by comparing the symptoms of the patients being tested positive with TB against those ones examined as negative. They explain that their objective of conducting the checks was to separate HIV patients into two distinct groups. However, the further evaluation is needed (Getahun et al., 2011). The researchers have also limited their diagnosis to the clinical symptoms that could be observed in any treatment setting (Getahun et al., 2011). The idea from the study by Getahun et al. (2011) is that the diagnosis of TB bases on the physiological symptoms and the screening through the scientific investigation of sputum cells that contain Mycobacterium tuberculosis when positive.

Treatment of TB

The TB treatment presents some major challenges, especially when it is a multiple drug resistant type of tuberculosis. Jacobson et al. (2010) discuss the threats that constrain the treatment of XDR tuberculosis. They state that the second-line antimycobacterial medicines have the lower effectiveness. They are more costly and toxic compared to the first-line types of drugs. Like Maruri et al. (2012), Jacobson et al. (2010) find that people with XDR TB develop resistance to most of the second-line drugs; and fluoroquinolone is one of them. Jacobson et al. (2010) state that the use of later-generations of fluoroquinolone in the treatment of TB improves the results with lower incidences of resistance (2010). Therefore, the researchers recommend that the well-designed clinical studies should test the outcomes of tuberculosis treatment using the later generations of fluoroquinolone that have the low chances of protection.

Explaining the concept of Extensively Drug-Resistant (XRD) TB, Jacobson et al. (2010) note the following thing. It refers to the condition where an individual has Mycobacterium tuberculosis that does not heal after the administration of the two first-line drugs: rifampin and isoniazid. Similarly, a patient with XDR is resistant to the most effective second-line TB drugs that include fluoroquinolone and injectable agents like capreomycin, kanamycin, and ikacin (Jacobson et al., 2010). It is necessary to find the more effective treatment approaches to XDR because the evidence points towards its increasing prevalence rates. For example, the Soviet Union accounts for 24% prevalence of XRD. Meanwhile Estonia has 15% of the incidences (Jacobson et al., 2010). The fact that 500,000 new cases of XDR tuberculosis are diagnosed yearly implies that it is a fast-growing problem. There is a need to find the precise treatment methods for XDR TB (Jacobson et al., 2010). It suggests the necessity for the further research around treating it.

The CDC guideline enumerates the treatment procedure for the drug susceptible TB within well-resourced settings. According to this guideline, the goal of antituberculosis therapy is to cure the patient while minimizing the transmission of infection to other people (Nahid et al., 2016). The other objectives are to reduce the risk of disability and death, as well as minimize the chances of the individual developing resistance during treatment (Nahid et al., 2016). The guideline also recommends the regimens that should be used in treating tuberculosis. Nahid et al., discuss that for TB the patients without resistance to multiple drugs, the most suitable treatment option is to use the regimen that comprises of Isoniazid. It is administered intensively for two months together with rifampin, pyrazinamide, and ethambutol (Nahid et al., 2016). Rifampin and isoniazid are used for the successive four months of tuberculosis treatment (Nahid et al., 2016). Consequently, treating drug-susceptible TB occurs in the two phases of intensive and continuation (follow-up) treatments. The first stage is significant. It is important for the patient to adhere strictly to the treatment plan. Firstly, the intensive phase follows daily rather than intermittent dosing (Nahid et al., 2016).

The research has also looked at the area of risk factors of death associated with TB. According to the peer review by Waitt and Squire (2011), there are some fatality cases of up to 25% in both the industrialized and less resourced countries. The reviewers discuss that the risk factor is death present throughout the treatment duration. However, the risky attributes vary according to the context. For example, in the situation with high HIV and TB prevalence rates, the risk factors that may cause death in TB patients include HIV positivity, increasing immunity suppression, malnutrition, and smear negative disease (Waitt & Squire, 2011). Environments where TB and HIV prevalence is low have the danger attributes like substance or drug abuse, non-infecting co-morbidities, and smear positive disease (Waitt & Squire, 2011). The researchers conclude that there is an urgent need for clinical studies to focus on the factors related to the clinical environment or patient specific aspects that formulate the hazard of death during the first six months of TB treatment (Waitt & Squire, 2011). However, the underlying finding is that the risk of death for such people is evident both within the well- and poorly-resourced settings.

Having analyzed the available literature on the diagnosis of treatment of TB, the treatment approaches to tuberculosis should be considered. They are broadly pharmacological and non-pharmacological.

Starting with the non-pharmacological treatment, this category entails the non-drug therapy measures being used to minimize the death risk and spread of infection within the environment. They are the physical means that contain the disease and keep the patient out of danger in the treatment period (Nahid et al., 2016). The first non-pharmacological measure is the isolation of the individual (Nahid et al., 2016). The treatment requires a personal room where the person is attended to in isolation from the rest people. The surrounding must have the negative (low) pressure. It is a factor that reduces the risk of spread through air. The second non-pharmacological observation is for the medical staff who visit the sick person. They should wear protective gadgets, for example disposable masks, which are efficient enough to filter the tuberculosis bacteria. Thirdly, the practice of isolation should be progressive. It is the stage where the sputum tests give negative results for tuberculosis three times consecutively (Nahid et al., 2016). Nahid et al. explain that this phase is usually achieved between two and four weeks after the onset of anti-TB treatment (2016). It is the indication is that the risk of infecting others with the bacteria is minimal when the sputum tests are negative.

The pharmacological treatment of tuberculosis plan varies according to the type, i.e. drug susceptible TB or XDR/MDR TB. For the initial one, there are four drug regimens that the patient should take as a part of pharmacological therapy (Nahid et al., 2016). The medicine is isoniazid, rifampin, pyrazinamide, and streptomycin or ethambutol (Nahid et al., 2016). Isoniazid and rifampin are given at the primary phase of treatment (first six months). Then, pyrazinamide, streptomycin or ethambutol are provided in the follow-up treating step (additional two months). However, there are some limitations when treating exceptional populations of TB patients like children and pregnant women. Ordinarily, pyrazinamide should not be used for their treatment except when they have the XDR type of TB (Nahid et al., 2016). The general guideline is that pregnant women should not take streptomycin completely (Nahid et al., 2016). The researchers also recommend that such females should receive treatment to prevent TB infection; especially if they are at a risk group, e.g. those with HIV (Nahid et al., 2016). For young children (under five years) diagnosed with TB, most of the cases involve drug susceptible tuberculosis. Therefore, the treatment plan is giving individuals isoniazid and rifampin for the first six months of treatment. During the follow-up period, they take pyrazinamide (Nahid et al., 2016).

The treatment plan also varies when taking care of the patients with HIV. For this group, it is necessary to adjust the dosage. For instance, HIV patients, who are on protease inhibitors, must not use rifampin. It should be substituted with rifabutin (Nahid et al., 2016). When the tuberculosis person is diagnosed with HIV, it is dangerous to put them on ART and anti-TB treatment simultaneously (Nahid et al., 2016). The need for ART depends on the CD4 or T-cells count. The ART use should begin early, e.g. 4 weeks after the start of tuberculosis therapy if the patient needs ART simultaneously with anti-TB therapy (the case of low T-cells). The aim is to minimize the risk of death or development of HIV to AIDS (Nahid et al., 2016).

TB treatment has two approaches: using first-line anti-TB drugs or second-line medicines. The initial group includes the drugs used in the treatment of susceptible tuberculosis, while the second-line drugs are the alternative regimens that apply to the follow-up treatment and to the patients with XRD/MDR-TB. The examples of the first-line drugs are isoniazid and rifampin (Jacobson et al., 2010). The second group includes fluoroquinolones like levofloxacin, ofloxacin, and ciprofloxacin (Nahid et al., 2016). Ethambutol, pyrazinamide, and rifabutin are also the members of these medicines.

The approach of using the first-line drugs is a preferred alternative. The evidence from Jacobson et al. (2010) states that their advantage is that they are highly efficient, cheap, and less toxic. On the contrary, the second-line alternatives are less efficient, expensive, and more toxic. Consequently, the first-line approach to TB treatment is good, but it is limited to the patients who have the drug susceptible type of TB (Nahid et al., 2016). They cannot help people with MDR or XDR-TB.

Conclusion

In conclusion, TB is a bacterial disease that affects the respiratory system. Its symptoms include endless coughing, fever, night-sweats, and the weight loss. The suspicion of the disease is based on these physical manifestations. Its prevalence is high in people with HIV and within the crowded settings like prisons. The research shows that HIV positive individuals are at a high risk of contracting tuberculosis Therefore, testing HIV positive formulates the suspicion and necessity of examining the patient for tuberculosis. Similarly, the facts show that prisons have the dense population of people who come from high-prone areas, yet there are no protective measures or TB treatment interventions.

The diagnosis of TB is based on the symptoms. Diagnosing involves screening, laboratory tests, and DNA checks to determine drug susceptibility. Non-pharmacological treatment includes treating the patient privately; especially during the first four weeks to avoid the spread of the disease. Therefore, the medical personnel should wear protective devices that filter the bacteria. The pharmacological treatment plan should be devised according to the type of tuberculosis. Drug susceptible TB requires the admission of first-line anti-TB drugs for the first six weeks. The follow-up treatment uses the second-line medicine. However, XDR or MDR-TB treatment is resistant to first-line drugs. Therefore, it is advisable that the medical staff use the second-line alternatives like fluoroquinolones. The approach of applying first-line medicine is a preferred method. The reason is that the drugs are more effective, cheaper, and less toxic compared to the second-line alternatives.