Management of TuberculosisGeneral overview of tuberculosis disease 1.1.1 Basic facts of tuberculosis Tuberculosis (TB) is a common respiratory disease that spread through one person to another and it is caused by bacteria which is Mycobacterium tuberculosis and occasionally by Mycobacterium bovis and Mycobacterium africanum. The bacteria also known as tubercle bacilli and it is under the group of acid-fast bacilli. For the bacteria that is under the acid-fast bacilli group, when the bacilli is stained with certain dyes and examined under the microscope, the bacilli will look red. It will still remain the colour when it is washed with acid and alcohol. Due to the difficulties to be washed out by the acid and alcohol, this type of bacteria is considered as dormant in tissues and persist for many years. That’s why tuberculosis is considered as the disease that cause most of the death cases after the HIV and heart diseases. The disease infects almost 33% of the world’s population. 95% of tuberculosis cases and 98% of tuberculosis death are in the developing countries. The age range of the people who have tuberculosis disease is between 15-50 years old. Among the population in worldwide, Sub- Saharan Afrika had the highest tuberculosis incidence rate and also the highest annual rate of increase of cases. To make the condition becomes even worse, according to WHO, there is one person in the world who will is newly infected by the tuberculosis disease every second. The facts above really make us feel shock. Yet, have u even think about what is main causes that lead to the prevalence of this disease. The main reason that caused the prevalence of this disease is due to the mode and the source of the infection. The mode of transmission of this TB is due to the air we breathe. The sources of the tuberculosis disease include the patient with TB of the lung, pulmonary TB (PTB) and also the one who is coughing, talking, sneezing, spitting and singing. Just like what mention above, the bacteria that cause TB is the tubercle bacilli. If a person who is infected by TB and he or she is coughing, the tubercle bacilli will be come out in the air with tiny infectious droplet nuclei. The infectious particles of the respiratory secretions is usually less than 5 micrometers. That’s why we cannot seen through properly. The dormant bacteria are kept by the body’s defence and it will not show its clinical signs and signs. After the release of the droplet nucleic, tubercle bacteria will be breathe in by other people, and then the tubercle bacilli will start to multiply and become numerous in the body. If the immune system of a person is weak and the bacteria tends to develop fast till can overcome the immune system of the person, he or she for sure will develop tuberculosis. At any time, any age and anywhere, a person can easily develop tuberculosis. The risk of getting the disease is depending on the extent of exposure to the droplet nuclei, the immunity of a person and also the time of the infection. The person can be infected past few years but he or she may develop the disease recently. It is because if the immune system of a person can suppress the disease, but due to some reason the disease might be develop in certain stress condition. A person is more susceptible to tuberculosis if he or she has HIV infection. Infants and children are more susceptible to the disease because the immune system is not mature. From the time the children are infected, usually he or she will usually develop the disease two years afterwards. The most vital reason is due to weakening immune resistance to beat with the disease. Other than this, physical and emotional stresses may be triggered by progression of infection. 1.1.2 Pathogenesis of tuberculosis There are two progress of the infection in tuberculosis which are primary infection and also post-primary infection. Primary infection Primary infection of tuberculosis is usually occurred on the people who haven’t got the disease before. The incubation for the primary infection of tuberculosis is usually 4-6 weeks starting from the infection of the disease. When the person is being infected, the droplet nuclei will try to escape from the ciliary action of the nose and try to embed in the alveoli of the lungs. If the droplet nuclei is able to escape themselves from the ciliary action of the nose, they will start to multiply in the alveoli of the lungs. The multiplication of the bacteria in the alveoli will lead to several effects. The effects can be mild till severe. The first outcome of the primary infection is that there is no clinical outcome of the disease. This outcome is the most frequent as about 90% of cases are under this outcome. At most of the time, the immune system of the host will be automatically escape from the infection but the tuberculin skin test is still positive because there is still infection in the host body. If the immune system of the host is not strong enough to resist with the infection, there will be some of the symptoms and manifestations of the disease. There will be hypersensitivity reactions occurs in the host. For example, erythema nodosum and phlyctenular conjuction as well as dactylitis which is the inflammation and swelling of the feet and hands. Besides, the lungs and also heart will be affected by tuberculosis. Tuberculosis pneumonia and pleural infection are the complications of the primary infection. Hyperinflation and collapse or consolidation of the lungs are also the effects of TB. The most severe effects of TB is when the bacteria is transmitted through the blood and becomes disseminated disease. Meningitis, pericarditis and military disease are also outcome of the primary infection. Post-primary infection After a latent period of months or even years, the primary infection will be progressed to become post-primary tuberculosis. Furthermore, the post-primary tuberculosis is happened when the dormant bacteria which is still alive after the treatment of the primary infection and the bacteria is capable to multiply themselves. Reactivation of the bacteria in the body will lead to a condition which is called as reinfection. Reinfection is the condition in which the person will has a repeat infection after the primary infection. The reasons why a person will be getting reinfection is due to the weakening of the immune system by HIV infection. The immune response of the patient results in lesions that is characteristically localized and this is often accompanied with the excessive tissue destruction and cavitation. The transmission of the disease is more common and easy if the person who is having the post-primary tuberculosis. Usually, the post-primary tuberculosis will affect the lungs but the others part of the body will also been affected. The manifestation of the lung will be more obvious in this case. There are some of the characteristics of the post-primary tuberculosis. There will be positive sputum smear and also lung destruction with cavitation. It is usually no intrathoracic lymphadenopathy. The effects of the post-primary tuberculosis has divided into two categories which are pulmonary tuberculosis and extra-pulmonary tuberculosis. Pulmonary tuberculosis has the following symptoms which are lung cavities, upper lobe infiltrates, fibrosis, endobronchial and also progressive pneumonia. In extra-pulmonary tuberculosis, there are some symptoms which are common and there are also some of the manifestations are less common. Pleural effusion, pericarditis, lymphadenopathy and also meningitis are the common symptoms of post-primary infection. Gastrointestinal such as ileocaecal and also peritoneal will be highly infected by tuberculosis too. In some cases that is less common, we can observe the symptoms in which kidney and adrenal gland will be affected. Empyema is one of the symptoms of the tuberculosis. Moreover, epididymitis and orchitis which are the symptoms that are related to the male genital tract are also the outcome of the extra-pulmonary tuberculosis. Extra-pulmonary tuberculosis will also affect the female genital tract like endometrium and tubo-ovarian. There will be also skin infection which include lupus vulgaris, tuberculids and military. Strategies for the management of tuberculosis There are many ways to manage tuberculosis include drug regimens and also vaccine development. The purposes of managing tuberculosis are that we can prevent the exacerbations of the disease and also we can totally remove the pathogens that present in our body. The management of tuberculosis will also prevent the transmission of the disease to other people and to prevent the recurrent infection of the patient in the future. Tuberculosis is a well-known disease in which it will affect the population in the world. The treatment for this disease in term of drug already exists for more than 50 years old. Yet, why the prevalence of the tuberculosis is not getting less instead it increases in a high rate? This is because the management of the disease is not proper although there are many drug regimens to treat the disease. In order to has a proper anti-tuberculosis drug treatment, short-course chemotherapy (SCC) has to be applied to the patients. In order to make sure that SCC is being carried out in a proper manner, well managed TB control programme (NTP) has to be done. In the standardized TB treatment, there are many treatment regimens available to treat tuberculosis. Each country will apply different standard regimens to fulfil the purposes of anti-TB drug treatment. The regimen for tuberculosis is the most cost- effective of all the interventions and it is affordable for all walks of life. There are certain drugs which are classified into first-line anti- TB drugs and they have different modes of action, potency and dose applied. The drugs include isoniazid (H), rifampicin (R), pyrazinamide (Z), thioacetazone (T), streptomycin (S), and also ethambutol (E). These drugs are divided into two main types which are bactericidal and bacteriostatic. Bactericidal drugs will kill the bacteria while bacteriostatic will only slow down the production and growth of the bacteria. Among these drugs, all of them can be used in the intermittent use except thioacetazone. Intermittent use of drugs mean that the drugs are consumed for a time and stop for a time, then continues back. Thioacetazone cannot be used for intermittent purpose and it has many side effects as it will cause toxicity to the people who consume it and it will also cause severe skin reactions. Besides, it also has low property of bacteriocidal action. Thus, it is now seldom be used. It is now been substituted with other drug like ethambutol. The above drugs that mention above act on different groups of bacilli. Tuberculosis bacilli in a tuberculosis patient are divided into different groups such as bacilli that are metabolically active, continuously growing in the host body. There are also bacilli that stay inside cells such as macrophages. Moreover, there is semidormant bacilli which will undergo occasional spurts of metabolic activity and also dormant bacilli. Dormant bacilli will fade away and die away. Among these bacilli, semidormant bacilli is the most difficult bacilli to remove. That’s why the anti- tuberculosis treatment needs longer period to act against different groups of bacilli. Isoniazid, rifampicin, pyrazinamide and streptomycin are the drugs that classified as bactericidal drugs. Among these drugs, isoniazid is the best to kill the metabolically active bacilli. It almost can kill 90% of continuously growing bacilli. Nevertheless, isoniazid cannot kill semidormant bacilli but rifampicin can. The bacilli that live inside the cells like macrophages are killed by pyrazinamide. This bacilli are killed in the acid condition inside the cells. The table below shows how the drugs are being consumed in order to help to eliminate the bacilli present in the body. First line anti-TB drugs Recommended dose (mg/kg of body weight) Intermittent (3 times a week) DailyIsoniazid(H) 10 5Rifampicin(R) 10 10Pyrazinamide(Z) 35 25Streptomycin(S) 15 15Ethambutol(E) 30 15Thioacetazone(T) Not applicable 2.5Like what had mentioned above, semidormant bacteria is the toughest bacilli to be removed through our body. Thus, rifampicin which is able to remove this bacteria is considered to be the most effective drugs to treat tuberculosis drugs. There are some of the bacilli that are considered to be drug-sensitive bacilli in which they are resistant to certain drugs and they are very difficult to be removed. This is why sometimes we need the combination of the drugs in order to provide a wide range of bactericidal and bacteriostatic action. Isoniazid and rifampicin are the best combination in order to prevent the bacilli which will easily develop the resistance property to some drugs. Stremptomycin and ethambutol are less effective if compared to combination of isoniazid and rifampicin.