Pyrazinamide Health Dictionary

One of the anti-tuberculous drugs. It has the advantages of being relatively non-toxic and of being active when taken by mouth. Unfortunately, like streptomycin, it may render the Mycobacterium tuberculosis resistant to its action. This tendency to produce resistance is considerably reduced if it is given in conjunction with RIFAMPICIN and PYRAZINAMIDE.... isoniazid

been recognised from earliest times. Evidence of the condition has been found in Egyptian mummies; in the fourth century BC Hippocrates, the Greek physician, called it phthisis because of the lung involvement; and in 1882 Koch announced the discovery of the causative organism, the tubercle bacillus or Mycobacterium tuberculosis.

The symptoms depend upon the site of the infection. General symptoms such as fever, weight loss and night sweats are common. In the most common form of pulmonary tuberculosis, cough and blood-stained sputum (haemoptysis) are common symptoms.

The route of infection is most often by inhalation, although it can be by ingestion of products such as infected milk. The results of contact depend upon the extent of the exposure and the susceptibility of the individual. Around 30 per cent of those closely exposed to the organism will be infected, but most will contain the infection with no signi?cant clinical illness and only a minority will go on to develop clinical disease. Around 5 per cent of those infected will develop post-primary disease over the next two or three years. The rest are at risk of reactivation of the disease later, particularly if their resistance is reduced by associated disease, poor nutrition or immunosuppression. In developed countries around 5 per cent of those infected will reactivate their healed tuberculosis into a clinical problem.

Immunosuppressed patients such as those infected with HIV are at much greater risk of developing clinical tuberculosis on primary contact or from reactivation. This is a particular problem in many developing countries, where there is a high incidence of both HIV and tuberculosis.

Diagnosis This depends upon identi?cation of mycobacteria on direct staining of sputum or other secretions or tissue, and upon culture of the organism. Culture takes 4–6 weeks but is necessary for di?erentiation from other non-tuberculous mycobacteria and for drug-sensitivity testing. Newer techniques involving DNA ampli?cation by polymerase chain reaction (PCR) can detect small numbers of organisms and help with earlier diagnosis.

Treatment This can be preventative or curative. Important elements of prevention are adequate nutrition and social conditions, BCG vaccination (see IMMUNISATION), an adequate public-health programme for contact tracing, and chemoprophylaxis. Radiological screening with mass miniature radiography is no longer used.

Vaccination with an attenuated organism (BCG – Bacillus Calmette Guerin) is used in the United Kingdom and some other countries at 12–13 years, or earlier in high-risk groups. Some studies show 80 per cent protection against tuberculosis for ten years after vaccination.

Cases of open tuberculosis need to be identi?ed; their close contacts should be reviewed for evidence of disease. Adequate antibiotic chemotherapy removes the infective risk after around two weeks of treatment. Chemoprophylaxis – the use of antituberculous therapy in those without clinical disease – may be used in contacts who develop a strong reaction on tuberculin skin testing or those at high risk because of associated disease.

The major principles of antibiotic chemotherapy for tuberculosis are that a combination of drugs needs to be used, and that treatment needs to be continued for a prolonged period – usually six months. Use of single agents or interrupted courses leads to the development of drug resistance. Serious outbreaks of multiply resistant Mycobacterium tuberculosis have been seen mainly in AIDS units, where patients have greater susceptibility to the disease, but also in developing countries where maintenance of appropriate antibacterial therapy for six months or more can be di?cult.

Streptomycin was the ?rst useful agent identi?ed in 1944. The four drugs used most often now are RIFAMPICIN, ISONIAZID, PYRAZINAMIDE and ETHAMBUTOL. Three to four agents are used for the ?rst two months; then, when sensitivities are known and clinical response observed, two drugs, most often rifampicin and isoniazid, are continued for the rest of the course. Treatment is taken daily, although thrice-weekly, directly observed therapy is used when there is doubt about the patient’s compliance. All the antituberculous agents have a range of adverse effects that need to be monitored during treatment. Provided that the treatment is prescribed and taken appropriately, response to treatment is very good with cure of disease and very low relapse rates.... nature of the disease tuberculosis has

(TB) n. an infectious disease caused by the bacillus Mycobacterium tuberculosis (first identified by Koch in 1882) and characterized by the formation of nodular lesions (tubercles) in the tissues.

In pulmonary tuberculosis – formerly known as consumption and phthisis (wasting) – the bacillus is inhaled into the lungs where it sets up a primary tubercle and spreads to the nearest lymph nodes (the primary complex). Natural immune defences may heal it at this stage; alternatively the disease may smoulder for months or years and fluctuate with the patient’s resistance. Many people become infected but show no symptoms. Others develop a chronic infection and can transmit the bacillus by coughing and sneezing. Symptoms of the active disease include fever, night sweats, weight loss, and the spitting of blood. In some cases the bacilli spread from the lungs to the bloodstream, setting up millions of tiny tubercles throughout the body (miliary tuberculosis), or migrate to the meninges to cause tuberculous *meningitis. Bacilli entering by the mouth, usually in infected cows’ milk, set up a primary complex in abdominal lymph nodes, leading to *peritonitis, and sometimes spread to other organs, joints, and bones (see Pott’s disease).

Tuberculosis is curable by various combinations of the antibiotics *streptomycin, *ethambutol, *isoniazid (INH), *rifampicin, and *pyrazinamide. Preventive measures in the UK include the detection of cases by X-ray screening of vulnerable populations and vaccination with *BCG vaccine of those with no immunity to the disease (the *tuberculin test identifies which people require vaccination). The childhood immunization schedule no longer includes BCG vaccination at 10–14 years of age; vaccination now targets high-risk groups, such as immigrants from countries with a high incidence of TB. There has been a resurgence of tuberculosis in recent years in association with HIV infection. The number of patients with multidrug resistant TB has also increased due to patients not completing drug courses. Many centres have introduced directly observed therapy (DOT), in which nurse practitioners watch patients taking their drugs or administer the drugs.... tuberculosis