Tuberculosis

Tuberculosis (TB) is a communicable infectious disease caused by Mycobacterium tuberculosis. It can produce silent, latent infection as well as 

Globally, 2 billion people are infected and 2 million to 3 million people die 

tuberculosis is transmitted from person to person by coughing or sneezing. Close contacts of TB patients are most likely to become infected. Fifty-four percent of TB patients in the United States are foreign born, most often from Mexico, the Philippines, Vietnam, India, and China. In the United States, TB disproportionately affects ethnic minorities (African Americans, Hispanics, and Asians). 

Human immunodeficiency virus (HIV) is the most important risk factor for active TB, especially among people 25 to 44 years of age. An HIV-infected individual with TB infection is over 100-fold more likely to develop active disease than an HIV-seronegative patient. 

Primary infection is initiated by the alveolar implantation of organisms in droplet nuclei that are small enough (1 to 5 mm) to escape the ciliary epithelial cells of the upper respiratory tract and reach the alveolar surface. Once implanted, the organisms multiply and are ingested by pulmonary macrophages, where they are killed, or, they continue to multiply. With bacterial multiplication, the macrophages eventually rupture, releasing many bacilli. 

Tuberculosis in the upper cervical spine is rare. In a recent study of 587 cases of tuberculous spondylitis there were 42 cases with cervical involvement and in 18% the affected vertebrae were Cj and C2 (Fang et al. 1983). 

Osteolytic erosion of the bones, destruction of the joints and ligaments, granulation tissue, swelling of soft tissue and abscess formation constitute the basis of pathological changes. 

As the pathological process is rarely localized in the posterior arches of the vertebrae, it is evident that debridement (excision of the affected bone. 

Most of the tumours here dealt with are extradural in the ventral craniocervical or upper cervical regions, at least in origin. 

In its early stages, the tumour usually erodes the bone causing only local or radiating pain. Later on compression causes symptoms of cranial nerve, spinal root, medullary or spinal cord lesion. 

Select Pharmacological Properties of Drugs Most Often Used in Treating Tuberculosis 

Isoniazid is bactericidal for growing tubercle bacilli, is absorbed orally, and is metabolized by acetylation. It is a structural analogue of pyridoxine and may cause pyridoxine deficiency, peripheral neuritis and, in toxic doses, pyridoxine-responsive convulsions. Its mechanism of action is not known. 

Streptomycin is given intramuscularly. It exerts its effects only on extracellular tubercle bacilli. When combined with other drugs, it delays the emergence of streptomycin-resistant mutants. It is ototoxic and may cause deafness. 

Rifampin is absorbed from the gastrointestinal tract and excreted mainly into bile. It binds to DNA-dependent RNA polymerase and inhibits RNA synthesis. In higher than therapeutic doses, rifampin may cause a flulike syndrome and thrombocytopenia. 

Ethambutol suppresses the growth of isoniazid- and streptomycin-resistant tubercle bacilli. The most important but not common side effects are optic neuritis, decreased visual acuity, and inability to perceive the color green. 

Every healthcare setting shonld conduct initial and ongoing evaluations for the risk of TB transmission. The TB risk assessment determines the types of administrative, environmental, and respiratory 

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The path from squalene (114) to the corresponding oxide and thence to lanosterol [79-63-0] (126), C qH qO, cholesterol [57-88-5] (127), and cycloartenol [469-38-5] (128) (Fig. 6) has been demonstrated in nonphotosynthetic organisms. It has not yet been demonstrated that there is an obligatory path paralleling the one known for generation of plant sterols despite the obvious stmctural relationships of, for example, cycloartenol (128), C qH qO, to cyclobuxine-D (129), C25H42N2O. The latter, obtained from the leaves of Buxus sempervirens E., has apparentiy found use medicinally for many disorders, from skin and venereal diseases to treatment of malaria and tuberculosis. In addition to cyclobuxine-D [2241-90-9] (129) from the Buxaceae, steroidal alkaloids are also found in the Solanaceae, Apocynaceae, and LiUaceae. 

During the most active period of investigation of sulfanilamide derivatives, 1935—1944, for systemic bacterial infections, the antimycobacterial activity of 4,4 -dianainodiphenylsulfone [80-08-8] (DDS, dapsone) was discovered (14). Although neither this compound nor its derivatives proved to be clinically usehil for human tuberculosis, it did evolve into the most important type of compound for leprosy (15). The diacetyl derivative has also... 

Antituberculin Agents. Rifampin [13292-46-17, a semisynthetic derivative of rifamycin SV, is a most valuable dmg for treatment of tuberculosis, an infection caused by mycobacteria, leprosy, and an expanding range of other infections (23). Cycloserine [64-41-7] has been used to a limited extent for treatment of tuberculosis as a reserve dmg. Although cycloserine inhibits bacteria by interfering with their cell wall biosynthesis, it has toxic side effects in humans in the form of neurotoxicity. Capreomycin [11003-38-6] and to a much lesser extent viomycin [32988-50-4] both of which are peptides, have also been used for treatment of this disease. 

R = R = H) are intermediate, and gentamicin and tobramycin are most susceptible (66). Resistance to streptomycin is widespread, and its use is currently confined primarily to infections caused by Mycobacterium tuberculosis Yersiniapestis and Francisella tularensis. 

Rifamycia B is not biologically active but is spontaneously converted in aqueous solution to the active rifamycias O, S, and SV. Rifamycia SV was chosen for further studies because of its good in vivo activity, low toxicity, and solubiUty properties. Rifamycia SV is effective against a variety of infections as well as being active against tuberculosis and leprosy (168). Rifamycia P is the most active of the naturally occurring rifamycias (174). 

Florfenicol (2) has been approved in Japan for the treatment of pseudo-tuberculosis caused by Pasteurellapiscicida and streptococcosis m. yeUowtail fish. The recommended dose is 10 mg/kg for up to one week and the drug withdrawal time is five days after cessation of treatment. Florfenicol is active in bovine respiratory disease caused by Pasteurella species and mastitis caused by Staphylococci and Streptococci. It is also effective in neonatal cohbacillosis caused by E. coli. The drug is being developed worldwide by Schering-Plough Animal Health for the treatment of aquatic and bovine diseases. 

Monoamine—Oxidase Inhibitors. In the mid-1950s, tuberculosis patients with depression being treated with iproniazid (42) were occasionally reported to become euphoric. This observation led to the discovery of irreversible monoamine—oxidase (MAO) inhibiting properties. Hydrazine and nonhydrazine-related MAO inhibitors were subsequentiy shown to be antidepressants (122). Three other clinically effective irreversible MAO inhibitors have been approved for treatment of major depression phenelzine (43), isocarboxazid (44), and tranylcypromine (45). 

Aminosalicylic acid and its salts have been used in the treatment of tuberculosis, Aminosalicylic acid can be prepared by the carboxylation of m- am in oph en o1 (32). Aminosalicylic acid USP assays not less than 98.5% and not more than 100.5%, calculated on the anhydrous basis. The antitubercular agents are likely to be used as the more tolerated salts calcium [133-15-3] potassium [133-09-5] sodium [133-10-8] and the ethyl [6069-17-2] and phenyl [133-11-9] esters of -aminosalicylic acid. 

Pasteurization, the heating of certain fluids, frequentiy milk or dairy products (see Milk and milk products), destroys potentially harmful organisms such as mycobacteria, M. tuberculosis M. bovis or M. avium. Pasteurization, carried out at 62°C for 30 min or at 72°C for 15 s, is not a sterilization procedure. 

Monoamine Oxidase Inhibitors. MAOIs inactivate the enzyme MAO, which is responsible for the oxidative deamination of a variety of endogenous and exogenous substances. Among the endogenous substances are the neurotransmitters, norepinephrine, dopamine, and serotonin. The prototype MAOI is iproniazid [54-92-2] (25), originally tested as an antitubercular dmg and a close chemical relative of the effective antitubercular, isoniazid [54-85-3] (26). Tubercular patients exhibited mood elevation, although no reHef of their tuberculosis, following chronic administration of iproniazid. In... 

During the early 1900s, vaccines against major human epidemic diseases such as pertussis, diphtheria, tetanus, and tuberculosis were developed. Vaccines for many animal diseases were also available. In the early 1950s, the development of cell culture techniques byj. E. Enders at Harvard was followed by another series of major advances in vaccine development. Vaccines against poHo, mumps, measles, and mbeUa were Hcensed during the 1960s. 

Gapreomycin, Viomycin, and Enviomycin. Capreomycin (Capastat, Lilly), a bacteriostatic, antimycobacterial peptide mixture isolated from Streptomjces capreolus was first reported in 1961 (106—108). This tuberactinomycin family member, shown in Table 4, was introduced into the U.S. market in 1971 where it has remained a usehil but nephrotoxic and ototoxic second-line alternative to first-line tuberculosis therapies. Because capreomycin is somewhat less toxic than viomycin (tuberoactinomycin B [32988-50-4]) C25H42N23O2Q (109,110), capreomycin has now displaced viomycin in the United States and most other markets. The stmcture of viomycin is shown in Figure 2. The related enviomycin (tuberactinomycin N [33103-22-9]), C23H43N23O2Q,... 

Alcohols, particularly ethanol [64-17-5] and 2-propanol [67-63-9] are important disinfectants and antiseptics. In the aUphatic series of straight-chain alcohols, the antimicrobial activity increases with increasing molecular weight up to a maximum, depending on the organism tested. For Staphylococcus aureus the maximum activity occurs using amyl alcohol [71-41-0], for Salmonella typhosa, octyl alcohol [111-87-5], CgH gO (43) ioT Mycobacterium tuberculosis... 

Eig. 1. The quasispeciftc effect ia the homologous series of o-alkyl-/)-chloropheaol derivatives agaiast A = Salmonella typhosa-, B = Staphyloccus aureus-, C = Mycobacterium tuberculosis-, D = Candidaalbicans. Pheaol coefficieat is the activity of the chemical tested compared to that of pheaol. 

Sudol uses fractions of coal tar rich in xylenols and ethylphenols. It is much more active and less corrosive than lysol, and remains more active in the presence of organic matter. The phenol coefficients of sudol against Mycobacterium tuberculosis, Staphylococcus aureus, and Pseudomonas aeruginosa are 6.3, 6, and 4, respectively. It also is slowly sporicidal (97). 

Before the discovery of streptomycin, pyrazinamide (126) was one of the front runners in the treatment of tuberculosis. A broad spectrum of biological activity has been associated with pyrazine derivatives, ranging from the herbicidal activity of (127) to antibiotic activity... 

Thiirane is more bactericidal than oxirane, and derivatives of 2-mei captomethylthiirane inhibit tuberculosis. The following pharmacological uses have been reported for compounds derived from thiirane derivatives gold complexes of the adducts of diethylphosphine and thiirane (antiarthritic), adducts of thiiranes and malononitrile (antibacterial, blood vessel dilators, muscle relaxants, sedatives), thermolysis products of thiirane 1-oxides and adducts of thiirane 1-oxides with sulfenyl chlorides (antibacterial), adducts of 2,3-diarylthiirene 1,1-dioxides with ynamines (antibacterial, parasiticidal), adducts of 2,3-diarylthiirene 1,1-dioxides with enamines (antifertility), adducts of p-aminophenylacetic esters with thiirane (immunosuppressants), adducts of amines and thiiranes (radioprotective drugs). 

Thiirane, 2-keto- — see a-Thiolactones Thiirane, 2-mercaptomethyl-thiophosphate insecticide, 7, 183 tuberculosis inhibition by, 7, 183 Thiirane, 2-methyl-adducts... 

M Wilson, J DeRisi, HH Kristensen, P Imboden, S Rane, PO Brown, GK Schoolmk. Exploring drug-induced alterations m gene expression m Mycobacterium tuberculosis by microairay hybridization. Proc Natl Acad Sci USA 96 12833-12838, 1999. 

Infectious patients present a difficult challenge when trying to protect health care workers. These patients must be isolated from the health care workers as well as from the other patients in the hospital. Special isolation rooms are used for this purpose. These rooms are generally used for isolation of infectious tuberculosis (TB) patients, but could be used for patients with other airborne-transmitted diseases. In the United States, there were 22 812 new cases of tuberculosis in 1993, equal to 8.7 per 100 000 population. This represents a 2.8% increase since 1985, following a 6-7% annual decline from 1981-1984.Several studies have documented higher than expected tuberculin skin test (TST) conversion rates in hospital personnel.The National Institute for Occupational Safety and Health " reports that multiple-drug-resistant (MDR) strains of TB have been reported in 40 states and have caused outbreaks in at least 21 hospitals, with 18-35% of exposed workers having documented TST conversions. 

The sources for this type of control are infectious hospital or clinic patients, w here the infection can be transmitted through the airborne route. The most common application is for control of the spread of tuberculosis, but it could be used for other airborne infections such as varicella or influenza. -... 

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