Diagnose
Usually, the initial diagnostic/screening test for tuberculosis is the skin test. A small amount of fluid is injected under the skin of the foreman: the fluid contains a protein derived from the micoorganism causing TB , and is absolutely harmless to the body. The area is visually examined by a health professional after 48-72 hours to determine the result of the test. A positive skin test does not mean that you have active diseases; rather, that you may have been exposed to the organism referred to as TB infection, at some time in the past. If the result of the skin test is positive, a chest x-ray must be obtained to ascertain whether there is any active diseases
Treatment
Current treatment
1. Isoniazoid
Isoniazid is the most widely used of the antituberculosis agents. In many respects it is an ideal agent -- bactericidal, relatively non-toxic, easily administered, and inexpensive. It is highly active against M. tuberculosis (most strains being inhibited in vitro by concentrations of 0.05 to 0.20 ug/ml). Absorption from the gastrointestinal tract is nearly complete, with peak blood concentrations occurring 1 to 2 h after administration. A usual dose of 3 to 5 mg/kg body weight produces a peak concentration of approximately 5 ug/ml. The drug penetrates well into all body fluids and cavities, producing concentrations similar to those found in serum.
The interaction of isoniazid and phenytoin increases the serum concentration of both drugs. When these drugs are given concomitantly, the serum level of phenytoin should be monitored, and the phenytoin dosage decreased if necessary.
2. Rifampin
Rifampin is bactericidal for M. tuberculosis. The drug is relatively non-toxic and is easily administered. It is quickly absorbed from the gastrointestinal tract, with peak serum concentrations (of 6 to 7 ug/ml) occurring 1.5 to 2 h after ingestion. Most strains of M. tuberculosis are inhibited in vitro by concentrations of 0.5 ug/ml. Although approximately 75% of the drug is protein-bound, it penetrates well into tissues and cells. Penetration through noninflamed meninges is poor, but therapeutic concentrations are achieved in cerebrospinal fluid when the meninges are inflamed.
The most common adverse reaction to rifampin is gastrointestinal upset. Other reactions include skin. In general, the frequency of these reactions is quite low.
Current developments drugs
There are a number of new drugs that have been evaluated in children or adults for activity against tuberculosis. These include amikacin, quinolones, rifamycin derivatives, clofazimine, and beta-lactams. None of these agents has been tested in multidrug regimens for treating tuberculosis; however, the recent increase in the occurrence of multidrug- resistant tuberculosis may create more situations where the use of these drugs must be considered. None of these drugs has been evaluated in well- designed, randomized trials for tuberculosis treatment or prophylaxis, and they should not be used to replace any of the previously recommended drugs until efficacy is established. Among the new drugs that have been studied as antituberculosis agents, the ones that are discussed subsequently include only those that are licensed or those that are available through an investigational new drug (IND) request, in the United States. Appropriate doses and intervals for the use of these drugs for tuberculosis have not been established.
Vaccines
Current vaccines BCG
The only available vaccine against TB is the Bacillus Calmette Guerin (BCG), alive attenuated strain of virulent bovine tubercle bacillus Mycobacterium.bovis. One the basis of promising results in animals models and >300 infants tested between 1921 and 1924, BCG vaccine was distributed around the world for the prevention of TB. Since then, BCG is given to several people. Although, BCG is among the world most widely used vaccine, and being directed against the world leading cause of infectious disease mortality, it is the most controversial vaccine in current use.
The use of BCG vaccination faces two additional problems:
BCG vaccination induces a delayed type hypersensitivity (DTH) responses that cannot be distinguished from exposure to M.tuberculosis and therefore it comprises the use of purified protein derivative (PPD) of M.tuberculosis in skin test testing for diagnostic or epidemiological.
BCG being alive vaccine is contraindicated in HIV infected individuals for fear of causing disease by itself.
1. Subunit vaccines – current development
The most popular vaccine is the subunit vaccine. The protein obtained from M.tuberculosis culture filtrate has been extensively tested, and individual proteins or mixtures of these proteins have provided good results. These pools or fraction contain proteins that are known to stimulate the memory T cell response specially, a property that could be very useful and indeed seems essential. Another type of subunit vaccine of promise involves fusion proteins. Here, the tactic has been to identify epitopes recognized by T cells from purified protein derivative (PPD) positive individuals and then express these epitopes in a fusion protein format.
2. DNA based vaccine
Much progress has been to use naked plasmid DNA as a system to deliver M.tuberculosis antigens because DNA based vaccines have inherit adjuvant activity ,does not have any problem with pathogenicity associated with live recombinant vaccines and induce long lasting immunity. In addition, a single immunization with DNA vaccines may be sufficient to induce a strong protective immune response, thus avoiding repeated immunization that is required for subunit vaccines in adjuvant combinations. Several trials with DNA vaccination have shown protection of mice against subsequent challenge with M.tuberculosis by establishing a cellular immune response dominated by antigen specific T lymphocytes that produce INF-y and are cytotoxic towards infected cells. The best results to date have been obtained with a DNA vaccine targeting the mycolyltransferase enzyme Ag85A. This is protective in mice and although it does not reduce the bacterial load in guinea pigs, it does prolong survival by stimulating a lymphocyte granulomatous response.
Although the effect of DNA vaccination has not been reported, there have been successful uses of DNA based vector for topical cytokine delivery in treating cardiovascular disease.
3. Adenovirus based TB vaccines
Adenovirus has widely been explored for gene therapy or gene transfer both in experimental animals and human trials and the initial success has been seen in treating certain human genetic and acquired diseases. Experimental evidence also supports the potential use of adenovirus based vaccines for preventing infectious diseases. However, this viral vector has not been explored for TB vaccination. We have initiated a program to develop adenoviral based recombinant TB vaccines. The results indicate that single immunization with an adenoviral TB vaccine expressing Ag85A triggers a stronger T cell IFN-g recall response to recombinant Ag85A or BCG stimulation suggesting that when Ag85A is expressed as such , a broader repertoire of T cells are activated.
Adenoviral based TB vaccines have the potential to be used not only to immunize newborns but to boost the immune response in BCG vaccines who have been infected with M.TB. They will be a safer vaccine to be used in HIV infected hosts to prevent or treat TB. These vaccines in conjunction with plasmid DNA based vaccines, may prove to be better than vaccinabased TB vaccine for the prime and boost immunization.
Within the next years, these three vaccines should be available for human testing.
Conclusion
I found that tuberculosis is increase since 1998 in some area of London, but it shows decrease in N ewham area. I found this information by watching the news on 22nd March 2002.
References
1. Stefan.H.E (2000).Immune response against tuberculosis: Implications for vaccine development. Journal of Biotechnology, 13-17
2. Xing.Z. (2001).The Hunt for New Tuberculosis Vaccines: Anti-TB Immunity and Rational Design of Vaccines .Current Pharmaceutical Design, 1015-1037
3. Triccas.A.J. (2000).Life on the inside: Probing Mycobacterium tuberculosis gene expression during infection. Immunology and Cell Biology, 311-317
4. Ian.M, McMurray. (2001).Tuberculosis vaccine development: recent progress. Trends in Microbiolgy, vol.9
5. Mustafa.A.S. (2001).Biotechnology in the Development of New Vaccines and Diagnostic Reagents Against Tuberculosis. Current Pharmaceuticals Biotechnology, 157-173
6. HF Chambers, D Moreau, D Yajko, C Miick. (2002) Can penicillins and other beta-lactam antibiotics be used to treat tuberculosis? Journal of Clinical Microbiology, p.943-950,Vol.40