Andi Cahyadi, dr.
Tuberculosis (TB) has become a major public health problem in the world and Indonesia with incidents increasing from year to year. BCG vaccine is a solution that is right for the prevention of TB disease in normal individuals, but not for people with HIV (+). BCG (Bacillus Calmete-Guerin) is a live attenuated vaccine of Mycobacterium bovis that has been weakened and either given to the child (infant). (Aditama, 2000; Simon 2002) BCG can be dangerous if given to the state of immunodeficiency such as in HIV infection / AIDS. BCG vaccine can trigger the occurrence of TB in people with HIV (+). To date, BCG vaccine candidates that can be given to persons with HIV (+) has not been obtained.
HIV/AIDS epidemic is associated with the TB epidemic. (WHO, 2007) pulmonary tuberculosis is the commonest opportunistic infection in people with HIV/AIDS. (Ravligone et al., 1995) WHO noted in 2005, there were 8.8 million new TB cases and 1.6 million deaths per year of which 195 thousand of them are infected HIV. Approximately 72% of the world's TB sufferers are in Asia and more than 1.3 million Asians are infected with HIV and TB is estimated simultaneously. (Ravligone et al., 1995) TB can worsen quality of life and hasten death in people with HIV (+). HIV/AIDS to facilitate the spread of primary TB infection and infection with Mycobacterium tuberculosis will speed up the trip early stages of HIV infection becomes advanced stage (AIDS) are fatal. (Antonucci, 1995; Moreno et al., 1993)
Coinfection with HIV and TB is a bad prognose of two-way interactions (pathogenic bidipzectional Interactions). WHO estimates that in 2000 will be an increase in global HIV-TB from 9% to 24% that launched a global emergency for TB disease in 1993. (WHO, 2006) TB in Indonesia in 1995 was 460,190 people, and in August 1999 there is addition of new cases for 583,000 people with the deaths of around 140,000. (Aditama, 2000) The amount is increased by the estimated number of people living with HIV / AIDS (PLWHA) in Indonesia in 2001-2002, amounting to 80,000 to 120,000 people.
The failure of BCG in preventing TB in people with HIV (+) has motivated scientists to develop a safe and effective vaccine is given in ppenderita HIV (+). Immunosuppression due to HIV infection may alter the response of vaccines and increase the risk of infection with Mycobacterium. (CDC, 1996) BCG (Bacillus Calmette-Guerin) is a weakened Mycobacterium that can still develop into TB in the state of immunodeficiency. Mycobacterium tuberculosis is a potential inducer of cellular immune response, characterized by levels of IFN-γ and TNF-α is high. Clinical impact of type 1 immune response is the increase in cases of TB in the HIV epidemic, especially in patients with low CD4 +. Protective effect of BCG varies between 0 - 80%. (Rodrigues and Smith, 1990) People with HIV (+) and HIV (-) have different responses to BCG. BCG vaccine has no efficacy in preventing extrapumonal TB in HIV patients. Specific cellular immune responses necessary to control the spread of the tubercle bacillus but a decrease of CD4+ lymphocytes and the production of T suppressor lymphocytes generated by HIV infection weakens the immune response. Issues need to be considered in the use of BCG in HIV pendrita.
HIV infects and destroys CD4+ T Lymphocytes. CD4+ T lymphocytes have an essential role in the coordination of cellular immune response against Mycobacterium tuberculosis. Interferon Gama as the result of activation of CD4+ and CD8+ will activate the macrophages and eventually control the replication of Mycobacterium tuberculosis. The function and the number of CD4+ decline in people with HIV so that cellular immune response against TB to be inadequate.
BCG (Bacille Calmete-Guerin) is a live attenuated vaccine given as the prevention of tuberculosis. BCG can trigger the occurrence of tuberculosis in HIV patients with BCG vaccine so that needed a new, more secure and productive. Re-formulated BCG needs to get a vaccine that is safe and protective and can be given to HIV patients. Scientific reasoning of a clinician is required to select the type of BCG vaccine is safe and protective for use. Selection of BCG modifications based on:
1. Protective effect against TB in HIV patients,
2. Security immunological mechanisms of vaccine against HIV patients who have immunodeficiency.
3. Immunological status of the past such as BCG immunization status of children, scar TB and TB disease in the past.
4. Current nutritional status,
5. Timing of which is on high-risk groups or who have no risk,
6. BCG repeat (booster) to increase the immunological status,
7. Immunological status at this time is the number of CD4 + cells associated with the success of BCG.
The above factors must be considered by clinicians in order to obtain results in accordance with the desired. Basis is also required to supply prefers the existing BCG vaccine.
From Mycobacterium bovis BCG developed a level of homology (similarity genome) more than 90% with Mycobacteium tuberculosis. A number of loci in BCG vaccine strains have undergone deletions are thought to be the cause of the failure of BCG over the years. Loci identified RD1-RD16 missing is a role in determining the virulence of bacteria. Locus was lost during the breeding process repeatedly to get the vaccine strain is not virulent. Mycobacterium bovis was first isolated in 1908 at the Institut Pasteur, Paris; carried 230 times pasasi to get the vaccine strain that later became the parent BCG. Mutation is also thought to be the cause of differences in the effectiveness of BCG in different countries.
Recombinant BCG vaccine that has entered clinical trials (phase I) was developed by a team from UCLA, the United States that is named rBCG30. The vaccine is designed to express the major proteins that excreted by Mycobacterium tuberculosis. Mycobacterium tuberculosis genes missing in BCG vaccine strains encoded back eg Ag85B protein-coding genes which are dominant antigens. Other genes such as ESAT-6, on the RD1 locus are responsible for the cellular immune response.
Another technique is to inhibit genes that play a role in the attenuation of BCG but are at risk because the vaccine can be highly virulent again. Another approach through DNA vaccines have many advantages that it is easily manipulated and can be designed or constructed with immunomodulatory molecules that are immunogenic strong cellular and humoral immune responses. A plasmid DNA vaccine encoding specific proteins or antigens is responsible for inducing protective immunity.
An alternative approach which also developed the vaccine sub-units are more compact than the BCG. Subunit vaccines are not using intact bacteria, such as BCG, but certain components of Mycobacterium tuberculosis, such as fat and carbohydrate constituent membranes or proteins as antigenic determinants. Subunit vaccine candidates under investigation are from the fusion protein Ag85B and ESAT-6 which proved to induce a degree of protection higher than conventional BCG.
A suitable vaccine candidate for HIV sufferers are DNA vaccines, namely MVA85A considered safer than a live attenuated vaccine (BCG). Currently MVA85A vaccine is still in development phase IIb clinical trial. However, from the test results, already obtained preliminary data showing a very good success rate in tests in adults (18-55 years) with positive tuberculin test results and negative and in patients with HIV. One week after vaccination, nearly 50% of antigen-specific T cells are positive for all four test methods during the study: IFN-γ, IL2, TNF-α and MIP-1b. And this response is maintained even six months after vaccination MVA85A. The vaccine is suitable for use in people with HIV, because it is not a vaccine of live attenuated bacilli, which means indicate the level of security is better than the existing BCG.
MVA85A DNA vaccine showed better results compared with a live attenuated vaccine. Therefore, it is necessary socialized that the existing BCG vaccine in Indonesia today is to show the level of vulnerability of the immune system is worse for people with HIV who are undergoing antiretroviral treatment. To establish the defense a better immune system for people with HIV to tuberculosis, DNA vaccines are a proven alternative to good and appropriate to prevent co-infection with HIV and TB and given to those with HIV in the infant.
Vaccines should also work to individuals who have co-infected with HIV. Individuals with HIV / AIDS has a number of T lymphocytes (mainly CD4 +) low. Immune cell types is precisely an important role in the body's defense against TB. In coming years, cases of TB / HIV coinfection certainly continue to rise given the vaccine to prevent HIV / AIDS also has not been successfully developed.
Thus, MVA85A DNA vaccine can be selected by the physician to be given to people with HIV. Giving the vaccine should still consider the patient's condition that is associated with a different immune response from the decrease in CD4 + cells. A wise physician always considers advantages and disadvantages of the BCG vaccine when given to people with HIV-positive.
BCG vaccine (live attenuated vaccine) that there can not be given to people with HIV because it can trigger the emergence of TB or reactivation of latent TB. Need to be re-formulated BCG vaccine for HIV patients can be given to them are suitable are recombinant BCG vaccine and protein fraction. MVA85A DNA vaccine is the main option BCG vaccine candidates that can be given to people with HIV. MVA85A DNA vaccine is still in the research stage so that the clinician should consider the advantages and disadvantages when given to people with HIV. Other BCG vaccine candidates still need to be tested in order to have results that have high efficacy in patients with HIV.
REFERENCES
Aditama TY. 2000. Sepuluh Masalah Tuberkulosis dan Penanggulangannya. J Respirologi Kedokt. 20 (9): 8-12.
Antonucci G, Giradi E, Raviglione MC et al., 1995. Risk Factor for Tuberculosis in HIV Infected Person: a Prospective Cokert Syudy. JAMA. 274: 143-148.
Bhat GJ, Diwan VK, Chintu C, et al. 1993. HIV, BCG and TB in children: a case control study in Lusaka, Zambia. J Trop Pediatr 1993;39:219–23.
Center for Disesase Control and Prevention. 1993. Estimated of Future Global Tuberculosis Morbidity and Mortality. MAWR; 42: 961-964.
Center for Disesase Control and Prevention. 1996. UpDate: Provesional public health service recommendation for chemoprophilaxis after occupational exposure to HIV. JAMA; 276: 90-92.
Centers for Disease Control and Prevention. 1986. Tuberculosis-United States 1985- and possible impact of human T-lymphotropic virus type III/lymphadenopathy-associated virus infection. JAMA; 255:1010-13.
Centers for Disease Control and Prevention. 1996. The role of BCG vaccine in the prevention and control of tuberculosis in the United States. A joint statement by the Advisory Council for the Elimination of Tuberculosis and the Advisory Committee on Immunization Practices. MMWR; 45(RR-4):1–18.
Comstock GW. 1988. Identification of an effective vaccine against tuberculosis. Am Rev Respir Dis;138:479–80.
Raviglione, MC., DE. Snider Jr, and A. Kochi. 1995. Global Epidemiology of Tuberculosis Morbidity and Mortality of a Worldwide Epidemic. JAMA;273(3):220-6
Rodrigues LC, Diwan VK, Wheeler JG. 1993. Protective effect of BCG against tuberculous meningitis and miliary tuberculosis: a meta-analysis. Int J Epidemiol;22:1154–58.
Rodrigues LC, Smith PG. 1990. Tuberculosis in developing countries and methods for its control. Trans R Soc Trop Med Hyg;84:739–44.
Simon, Harvey E., 2002. Infections due to Mycobacteria, in Infectious Disease: The Clinician’s Guide to Diagnosis, Treatment, and Prevention, WebMD Prof. Publishing.
World Health Organization (WHO) report 2007: Global tuberculosis control.
World Health Organization (WHO). 1999. What is DOTS?A Guide to understanding the WHO-recommended TB control strategy known as DOTS. WHO/CDS/CPC/TB/99.270. Geneva, Switzerland
World Health Organization (WHO). 2002. An expanded DOTS framework for effective TB control. World Health Organization, Geneva (WHO/CDS/TB/2002.297).
World Health Organization (WHO). 2003. Treatment of Tuberculosis, Guideline for National Programmes. WHO/CDS/TB/2003.313. Geneva
World Health Organization (WHO). 2006. AIDS epidemic update: Special report on HIV/AIDS: UNAIDS and WHO: December 2006.
Tidak ada komentar:
Posting Komentar