Bacillus Calmette Guerin Vaccine - Essay Example

Bacillus Calmette Guerin Vaccine Introduction Tuberculosis is one of the most common infectious diseases in the world affecting many countries in the world (WHO, 2010). The disease is caused by Mycobacterium tuberculosis or M. tuberculosis and can affect any part of the body (Herchline and Amorosa, 2010). Those who are infected can transmit the disease to others easily through droplet infection and hence the rate of spread of this infection is very high. While immense research, education, treatment and prevention strategies have been able to decrease the incidence of this disease in developed countries, the disease continues to be a challenge in developing and underdeveloped countries. Also, the growing HIV endemic in the world behaves as a fodder to tuberculosis, thus contributing to incidence and prevalence. One of the important strategies to prevent tuberculosis has been vaccination with Bacillus Calmette Guerin vaccine or BCG vaccine (WHO, 2010). In this research paper, BCG vaccine will be discussed. Prior to initiation of discussion on the vaccine, a brief discussion on tuberculosis will be done. Tuberculosis Tuberculosis is an infectious disease that is caused by M.tuberculosis (Herchline and Amorosa, 2010). It is contagious through droplets in air like common cold. Only those individuals who have the disease in their lungs are infectious. Transmission of bacteria occur while coughing, sneezing, talking or spitting. The airborne droplet nuclei contain less than 10 bacilli. Untreated individuals with active tuberculosis in their lungs can infect about 10- 15 people a year. However, not every person exposed to tuberculosis bacteria develop the disease because the immune system has the capacity to make the bacteria lie dormant for several years. The bacteria may become active, once the immune system of the individual wanes off or is weakened due to some reason (Herchline and Amorosa, 2010). Incidence1 Prevalence 2 Mortality WHO region no. in thousands % of global total rate per 100 000 pop3 no. in thousands rate per 100 000 pop no. in thousands rate per 100 000 pop Africa 2 828 30% 351 3 809 473 385 48 The Americas 282 3% 31 221 24 29 3 Eastern Mediterranean 675 7% 115 929 159 115 20 Europe 425 5% 48 322 36 55 6 South-East Asia 3 213 34% 183 3 805 216 477 27 Western Pacific 1 946 21% 109 2 007 112 261 15 Global total 9 369 100% 139 11 093 164 1 322 20 1Incidence is the number of new cases arising during a defined period. 2Prevalence is the number of cases (new and previously occurring) that exists at a given point in time. 3Pop indicates population. Table 1: Estimated TB incidence, prevalence and mortality, 2008 (WHO, 2010) Figure 1: Estimates rates of incidence TB in the world (WHO, 2010) M. Tuberculosis is an acid fast bacillus that grows very slowly, like 4-8 weeks over solid medium in the lab. It grows in parallel groups which are known as cords. Even after decoloration with acid-alcohol, the organism tend to retain the stains of coloring and hence is known as acid fast bacillus (Herchline and Amorosa, 2010). The only known reservoir for mycobacterium tuberculosis is human being (Herchline and Amorosa, 2010). Figure 2: Tuberculosis. Acid-fast bacillus smear. This picture shows cording in culture (Herchine and Amorosa, 2010) According to WHO, one third of the population in the world is infected with tuberculosis and every second some one or the other is newly infected with these bacteria (WHO Fact Sheet.). 5-10 percent of individuals infected with TB bacilli either develop infection or begin to be infectious some time during their life time (Herchline and Amorosa, 2010). Tuberculosis is more common in the third world countries. Estimates have shown that one in every 4 Brazilian is infected with tuberculosis. Every year, about 90,000 cases of tuberculosis are diagnosed in the country, more than 53 percent being pulmonary tuberculosis (Barreira and Grangeiro, 2007). In India, another developing country, tuberculosis is a leading cause of mortality with almost 2 persons dying every 3rd minute (TB India, 2010). According to the WHO (2010), the highest incidence of the disease occurs in South-East Asia which actually accounts for 34 percent of cases globally. According to Herchline and Amarosa (2010), with reference to mortality, tuberculosis is the most common infectious disease all over the world. It has been estimated that about 2 billion people in the world have latent tuberculosis. Also, about 3 million people die of this disease, each year worldwide. The rates of tuberculosis are decreasing in the United States, but they are increasing in several other parts of the world. Of concern is the rise in drug-resistant tuberculosis which is associated with severe morbidity and mortality. One of the important factor in the development and spread of resistant varieties is co-infection with HIV (Herchine and Amorosa, 2010). Tuberculosis is the most common opportunistic infection afflicting those with HIV positive status (Herchline and Amorosa, 2010). Table-2. WHO Report on Tuberculosis in Brazil: 2009 (WHO, 2010) Figure 3: Comparison of incidence rates of tuberculosis in Brazil from 2003 to 2007 (USAID, 2009). Clinical presentation of tuberculosis Clinical features depend on the site of involvement of the infection. The most common presentation of tuberculosis is pulmonary tuberculosis which presents as low grade fever, cough which is productive, and weight loss. Some patients may cough up blood from the cavities or develop chest pain. Other symptoms include easy fatiguibility, anorexia and night sweats. Those with tubercular meningitis present with intermittent head ache, fever, vomiting and subtle alterations in mental status. Seizures also may occur. If untreated, the patient may progress to coma over a period of few days (Herchline and Amorosa, 2010). Patients with skeletal tuberculosis have symptoms pertaining to the site of involvement. The most common site of involvement is spine. This condition is commonly known as Pott disease. It can present as pain or stiffness in the back and paralysis of the lower extremities. Tuberculosis can affect joints also, the most common one being knees and hips. When genitourinay system is involved, the patient develops dysuria, flank pain and increased frequency. In men, epididymitis can occur which can manifest as painful scrotal mass. In females, the disease presents as pelvic inflammatory disease. It can contribute to sterility. When the gastrointestinal system is involved, patients may develop nonhealing ulcers in the mouth, difficulty in swallowing, non specific abdominal pain, malabsorption syndrome, diarrhea and hematochezia. Lymph nodes can also become infected with the bacteria and develop the disease. It is known as tuberculous lymphadenitis or scrofula. The most common site of scrofula is the neck. More often than not, the disease is unilateral and associated with mild or no pain. In advanced cases, suppuration can occur. Very rarely even skin can get affected with tuberculosis and present like a non-healing chronic ulcer. Infection from here can spread to a lymph node and result in draining sinus. Hematogenous spread can also occur (Herchline and Amorosa, 2010). Figure 4: Clinical presentation of tuberculosis (Gosavi, 2008) Children are easily prone to tuberculosis because of their proximity to adults. The natural history and clinical presentation differs in them when compared to adults. Those infected at a tender age develop clinical disease rapidly (Batra and Ang, 2009). Figure 4: Tuberculosis in a child (Googleimages) Investigations The main test for pulmonary tuberculosis is smear and culture of sputum. Early morning sample of sputum must be taken for 3 consecutive days. In those with no spontaneous production of sputum, administration of hypertonic saline can help in the induction of sputum. In children, early morning gastric aspirate is a good specimen. Culture of the specimens may take several weeks to identify tubercle bacilli. Recent technologies use DNA polymerase chain reaction or ribosomal RNA probe for identification within few hours. Some DNA probes can be applied directly over smears itself. For drug susceptibility, direct sequencing analysis is a rapid method than the conventional method which takes several days. Other tests which may need to be done in tuberculosis are dependent on the site of the disease and findings of physical examination. All patients with tuberculosis must be checked for HIV status. Chest radiography may show a nodular infiltrate or a patchy zone. The most common site of involvement is the upper lobe. Other findings in chest X-ray include cavity, non-calcified infiltrates, homogenous calcified nodules and numerous small nodules suggestive of miliary tuberculosis (Herchline and Amorosa, 2010). Figure 5 : Chest-X-ray findings of pulmonary tuberculosis (Herchline and Amorosa, 2010) Treatment The main treatment for tuberculosis, whatever be the site of involvement is antitubercular agents. The most commonly used agents are rifampicin, isoniazid, pyrizinamide, streptomycin and ethambutol. These drugs are administered as fixed regimen (Herchline and Amorosa, 2010). Empiric treatment involves use of 4-drug regimen. The treatment is given for 4-6 months. After 2 months, the number of drugs given may be reduced based on clinical improvement (Herchline and Amorosa, 2010). In countries like India, where the incidence and prevalence rates are high, the WHO has recommended Directly Observed Treatment, Short Course (DOTS) strategy under the Revised National TB Control programme of 1997. According to WHO (cited in TBC India, 2010), DOTS prevents the emergence of multi-drug resistant tuberculosis (TBC India, 2010). Prevention BCG is good vaccine which can be used to prevent tuberculosis. However, the vaccine is not highly efficacious. In some countries like Brazil and India vaccination for the new born is mandatory. For those who are exposed to tuberculosis, prevention of the disease can be done by taking isoniazid daily. Currently, a new anti-tuberculosis vaccine, a live recombinant type, called AERAS-422, developed by the Aeras Global TB Vaccine Foundation has entered clinical testing and results are awaited (Medinews, 2010). According to the company, "Bacille Calmette Guérin (BCG) is widely viewed as insufficient in preventing pulmonary TB, and this trial is part of a wider global effort to develop safer and more immunogenic TB vaccines that would be effective against all forms of TB" (Medinews, 2010). AERAS-422 has mainly 3 key proteins: 85A, 85B and Rv3407 (Medinews, 2010). Primary prevention of the disease can be done by education of the public including information and teaching. Local health departments play a major role in educating the public about the disease process, mode of spread, early signs and symptoms, etc. In countries like India, tuberculosis is a social stigma and public education is a major tool in decreasing the incidence of the disease (Schiffman and Stoppler, 2010). BCG Vaccine Bacillus Calmette Guerin vaccine or BCG vaccine is a vaccine against tuberculosis that was first developed in 1921 by Albert Calmette, a French microbiologist and Camille Guerin, a veterinary surgeon. Currently, BCG is the only vaccine against tuberculosis. The mechanism of immunity induced by this vaccine is cell-mediated immunity (Serum Institute of India). The vaccine is not very efficacious. Infact, the protective effect for tuberculosis is less than 50 percent. However, in some countries with high incidence and prevalence like India, it is mandatory for all children to receive this vaccine at birth to have the benefits of whatever little protection the vaccine offers. The efficacy of this vaccine in preventing meningeal and miliary tuberculosis is higher, about 50- 80 percent. Both these types of tuberculosis are associated with high mortality and morbidity (WHO, 2010). Figure 6: BCG Vaccine (Serum Institute) The most commonly used strains in the vaccine are Copenhagen and Danish 1331. Both these are strains of mycobacterium bovis (Serum Institute of India, 2008). In each 0.1ml of the vaccine, 0.1- 0.4 million live viable bacilli are present. The vaccines are supplied in multi-dose ampoules which are dark colored. 10-dose and 20-dose vials are available. The preparation is vacuum sealed. Hence the ampoule must be opened carefully to avoid sudden entry of air and spillage of the constituents of the vaccine. The constituents of the vaccine are freeze dried. The vaccine can be stored between 2- 8 degree centigrade for one year. It must be reconstituted with normal saline only. The vaccine does not have any preservatives and hence the chances of bacterial contamination are very high. It if for this reason that it is recommended not to use the reconstituted vaccine after 4 hours after reconstitution. Even in those 4 hours, the vaccine must be stored in the refrigerator between 2- 8 degree centigrade. When stored under appropriate conditions, the shelf life of the vaccine is 24 months (Serum Institute of India, 2008). Figure-7: Administration of BCG vaccine (googleimages.com) The recommended dose for vaccination is 0.1ml of the reconstituted vaccine. The dose is irrespective of the weight and age of the individual. Ideal syringe that needs to be used for vaccination is the tuberculin syringe with 25/26G needle. The vial has to be swirled gently before draining up for each dose. The solution drawn must be colorless, homogenous and opaque. The vaccine has to be administered strictly intradermal. Subcutaneous administration can result in BCG adenitis. The site of vaccination must be cleaned with saline swab. Ideally, the vaccine can be administered anywhere in the body. But the recommended site of administration is the convex contour of the upper left shoulder for facilitating easy visualization of scar. Most physicians prefer to inject over the region where deltoid muscle inserts into the humerus. This is because injection in areas higher than this is likely to cause keloid development (Serum Institute of India, 2008). Response to BCG vaccine is typical. First of all, development of atleast 5mm of wheal is the most important indicator for appropriate administration of vaccine. 2-3 weeks later, a small papule is noticeable at the site of injection. This papule gradually increases to 4-8mm by the end of 5-6 weeks. Thereafter, the papule formed thus ruptures leading to development of an ulcer. This ulcer heals slowly over 6-12 weeks by secondary intention leading to a scar. Absence of any of the above reactions even by 12 weeks after administration of the vaccine is an indication of failure of the vaccine. The vaccine has to be repeated in such case (Serum Institute of India, 2008). Figure 7: Typical wheal after BCG administration (googleimages) Adverse reactions to BCG vaccine are rare and even when they occur they are mild. Adverse reactions occur in 1-10 percent cases. Immediate adverse reactions include swelling at the site of administration of injection and mild soreness. Late adverse reactions also occur, the most commonly reported one being delayed healing of the ulcer. Since the ulcer heals on its own, there is no need to administer any treatment for the ulcer. Other late effects include secondary bacterial infection which can be treated with local antibiotics, lymphangitis and enlargement of ipsilateral axillary and cervical lymph nodes. There is no treatment recommended for these and they will settle down on their own. Fine needle aspiration cytology studies will reveal acid-fast bacilli, but they are actually bovine bacilli. Another rare reaction is abscess formation of the nodes. This may need repeated fine needle aspiration or surgical removal. Even this condition does not require antitubercular treatment. Osteomyelitis occurs in 1 in million cases and a worse adverse effect is disseminated BCG infection. Dissemination mainly occurs in those with cellular immunodeficiency. It occurs in 1- 10 cases per 10 million vaccines. The condition requires treatment with antitubercular drugs and can be fatal (Serum Institute of India, 2008). Figure 9: Post BCG Vaccination Ulcer formation Age-specific estimated risks for complications after administration of Bacillus of Calmette and Guerin (BCG) vaccine ========================================================================================= Incidence per 1 million vaccinations ------------------------------------ Complication Age Herchline, T., and Amorosa, J.K. (2010). Tuberculosis. Emedicine from WebMD. Retrieved on 3rd Nov 2010 Gosavi, S. (2008). Tuberculosis in children. Student BMJ Archive. Retrieved on 5th Nov 2010 http://archive.student.bmj.com/issues/08/09/education/326.php Kuyucu, N., Kuyucu, S., Bakirtas, A. and Karacan, C. (2001). BCG Revaccination and Tuberculin Reactivity. Indian J Pediatr., 68 (1), 21-25. Medinews. (2010). New TB Vaccine Enters Clinical Testing. Retrieved on 3rd Nov 2010 Serum Institute of India.(2008). BCG Vaccine: product Information. Retrieved on 3rd Nov 2010 TBC India. (2010). Tuberculosis Control India. Retrieved on 3rd Nov 2010 Schiffman, G., and Stoppler, M.C. (2010). Tuberculosis. Emedicine Health. Retrieved on 3rd Nov 2010 USAID. (2009). Infectious Diseases. Retrieved on 5th Nov 2010 http://www.usaid.gov/our_work/global_health/id/tuberculosis/countries/lac/brazil_profile.html WHO Fact Sheet. (2010). Tuberculosis. Retrieved on 3rd Nov 2010 WHO. (2010). BCG Vaccine. Retrieved on 3rd Nov 2010 Read More