Tuberculosis, a Cause for Concern?

Despite advances in treatments available, tuberculosis (TB) still remains a global pandemic. One third the human population is currently infected with tuberculosis. What is tuberculosis?

The disease tuberculosis is caused by the bacteria Mycobacterium tuberculosis. Tuberculosis can affect any part of the body but usually infects the lungs. Tuberculosis is spread through airborne droplets occurring when an infected individual sneezes, talks, or coughs. However, prolonged exposure to the infected individual must occur before you may become infected. The body may harbor the bacteria while the immune system prevents sickness. For this reason, there are two forms of TB: latent tuberculosis and active tuberculosis.

With latent tuberculosis, the immune system is able to prevent the bacteria from growing. The tuberculosis bacteria remain alive within the body but are inactive at this time. However, the bacteria can become active later in life. Those with latent tuberculosis have no symptoms, do not feel sick, are not contagious, and may develop TB later in life if they do not receive treatment.

Active tuberculosis simply means that the tuberculosis bacteria are growing within the body causing an active infection. Signs and symptoms of active tuberculosis include fatigue, slight fever, chills, night sweats, loss of appetite, unintended weight loss, a cough that lasts three or more weeks producing discolored or bloody sputum, and pain with coughing or breathing. Active tuberculosis is highly contagious.

What is causing the tuberculosis pandemic? Improved public health programs have helped to create a steady decline of tuberculosis cases in the United States. However, the problem is far from solved. Factors that contribute to the spread of tuberculosis in the U.S. and elsewhere include the increase in number of foreign born nationals, crowded living conditions, increase in drug resistant strains of tuberculosis, lack of access to medical care, and the increase in poverty.

Poorly ventilated and crowded conditions help to spread TB. This is one reason tuberculosis cases have reached epidemic proportions. Although the incidence of TB cases in the U.S. is declining, the incidence in other parts of the world is increasing. Half of the reported cases in the U.S. (in 2000) occurred in individuals that were born outside of the U.S. Individuals that live in poverty, move or migrate often usually do not finish the tuberculosis treatment. This is leading to drug resistant forms of tuberculosis.

Drug resistant strains of tuberculosis are a serious problem. Tuberculosis bacteria have developed strains of the bacteria that are resistant to each of the major tuberculosis medications. There are also strains of tuberculosis that are resistant to at least two tuberculosis medications. This multidrug-resistant TB (MDR-TB) is posing an even deadlier threat to those affected. Individuals affected with MDR-TB are much more difficult to treat requiring a long term therapy of up to two years. The medications required to treat these strains can cause serious side effects. This is one great reason to complete the entire course of medication as prescribed by your doctor.

Certain factors increase your risk of contracting tuberculosis. An individual in an immunocompromised state is at risk of developing TB. A number of factors can cause the immune system to be in a weakened state. Some diseases can suppress the immunity such as diabetes, HIV/AIDS, and silicosis. Certain medications can affect the body’s immune system which includes chemotherapy drugs and corticosteroids. An increased risk of reactivated tuberculosis has been associated with the use of arthritis medications Enbrel and Remicade.

Individuals within close proximity of those infected with tuberculosis are at an increased risk of developing disease. Individuals in areas of high rates of tuberculosis (Asia, Africa, Latin America, former Soviet Union) have an increased risk of developing tuberculosis. Certain races (Hispanics, American Indians, Asian Americans, African Americans) in the U.S. are at risk of developing tuberculosis. What other factors may increase your risk of developing tuberculosis?

The older adult is at an increased risk of developing tuberculosis due to a weakened immune system. Individuals who are malnourished, lack adequate medical care, or who suffer from long term drug or alcohol abuse are at increased risk of developing tuberculosis. Health care workers are at increased risk of developing tuberculosis also.

If you develop any of the signs or symptoms listed above, you should seek medical advice. Individuals with HIV should be tested for tuberculosis, since the leading cause of death in the AIDS patient is tuberculosis. HIV and tuberculosis have a deadly symbiosis, in which TB increases the rate at which the AIDS virus replicates and HIV reactivates inactive TB. Health care workers are usually tested at least yearly for tuberculosis by Mantoux test. Individuals with latent tuberculosis reveal a positive Mantoux even though no symptoms of the disease are evident. Tuberculosis is also tested by chest x-ray and culture tests (urine, sputum).

Tuberculosis is a preventable disease. There are a few measures one can take to protect their health. First, you should be tested regularly. If you have an immune suppressing disease, live or work in a prison or nursing home, were born in a TB prevalent country, or have other risk factors, then a Mantoux test should be done every six months.

If you test positive without symptoms, speak with your doctor about treatments to reduce the risk of developing active tuberculosis. The most important step you can do for the public and yourself is to finish the entire course of medication.
by: Kristy Haugen
Read Full Article...>>>

Tuberculosis and 2 Billion People

Tuberculosis, a bacterial infection, most commonly affects the lungs. Tuberculosis can also affect the central nervous system, lymphatic system, circulatory system, genitourinary system, bones and joints. Often Called TB for short, tuberculosis is the most common major infectious disease today. With that title the virus is infecting two billion people which is approximately one-third of the world's population. Nine million new cases of active disease annually, resulting in two million deaths. Most of these cases and deaths are in developing countries.
Ninenty percent of...

those that are infected have asymptomatic latent TB infection (LTBI). This is alot of numbers: There is a ten percent chance that in the lifetime of LTBI that it will progress to active TB disease. This active disease if left untreated, will kill more than fifty percent of its victims. All of these numbers make tuberculosis one of the top three infectious killing diseases in the world. HIV/AIDS kills 3 million people each year, TB kills 2 million, and malaria kills 1 million.

Tuberculosis is caused by a slow-growing aerobic bacterium that divides every 16 to 20 hours. This division is extremely slow when compared to other bacteria, which tend to have division times that are measured in minutes.

In many patients the infection of Tuberculosis waxes and wanes. Treatment with appropriate antibiotics kills bacteria and allows healing to take place. Areas where Tuberculosis has affected will eventually be replaced by scar tissue. A complete medical evaluation for Tuberculosis includes a medical history, a physical examination, a tuberculin skin test, a serological test, a chest X-ray, and microbiologic smears and cultures. This is quite an extensive procedure as you can see, but if you look at the numbers above it is a necessary process.
by: Ryan Fyfe
Read Full Article...>>>

Tuberculosis

Disease Burden
Based on available data, S. pneumoniae is estimated to kill annually close to one million children under five years of age worldwide, especially in developing countries where pneumococcus is one of the most important bacterial pathogens of early infancy.
In developed countries, virtually every child becomes a nasopharyngeal carrier of S. pneumoniae during the first year of life. Many go on to develop one or more episodes of otitis media, whereas a smaller number develop more serious invasive pneumococcal infections. Bacteraemic pneumonia is a...

common form of invasive pneumococcal disease, the next most common being pneumococcal meningitis, with or without bacteraemia. S. pneumoniae is the leading cause of nonepidemic childhood meningitis in Africa and other regions of the developing world. In the USA, most cases of invasive pneumococcal disease are characterized by febrile bacteraemia without specific localization. Less severe but more frequent forms of pneumococcal disease include middle-ear infection, sinusitis or recurrent bronchitis. Thus, in the USA alone, seven million cases of otitis media are attributed to pneumococci each year. Although all age groups may be affected, the highest rate of pneumococcal disease occurs in young children and in the elderly population. In addition, persons suffering from a wide range of chronic conditions and immune deficiencies are at increased risk. In Europe and the USA, pneumococcal pneumonia accounts for at least 30% of all cases of community-acquired pneumonia admitted to the hospital, with a reported annual incidence of 5500 to 9200 per 100 000 persons 65 years of age or older, and a case fatality rate of 10–30%. S. pneumoniae is an under-appreciated cause of nosocomial pneumonia in hospital wards, intensive care units, as well as in nursing homes and long-term care institutions.
Bacteriology

S. pneumoniae is a Gram-positive encapsulated diplococcus. Based on differences in the composition of the polysaccharide (PS) capsule, 90 serotypes have been identified. This capsule is an essential virulence factor. The majority of pneumococcal disease in infants is associated with a small number of these serotypes, which may vary by region. Current data suggest that the 11 most common serotypes cause at least 75% of invasive disease in all regions. Several other virulence factors have been described, including pneumolysin which leads to pore formation and osmotic lysis of epithelial cells, autolysin, and pneumococcal surface protein A (PspA), which interferes with phagocytosis and immune function in the host. Pneumococci are transmitted by direct contact with respiratory secretions from patients and healthy carriers. Although transient nasopharyngeal colonization rather than disease is the normal outcome of exposure to pneumococci, bacterial spread to the sinuses or the middle ear, or bacteraemia following penetration of the mucosal layer, may occur in persons susceptible to the involved serotype. Pneumococcal resistance to essential anti-microbials such as penicillins, cephalosporins and macrolides is a serious and rapidly increasing problem worldwide.
Vaccine

Protective immunity is conferred by type-specific, anticapsular antibodies, although the serological correlates of immunity are poorly defined. Antibodies to pneumococcal surface proteins (PspA) have been demonstrated to confer protection in animal models but the role of these antibodies in humans is yet to be determined.

Currently licensed vaccines are polyvalent PS vaccines containing per dose 25 µg of purified capsular PS from each of the 23 serotypes of S. pneumoniae that together account for most cases (90%) of serious pneumococcal disease in western industrialized countries. Relatively good antibody responses (60–70%) are elicited in most healthy adults within 2–3 weeks following a single intramuscular or subcutaneous immunization. The immune response is however mediocre in children less than two years of age and in immunocompromised individuals (HIV/AIDS). Furthermore, PS vaccines do not induce immunological memory which is required for subsequent booster responses. The polyvalent PS vaccine is recommended for healthy people over 65 years of age, particularly those living in institutions. Randomized controlled trials in healthy elderly people in industrialized countries have, however, failed to show a beneficial effect of the vaccine, so that recommendation for its use in the elderly is based on data from observational studies showing a significant protective effect against invasive (bacteraemic) pneumococcal disease, but not pneumonia.

Following the vaccination of pregnant women with PS vaccines, anti-PS antibodies are transferred both via the placenta and in the breast milk, but formal demonstration that maternal vaccination actually protects newborn infants against pneumococcal disease is still lacking.

Over the past 15 years, several vaccine manufacturers have developed pneumococcal conjugate vaccines in which a number of S. pneumoniae PS are covalently coupled to a protein carrier. Conjugate vaccines elicit higher antibody levels and a more efficient immune response in infants, young children, and immunodeficient persons than the PS vaccines, as well as a significant immunological memory resulting in a booster antibody response on subsequent exposure to the antigen. Moreover, these vaccines suppress nasopharyngeal carriage of the pathogen and reduce bacterial transmission in the community through herd immunity, which adds considerable value to their implementation. Conjugate vaccines immunization followed by PS vaccine boosting might provide a foundation for lifelong protection against pneumococcal disease.

Introduction of the conjugate vaccine in early 2000 in the USA resulted in dramatic decline in the rates of invasive pneumococcal disease, with reductions also seen in unvaccinated individuals as a result of herd immunity. In a double-blind Phase III study of the 7-valent vaccine, Prevnar (Wyeth), conducted at northern California Kaiser Permanente medical centres on 37,868 infants, 40 cases of invasive S. pneumoniae disease were seen in the study population, 39 of which were in the control group, representing a 97% vaccine efficacy. The vaccine was found to be 100% efficacious in the few low birth-weight and preterm infants included in the study. Post-licensure follow-up studies conducted in the same setting have shown an 87% reduction in invasive pneumococcal diseases caused by vaccine serotypes in children less than one year of age, and a 62% reduction in children less than five years of age, with no difference between a two-dose or a three-dose immunization regimen. The vaccine also elicited moderate protection against otitis caused by vaccine serotypes. However, the decrease in cases of vaccine-type otitis media was offset by an increase in those due to non-vaccine-types of S. pneumoniae and by H. influenzae, a phenomenon referred to as "replacement disease". This phenomenon also has recently been observed for invasive pneumococcal disease, although the increase in non-vaccine types was small relative to the decrease in vaccine-type invasive disease caused by vaccination.

The currently licensed 7-valent vaccine, Prevnar, does not contain some of the serotypes that cause severe disease in developing countries, notably serotypes 1 and 5. New conjugate vaccines that provide more optimal serotype coverage in these countries are in clinical development, including a 9-valent Wyeth vaccine, and an 11-valent GSK and Sanofi-Pasteur vaccines. The protein carrier used by Wyeth is CRM197, a genetically detoxified mutant of diphtheria toxin, whereas that used by GSK is the H. influenzae protein D. Merck is using the outer membrane protein complex (OMPC) from N. meningitidis. The 9-valent vaccine has been tested in South Africa with remarkable efficacy results in children less than two years of age, including HIV-positive infants. In addition, an unexpected benefit of vaccination was the decrease of symptomatic pneumonia cases associated with a viral infection, whether influenza virus or one of the paramyxoviruses. The vaccine is now being tested in the Gambia. Sanofi-Pasteur 11-valent vaccine is undergoing an efficacy trial in the Philippines, but it is not clear at this time whether all these conjugate candidate vaccines will be taken to licensure.

Newer vaccine approaches are being developed in order to provide protective immunity against a larger number of S. pneumoniae serotypes, and to circumvent the complexity of manufacture of conjugate vaccines. Several pneumococcal proteins, including pneumolysin, PspA, pneumococcal surface adhesin (PsaA), neuraminidase, and autolysin are at an early clinical stage development. PiaA and PiuA, two newly identified lipoprotein components of S. pneumoniae iron uptake ABC transporters, elicit protective immunity against invasive pneumococcal disease in mice through induction of opsonophagocytosis-promoting antibodies.

Through screening with human convalescent sera of a S. pneumoniae genomic expression library, Shire Biologicals, Canada (now ID BioMedical) has identified what appear to be remarkably conserved bacterial surface proteins (BVH-3 and BVH-11) able to induce protective anti-pneumococcal antibodies in the mouse model. A recombinant 100 kD hybrid protein, BVH3/11V, was engineered by fusion of parts of the two genes and expressed with high yields in E. coli. The fusion protein has successfully been tested in Phase I dose ranging clinical trials in toddlers and elderly volunteers. A 2-dose immunization regimen was able to induce a 50-fold increase in anti-S. pneumoniae antibody levels. Phase II clinical studies in infants and elderly persons have been initiated. This vaccine should be serotype-independent as the BVH3 and BVH11 antigens are common to all 90 serotypes of S. pneumoniae.

Read Full Article...>>>