Tuberculosis and New Tuberculosis Vaccines

Microbiology Please develop your own strategy for TB prevention. The Source of the Disease As mentioned in the above question, tuberculosis is a complex disease that has ravaged society for centuries. Whereas in the Western countries, it is now possible to receive treatment and become healthy despite contacting tuberculosis, there are areas of the world where, due to societal or environmental and political problems, it is difficult both to seek and obtain care, but also to achieve a satisfactory rate of healing are at least preventing this disease.

Due to the fact that people in the Western Pacific and Africa are weakened by such factors as mentioned above, their situation with regards to the disease thus becomes even more of a threat to their well-being. For this reason, this section will discuss certain aspects of tuberculosis as it relates to these people and will develop a strategy for TB prevention. To begin, one must address some basic facts about the disease.

According to the World Health Organization (WHO) 2009 statistics, tuberculosis has caused much suffering, including contributing to impoverishment and death for decades, and one could say that these have surpassed the suffering caused by any other disease in human history. WHO further states that during the 1990s, TB actually reemerged in the Western Pacific. Since then, cases multiplied, which led to the alarm of officials.

As a result, statistics rest at over 1/3 of the 8 million global cases of TB being attributed to the Western Pacific, and the WHO further states that deaths have reached in the thousands per day. Clearly, the situation of TB around the world, and especially in the above-mentioned regions, is deteriorating and it is paramount to address this. The source of the disease is, as often happens, the patient. The way tuberculosis works is that it is airborne, like the common cold, but it is highly contagious.

According to WHO statistics, one in ten people will develop the disease if their immune system is well-equipped. However, as described above, the problem in poor African regions and other such regions around the world, is that these immune systems are quite ill-equipped to handle this disease. What is worse is that once infected with TB, and if a strong immune system becomes weak, the patient will be susceptible to the disease hitting in full force.

There are also various conditions that accelerate transmission for the disease from the source and they include certain factors that can accelerate the transmission of the disease, such as crowded housing conditions, poor nutrition, ill health and generally poor living and eating conditions. According to statistics given by Doctors Without Borders (2005), "Mycobacterium tuberculosis […] affects the lungs. Called pulmonary TB, this form of the disease is characterized by a persistent cough, shortness of breath and chest pain. Other symptoms include weight loss, fever and night sweats.

Left untreated, each person with active pulmonary TB will infect on average between 10 and 15 other people every year. The mycobacteria can also infect almost any part of the body, such as the lymph nodes, the spine or bones. In this form, TB may not be contagious, but it is equally vital to diagnose and treat the disease rapidly, as all forms are deadly if left untreated." 2) Route of Transmission, Vaccines & Prophylaxis As mentioned in the paragraphs above, TB is transmitted through the air.

Despite the fact that the disease description given by Doctors Without Borders seems quite serious, there have been vaccines that can treat the disease quite effectively. This is why it has but been eradicated in richer countries. However, in poorer countries, vaccines are not only not as prevalent, but many cannot afford them despite their low prices. When one lives on less than $1 a day, as most do in certain poor countries, one cannot afford $15-$20 on vaccines (Doctors Without Borders, 2005).

Due to the fact that the vaccines are expensive and many who need them cannot afford them, Doctors without Borders recommends taking drugs if vaccines are not readily available; however, they do not give any information as to the price of these drugs. However, the study does state that in order to prevent the emergence of any resistance, these drugs should be taken in fixed-dose combinations and treatment should be continued until all mycobacteria are dead.

Though one must ask how much these cost, especially if they must be taken until all bacteria are dead, and must take note of the fact that these drugs may not be readily available, especially if they cost a lot, to the regular person in a poor country. The Doctors without Borders study also states that patients must be encouraged to stick to treatment until its completion, but again, cost is one of the most important factors, and many cannot afford these vaccines and these drugs.

Thus, as soon as a patient abandons the course the symptoms come back. With regards to specifics about vaccines and drugs, there are, as mentioned above some vaccines for TB, and about eleven compounds in clinical or advanced preclinical development by various sponsors.

According to the WHO, key milestones for "discovery-stage" compounds "will be achieved when lead compounds meet sponsor criteria for the advancement of leads into advanced preclinical development." The organization also states that most of the go/no-go decisions are driven both by the development of the drug and the way it is utilized clinically.

WHO further mentions that "criteria for these milestones may differ between a drug that would be added to existing regimens, with daily dosing for many months, versus a drug that would be used for prophylaxis with intermittent dosing." As of now, there are various clinical trials that utilize tuberculosis drugs conducted worldwide and are sponsored by various organizations, including: The National Institute of Pharmaceutical Education and Research (NIPER), CDC's Tuberculosis Trials Consortium (TBTC), The European and Developing Countries Clinical Trials Partnership (EDCTP), The South African Medical Research Council (MRC), The International Union against Tuberculosis and Lung Disease (IUATLD), The National Institute of Allergy and Infectious Diseases (NIAID), and The NIAID/Case Western Reserve University funded Tuberculosis Research Unit (TBRU).

These sponsors were chosen as the most important by the WHO due to the fac that they have carried out successfully trials with existing drugs in the past and are thus recommended as possibly the most successful sites for developing new drugs and vaccines that are both more effective and cheaper. 3) The Population at Risk The sad thing is that the poor are the most risk-prone, as stated and restated above.

I will not harp upon this point here, as I think the point has already been made previously; however, statistics are important to see just how bad the situation is. While the WHO states that TB case detection under various programs, including the DOTS (Directly Observed Therapy, Short-course) strategy "has accelerated over the past few years with implementation of the Global DOTS Expansion Plan," and while "TB cases notified under DOTS programmes in 2003 represented 45% of estimated new smear-positive TB cases," the problem still remains widespread.

This is because despite a continuation in the upward trend of case detection (60% by 2015), the treatment success rate, according to the organization, "remains substantially below the average in the WHO regions of Africa (73%) and Europe (76%)." According to the group, there are eight TB regions, which include: 1. The Established Market Economies (EME) and Central Europe 2. African countries with high HIV prevalence (AFR High HIV) 3. African countries with low HIV prevalence (AFR Low HIV) 4. The American Region (AMR) -- Latin America Countries (LAC) 5. Eastern Europe Region (EEUR) 6. Eastern Mediterranean Region (EMR) 7.

South-East Asia Region (SEAR) 8. The Western Pacific Region (WPR). Due to the relative high income of the first group, the programs implements focus on the latter seven regions. With regards to these regions, in 2003, according to the organization, there were "8.8 million new cases of TB, of which 3.9 million were smear-positive; 674-000 of the patients were coinfected with HIV. There were a total of 15.4 million prevalent cases, of which 6.9 million were smear-positive.

An estimated 1.7 million people died from TB, including 229-000 people coinfected with HIV." It is, thus clear that the HIV-TB combination is lethal, which will be further discussed below, but it is also clear that that poor are still in great danger and despite advances, much remains to be done. 4) Criticisms The fact that organizations such as WHO, Doctors without Borders, and other independence or private groups have done their best to combat the disease means that criticisms, although they abound, cannot be wholly negative, as progress has been achieved.

As always, however, more could be done, and this has been stressed. For example, more could be done with regards to prevention. For example, the clinics in Africa are both underequipped due to lack of funding. Though the United Nations Organization is doing its best to distribute funds accordingly to all its organizations, political, economic and societal pressures often prevent the delivery of resources, both at the organization and on the ground.

Furthermore, there is criticism abound with regards to new drugs, especially since there is strain of TB that has been proven resistant to drugs. According to the StopTB Partnership, and a WHO working paper in 2006, "Multidrug-resistant TB threatens the potential salutary impact of DOTS programmes. Although progress in widespread DOTS implementation will help prevent the further emergence of drug-resistance, expansion of effective DOTS-Plus programmes is vital to stem the contribution of drug-resistant cases to the overall TB epidemic.

Too few countries have national policies for the diagnosis and treatment of MDR-TB. In some of those that do, treatment commonly fails to meet acceptable standards." Thus, as aforementioned and as one always states with regards to deteriorating health and social situations, more could always be done. 5) Going beyond Governmental Guidelines Though the WHO strategies are great, they do not always provide the most comprehensive treatment for TB.

Thus, there are limitations to these programs, and some organizations have already begun addressing how one can go beyond governmental programs to better treat the disease and help the regions most affected. The most important fact to recognize is that the overlap of HIV and TB leads to a lethal combination with catastrophic effects.

According to the Global Health Council, "synergistic impacts […] worsen each disease [and] have caused an unprecedented public health crisis in countries reeling under the burden of generalized HIV epidemics." The Council also states that the DOTS is not sufficient, for example in countries where dual HIV/TB epidemics are present. For example, in Botswana where the HIV prevalence rate is at 30%, in the 1980's, the government implemented a "comprehensive TB control program" that encompassed all the elements that DOTS suggested.

These elements included, according to the Council, "government commitment, case detection by sputum smear microscopy, a sound supply of tuberculosis treatment, a recording and reporting system, and a short-course treatment regimen under Directly Observed Therapy (DOT)." Despite the fact that the program was successful with case detection and cure rates that were above 90%, by the early 1990s, HIV prevalence rose and was accompanied by a rise in TB cases that, according to the Council, "is best categorized as unparalleled and disastrous." The reason that the DOTS program stopped being effective was because of the epidemiology of TB, which had changed due to dual infections, but also due to the fact that HIV infected people have a tremendous risk of being affected with TB due to weakened immune systems.

In the absence of effective governmental programs one must thus come up with strategies to reign in the disease. One suggestion from the Global Health Council is CREATE: Three Simple Strategies, a program composed of investigators, TB and HIV program officials, clinicians and others involved in TB and HIV control, and which was established in 2004 to respond to the afore-mentioned crisis.

The intention of CREATE is self-stated by the Council as to "go beyond DOTS by creating an evidence base for new strategies implemented through ambitious community trials in three countries with high incidence of dual infections - that have been gearing up to the challenge: Brazil, Zambia and South Africa.

The results from CREATe's studies will be used to transform global public health policies relating to TB control through evidence-based advocacy." Since create is funded privately, more specifically by the Bill & Melinda Gates Foundation, it has been able to focus on three strategies to control TB, namely: 1. Active TB case finding as opposed to relying on patients to declare themselves ill (passive case finding). 2.

Widespread treatment of latent TB infections in populations that are at high risk populations with isoniazid preventive therapy, which is an alternative and inexpensive treatment, according to the organization, that "considerably reduces the risk of tuberculosis progressing to active disease." 3. A combination of antiretroviral and tuberculosis preventive treatment programs in order to reduce the progress of the disease from latent to active.

Question 3: Why is there a need for a new TB vaccine although we already have the BCG vaccine? 1) The Effectiveness of the BCG Vaccine over Time and the HIV Duality In order to determine the need for a new TB vaccine one must address the limits in existing vaccines. Bacillus Calmette-Guerin (BCG) vaccines are produced by dozens of manufacturers internationally. The major commercial producers are Oasteur-Merieux-Connaught, Evans-Medeva, and the Japan BCG Laboratory, which account for 85% of 217 million doses provided through UNICEF in 1996, according to a 1999 WHO report.

The same paper speaks about efficacy of the vaccines. For example, it metions that the "(clinical) efficacy of a vaccine is measured in terms of the percentage reduction in disease among vaccinated individuals that is attributable to vaccination." Further, the WHO report states that "BCG vaccines are generally given to protect against tuberculosis. Though the WHO now emphasizes BCG's utility in prevention of severe childhood disease (e.g. tuberculous meningitis), the main public health burden of tuberculosis is associated with adult pulmonary disease.

It is therefore important to consider BCG vaccine efficacy against childhood tuberculosis, separately from that against adult tuberculosis, leprosy and other mycobacterial infections." With regards to specifically speaking about the efficacy of the vaccine, and especially with regards to the declining efficacy, the WHO states that BCG vaccines differ due to a number of causes, including dosage and environmental factors.

According to a referenced study by the organization, it is suggested that efficacy "declined with passage number of the seed substrain60, interpreting this as evidence that manufacturers selected their strains to reduce lymphadenopathic reactions, and thereby compromised their efficacy." Other specifically mentioned causes are: some BCG vaccine strains have been shown to perform to varying degrees in varying populations environmental mycobacteria human genetic make-up differences in M. tuberculosis the potential effect of UV light exposure (as BCG bacilli are sensitive to UV exposure) nutritional differences between populations local.