Abstract
Tuberculosis (TB) is a contagious disease and the number of cases is increasing worldwide among the public. Each year worldwide, over More than 12 million people are diagnosed with TB and over 4000,000 people die due to the disease. The large population and poor standards of living can have a major impact on TB epidemics. Can there be a new alternative to traditional use of drugs for treatment of tuberculosis? Most of the drugs approved by the FDA have no lasting effect on patients with tuberculosis, since the strains of bacteria have acquired resistance leading to a state of Multi-drug resistance. An observational Case-control study was to be carried out in order to depict the nature of other drugs in comparison with a novel drug which was hypothesized to have novel effect in terms of efficacy, toxicity and treatment of tuberculosis. The sample population will only include patients currently suffering from tuberculosis. The age limit for the study would be in the range of 18 to 49 years. There will be two groups of study population. The case (testing population) will be treated with the novel drug while the control population will be treated with traditional drug therapy. The online survey, television broadcast and flex posters led to a large number of patient recruitment. However studies regarding the efficacy of the novel drug against conventional drug therapy had to be found out. (Bagchi S. et al; 2010)
Tuberculosis among the public
Tuberculosis (TB) is a contagious disease and the number of cases is increasing worldwide among the public. Each year worldwide, over More than 12 million people are diagnosed with TB and over 4000,000 people die due to the disease. Among the general public, the main problem arising in treatment of TB patients is not the number of cases but the number of multi-drug resistant TB cases. Over the past 20 years, multi-drug resistance has increased ten-fold and is has become one of the major community problems worldwide. Many organizations and governments has come up with numerous interventions for the treatment for TB. Most widely used method is DOTS (Directly Observed Treatment Short) treatment, which was initiated by WHO. It is the most widely accepted and effective way of treatment for TB, however patients are advised to adhere to the treatment to avoid relapse or complications if treatment is discontinued. Discontinuation also led to Multi-drug resistant TB patients which is now a major problem among the general public. (Karande et al; 2002)
12 million people and counting, the number of people that live in the metropolis city of India, Mumbai. More than 4 million people live in low quality housing or slums which is the major source of TB patients. There is an increase of TB cases since 2005 in Mumbai owing to poor sanitation, high population density and lack of proper health care facilities. Since 2005, the local authorities have taken initiatives to curb the life-threatening disease by implementing many programs for uneducated people who suffer from TB. The main cause also lies in discontinuation of treatment which today has cause drug-resistant strains of TB. Majority of patients are in the group of 20 to 40 years and death rate are higher in patients who have contracted AIDS. Children have also been reported to contract TB but the number is substantially low. The major concern is now treating TB and solving the community problem of Drug resistant Tuberculosis (TB). (Karande et al; 2002)
Tuberculosis: A major Public health problem.
Heavily populated cities and towns face many concerns, especially in terms of infectious and Communicable diseases. The large population and poor standards of living can have a major impact on TB epidemics. The pathogenic Mycobacterium Tuberculosis can easily spread through cough, sneeze or bodily fluids present in air of from a TB infected individual to a healthy individual.
Many Non-governmental organizations (NGO) with the local authorities in different communities among general public have implemented GRAND plan for the Diagnosis, treatment, reduction and ultimately elimination of TB in the city. Many organization and groups have come up with health care facilities for treating Tuberculosis.
In the year 2013, there were a total of 15,515,872 cases of TB worldwide, of which 844,920 reported for positive Total smear tests while 60,42,321 for new smear tests. The number is an approximate on the basis of notified and documented cases in health care centers and hospitals. A total of 226,965 cases were reported to have pulmonary TB which is a severe form of the disease and requires needed and urgent treatment. Many individuals either drop out from treatment or fail to continue medication due to financial and other reasons. This leads to retreatment of patients due to relapse and other complications. 304,431 cases were reported for re-treatment in the year 2011. (WHO, Global tuberculosis report 2013)
In many countries, the burden of TB is high due to lack of proper medication or negligence. Some of the TB burden countries include Africa, India, Bangladesh and Myanmar. There were a total of 13,335,281, TB cases reported in 2013 in these countries. Majority of Individuals reported with positive TB Total smear test were in the age group of 20 to 40 years, 175,319 of such cases were reported. Majority of the patients belonged to slums or places where population density was extremely high.(WHO, Global tuberculosis report 2013)
Research Hypothesis: Combating Multi-drug Resistant Tuberculosis (MDRT)
Can there be a new alternative to traditional use of drugs for treatment of tuberculosis? Most of the drugs approved by the FDA have no lasting effect on patients with tuberculosis, since the strains of bacteria have acquired resistance leading to a state of Multi-drug resistance. In order to combat such cases, new interventions have to be developed and compared to traditional drug therapies. (Mitnick CD et al; 2008)
Efficacy and toxicity of these new drugs have to be tested and compared. The Risk-benefit ratio need to be calculated at the same time. The purpose of this research is to evaluate the efficacy of a novel drug in comparison to drugs which have been traditionally used and have no vital significant role in treatment of TB at present. (Mitnick CD et al; 2008)
The study will demonstrate the efficacy in terms of pharmacodynamics and pharmacokinetics of the novel drug in sole comparison with traditional drug therapy and other interventions for the treatment of Tuberculosis. The drug will be tested on two groups, Individuals with Tuberculosis without prior treatment and patients with tuberculosis with prior treatment for tuberculosis but however discontinued treatment for more than 2 weeks.
The study should demonstrate higher efficacy and should also show a negative testing against Drug susceptibility, stating that the novel drug has implications towards treating new strains of Mycobacterium which have acquired resistance to previously approved drugs and therapies for the treatment of tuberculosis. (Suparna Bagchi, et al; 2010)
An Observational Case-Control Study, Comparing Traditional Drugs in treating Tuberculosis and New Drug Therapy.
Over 25 countries have been declared TB burden by the WHO in the year 2013. This is often blamed to countries having an overly crowded metropolis, which is a prime suspect for contagious disease. Tuberculosis has widely spread in the past decade and mortality rates have increased due to lack of proper health care facilities and preventive methods. Majority of patients undergoing treatment discontinue medication. This in turn allows the replication of Mycobacterium tuberculosis within the body, multiply and further on acquire resistance to the drug. The improper drug dosage have led to several multi-drug resistant cases in Mumbai. This on the other hand has led to higher mortality rates.
In many communities, the rise of Multi-drug resistant Tb (MTDR) is increasing and many relapses and death have been recorded. This has brought major concerns among the general public. This led to a survey in many countries worldwide, especially in the TB burden countries. The survey was conducted to determine the impact of multi-drug resistant strains, the number of patients enrolled for re-treatment in a clinical trial setting, hospitals and health care centers. The burden of the disease was significant enough, since traditional therapy was showing no significant improvement in a patient’s health. There was a need for providing an alternative therapy or remedy for the treatment of tuberculosis.
An observational Case-control study was to be carried out in order to depict the nature of other drugs in comparison with a novel drug which was hypothesized to have novel effect in terms of efficacy, toxicity and treatment of tuberculosis. A treatment is necessary for Multi-drug resistant tuberculosis (MDRT). Methods like DOTS and a combination of other drug interventions were needed to be compared in order to provide a significant role of a novel drug treatment/therapy against multi-drug MDRT. (Nerges Mistry et al; 2012)
The study would include an analytical observational study. It will be a Case-Control study.
The sample population will only include patients currently suffering from tuberculosis. The age limit for the study would be in the range of 18 to 49 years. There will be two groups of study population. The case (testing population) will be treated with the novel drug while the control population will be treated with traditional drug therapy.
The patient recruitment will only include patients suffering from tuberculosis. The control group will be a tuberculosis patient, however with or without prior treatment of traditional drug therapy. In order to avoid bias, the control group may not have undertaken any new possible drug treatment in the past two weeks. The possible recruitment strategy for control group would be selection of only patients treated with only traditional drug therapy. These include DOTS and the use of anti-tubercular drugs, Isoniazid, Rifampicin, Pyrazinamide and Ethambutol. (Desiree TB D'souza, et al; 2009)
The patient group being administered with the novel new drug would be under strict observation for efficacy and any possible side-effects of the drug on the body. Blood pressure, blood glucose level, Chest x-rays and blood count are to be monitored once in two days. Total sputum analysis are to be carried out on a daily basis followed by chest x-rays once a week. The sputum analysis will enable to study the efficacy of the drug in total and also to detect possible decrease in multi-drug resistant Mycobacterium.
For statistical analysis of entire data SPSS system version 10 can be used to check for possible errors, peak values and graphical representations. The patient case and control population both are analyzed in terms of Drug susceptibility, the origin of the individual and the time period (in days) the patient suffered from TB. (PY Kulkarni et al; 2013)
Summary of Data Collection
Recruitment of patients for any trial is a tedious process. Online survey forms and advertisement brochures were displayed in Health care centers, hospitals and TB development centers. Online survey forms included Age, Sex, Date of TB diagnosis (Confirmation) and the place of stay. Prior treatment or medication for tuberculosis should be answered in Yes or No. Both treated and untreated individuals suffering from tuberculosis were taken for the study. (Dyas J, Apekey et al; 2009)
Colorful and attractive brochures were made and put in hospitals and care centers. These mentioned about the time of treatment and the age group and the time taken for the trial. A small compensation for travel to individuals participating in the study was also mentioned.
An innovative method of recruiting patients were broadcasting a 30 second video clip over the television on local channels. The 30 second clip mentioned a new way of treatment for drug resistant tuberculosis and also mentioned that it would be a study and success of the study could only be possible if large number of patients would turn back.
Flex posters can be displayed in Railway stations, Bus stops and public grounds. Since there is a high number of people traveling by local trains, message for conducting the study was spread easily and on a faster rate. The Flex poster also mentioned preventive methods of tuberculosis. It also mentioned the early signs and symptoms of tuberculosis. Recommending general public to visit their general health care practitioner in case symptoms of tuberculosis were observed. (Dyas J, Apekey et al; 2009)
The online survey, television broadcast and flex posters led to a large number of patient recruitment. However studies regarding the efficacy of the novel drug against conventional drug therapy had to be found out. (Dyas J, Apekey et al; 2009)
References
Karande S, Bavdekar SB. Children and multidrug-resistant tuberculosis in Mumbai (Bombay), India. Emerging Infectious Diseases. 2002;8(11):1360–1361.
WHO TB Statistics. WHO website. Global tuberculosis report 2013.
TB India 2012 Revised National TB Control Program. Annual Status Report, New Delhi, 2012.
Mitnick CD, Appleton SC, and Shin SS. Epidemiology and treatment of multidrug resistant tuberculosis. Seminars in Respiratory and Critical Care Medicine. 2008 Oct;29(5):499-524. doi: 10.1055/s-0028-1085702
Bagchi S, Ambe G, Sathiakumar N. Determinants of poor adherence to anti-tuberculosis treatment in Mumbai, India. International Journal of Preventive Medicine. 2010;1:223–32.
Mistry N, Tolani M, and Osrin D. Drug-resistant tuberculosis in Mumbai, India: An agenda for operations research. Science Direct. 2012. 1(2-3).
D’souza DT, Mistry NF, Vira TS, Dholakia Y, Hoffner S, Pasvol G, et al. High levels of multidrug resistant tuberculosis in new and treatment-failure patients from the Revised National Tuberculosis Control Program in an urban metropolis (Mumbai) in Western India. BMC Public Health. 2009;9:211.
PY Kulkarni, SV Akarte, RM Mankeshwar, JS Bhawalkar, A Banerjee, and AD Kulkarni. Non-Adherence of New Pulmonary Tuberculosis Patients to Anti-Tuberculosis Treatment. Annals of Medical and Health Sciences Research. 2013 Jan-Mar; 3(1): 67–74. doi: 10.4103/2141-9248.109507
Dyas J, Apekey T, Tilling M, Siriwardena AN. Strategies for improving patient recruitment to focus groups in primary care: a case study reflective paper using an analytical framework. BMC Medical Research Methodology. 2009;9:65. doi: 10.1186/1471-2288-9-65.
