Friday, January 23, 2015

WHO’s Tuberculosis Treatment Interventions in Developing Countries to Prevent Occurrence of Multi-Drug Resistant (MDR) and Extensive Multi-Drug Resistant (XDR) Tuberculosis - Jesse Huang

The recent tuberculosis (TB) epidemic has been a major topic in global infectious diseases being consistently recognized as one of the worlds deadliest communicable diseases (1,2). In the 2014 Global Tuberculosis Report, the World Health Organization estimates over 9 million new cases of tuberculosis and 1.5 million casualties resulting from TB complication in the year 2013 alone(2). Even with the numerous intervention programs, this number has been continuing to rise at a steady rate.
Caused by the pathogenic bacteria mycobacterium tuberculosis, TB is very  adaptive and infectious pathogen. With the rising overuse of antibiotics along with inadequate treatment management of medical staff, the prevalence of drug-resistant tuberculosis has increased tremendously ever since the first introduction of TB antibiotic treatment almost 60 year ago (3). Multidrug resistant (MDR) and extensively drug resistant (XDR) tuberculosis are the result of mutations in the bacteria that make it resistant to certain antibiotic medications. Specifically, MDR tuberculosis is when the organism is resistant to one or more drugs while XDR TB, a much more serious type, is when the organism is resistant to most major first-line TB drugs such as isoniazid, rifampin, fluoroquinoline, and at least one of three second-line drugs such as amikacin, kanamycin, or capreomycin (4).
After first declaring tuberculosis as a global emergency in 1993, the World Health Organization (WHO) started implementing the Stop TB Strategy to reduce worldwide TB prevalence along with reducing the emerging problems of drug resistant TB (5,6). DOTS, standing for Directly Observed Treatment Short course, is one of WHO’s main strategies for controlling tuberculosis. It contains five elements which are further explained below: government commitment, early detection, standardized drug treatment, consistent delivery of drugs, and monitoring results. These guidelines were made to provide clear objectives for its global intervention program against TB with the major hope to minimize case re-occurrence and reduce likelihood of future outbreaks of MDR and XDR tuberculosis (6).

The Directly Observed Treatment Short Course (DOTS)
The Five Components of DOTS*
1. “Political commitment with increased and sustained financing”
- Government support in following through interventions and policies
2. “Case detection through quality-assured bacteriology”
- Increased use of diagnostic techniques to promote early detection of TB
3. “Standardized treatment with supervision and patient support”
- Drugs are implemented according to standards to achieve maximum effectiveness and to prevent re-occurrence.
4. “An effective drug supply and management system”
- Consistent resources to increase recovery
5. Monitoring and evaluation system and impact measurement
- Making sure health intervention are regulated correctly

*Obtained from the World Health Organization on 12/10/2014
Critique of Current Public Health Interventions

Different Sources of Drug Resistant TB
The efficient management of an epidemic of any disease requires proper knowledge of the source of infection. This has frequently stemmed the question: “How does the majority of patients become infected with drug-resistant TB”. An infection of drug resistant TB can come from either transmission where drug resistant TB is obtained from another individual or self-acquisition where it is developed within an individual’s own body. Recently, self-acquisition has been the major focus among intervention programs. Since drug resistant TB can be “created” from poor adherence to treatment and long ineffective use of medication, it has been a significant concern of health officials whether or not new MDR or XDR TB cases will emerge from improper distribution and control of antibiotic medication.
In a 2005 research study conducted by Neel R. Gandhi, researchers surveyed rural South African hospitals to measure the impact of HIV on TB prognosis (7). During their observation, they found that a majority of XDR TB patients that were surveyed have never been previously treated for TB. This meant that most incidences of XDR TB were not likely self-acquired but obtained through transmission from another patient infected with XDR TB. Major concerns then came onto the possible outbreak of XDR TB through primary transmission especially in a susceptible population with a high prevalence of immunodeficient people where drug resistant TB is more likely to develop.
In the DOTS intervention program, WHO focuses a significant amount of resources toward treatment management and follow-through to prevent the occurrence of self-acquired drug resistant TB. Two out of the five major components (Components 3-4) of DOTS’s intervention focuses on treatment management while there were no specifically designated component for preventing and controlling transmission of TB between patients (6). Although previous interventions that focused on self-acquired drug resistant TB had a significant role in reducing the occurrence of drug resistant tuberculosis, the result of Gandhi’s study in rural South Africa shows that most of the current drug resistant TB are from transmission and not through self-acquisition. Therefore, it would be resourceful to redirect much needed focus towards preventing TB transmission and to not focus entirely on TB treatment follow-through.

Problems with Follow Through of Antibiotic Treatment
The current treatment plan for TB provides a significant challenge to proper public health intervention. As recommended by the CDC and WHO, the standard treatment regimen for tuberculosis is an initial two month treatment of isoniazid, rifampicin, ethambutol, and pyrazinamide followed by a second stage of treatment using isoniazid and rifampicin for another 4 months. The entire treatment procedure would often require six to nine months of commitment with numerous potential side-effects. This is not only difficult for the patient but also poses many financial limitation to public health intervention.
Problems with TB treatment follow up is seen the most in low resource environments. These locations have a high rate treatment defaulting due mainly to insufficient resources for physicians to contact and monitor patients. Therefore, patients often stop or reduce treatment for long duration of time which is often a precursor to developing drug resistant TB. It is important to strengthen treatment monitoring programs to follow patients and successfully treat more TB patients to reduce spread and chances of MDR and XDR TB.
WHO’s DOT program tries to improve follow up of its treatments through its belief of rigorous surveillance as stated below:

“with rigorous monitoring of and accountability for ensuring cure... We believe that evidence and experience show that the only way to achieve these high cure rates on a programme basis is through direct observation of treatment given by a person accountable to the health system and accessible to the patient.”(WHO)(8)

However, this method of intervention can be a potential problem as it creates  reactance in patients. Reactance is behavior theory where individuals will have the desire to do the opposite choice of what is given or demanded of them as an assurance of personal freedom (9). If patients are constantly watched and demanded to follow rigorous treatment procedure, they might feel that their freedom of choice is being taken away. Even though the treatment is benefiting the patient’s own well-being, discomforting treatment side-effects and the lack of understanding the dangers of TB can reduce willingness for patients to participate to the full extent necessary. Therefore, it would be better use an intervention that would be able to provide access to freedom and have them use their own free will to follow through treatment.

Early Detection Techniques
Treatment of infectious disease is highly dependent on early detection. One important early detection method is contact tracing is the act of tracking and investigating previous contacts of an infected individual during their infectious period. It is relevant to tuberculosis surveillance because it is one of the most efficient methods of detecting early spreads of TB infection which improves treatment success rate. Current diagnostic tests for TB and drug resistance relies on mycobacterial cultures which can be expensive especially costly for low income and resource areas of the developing world. It is of great importance to find newer, faster, and cheaper ways of successfully diagnosing patients with the correct form of TB.
As shown through its perseverance in history, tuberculosis is not an easy disease to control in a population. Due to it contagious and dormant qualities along with its already global spread, it takes a significant international effort to keep incidence rate manageable. In the current targets of the Stop TB Strategy, the WHO predicted that it would take at least 40 year to eliminate TB as a public health problem. Therefore, it is essential to implement not only short term interventions but also interventions with long term effects that will provide a much more powerful overall investment.
WHO’s current tuberculosis program focuses significantly on direct intervention methods such through expensive antibiotic drug treatments and sometimes unreliable follow up procedures. With a significant investment of direct treatment, early detection techniques such as contact tracing as discussed would be a valuable intervention tool. Although very powerful when implemented, many of these intervention are very costly and only result in short term effects with no significant long term use.A common concept in both medicine and in public health is “An ounce of prevention is worth a pound of cure” (13). As a long term investment, prevention through social intervention could prove to be more efficient and far less costly when compared to direct intervention.

Potential Public Health Intervention Methods

Infection Control and Isolation in Health Care
Since many of the current drug resistant TB are transmitted and not acquired through incomplete treatment as shown by the Gandhi’s study, it is important to invest resources into infectious disease control and prevention. TB is a highly contagious disease being able to become airborne simply through coughing or even speaking (5). There a number of effective methods to deal with airborne infectious diseases such as by implementing the wearing of surgical masks or reducing accessibility to crowded community structures. However, it is important consider that many TB patients are located in rural undeveloped countries were there already are wide spacing between individuals. Therefore to deal with TB transmission, it is important to intervene at its source, hospitals.
Since the turn of the century, hospital environments has been a major source of TB outbreaks especially in developing countries. Heavy TB patient crowding, lack of proper ventilation, and poorly-sanitized operating conditions of some rural hospitals create an incredibly dangerous breading ground for TB. Following with the often poor drug adherence in these areas, many TB outbreaks in hospitals or clinics such as the MDR and XDR outbreak incidence in South Africa during March 2008 are drug resistant TB (10).
To combat hospital TB transmissions, one of the most suggested interventions is to promote immunological and infection control education to first-line health care provides such as doctors and nurses along with medical administrative staff. Doctors and nurses have the quickest and most frequent access to patients. Therefore, well-organized educational seminars can provide long term investment to reduce not only TB infection but other hospital-related infections. Along with doctors and nurses, medical administrative staff should be especially encouraged to be involved in infection control. Since many administrator control over funding and construction projects, getting the knowledge of proper disease control in a hospital setting could be long term benefit to the proper management of hospitals.
Continued education interventions has has numerous successes. In the US, hospital-acquired infections are an ongoing problem tackled by surgeons and the post-surgical staff with over a 10 billion dollar financial burden each year to the US health care system (11). This burden has been tackled through workshops and seminars that teaches physicians the various methods of infections and develop new techniques to prevent them.

Redirect treatment emphasis and
An integrative intervention method to combat the current problem of follow up requires two steps . First, it is important to implement the right ratio of funding for treatment and follow up. Following from the discussion of “all or nothing”, lets consider two intervention methods. The first method places more emphasis on TB treatment and attempts to treat 100 people. The second method places more following through each TB treatment and attempts to treat only 20 people. If we assume that 10% of people follow through in intervention one and 50% followed through in intervention two, the resulting number of recovered TB patients would be the same. However considering how many people  Therefore, the point of this illustration is that it would be more resourceful to treat fewer people with higher success rate than to treat more people with a lower success rate even if the end is the same number of recovered people.
From our first intervention, there would be an decrease in the number of available treatment. The second intervention is complement of the first intervention by creating an application pool. It is important to visualize the association of treatment and results for TB to determine the method of intervention. In a broad view, treatment of TB is an “all or nothing” situation. It is necessary for patients to follow the duration of treatment plan for the patient to fully recover. If dropped out of treatment, the patient is likely to redevelop TB and be infectious. Therefore, any form of service or treatment provided to individuals that do not follow through will potential be wasted. In actuality, the “all or nothing” statement is not entirely true since patients who took TB medication and did not follow through are likely to develop drug resistant TB which is more difficult to treat in the future and can cause further transmission of MDR and XDR TB to others.

Marketing and Focusing on Immunodeficient Groups
A potential social intervention to prevent cases of tuberculosis is to expose young children and school programs to the proper techniques in preventing disease transmission. As social cognitive theory suggests, individuals often learn through social context and observation (15). Young children are often the most susceptible to this theory and will most likely provide more effective results. In this intervention, school student would be taught at an early age to wash hands, cover up coughs, or wear surgical masks when sick. Marketing campaigns such as posters and basic sanitary equipment are potentially important tools to introduce proper prevention of disease transmission.
The practicality of this social theory can be seen in the recent cultural changes of certain Asian countries. In Japan, wearing surgical masks has become a standard for people who are sick or have symptoms of coughing or sneezing. The habit which is often learned at an early age has become so deeply embedded in Japanese culture that it is constantly enforced through pressures of social conformity (15).
Additional benefits to the early exposure of daily sanitation techniques, children can become more knowledgeable about the role of health care providers. In many developing countries of Africa, many TB patients refuse treatment from doctors and hospital due to fear and misrepresented images of health care workers. This has been seen significantly in the recent Ebola epidemic where individuals infected with the deadly Ebola virus would hide and prevent themselves from being quarantined and treated by health care professionals. By introducing children consistently to the positive image of the hospital environment and health care workers, it would likely improve the general image of health care to the population at risk for TB potentially increasing future participation in TB treatment and supporting earlier diagnosis.


Using Complementing Long-Term Social/Behavior Interventions
The DOTS program has had many accomplishments since its initiation in 2006 having treated millions of tuberculosis patients world-wide(6). Although the DOTS program provided an essential springboard towards the management of TB treatment in developing countries, many direct intervention methods such as importing antibiotics and implementing expensive testing methods creates significant self-limitation to its own intervention’s availability and applicability.
Considering the staggering costs of Stop TB Strategy and DOTS program, the current TB management is very time consuming and resource draining to WHO and many supporting organizations and countries. The solution is to direct portion of the funds towards long term investment. Many of the potential interventions discussed in this article such as infectious control education and health awareness in youth provide a much longer lasting effect than direct intervention. Direct interventions are necessary and has been an important effort in stopping the immediate spread of TB, but it is important to think about the long run and properly invest in long-term invention methods to complement ongoing direct interventions.
1. New Jersey Medical School: Global Tuberculosis Institute. A History of Tuberculosis Treatment.

2. World Health Organization. Global Tuberculosis Report 2014. xii

3. Mayo Clinic. Tuberculosis Causes. uberculosis/basics/causes/con-20021761

4. Centers for Disease Control and Prevention. Multidrug-Resistant Tuberculosis (MDRTB). Tuberculosis Fact Sheet drtb/mdrtb.htm

5. National Institute of Allergy and Infectious Diseases, Tuberculosis

6. World Health Organization, The Stop TB Strategy

7. Gandhi NR, Moll A, Sturm AW, Pawinski R, Govender T, Lalloo U, Zeller K, Andrews J, Friedland G. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet. 2006 Nov 4;368(9547):1575-80.

8. Thomas R Friedena, John A Sbarbaro. World Health Organization. Promoting adherence to treatment for tuberculosis: the importance of direct observation.

9. Silvia, P. J. (2005). Deflecting reactance: The role of similarity in increasing compliance and reducing resistance. Basic and Applied Social Psychology, 27, 277-284.

10. IRIN. SOUTH AFRICA: Prison-like hospitals for drug-resistant TB patients.

11. Goodman, Brenda. Health Day Reporter. US News. Five most common health care-associated infections strike 440,000 U.S. patients each year.

12. Centers for Disease Control and Prevention. Tuberculosis (TB). Tuberculosis Treatment

13. Benjamin Franklin. Good Reads.

14. Baseel Casey. Why do Japanese people wear surgical masks? It’s not always for health reasons. Japan Today.

15. Frank Pajares. Emory University. Overview of Social Cognitive Theory

and of Self-Efficacy

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