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Posts Tagged ‘Drug Resistance’

By Savannah Keller

When we think about modern pharmaceutical products, we look across the Charles River to the biotech companies that are developing cutting-edge drugs to combat rare clinical diseases. When we think about the burden of bacterial disease, we feel safe that simple antibiotics will keep us protected from such infections. Thus, our fears are averted towards the more complex viruses such as HIV and Malaria; a reasonable mindset due to the higher global death toll attributed to these viruses. But what will happen to us all when the basic antibiotics we so heavily take for granted stop working? (more…)

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By Danielle Taylor

Antimicrobial resistance, a crisis gaining global prevalence, threatens the efficacy of existing treatments for a multitude of diseases and infections. Some projections estimate that by 2050, drug resistance will kill over 10 million people each year1. Doctors and researchers scramble to keep up with these mutating organisms, constantly trying to formulate effective drugs and treatment regimens to prevent and treat the resistance.

Tuberculosis (TB) is a disease susceptible to antimicrobial resistance, and once diagnosed, physicians need to accurately prescribe medications and patients must complete the full regimen. Resistance can occur when medications are stored and distributed improperly or if patients prematurely end treatment2. When tuberculosis is maltreated it can mutate and change within the human body, forming strains difficult to cure known as Multidrug Resistant TB (MDR-TB), or strains almost impossible to cure, called extensively drug-resistant TB (XDR-TB)2, and in 2014 approximately 480,000 people globally were thought to have contracted MDR-TB3. Patients with active MDR-TB are estimated to expose 10-15 other people to the disease in their lifetime4. Those exposed, called contacts, are at risk of developing symptomatic, active TB, or an asymptomatic latent form. Thirty percent of the world’s population has a latent form of TB, and although it is not contagious, they have a 10% chance of the disease becoming active in their lifetime4. Additionally, certain populations such as children and people with HIV or other immuno-compromising diseases are at a much higher risk of becoming ill, and once diagnosed their prognosis is especially bleak4. There are tests that can detect latent TB, however, they are not very specific and cannot predict TB activation5.

There is a fair amount of research in place to combat MDR-TB, primarily aimed at formulating the best treatment regimen for people with the active form6. However, once a treatment for MDR-TB is developed, it can be toxic, causing thyroid dysfunction in around half of treated children, it is expensive, often times cutting into general tuberculosis budgets, and not very effective, as globally only about 50% of patients were successfully treated for MDR-TB1,3. Researchers can keep coming up with new medications and regimens, but the disease can and will continue to form resistances, possibly increasing the number of XDR-TB cases. Ultimately a higher rate of these fairly untreatable cases will result in more deaths. Thus this research approach is not doing much to prevent drug resistant strain incidence and possibly driving the disease to becoming more and more untreatable. Doctors should not have to wait for these cases to become active, and due to the lack of reliability in latent TB testing, it makes sense to forgo this step and treat immediate contacts right away. In theory by treating contacts as soon as possible, the chance that someone who had immediate contact with the MDR-TB patient will contract active or even latent MDR-TB will decrease, eventually reducing MDR-TB incidence.

It is known that treating latent TB patients with some of the same medications used to treat active TB will reduce their risk of developing the disease by 60%5. However little has been done to research this medicating effect specifically in contacts. One observational study in Cape Town, South Africa observed children MDR-TB contacts, and of those given medication, only 5% developed the disease over time. Of those who did not receive any medication, 20% developed the disease1. However, because these studies were not clinical trials legitimizing the direct effect of taking drugs on developing or not developing active MDR-TB in contacts, WHO currently advises no treatment for contacts specifically1. This makes sense, as WHO likely does not want to mandate an allocation of time, money, and medication to treat a potentially large amount of people without tangible evidence of efficacy. However due to the global burden of the disease, researchers would be remiss if they did not further investigate contact treatment.

There is currently an approved clinical trial looking to provide concrete scientific evidence backing the claim that using specific medications is in fact effective in preventing latent MDR-TB activation in contacts7. This study will do this by treating household contacts of MDR-TB patients either with medication or a placebo and following them over time to track MDR-TB status7. Hopefully findings from studies like this will provide the World Health Organization with the necessary information to establish a global protocol for preventive treatment, so that MDR-TB contacts no longer have to live in fear that this disease will one day activate and put them at risk of death.

 

 

 

  1. “Post-Exposure Management of Multidrug-Resistant Tuberculosis Contacts: Evidence-Based Recommendations” Harvard Policy Brief . Number 1. October 2015. Retrieved February 20th 2016 from http://sentinel-project.org/wp-content/uploads/2015/11/Harvard-Policy-Brief_revised-10Nov2015.pdf

 

  1. “What is multidrug-resistant tuberculosis (MDR-TB) and how do we control it?” World Health Organization. Retrieved February 20th 2016 fromhttp://www.who.int/features/qa/79/en/

 

  1. “Global Tuberculosis Report” World Health Organization. Retrieved February 20th 2016 from http://apps.who.int/iris/bitstream/10665/191102/1/9789241565059_eng.pdf?ua=1

 

  1. “Tuberculosis” World Health Organization. Retrieved February 20th 2016 from http://www.who.int/mediacentre/factsheets/fs104/en/

 

  1. “Latent Tuberculosis Infection (LTBI)” World Health Organization. Retreived February 20th 2016 from http://www.who.int/tb/challenges/ltbi/en/

 

  1. “DR-TB Clinical Trials Progress Report” RESIST-TB. Retrieved February 20th 2016 from http://www.resisttb.org/?page_id=1602

 

  1. Australian New Zealand Clinical Trials Registry. Retreived February 23rd 2016 https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369817

 

 

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