Navigation Links
TB treatment paradox: Mouse studies show body's own response helps TB bacteria survive
Date:6/28/2012

Inhibiting a key immune response in mice during initial multi-drug treatment for tuberculosis could paradoxically shorten treatment time for the highly contagious lung infection according to new research from Johns Hopkins Children's Center and the Center for TB Research.

Shorter duration of drug therapy is key, researchers say, to increase treatment compliance for the growing global health threat posed by the disease.

In experiments described in the June 27 issue of PLoS ONE, the Johns Hopkins investigators compared a group of TB-infected mice receiving standard TB treatment of rifampin, isoniazid and pyrazinamide with another group that received standard TB treatment plus etanercept, a drug used to inhibit a protein known as tumor necrosis factor alpha, or TNF-α, to prevent immune responses.

TB infection causes an immune response that notoriously includes production of TNF-α, which is critical for the formation of TB granulomas the hallmark tumors that form in the lungs and other parts of the body when the immune system tries to contain these bacteria. Paradoxically, this immune response is believed to wall off the bacteria, creating a sanctuary for "persistent" bacteria and, in turn, leading to the need for extended courses of treatment. Compliance with such treatment daily doses of antibiotics for six months or more is particularly challenging in the developing world and has fueled an epidemic of multi-drug resistant TB, the researchers say.

"New and shorter TB treatments are needed to stop this scourge globally, but current treatments largely target actively replicating bacteria, rather than slow-replicating, persistent TB bacteria," says Sanjay Jain, M.D., an infectious disease specialist at Hopkins Children's Center and the senior author of this study.

Aware that TB patients taking TNF-α inhibitors to treat other conditions such as rheumatoid arthritis and Crohn's disease can "wake up" persistent TB bacteria, Jain and his team speculated that it might be possible to shorten TB treatments by using TNF-α inhibitors that keep microbes "awake" so that they could be "zapped" with standard TB treatments.

"We were surprised to find that this paradoxical approach actually works in mouse models of TB," Jain says.

During the initial six weeks of treatment, when TB bacteria were actively replicating, there was no significant difference in bacterial killing observed between the two groups of mice, Jain noted. But at weeks eight and 10, the group receiving standard TB treatment plus etanercept had a significantly lower bacterial burden than the group receiving just the standard TB treatment.

"This finding is important because it is during this later phase of infection and treatment, that TB bacteria multiply much more slowly, making up the so-called 'persisters' that lie 'asleep' and require protracted treatment," says Ciaran Skerry, Ph.D., the journal report's first author.

At 12 weeks, both groups had no bacteria visible on culture, but 27.8 percent of the group receiving standard TB treatment relapsed, while only 10.5 percent of the ones treated with the standard treatment plus etanercept relapsed.

Jain says due to risks of reactivation disease with the use of TNF-α inhibitors, more studies for safety and efficacy need to be done in the laboratory before the treatment can be used in people.


'/>"/>

Contact: Kim Martin
kmartin7@jhmi.edu
410-502-9429
Johns Hopkins Medical Institutions
Source:Eurekalert

Related medicine news :

1. Success of fertility treatment may approach natural birth rate
2. Medical Tourism: Uncharted Territory for Patients James Goldberg, Author of the American Medical Money Machine, Is Offering a New Consulting Service to Medical Patients Considering “Medical Tourism” Treatment
3. Vision Therapy Expert Announces Vision Therapy Best Treatment for Amblyopia
4. Under Right Conditions, Fertility Treatment Can Equal Natural Conception Rates: Study
5. Feinstein Institute to Receive Grant from Centers for Medicare & Medicaid Services to Improve Schizophrenia Treatment
6. New treatment protocol extends survival in some cases of once inoperable pancreatic cancer
7. Progress in quest to reduce use of radiation in treatment of pediatric Hodgkin lymphoma
8. LA BioMed investigators, Drs. Kevin Bruhn and Noah Craft, develop novel treatment for melanoma
9. Feinstein Institute to receive grant to improve schizophrenia treatment
10. Novel Anti-Inflammatories May Offer a New Approach for the Treatment of Stroke
11. Herpes Treatment Site: Top Reasons to Avoid Prescription HSV Drugs
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/24/2017)... ... 2017 , ... In the Health Care IT campaign, Robert Herjavec discusses health ... if you will be attacked, but when.” However, he and many others involved highlight ... , Improvements in auditing and monitoring have taken security in health care a very ...
(Date:2/24/2017)... ... ... The narrative in “ Signal 8: An Australian Paramedic’s Story ” (published by ... Schanssema describes the tragedies he saw, as well as his struggles with grief and ... unsure of the career path he wanted to take, found fulfillment in a career ...
(Date:2/24/2017)... ... February 24, 2017 , ... Yisrayl Hawkins, Pastor and Overseer ... Prophecy concerning this present generation. Yisrayl makes an astounding statement when he says ... He explains that the Bible details the current times so plainly that anyone should ...
(Date:2/24/2017)... ... February 24, 2017 , ... The Radiology Business Management ... radiology marketing programs at the annual Building Better Radiology Marketing Programs conference, ... Hotel in Fort Worth, Texas. Nine awards are given out in five categories. They ...
(Date:2/24/2017)... ... 2017 , ... Castle Farms, the celebrated Northern Michigan ... the winning couple announced on Feb. 14, 2017, on Facebook. The free wedding ... A Matter of Taste, Ryan Rousseau Enterprises, A Touch of Spring and Other ...
Breaking Medicine News(10 mins):
(Date:2/24/2017)... , Feb. 24, 2017  Xynomic Pharmaceuticals, Inc., ... announced that it has acquired exclusive worldwide rights ... best-in-class innovative HDAC inhibitor targeting hematological and solid ... 14 Phase 1 and 2 clinical trials of ... have already been completed, demonstrating that ...
(Date:2/23/2017)... SEOUL , Südkorea, 23. Februar 2017 ... LED für Sterilisationsaufgaben vorgestellt. Die Sterilisationsleistung beträgt das 1,5-fache ... kurzwellige ultraviolette Strahlung im Bereich zwischen 200 und 280 nm ... Ausbreitung von Bakterien, indem es ihre DNA zerstört. Das ... 280 nm. ...
(Date:2/23/2017)... , 23. Februar 2017 Im Rahmen ... eine nationale Wirtschaftszone in der südwestlichen chinesischen Provinz Guizhou, 2017 ... Errichtung einer Innovationsplattform aktiv an der Entwicklung einer eingebetteten Hightech-Schlüsselindustrie. ... Continue Reading ... ...
Breaking Medicine Technology: