Picot Question Essay

INH and INH-RPT Treatment for LTBI

Latent Mycobacterium tuberculosis infection is itself, a latent disease requiring chemical prophylaxis to forestall the onset of active tuberculosis. Treatment of latent tuberculosis (TB) infection is a critical for patients with a high risk of developing active TB. This treatment is also considered central to the complete elimination of TB in the US and elsewhere in the world. Patient education on the risks of TB onset and medication discontinuation is important for the therapy’s success. While INH therapy can mitigate the risk of onset of TB diseases in immune-competent individuals by up to 90%, the failure to take INH properly can reduce the effectiveness to as low as 25%. Other studies estimate the treatment’s effectiveness at 69 to 93%. Effectively, the determination of the effectiveness of INH-RPT treatment among populations that are prone to stress and risk of irregular administration would help bolster the effectiveness of LTBI treatment.

In Soldiers with latent tuberculosis, what is the effect of taking isoniazid (INH), compared to INH and rifapentine (RPT) regimen in preventing tuberculosis during basic combat training?

Research Questions

What is the effect of the duration LTBI treatment therapy on the treatment regimen adherence among soldiers in basic combat training?

Feasibility – Determine if the long treatment duration and stresses of war affect the discipline of adhering to the treatment regimen

What is the effectiveness of isoniazid in the treatment of LTBI among soldiers in basic combat training?
Feasibility – Determine the rates of preventing TB onset and treatment adherence
What is the effectiveness of isoniazid- rifapentine regimen in the treatment of LTBI among soldiers in basic combat training?
Feasibility – Determine the rates of preventing TB onset and treatment adherence
What is the effect of irregular isoniazid- rifapentine administration in the treatment of LTBI among soldiers in basic combat training?
Determine the TB onset rates and compare them to adherence to treatment
What is the effect of irregular INH administration in the treatment of LTBI among soldiers in basic combat training?
Determine the TB onset rates and compare them to adherence to treatment
PICOT Elements
Population - The Centres for Disease Control and Prevention recommends targeted tuberculin testing of persons with known TB risk factors (based on epidemiologic risk assessment) in order to improve efficiency and logistic advantages as against universal testing. However, even with the positive diagnosis of LTBI and INH treatment, the difficulty in managing DOT especially given the disruptive effects of armed conflict, overcrowding, combat injury, use of corticosteroids, and associated stress that can affect adherence to treatment regimens and thus lead to the development of TB (including the multi-drug resistant strain). Since INNH-RPT dosage lasts only four months and can accommodate irregular dosages, it is natural to expect that it may be more effective among soldiers in combat. The population in this study is chosen because of the confirmed LTBI diagnosis, high risk for developing TB and higher benefits compared to risks.
Intervention - Isoniazid (INH) is the only FDA-approved medication for preventive tuberculosis therapy (usually administered for 6 or 9 months), and evidence of the drug’s effectiveness in treating LBTI has been proven among diverse patients leading to the expansion of the regimen on the strength of expert opinions. However, daily INH regimens under self-supervision is characterised by less than 60% completion rates largely blamed on the treatment duration lasting more than six months. Further, the possibility of severe liver damage, contraindication, low patient toleration and concern over the same has reduced acceptability of the treatment. In the proposed study, soldiers who are newly diagnosed and receiving INH therapy will be monitored to determine their adherence to the treatment regime, unexpected adverse events, side effects, attitudes to treatment and effectiveness in treating LTBI.
Comparison- RPT is a rifamycin-class antibiotic with FDA-approved indication for tuberculosis, but its use in LBTI treatment is off-label. It allows infrequent dosing and thus increases directly observed treatment (DOT) convenience and adherence. A combined four-month INH-RPT regimen is recommended as an equally effective alternative to INH, despite the requirements for closer monitoring for adverse effects.

Outcomes- Outcomes will include adherence to treatment, patient attitudes and effectiveness in reducing the onset of TB

Time -The time required for basic combat training. It should be between three to 12 months
Words and phrases for Literature Search
Effectiveness of INH for immune-competent patients – will give the effectiveness and side effects
Effectiveness of INH-RPT for immune-competent patients – Will give its effectiveness and side effects
Stress and immunosuppression – will link combat to immunosuppression
INH-RPT treatment of LTBI - Effectiveness
LTBI treatments – Should give the treatment options, importance and effectiveness
Reasons for TB and LTBI treatment ineffectiveness – Causal factors to lay the foundation for effective use of RPT-INH and INH
Impact of LTBI treatment – effectiveness in reducing TB onset
LTBI treatment among soldiers – High-stress populations may suffer from immunosuppression
TB medication adherence support – Education and support increases adherence
INH+RFP and INH + RPT in LTBI treatment – combinations of these drugs are mainly not approved by regulatory agencies across the world, but it interesting to determine if they are effective

Summary

Latent Mycobacterium tuberculosis infection plays a central role in the control and complete elimination of tuberculosis. While the current 9-month INH regimen is effective in treating LTBI, it is limited by low treatment completion and possible toxicity. For populations that are prone to stress, immune-incompetence and high risk of non-completion such as soldiers in combat, shortened courses of intermittent treatment would help to bolster treatment effectiveness (Sterling, et al., 2011; Centres for Disease Control and Prevention, 2011). RPT’s long plasma half-life and increased potency (relative to (rifampin) allows for infrequent dosing that can improve DOT convenience and treatment adherence. In addition, since animal models have proven the effectiveness of INH-RPT in treating LTBI, the proposed research is critical to the successful elimination of TB in the military and the country.

References

Centres for Disease Control and Prevention. (2011, Dec 9). Recommendations for Use of an Isoniazid-Rifapentine Regimen with Direct Observation to Treat Latent Mycobacterium tuberculosis Infection. Retrieved Mar 14, 2015, from http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6048a3.htm
Davies, K. S. (2011). Formulating the Evidence Based Practice Question: A Review of the Frameworks. Milwaukee: University of Wisconsin.
Mancuso, J. D., Tribble, D., Mazurek, G. H., Li, Y., Olsen, C., Aronson, N. E., et al. (2011). Impact of Targeted Testing for Latent Tuberculosis Infection Using Commercially Available Diagnostics. Clin Infect Dis.53 (3), 234-244. doi: 10.1093/cid/cir321.
Prevention Committee of the Japanese Society for Tuberculosis. (2014). Treatment guidelines for latent tuberculosis infection. Kekkaku 9(1), 21-37.
Sterling, T. R., Villarino, E., Borisov, A., Shang, N., Gordin, F., Bliven-Sizemore, E., et al. (2011). Three Months of Rifapentine and Isoniazid for Latent Tuberculosis Infection. N Engl J Med 365, 2155-216.