Tuberculosis future or investigational therapies: Difference between revisions
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__NOTOC__ | __NOTOC__ | ||
{{Tuberculosis}} | {{Tuberculosis}} | ||
{{CMG}} ; {{AE}} {{Ammu}} | {{CMG}} ; {{AE}} {{Mashal Awais}}; {{Ammu}} ; {{marjan}} | ||
==Overview== | ==Overview== | ||
With emergence of new drug-resistant tuberculosis, the role of future therapies is crucial in curbing outbreaks. The new drugs should be more effective than the current regimen and a few drugs in clinical trials have been showing promising results. | |||
==Future investigations== | ==Future investigations== | ||
1 | ===Principles of future investigations=== | ||
Any future regimen must fulfill the following recommendations: <ref name="Cost">{{cite web | title = Future therapy purposed by WHO| url = http://www.who.int/bulletin/volumes/92/1/13-122028/en/}}</ref> | |||
*It should not have more than a maximum duration of 6 months | |||
*The dosing schedule must be simple | |||
*The ideal number of drugs should not exceed 3-5 drug from a different class | |||
*It should have a minimum side effect profile so that we could have minimum monitoring | |||
*It should be effective against [[MDR]], [[XDR]], and [[XXDR]] strains | |||
*It should be administered orally | |||
*It should have minimum interaction with antiretroviral drugs. | |||
*It should have at least one new class of drug | |||
===New drugs involved in a clinical trial for the treatment of tuberculosis=== | |||
3) | {| style="border: 0px; font-size: 90%; margin: 3px;" align="center" | ||
| valign="top" | | |||
|+ | |||
! style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Drug}} | |||
! style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Phase}} | |||
! style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Class}} | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[Moxifloxacin]] | |||
| style="padding: 5px 5px; background: #F5F5F5;" |Phase III | |||
| style="padding: 5px 5px; background: #F5F5F5;" |[[Fluoroquinolone]] | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Linezolid]] | |||
| style="padding: 5px 5px; background: #F5F5F5;" |Phase II | |||
| style="padding: 5px 5px; background: #F5F5F5;" |[[Oxazolidinone]] | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |AZD-5847 | |||
| style="padding: 5px 5px; background: #F5F5F5;" |Phase II | |||
| style="padding: 5px 5px; background: #F5F5F5;" |[[Oxazolidinone]] | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Sutezolid]] | |||
| style="padding: 5px 5px; background: #F5F5F5;" |Phase II | |||
| style="padding: 5px 5px; background: #F5F5F5;" |[[Oxazolidinone]] | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Clofazimine]] | |||
| style="padding: 5px 5px; background: #F5F5F5;" |Phase II | |||
| style="padding: 5px 5px; background: #F5F5F5;" |[[Riminophenazine]] | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |SQ-109 | |||
| style="padding: 5px 5px; background: #F5F5F5;" |Phase II | |||
| style="padding: 5px 5px; background: #F5F5F5;" |[[Ethylenediamine]] | |||
|- | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |PA-824 | |||
| style="padding: 5px 5px; background: #F5F5F5;" |Phase IIb | |||
| style="padding: 5px 5px; background: #F5F5F5;" |[[Nitroimidazole]] | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Delamanid]] | |||
| style="padding: 5px 5px; background: #F5F5F5;" |Phase III | |||
| style="padding: 5px 5px; background: #F5F5F5;" |[[Nitroimidazole]] | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Bedaquiline]] | |||
| style="padding: 5px 5px; background: #F5F5F5;" |Phase III | |||
| style="padding: 5px 5px; background: #F5F5F5;" |[[Diarylquinoline]] | |||
|- | |||
| colspan="3" style="padding: 5px 5px; background: #F5F5F5;" |Data provided by WHO<ref name="CDC">{{cite web | title = Tuberculosis (TB) Future drugs| url = http://www.who.int/bulletin/volumes/92/1/BLT-13-122028-table-T1.html }}</ref> | |||
|} | |||
==Tuberculosis vaccine development== | |||
*[[Infant|Neonatal]] [[BCG]] [[vaccination]] is partially effective at protecting infants and children, especially from the most severe [[complications]] of [[Tuberculosis|TB]] disease.<ref name="urlWHO | Tuberculosis vaccine development, SYSTEM DO NOT MOVE OR EDIT">{{cite web |url=https://www.who.int/immunization/research/development/tuberculosis/en/ |title=WHO | Tuberculosis vaccine development, SYSTEM DO NOT MOVE OR EDIT |format= |work= |accessdate=}}</ref> | |||
*[[BCG]] is poorly effective at protecting against [[pulmonary disease]] in adults, and hence at decreasing [[Mycobacterium tuberculosis]] [[Transmission (medicine)|transmission]].<ref name="urlWHO | Tuberculosis vaccine development, SYSTEM DO NOT MOVE OR EDIT">{{cite web |url=https://www.who.int/immunization/research/development/tuberculosis/en/ |title=WHO | Tuberculosis vaccine development, SYSTEM DO NOT MOVE OR EDIT |format= |work= |accessdate=}}</ref> | |||
*A new novel vaccine is needed to reduce the [[Incidence (epidemiology)|incidence]] and [[Mortality rate|mortality]] of [[tuberculosis]]; a vaccine that is effective in adult individuals who have not yet been infected with [[mycobacterium tuberculosis]], in addition to in those with latent [[mycobacterium tuberculosis]] infection.<ref name="urlWHO | Tuberculosis vaccine development, SYSTEM DO NOT MOVE OR EDIT">{{cite web |url=https://www.who.int/immunization/research/development/tuberculosis/en/ |title=WHO | Tuberculosis vaccine development, SYSTEM DO NOT MOVE OR EDIT |format= |work= |accessdate=}}</ref> | |||
*This new novel [[vaccine]] will also provide the best way to counteract accelerating spread of [[Multi-drug-resistant tuberculosis|multi-drug resistant tuberculosis]].<ref name="urlWHO | Tuberculosis vaccine development, SYSTEM DO NOT MOVE OR EDIT">{{cite web |url=https://www.who.int/immunization/research/development/tuberculosis/en/ |title=WHO | Tuberculosis vaccine development, SYSTEM DO NOT MOVE OR EDIT |format= |work= |accessdate=}}</ref> | |||
*To this date, this new vaccine has not been developed but many [[Tuberculosis|TB]] [[vaccine]] candidates are in pipeline.<ref name="urlWHO | Tuberculosis vaccine development, SYSTEM DO NOT MOVE OR EDIT">{{cite web |url=https://www.who.int/immunization/research/development/tuberculosis/en/ |title=WHO | Tuberculosis vaccine development, SYSTEM DO NOT MOVE OR EDIT |format= |work= |accessdate=}}</ref> | |||
*Potential vaccines are either whole-cell vaccines, adjuvanted proteins, and vectored subunit vaccines.<ref name="urlWHO | Tuberculosis vaccine development, SYSTEM DO NOT MOVE OR EDIT">{{cite web |url=https://www.who.int/immunization/research/development/tuberculosis/en/ |title=WHO | Tuberculosis vaccine development, SYSTEM DO NOT MOVE OR EDIT |format= |work= |accessdate=}}</ref> | |||
*A document highlighting [[World Health Organization|WHO]] preferred Product Characteristics (PPC) for new TB vaccines has been devised based on a high unmet medical need and technical feasibility assessment.<ref name="urlWHO | Tuberculosis vaccine development, SYSTEM DO NOT MOVE OR EDIT">{{cite web |url=https://www.who.int/immunization/research/development/tuberculosis/en/ |title=WHO | Tuberculosis vaccine development, SYSTEM DO NOT MOVE OR EDIT |format= |work= |accessdate=}}</ref> | |||
*The vaccine PPCs are built through a large consensus building process and originate from interactions with different stakeholders.<ref name="urlWHO | Tuberculosis vaccine development, SYSTEM DO NOT MOVE OR EDIT">{{cite web |url=https://www.who.int/immunization/research/development/tuberculosis/en/ |title=WHO | Tuberculosis vaccine development, SYSTEM DO NOT MOVE OR EDIT |format= |work= |accessdate=}}</ref> | |||
*The new vaccine, made by GSK and now known as M72/AS01E, was tested in about 3,300 adults in Kenya, South Africa, and Zambia. | |||
*All of them already had latent [[tuberculosis]], Of those who got two doses of the GSK vaccine, only 13 developed active [[tuberculosis]] during three years of follow-up, according to the new study which was published in The New England Journal of Medicine. On the other hand, 26 of those who received a [[placebo]] progressed to active tuberculosis. | |||
<br /> | |||
==References== | ==References== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
{{WH}} | |||
{{WS}} | |||
[[Category:Disease]] | [[Category:Disease]] | ||
[[Category: Pulmonology]] | |||
[[Category:Pulmonology | |||
[[Category:Bacterial diseases]] | [[Category:Bacterial diseases]] | ||
Latest revision as of 05:47, 27 March 2021
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Mashal Awais, M.D.[2]; Ammu Susheela, M.D. [3] ; Marjan Khan M.B.B.S.[4]
Overview
With emergence of new drug-resistant tuberculosis, the role of future therapies is crucial in curbing outbreaks. The new drugs should be more effective than the current regimen and a few drugs in clinical trials have been showing promising results.
Future investigations
Principles of future investigations
Any future regimen must fulfill the following recommendations: [1]
- It should not have more than a maximum duration of 6 months
- The dosing schedule must be simple
- The ideal number of drugs should not exceed 3-5 drug from a different class
- It should have a minimum side effect profile so that we could have minimum monitoring
- It should be effective against MDR, XDR, and XXDR strains
- It should be administered orally
- It should have minimum interaction with antiretroviral drugs.
- It should have at least one new class of drug
New drugs involved in a clinical trial for the treatment of tuberculosis
| Drug | Phase | Class |
|---|---|---|
| Moxifloxacin | Phase III | Fluoroquinolone |
| Linezolid | Phase II | Oxazolidinone |
| AZD-5847 | Phase II | Oxazolidinone |
| Sutezolid | Phase II | Oxazolidinone |
| Clofazimine | Phase II | Riminophenazine |
| SQ-109 | Phase II | Ethylenediamine |
| PA-824 | Phase IIb | Nitroimidazole |
| Delamanid | Phase III | Nitroimidazole |
| Bedaquiline | Phase III | Diarylquinoline |
| Data provided by WHO[2] | ||
Tuberculosis vaccine development
- Neonatal BCG vaccination is partially effective at protecting infants and children, especially from the most severe complications of TB disease.[3]
- BCG is poorly effective at protecting against pulmonary disease in adults, and hence at decreasing Mycobacterium tuberculosis transmission.[3]
- A new novel vaccine is needed to reduce the incidence and mortality of tuberculosis; a vaccine that is effective in adult individuals who have not yet been infected with mycobacterium tuberculosis, in addition to in those with latent mycobacterium tuberculosis infection.[3]
- This new novel vaccine will also provide the best way to counteract accelerating spread of multi-drug resistant tuberculosis.[3]
- To this date, this new vaccine has not been developed but many TB vaccine candidates are in pipeline.[3]
- Potential vaccines are either whole-cell vaccines, adjuvanted proteins, and vectored subunit vaccines.[3]
- A document highlighting WHO preferred Product Characteristics (PPC) for new TB vaccines has been devised based on a high unmet medical need and technical feasibility assessment.[3]
- The vaccine PPCs are built through a large consensus building process and originate from interactions with different stakeholders.[3]
- The new vaccine, made by GSK and now known as M72/AS01E, was tested in about 3,300 adults in Kenya, South Africa, and Zambia.
- All of them already had latent tuberculosis, Of those who got two doses of the GSK vaccine, only 13 developed active tuberculosis during three years of follow-up, according to the new study which was published in The New England Journal of Medicine. On the other hand, 26 of those who received a placebo progressed to active tuberculosis.