Developing Infectious Disease Strategies for the Developing World
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Published on: October 31, 2010
Paul J Lee1, Leonard R Krilov1
1Division of Pediatric Infectious Diseases, Winthrop University Hospital, Mineola, NY 11501, USA.
Abstract:
This chapter discusses various drugs for human influenza A (H5N1) and multidrug-resistant mycobacterium tuberculosis (MDR-TB). The H5N1 avian influenza does not presently meet the criteria of an antigenically shifted strain. It is presently an avian strain that has not undergone reassortment with a human strain and is not well adapted to humans. H5N1 isolates are resistant to the M2 inhibitors amantadine and rimantadine; these antivirals do not have a role for the treatment or prophylaxis against the strain. The neuraminidase inhibitors, oseltamivir and zanamivir, have in vitro activities against the human H5N1 isolates; however, recent data suggest that higher doses for longer periods may be required to be effective. Oseltamivir is an oral agent approved for prophylaxis and the treatment of influenza infections. Zanamivir is delivered topically to the respiratory tract with similar indications. The drugs discussed in the chapter for MDR-TB fall into three categories-quinolones, nitroimidazoles, and pyrroles. Drugs such as moxifloxacin are methoxyfluoroquinolones, which are already available and approved for the treatment of acute respiratory infections, such as community-acquired pneumonia, intra-abdominal infections, acute sinusitis, and skin infections. Gatifloxacin 5, is another methoxyfluoroquinolone that is in clinical development for tuberculosis treatment.
Insights
This chapter reviews treatments for H5N1 avian influenza and multidrug-resistant tuberculosis (MDR-TB). Current H5N1 strains resist amantadine/rimantadine, while neuraminidase inhibitors may need higher doses. New quinolones show promise for MDR-TB.
Area of Science:
- Virology
- Microbiology
- Pharmacology
Background:
- Human influenza A (H5N1) is an avian strain not well-adapted to humans.
- H5N1 isolates exhibit resistance to M2 inhibitors like amantadine and rimantadine.
- Multidrug-resistant Mycobacterium tuberculosis (MDR-TB) requires novel therapeutic strategies.
Purpose of the Study:
- To discuss current and emerging drug therapies for H5N1 influenza.
- To review drug categories for treating MDR-TB, including quinolones, nitroimidazoles, and pyrroles.
Main Methods:
- Review of existing literature on antiviral and anti-tuberculosis drugs.
- Analysis of drug efficacy and resistance patterns for H5N1 and MDR-TB.
Main Results:
- Amantadine and rimantadine are ineffective against H5N1.
- Neuraminidase inhibitors (oseltamivir, zanamivir) show in vitro activity against H5N1, potentially requiring higher doses.
- Methoxyfluoroquinolones like moxifloxacin are approved for other infections and gatifloxacin is in development for MDR-TB.
Conclusions:
- Amantadine and rimantadine have no role in treating H5N1 avian influenza.
- Oseltamivir and zanamivir are options for H5N1, but efficacy may be dose-dependent.
- Quinolones represent a promising class of drugs for MDR-TB treatment.
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