Infectious Diseases & Biodefense at UVa Biodefense and infectious diseases in 2008 will move into...
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Infectious Diseases & Biodefense at UVa
• Biodefense and infectious diseases in 2008 will move into the new Carter-Harrison Research Building – 23,800 nsf of lab and support space – 4375 nsf of biosafety
level three
(BSL3/animal BSL3)
Infectious Diseases & Biodefense at UVa
• The 26 faculty in ID/BioD are– 100% NIH supported (median annual direct costs
$648,000), – interactive (65% co-published), and – come from 7 Departments.
• Rich tradition of ID at UVA
Diseases Studied
• Virology: HIV/AIDS, Influenza, Respiratory Syncytial Virus, Ebola, KSHV, Hepatitis C
• Bacteriology:E. coli (including EAgg, STEC), anthrax, tularemia, legionella, pertussis, yersinia, community-acquired MRSA, Ps. aeruginosa, H. pylori, Salmonella
• Eukaryotes: Candida, Amebiasis, Cryptosporidiosis
Host Response
• Human innate and acquired immunity to enteric infections, HIV, influenza
• Human genetic epidemiology of infectious diseases
• Animal models (rodent and C. elegans) to study host response to amebiasis, cryptosporidiosis, hepatitis C, KSHV, influenza
International Health Aspects
• Bangladesh: child cohort being studied for enteric and respiratory infections.
• Tanzania and Uganda: at KCMC studies of HIV, TB, enteric infect-ions. At Kampala studies of sepsis in HIV/AIDS
• Brazil & Haiti: impact of enterics on HIV treatment and malnutrition
Biodefense
• Category A: Anthrax, Tularemia, Ebola, Smallpox, Plague
• Category B: Food & waterborne pathogens (amebiasis, cryptosporidiosis, giardiasis, E. coli, salmonella), Burkholderia
• Category C: Influenza, rabies, antibiotic resistant bacteria
Nitazoxanide: A Broad Spectrum Anti-bacterial Anti-parasitic and Anti-viral Drug
• Romark Laboratories markets this drug as Alinia
• FDA approved for Cryptosporidium and Giardia
• USDA approved for Sarcocystis neurona
• Off label – Entamoeba, Trichomonas, helmiths
• Anaerobic bacteria – Clostridium, C. difficile, etc.
• Microaerobic bacteria – Helicobacter pylori, Campylobacter jejuni
• Viruses – active against Influenza A and B, Hepatitis C and rotavirus, but not paraFlu
Anti-parasitic Drugs
0
50
100
150
200
250
300
350
400
µg/ml
CDC085
CDC520
EMU1
EMU7
EMU17
EMU32
EMU33
EMU56
MSA802
MSA803
MSA808
MSA812
CDC697
CDC698
MSA814
MSA815
Strain
MLCs of Metronidazole, Nitazoxanide and Tizoxanide: Aerobic Conditions
MetronidazoleNitazoxanideTizoxanide
IN VITRO ACTIVITY OF NITAZOXANIDE AGAINST METRONIDAZOLE-SENSITIVE AND RESISTANT TRICHOMONAS VAGINALIS
PFOR
Glucose
CoA
Acetyl -CoA
Pyruvate
CO 2
Fd or Fld(Reduced)
Fd or Fld(Oxidized)
Hydrogenase(H 2) or
Reductases(NADPH)
PFOR
Glucose
CoA
Acetyl -CoA
Pyruvate
CO 2
Fd or Fld(Reduced)
Fd or Fld(Oxidized)
Hydrogenase(H 2) or
Reductases(NADPH)
Nitazoxanide blocks pyruvate ferredoxin oxidoreductase by reversing pyruvate binding to thiamine pyrophosphate
Discovery strategy – Can we make second generation drugs based on knowledge of mode of action and importance of pKa?Paul Hoffman, Ph.D., UVA