1. HPV and Zoster, Etc.
MedCh 401
Lecture 9
2Jun06
KL Vadheim Lecture 9

2. Human Papillomavirus Papillomaviridae; ds DNA genome
~100 different types
Causes warts on various body parts
30-40 types infect genital tissue
Low risk: e.g., types 6 and 11
genital warts
High risk: ~ 15 types
16, 18, 31, 45 cause most cancers
2Jun06
KL Vadheim Lecture 9

3. HPV infections Most common STD worldwide ~20 million infected in U.S.
~5.5 million new infections annually
Often asymptomatic
Most infections spontaneously resolve
Infects cervix, vagina, vulva, anus, penis
2Jun06
KL Vadheim Lecture 9

4. High Risk HPVs Cause intraepithelial neoplasias
Can progress to cancer if undetected/untreated
HPV viral sequences (oncogenes) integrated in cellular DNA
Viral E6 protein binds/degrades p53, a tumor suppressor gene
2Jun06
KL Vadheim Lecture 9

5. HPV Vaccines Under Review
Merck - Gardasil
Quadravalent (6, 11, 16, 18)
Recombinant
Recommended for approval by VRPAC
GSK
Bivalent (16 and 18)
Phase III trials ongoing
2Jun06
KL Vadheim Lecture 9

6. Merck’s Gardasil Targeted for women 9-26 years of age
100% effective in preventing type 16 and 18 infection (~70% cervical CA)
99% effective in preventing type 6 and 11 infection (90% of genital warts)
Complement to - not replacement for - Pap smears
$300 - $500 per vaccination
2Jun06
KL Vadheim Lecture 9

7. Cervical Cancer in U.S. >9,000 women diagnosed annually
~3,700 deaths
Risk factors for development of cervical CA
high-risk type HPV infection
smoking
having many children
long-term oral contraceptive use
HIV infection
2Jun06
KL Vadheim Lecture 9

8. Zostavax Merck’s shingles vaccine Licensed May 25, 2006
Reduce risk of herpes zoster in people >60
50% efficacy in all people >60
64% efficacy in people 60-69
Three-year study
2Jun06
KL Vadheim Lecture 9

9. Merck’s Zostavax & Varivax
Oka/Merck strain of live, attenuated VZV
Initially obtained from child with natural varicella infection
Attenuation
Human embryonic lung cells
Embryonic guinea pig cells
Human diploid cells (WI-38)
Lyophilized
Subcutaneous administration
2Jun06
KL Vadheim Lecture 9

10. Varicella zoster Vaccines
2Jun06
KL Vadheim Lecture 9

11. Tuberculosis 2 million deaths annually worldwide
2 billion people are infected worldwide
1 in 10 infected will develop active TB
98% of deaths are in the developing world, affecting primarily young adults
8.8 million new TB cases in 2003
80% in 22 countries
2Jun06
KL Vadheim Lecture 9

12. Pandemic TB Global incidence is growing at 1% per year
25% of all cases are in Africa
50% of new cases are in six Asian countries
Bangladesh
China
India
Indonesia
Pakistan
The Philippines
2Jun06
KL Vadheim Lecture 9

13. TB Transmission Airborne No animal vector known 2Jun06
KL Vadheim Lecture 9

14. Multi-Drug Resistance
Curable, but 5,000 people die daily
MDR-TB present in nearly all 109 countries surveyed by WHO
425,000 new MDR-TB cases every year
highest rates in former URRS and China
up to 14% of all new cases are not responding to standard drug treatment
2Jun06
KL Vadheim Lecture 9

15. TB control strategies U.S. Europe test and treat
Mantoux test (PPD skin reactivity test)
Europe
BCG vaccination
attenuated TB strain
Efficacy doubtful
Recent studies place efficacy near zero
2Jun06
KL Vadheim Lecture 9

16. New TB control strategies
Government commitment to TB control
Diagnosis through bacteriology and an effective lab network
Standardized short-course chemotherapy with full patient support
Uninterrupted supply of quality-assured drugs
documenting patient outcomes
2Jun06
KL Vadheim Lecture 9

17. Malaria >1 million deaths annually
million acute illnesses each year
Endemic in >100 countries
>80% of deaths in sub-Saharan Africa
Most deaths in infants and young children
3,000 children die of malaria every day
2Jun06
KL Vadheim Lecture 9

18. Malaria transmission
Single-celled parasite carried by Anopheles mosquito
Many animal hosts in addition to humans
Complex life cycle makes control difficult
2Jun06
KL Vadheim Lecture 9

19. Malaria Control Insecticide-laced mosquito nets Chloroquine
reduces childhood deaths ~20%
Chloroquine
effective against P. vivax, ~30% of cases
Sulphadoxin-Pyrimethamine (SP)
P. falciparum
Drug resistance a problem
Artemisinin-based Combination Therapy (ACT)
2Jun06
KL Vadheim Lecture 9

20. Malaria Vaccine Development
PATH
Malaria Vaccine Initiative
GSK’s candidate vaccine ~50% efficacy against most lethal forms of disease
2Jun06
KL Vadheim Lecture 9

21. Specific Immune Globulins
Botulinum antitoxin
Botulism IGIV
Cytomegalovirus IG IV
Hepatitis B IGIV
Rabies IG (Human)
RSV IGIV (Human)
Tetanus IG (Human)
2Jun06
KL Vadheim Lecture 9

22. Non-specific IGIV Immune Globulin (Human) Immune Globulin IV (Human)
Immune Globulin Subcutaneous (Human)
can be self-administered
2Jun06
KL Vadheim Lecture 9

23. Non-specific IGIVs Highly purified IgG preparation
Made from donated human plasma
Used to treat people with insufficient antibody production
Usually given every 3-4 weeks
Treatment may be life-long
2Jun06
KL Vadheim Lecture 9

24. 2Jun06
KL Vadheim Lecture 9

25. Complaints Call or write the manufacturer
Provide as much information as possible
Expect an investigation and written response
2Jun06
KL Vadheim Lecture 9

26. Recalls and Withdrawals
2Jun06
KL Vadheim Lecture 9