The Struggle with Infectious Disease. Lecture 6

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1 The Struggle with Infectious Disease Lecture 6

2 HIV/AIDS It is generally believed that: Human Immunodeficiency Virus causes Acquired Immunodeficiency Syndrome

3 History of HIV HIV is believed to have developed from SIV in chimpanzee or gorilla (depending upon strain) Most logical explanation is through bushmeat Correlation between bushmeat and SIV antibodies in Camaroon

4 History of HIV Geographic regions around (Kinshasa) DRC Genetic back-analysis indicates emergence about Period of rapid urbanization and colonization Hypothesized that spread was by: Sexual practices Genital Ulcers Non-sterile needles in vaccination campaigns No definitive answer on source or spread

5 Spread of HIV 1959: David Carr Manchester (spurious) DRC: 2 cases from re-examination of autopsies 1969: 15 year old African- American boy Kansas City Norwegian Sailor Spread from Africa to Haiti Circa 1966 Profession links with DRC Mini-epidemic 1969 Brought to US by unknown individual Late 60 s, early 70 s Almost all cases outside Africa can be traced to this one individual

6 Spread of HIV Eventually made it s way into homosexual community Spread widely before AIDS phase was observed/identified Unknown disease, link between virus and fatal opportunistic infection High death rate, not known cure and specific community led to activism

7 Spread of AIDS in Africa Largely through heterosexual sex Spread from large urban centres (poverty) to rural areas (poorer) Major compounding factors: Ignorance Community beliefs Government inaction

10 By the Numbers Estimated 33 million living with HIV More than 33 million had died (2008) 2.7 million new HIV infections per year 1.7 million AIDS related deaths per year (2008) Joint UN program on HIV/AIDS

11 By the Numbers 280,000 child deaths/yr 14.8 million orphans (under 18 years) Largely in Africa ~50% of HIV patients are female

Swaziland: 26% People with AIDS do not live as long as

12 68% of all people living with HIV are in sub- Saharan Africa Only 12% of the world s population Highest in Swaziland: 26% People with AIDS do not live as long as in developed countries 1 yr. vs ~10-40 yrs. By the Numbers

13 AIDS in Canada Over 13,000 have died Largely in males 19,000/2,000 New cases in 2009: 181 male 42 female 65,000 living with HIV 2,700 4,300 new cases annually

14 What Makes HIV Special HIV is a retrovirus Synthesizes DNA HIV is a lentivirus Slow acting Can remain asymptomatic for a long time HIV attacks cells of the immune system It is the complications that are fatal

15 Retrovirus Starts with RNA Uses reverse transcriptase to copy DNA Enters nucleus and integrates DNA into cells DNA using Integrase enzyme

16 Retrovirus

17 Retrovirus DNA Replication DNA to RNA transcription

18 Integrates it s own reproduction pattern into the cell In a latent state it is reproduced with the cell (undetectable) When not in latent state in can rapidly produce RNA and Protein copies (millions per day) Retrovirus

19 Influenza Replication Uses ribosomes outside nucleus to copy RNA Uses cell nucleus to replicate and assemble Kills the cell in the process No possibility to pass on genome

20 Reverse transcriptase makes random errors Error rate similar to influenza Viral production is orders of magnitude greater than Flu virus Recombination allows for antigenic shifts Evades immune system Makes vaccine difficult Antigenic Shift

21 Long incubation period Infective during incubation period Can infect non-dividing cells Unique among retrovirus Three common viruses: HIV (human) SIV (monkey) FIV (cat) Lentivirus

22 Attacks Immune System HIV is transmitted through body fluids Attaches to dendritic cells in the mucosal immune system Throat, nose rectum, vagina, penis Transported by dendritic cells to lymph nodes

23 Attacks Immune System Primary target of infection is T helper cells (CD4+) CD4+ coordinate immune response through signalling Kills cells if there is high virus production Apoptosis (cell suicide) Innocent Bystander Cells (HIV binding to surface) Infected T cell Normal T cell Apoptosis in T cell

24 HIV Causes AIDS Viral load in blood may increase slowly More and more T cells are destroyed Normal /mm 3 AIDS defined as <200/mm 3 Sometimes as few as 50 in entire body

25 Opportunistic Infections Suppressed immune system allows infections TB 25% of deaths Pneumonia Cancers Kaposi s sarcoma Non-Hodgkin lymphoma Neurological disorders Long list of other infections

26 Treatment Complicated by rapid antigenic shifts and extremely high viral production rates (active phase) Difficult to deal with latent stages within organs

27 Antiretroviral Therapy A variety of anti-viral medications have been developed (31 approved) They attack different parts of the replication cycle Multidrug combinations: Highly active antiretroviral therapy (HAART) is most effective

Antiretroviral Therapy Can extend life from 1-3 years (without) to 10 40 years

28 Antiretroviral Therapy Can extend life from 1-3 years (without) to years Must be taken continuously Patient remains infective Drug resistance remains a concern

Acquired Immune Deficiency Syndrome (AIDS)

Acquired Immune Deficiency Syndrome (AIDS) By Jennifer Osita Disease The disease I am studying is AIDS (Acquired Immune Deficiency Syndrome) which is when the immune system is too weak to fight off many