1. Ch 18 Infectious Diseases Affecting Cardiovascular and Lymphatic Systems

2. Highlight Disease: Malaria
World’s dominant protozoal disease.
Four species of Plasmodium: P. falciparum (malignant), P. vivax (begnin), P. malariae......
Vector: Anopheles mosquito
Worldwide million cases; ~ 1.5 – 3 million people die; ~ 1,200 cases in US
Plasmodium infects red blood cells  microscopic diagnosis
Symptoms: chills, fever, vomiting, headache; at intervals of 2 to 3 days
New drugs are being developed as the protozoa develop resistance to drugs such as chloroquine.

3. Microscopic Diagnosis
Compare to Fig 18.3
Diagnostic!

4. Fig 18.4

5. Compare to Fig 18.1

6. Sickle cell trait provides protection!

7. Highlight Disease: HIV Infection and AIDS
Origin and History
1981: In US, cluster of Pneumocystis pneumonia and Kaposi's sarcoma in young homosexual men discovered. The men showed loss of immune function.
1983: Discovery of virus causing loss of immune function.
1986: Scientists started to identify the virus with "HIV" abbreviation.
HIV is thought to have crossed the species barrier into humans in central Africa about 1908.
Patient who died in 1959 in Congo is the oldest known case.
Virus spread in Africa as result of urbanization. World-wide spread through modern transportation and unsafe sex.
Norwegian sailor who died in 1976 is the first known case in Western world.
> 30,000,000 peopled died so far worldwide

8. Human Immunodeficiency Virus

9. Multiplication Cycle of HIV
Compare to Table18.4

10. HIV cellular targets :
Th cells
APCs
brain cell
intestinal epithelium

11. HIV Infection  AIDS is Final stage
HIV: Retrovirus with ssRNA, RT, and envelope with gp120 spikes. Gp120 attach to CD4 on ________ cells, M, Function of RT? Provirus latent or directs active virion synthesis HIV evades IS via latency, vacuoles, antigenic change
Compare to Fig 18.7

12. Fig 18.7

13. HIV Attachment, Fusion, and Entry

14. Signs and Symptoms Phase 1: Asymptomatic or chronic lymphadenopathy
Phase 2: Symptomatic; early indications of immune failure
Phase 3 is AIDS: Characterized by “defining illnesses”, such as: CMV, TB, Pneumocystis, toxoplasmosis, and Kaposi's sarcoma (see Table 19.5)
Phases 1 and 2 are reported as AIDS if CD4+ T cells <200 cells/µl; Phase 3 always reported as AIDS
Progression from HIV infection to AIDS:  10 y
The life of an AIDS patient can be prolonged by the proper treatment of opportunistic infections
People lacking CCR5 are resistant to HIV infection

15. The Progression of HIV Infection

16. Exposed, but not infected
CCR5 mutation
Survival with HIV Infection
Long-term nonprogressors
1 in 300
Measurable PVL, CD4 count slightly 
Highly effective CTLs

17. Some Diseases Commonly Associated with AIDS
See Table 18.3
Pneumocystis jirovecii

18. Diagnostic Methods Seroconversion takes up to 3 months
Standard test: ELISA to detect___________
Confirm by Western blot
Alternative: APTIMA HIV-1 RNA Qualitative Assay (combination of target amplification, hybridization and magnetic capture)
Conventional PVL is determined by PCR or NA hybridization

19. To be conclusive (HIV-positive), a Western Blot must have 5 horizontal stripes.

21. HIV Transmission Sexual contact Breast milk
HIV survives 6 h outside a cell and > 1.5 d inside a cell
Infected body fluids transmit HIV via
Sexual contact
Breast milk
Transplacental infection of fetus
Blood-contaminated needles
Organ transplants
Artificial insemination
Blood transfusion
In developed countries, blood transfusions are not a likely source of infection anymore

22. AIDS Worldwide Heterosexual intercourse (85%) Injected drug use (IDU)
Women comprise 42% of infected
1.5 mio

23. AIDS Prevention Condoms and sterile needles!
Health care workers use Universal Precautions:
Wear gloves, gowns, masks, and goggles
Do not recap needles
Risk of infection from infected needle stick injury is 0.3%
Vaccine difficulties due to
Mutations
Geographical clades
Quick integration into DNA
Need to also stimulate CTLs
Many failed vaccines. Current Phase III trial

24. AIDS Chemotherapy The End
Treatment has much improved with HAART Highly Active Anti-Retroviral Therapy - cocktail)
Reverse transcriptase inhibitors (most are nucleoside /-tide analogs, e.g.: AZT)
Fusion inhibitors / Cell entry inhibitors
Protease inhibitors
Integrase inhibitors
HIV protease cleaves viral polypeptide into functional proteins
Protease inhibition  HIV cannot mature and noninfectious viruses are produced.
The End

25. End of part 1