Ch 18 Infectious Diseases Affecting Cardiovascular and Lymphatic Systems

Highlight Disease: Malaria World’s dominant protozoal disease. Four species of Plasmodium: P. falciparum (malignant), P. vivax (begnin), P. malariae...... Vector: Anopheles mosquito Worldwide 300-500 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.

Microscopic Diagnosis Compare to Fig 18.3 Diagnostic!

Fig 18.4

Compare to Fig 18.1

Sickle cell trait provides protection!

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

Human Immunodeficiency Virus

Multiplication Cycle of HIV Compare to Table18.4

HIV cellular targets : Th cells APCs brain cell intestinal epithelium

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

Fig 18.7

HIV Attachment, Fusion, and Entry

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

The Progression of HIV Infection

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

Some Diseases Commonly Associated with AIDS See Table 18.3 Pneumocystis jirovecii

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

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

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

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

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

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

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