MICROBIOLOGY AND IMMUNOLOGY (BIOL200/343), SUMMER, 2017 Lecture:8 MICROBIOLOGY AND IMMUNOLOGY (BIOL200/343), SUMMER, 2017 Dr.Q.M.I.Haq
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Human Immunodeficiency Virus Acquired Immune Deficiency Syndrome HIV Human Immunodeficiency Virus (Gradually affects our immune system) AIDS Acquired Immune Deficiency Syndrome (A condition caused by deficiency in body’s immune system due to HIV. It is a syndrome: a group of symptoms of various ilness taking place at the same time)
HIV is thought to have entered into humans somewhere between 1914 and 1940. In 1983, a retrovirus, now called human immunodeficiency virus (HIV), had been identified as the cause of AIDS.
Sub-Saharan Africa is the region of the world that is most affected by HIV & AIDS. An estimated 25.8 million people were living with HIV at the end of 2005 and approximately 3.1 million new infections occurred during that year. More than twelve million children have been orphaned by AIDS.
HIV infects the immune system cell called the Helper T cells (-most important white blood cell involved in identifying infections.) The immune crippling disease caused by the HIV virus in which the body becomes unable to protect itself against any secondary infections. HIV particles (grey) covering a white blood cell.
HIV-1 is more common worldwide and HIV-2 is found in West Africa, Mozambique, and Angola. HIV-2 is less easily transmitted and less pathogenic. Duration of HIV-2 infection is shorter. MTCT is relatively rare with HIV-2. MTCT of HIV-2 has not been reported from India.
The progression from initial infection with HIV to end-stage AIDS varies from person to person and can take more than 10 years.
Former names of the HIV include: Human T cell lymphotrophic virus (HTLV-III) Lymphadenopathy associated virus (LAV) AIDS associated retrovirus (ARV)
Structure of Human Immunodeficiency Virus An RNA retrovirus – subfamily Lentivirus Contains: 2 copies of RNA Enzymes: Reverse Transcriptase Integrase Protease Two major envelope proteins: gp120 gp41
The HIV replication cycle:
Life Cycle of HIV virus Interaction between viral envelope proteins and CD4 receptor and co-receptors leads to binding of the viral envelope and host cytoplasmic membrane. Viral reverse transcriptase catalyses the conversion of viral RNA into DNA. Proviral DNA enters the nucleus and becomes integrated into chromosomal DNA of host cell (catalyzed by integrase). Expression of viral genes leads to production of viral RNA and proteins. Protease enzyme cleaves proteins into functional mature products. Viral proteins and viral RNA are assembled at the cell surface into the new viral particles and leave the host through budding.
From Infection to Disease (Pathophysiology) Infected body fluids are introduced into the body of an un-infected person. The HIV virus crosses into the T-4 White Cell (Immune Cells). The virus uses the genetic mechanisms of the cell to produce millions of new viruses. The cell dies and the new viruses are released into the blood to infect new un-infected cells. The T-4 are killed and the patient becomes immuno- deficient. The person becomes susceptible to opportunistic infections or AIDS related cancers.
Progression from HIV infection to stage of AIDS Normal Healthy Individual Gets infected with HIV Window period (3-12 weeks or even 6 months) (Antibodies to HIV not yet developed, test does not capture the real status but person can infect others) HIV Positive (Development of antibodies, can be detected in test) No exclusive symptoms (mild fever or flu like features in some cases) May take up to 10 to 12 years to reach the stage of AIDS, the period can be prolonged through available treatment Note: The Window Period – (the time between infection and when a person tests positive. During this time a person is infectious even though their tests are negative).
Progression of HIV (4 stages)
Four Stages of HIV Stage 1 - Primary Short, flu-like illness No symptoms at all Infected person can infect other people Stage 2 - Asymptomatic This stage is free from symptoms There may be swollen glands HIV antibodies are detectable in the blood
Stage 3 - Symptomatic The symptoms are mild The immune system deteriorates emergence of opportunistic infections and cancers Stage 4 - HIV AIDS The immune system weakens The illnesses become more severe leading to an AIDS diagnosis
Major Signs / Symptoms of AIDS: (A) Major Signs: Weight loss (> 10% of body weight) Fever for longer than a month Diarrhea for longer than a month (B) Minor Signs: Persistent cough General itchy skin diseases Thrush in mouth and throat Recurring shingles (herpes zoster) Long lasting, spreading and severe cold sores Long lasting swelling of the lymph glands Loss of memory Loss of intellectual capacity Peripheral nerve damage
Opportunistic Infections Bacterial Tuberculosis (TB) Strep pneumonia Viral Kaposi Sarcoma Herpes Influenza (flu) Parasitic Pneumocystis carinii Fungal Candida Cryptococcus Mycobacterium Avium Complex Salmonellosis Syphilis and Neurosyphilis Tuberculosis Bacillary angiomatosis Aspergillosis Candidiasis Coccidioidomycosis Cryptococcal Meningitis Histoplasmosis Kaposi’s Sarcoma Systemic Non-Hodgkin’s Lymphoma Primary CNS Lymphoma Cryptosporidiosis Isosporiasis Microsporidiosis Pneumocystis Carinii Pneumonia Toxoplasmosis Cytomegalovirus Hepatitis Herpes Simplex Herpes Zoster Human Papillomavirus Molluscum Contagiosum Oral Hairy Leukoplakia Progressive Multifocal Leukoencephalopathy AIDS Dementia Complex Peripheral Neuropathy Apthous Ulcers Malabsorption Depression Diarrhea Thrombocytopenia Wasting Syndrome Idiopathic Thrombocytopenic Purpura Listeriosis Pelvic Inflammatory Disease Burkitt’s Lymphoma Immunoblastic Lymphoma Valley Fever MRSA Source: AIDS Education Global Information System
HIV - Opportunistic Infections CD4 > 500/mm3 Acute HIV Vaginal candidiasis CD4 of 200-500/mm3 Bacterial pneumonias Pulmonary tuberculosis Oral thrush (candidiasis) Oral hairy leukoplakia Herpes Zoster Kaposi’s sarcoma CD4 < 200 Candida esophagitis Toxoplasmosis Cryptococcosis Pneumocystis jiroveci pneumonia CD4 < 50 Disseminated Mycobacterium avium complex
Can HIV be cured? NO! Drugs are available to manage the disease, but HIV stays in the body forever! PROBLEM: RNA viruses mutate at a very high rate. A person with HIV under control can evolve resistance to the drug treatments. Some infected persons have several strains of HIV in their bodies.
Cures & Prevention There is no actual cure for HIV & AIDS. However there are ways you can prevent yourself from catching the virus. You can prevent yourself from getting AIDS by using contraception when having sex with people who are HIV+ and not coming in close contact with their blood. If you already have HIV you can use antiretroviral medication, which slows the progression from HIV to AIDS and keeps some people healthy for many years.
Treatment for HIV and AIDS AIDS is still incurable but treatment to prolong life available, called Anti Retroviral Treatment (ART) HIV positive person does not need ART immediately With ART, life can be prolonged substantially ART is life long, treatment adherence is the key as well as training of doctors Several countries are providing free ART to their people.
Nucleoside Reverse Transcriptase inhibitors -AZT (Zidovudine) Antiretroviral Drugs Antiretroviral medication can slow down the time of change between HIV and AIDS. Nucleoside Reverse Transcriptase inhibitors -AZT (Zidovudine) Non-Nucleoside Transcriptase inhibitors -Viramune (Nevirapine) Protease inhibitors -Norvir (Ritonavir)
Transmission
How is HIV Spread? ANY type of sexual activity (highest risk) Sharing used drug needles Blood transfusions Mother to baby during pregnancy or birth Breast feeding (mother to baby) Sharing razors- if blood is present Kissing- if even the smallest amount of blood is present. (-membranes of mouth are thin enough for HIV to enter straight into the body.) Tattoos/body piercing if equipment is not clean.
The Risk of HIV Transmission is dependent on: The concentration of HIV in the infected fluid. The QUANTITY of fluid introduced into the Body. The ACCESS of the infected fluid to the T4 cell.
Body Fluids with High Concentrations of HIV (&High risk of transmission) Semen Blood & Blood components Menstrual Flow Vaginal Secretions Pre-Ejaculatory Fluid Breast Milk Cerebral Spinal Fluid Body Fluids with Low Concentrations of HIV (& Low risk of transmission) Pus Saliva Tears Urine Feces Vomit Nasal Mucous
HIV is not transmitted by Coughing, sneezing Insect bites Touching, hugging Water, food Kissing Public baths Handshakes Work or school contact Using telephones Sharing cups, glasses, plates, or other utensils
Confidential Testing Person’s name is recorded along with HIV results Name and positive results are reported to the State Department and the Centers for Disease Control and Prevention Results issued only to test recipient
Enzyme-Linked Immunosorbent Assay (ELISA) Or Enzyme Immunoassay (EIA) Blood Detection Tests Enzyme-Linked Immunosorbent Assay (ELISA) Or Enzyme Immunoassay (EIA) Radio Immunoprecipitation Assay (RIP) Indirect Fluorescent Antibody Assay (IFA) Polymerase Chain Reaction (PCR) Western Blot Confirmatory test
Urine Testing Urine Western Blot As sensitive as testing blood Safe way to screen for HIV Can cause false positives in certain people at high risk for HIV
Oral Testing Orasure The only FDA approved HIV antibody. As accurate as blood testing Draws blood-derived fluids from the gum tissue. NOT A SALIVA TEST!
Think about it… A person can be contagious for more than 10 years before any sign of the disease is apparent. HIV becomes AIDS when the number of immune cells drops below a predetermined number. No one dies from HIV or AIDS; people die from secondary infections (ranging from the common cold to cancer)