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Aids Aids Presentation Transcript

  • INTRODUCTION  First indication came in 1981 from New York and LA,of a sudden outbreak of two very rare diseases, Kaposi sarcoma and Pneumocystis carini pneumonia in young adults who were homosexuals or addicted to injected narcotics. This condition was named AIDS.  Discovered independently by Luc Montagnier of France and Robert Gallo of the US in 1983-84  AIDS in India was 1st detected in commercial sex workers in Tamil Nadu in 1986& has been growing very fast since then.  Causative agent- Human Immunodeficiency Virus(HIV), lentivirus subgroup of family retroviridae.  AIDS is a global pandemic  2007-33.2 million individuals living with AIDS
  • ROUTES OF TRANSMISSION  Sexual route  IV drug use  Mother to baby  Body fluids
  • HUMAN IMMUNODEFICIENCY VIRUS    Icosehadral(20 sided) enveloped virus 90-120 nm in size Outer icosehedral shell and a inner core enclosing RNAs
  •  2 genetically different but related forms of HIV-HIV1 and HIV 2  HIV 2 more common in India  On basis of genetic analysis,HIV 1 can be subdivided into 3 subgroups-M(major).O(outlier),N(neither)  Group M most common worldwide  M further divided into subtypes A to K.  Clade C is the fastest spreading worldwide.
  • THE HIV GENOME Structural genes-gag, pol, env  Nonstructural genes and regulatory genes tat (transactivating gene)  nef (negative effector gene)  rev (regulator of virus gene)  vif (viral infectivity factor gene)  vpu (viral protein U)  vpr (viral protein R)  LTR (long terminal repeat) 
  • PATHOGENESIS Two major targets of HIV-immune system and central nervous system  Profound cell mediated immunodeficiency is the hallmark  Mainly affects CD4+Tcells,dendritic cells and macrophages.  Enters body through mucosal tissues and blood--infects T cells,dendritic cells and macrophages--infection establishes in lymphoid organs---virus remains latent ----active viral replication associated with infection 
  • In addition to direct killing of CD4+T cells,other mechanisms are:  HIV cause progressive architectural and cellular destruction of lymph nodes  Chronic activation of uninfected cells leads to activation induced cell death  Loss of precursors of CD4+ T cells  Fusion of infected and uninfected cells-leads to balloning and cell death  Apoptosis of uninfected CD4+T cells by binding of soluble gp120 to CD4 molecule—activation through T cell receptorby antigens
  • INFECTION OF NON T CELLS  Macrophages  HIV1 can infect and multiply in terminally differentiated macrophages They are reservoirs of infection  Dendritic cells   Mucosal dendritic cells transport to regional lymph nodes Follicular ones are potent reservoir  B cells   Polyclonal activation ---germinal centre B cell hyperplasia, BM plasmacytosis, hypergammaglobulinimia, formation of circulating immune complexes
  • MAJOR ABNORMALITIES OF IMMUNE SYSTEM  Decreased T cell function:  Preferential loss of activated and memory T cells Decreased delayed type hypersensitivity Susceptibility to opportunistic infection Susceptibility to neoplasm  Polyclonal B cell activation :     Hypergammaglobulinimia,circulating immune complexes Inability to mount immune response to new antigens  Altered monocyte/macrophage function:     Decreased chemotaxis and phagocytosis Decrease class II MHC expression Diminished capacity to present antigen to T cells
  • T CE
  • CDC CLASSIFICATION CATEGORIES OF HIV Clinical categories 1 ≥500cells/μl 2 200-499cells/μl 3 ≤200cells/μl A.asymptomatic,acute HIV,persistent generalized lymphadenopathy A1 A2 A3 B.Symptomatic ,not A or C B1 B2 B3 C.AIDS indicator conditions
  • AIDS DEFINING OPPORTUNISTIC INFECTION AND NEOPLASMS  Protozoal and helminthic infection  Cryptosporidiosis Toxoplasmosis  Fungal infection   Pneumocystosis Candidiasis Cryptococcosis Coccidioidomycosis Histoplasmosis  Bacterial infections      Mycobacteriosis Nocardiosis  Viral infections      Cytomegalovirus HSV Varicella zoster Progressive multifocal leukoencephalopathy
  • NEOPLASMS  Kaposi’s sarcoma  Non-hodgkin B cell lymphoma  Cervical cancer in women  Anal cancer in men 25-40% of HIV patients develop malignancy
  • EXPANDED WHO CASE DEFINITION FOR AIDS An adult or adolescent(>12yrs) is considered to have AIDS if a test for HIV Ab gives +ve result,and one or more of the following conditions are present  ≥10% body wt loss or cachexia with diarrhoea or fever or both,intermittent or constant,for atleast 1 month,not known to be due to a condition unrelated to HIV infection  Cryptococcal meningitis  Pulmonary/extrapulmonary TB  Kaposi’s sarcoma  Neurological impairment  Candidiasis of esophagus  Clinically diagnosed life threatening or recurrent episodes of pneumonia with or without etiological confirmation  Invasive cervical cancer
  • LABORATORY INVESTIGATIONS  Hematological investigations- anaemia of chronic disease,neutropenia,lymphopenia(CD4+Tcell),thromb ocytopenia.Raised ESR.  p/s: atypical lymphocytes having a plasmacytoid appearance.  CD4+:CD8+T cells- ratio is reversed  Hypergammaglobulinemia : IgG & IgA levels raised  Lymph node biopsy -follicular hyperplasia  CSF- lymphocytic pleocytosis
  • HIV POSITIVITY  The presence of antibodies against HIV in human body is termed HIV positivity & the person is called HIV positive  It takes 6-12 weeks after infection for antibodies to rise to detectable levels.  So,there is a window period during which infected person may transmit the infection despite being seronegative.  During this window period p24 antigen capture assays are useful
  • LABORATORY DIAGNOSIS OF HIV INFECTION  Methods utilized to detect:  Antibody  Antigen  Viral nucleic acid  Virus in culture
  • ELISA  Antibodies detected in ELISA include those directed against: p24, gp120, gp160 and gp41, detected first in infection and appear in most individuals Standard blood screening test  Sensitivity->99.5%   4th generation EIA test combine detection of Abs to HIV with detection of p24 Ag for HIV  False positive EIA-  Abs to class II Ag  Auto antibodies  Hepatic disease  Recent influenza  Acute viral infections  So EIA confirmed by western blot, p24 Ag capture assay or HIV RNA tests.
  • WESTERN BLOT  Most popular confirmatory test  The following antigens must be present: p17, p24, p31, gp41, p51, p55, p66, gp120 and gp160.  Antibodies to gp31, gp41, gp 120, and gp160 appear later but are present throughout all stages of the disease.  Advantage-multiple antigens elicit production of specific antibodies and can be detected as discrete bands on western blot
  • Interpretation of results. No bands, negative. In order to be interpreted as positive a minimum of 3 bands directed against the following antigens must be present: p24, p31, gp41 or gp120/160. CDC criteria require 2 bands of the following: p24, gp41 or gp120/160
  • INDIRECT IMMUNOFLOURESCENCE  Can be used to detect both virus and antibody to it.  Antibody detected by testing patient serum against antigen applied to a slide, incubated, washed and a fluorescent antibody added.  Virus is detected by fixing patient cells to slide, incubating with antibody.
  • P24 ANTIGEN CAPTURE ASSAY  The p24-antigen screening assay is an EIA performed on serum or plasma.  P24 antigen only present for short time, disappears when antibody to p24 appears.  Greatest use as a screening test for persons suspected to have acute HIV syndrome.  Test not recommended for routine screening as appearance and rate of rise are unpredictable.  Sensitivity lower than ELISA.
  •  Most useful for the following:  early infection suspected in seronegative patient  newborns  CSF  monitoring disease progress
  • CD4+ T CELL COUNT  Most widely used predictor of HIV progression.  Risk of progression to an AIDS opportunistic infection or malignancy is high with CD4+T cell<200 cells/mcl  Percentage may be more reliable than CD4 count  Risk of progression to an AIDS opportunistic infection or malignancy is high with percentage <20% in absence of treatment
  •  Routine blood donor screening is done by nucleic acid testing.  3 assays are used where measurement of anti HIV Ab may be misleading—  RT-PCR  Branched DNA  Nucleic acid sequence based amplification (NASBA)  USE-  Diagnosis  Initial prognosis  Determining need for therapy  Monitoring effects of therapy
  • VIRUS ISOLATION  Virus isolation can be used to definitively diagnose HIV.  Best sample is peripheral blood, but can use CSF, saliva, cervical secretions, semen, tears or material from organ biopsy.  Cell growth in culture is stimulated, amplifies number of cells releasing virus.  Cultures incubated one month, infection confirmed by detecting reverse transcriptase or p24 antigen in supernatant
  • VIRAL LOAD TEST       Viral load or viral burden is the quantity of HIV-RNA that is in the blood. RNA is the genetic material of HIV that contains information to make more virus. Viral load tests measure the amount of HIV-RNA in one milliliter of blood. Take 2 measurements 2-3 weeks apart to determine baseline. Repeat every 3-6 months in conjunction with CD4 counts to monitor viral load and T-cell count. Repeat 4-6 weeks after starting or changing antiretroviral therapy to determine effect on viral load.
  • TESTING OF NEONATES  Difficult due to presence of maternal IgG antibodies.  Use tests to detect IgM or IgA antibodies, IgM lacks sensitivity, IgA more promising.  Measurement of p24 antigen.  PCR testing may be helpful but still not detecting antigen soon enough: 38 days to 6 months to be positive
  • TESTING IN PREGNANT MOTHER  Screening to be done in 1st trimester of pregnancy  Maternal IgG crosses placenta & persists in infant blood for 15 standard EIA HIV serologic tests cannot be used to diagnose infection in infant  IgM & IgA in infants are assayed (but not reliable in 1st 3 mths after birth)  HIV DNA PCR- diagnostic at 1 mth of age
  • TREATMENT  Antiretroviral drugs target-protease,integrase,reverse transcriptase.  Highly active anti retroviral therapy( HAART )  Four approved classes of drugs in the HAART regimens  Nucleoside and nucleotide reverse transcriptase inhibitors  Non-nucleoside reverse transcriptase inhibitors  Protease inhibitors  Fusion inhibitors Major causes of morbidity are-cancer,accelerated cardiovascular diseases,kidney diseases and liver diseases.
  • PREVENTION  Monogamous Relationship  Protected Sex  Sterile needles  Proper screening of blood products before transfusion