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The first indication of new disease – Acquired Immunodificiency Syndrom (AIDS) began in the summer of 1979, when reports came from great city of USA (New York, Los Angeles, San Francisco) of a sudden increase in the incidence of two very rare diseases Kaposi's sarcoma (before registrated only at elderly Africans) and Pneumocystis carinii pneumonia (before described as epidemics at the closed children’s establishments) in young adults who were homosexuals or addicted to heroin or other injected narcotics. They appeared to have lost their immnune competence, rendering them vulnerable to overwhelming and fatal infections with relatively avirulent microorganisms, as well as to lymphoid and other malignancies.
Statistics Every day in the world infect with HIV 14.000people, about 6.000 – young men and women 15 - 24 years old. • The latest statistics on the world epidemic(UNAIDS/WHO) - 2005 • People living with HIV/AIDS 36,6 million • Adults living with HIV/AIDS 36,3 million • Women living with HIV/AIDS 17,3million • Children living with HIV/AIDS 2,3 million • New infections with HIV/AIDS 4,1 million • AIDS deaths in 2005 2,8 million
HIV: A Global Pandemic Eastern Europe & Central Asia 1.2 – 1.8 million Western Europe 520 000 – 680 000 North America 790 000 – 1.2 million East Asia & Pacific 700 000 – 1.3 million North Africa & Middle East 470 000 – 730 000 South & South-East Asia 4.6 – 8.2 million Caribbean 350 000 – 590 000 Sub-Saharan Africa 25.0 – 28.2 million Latin America 1.3 – 1.9 million Australia & New Zealand 12 000 – 18 000 Adults and children estimated to be living with HIV/AIDS (2003): 34 – 46 million total
Further statistics • 48% of adults living HIV/AIDS are women and 59% in the Sub-Saharan Africa • 24,5 million of adults and children living with HIV is in the Sub-Saharan Africa • Although the Sub-Saharan has just over 10% of the worlds population but it is close to two thirds of those who live with HIV/AIDS
NOTE: • More than 25 million people died of AIDS since 1981 and AFRICA has more than 12 million orphans
HIV, the etiologjcal agent of AIDS, belongs to the lentivirus subgroup of the family Retroviridae. The lentivirus subgroup (L. lentus = slow) includes the causative agents of the slow virus diseases visna/maedi in sheep and others. Besides HIV, the related animal immunodeficiency viruses also are assigned to this group.
Types of HIV Virus • HIV 1 • Most common in sub-Saharan Africa and throughout the world • Groups M, N, and O • Pandemic dominated by Group M • Group M comprised of subtypes A - J • HIV 2 • Most often found in West Central Africa, parts of Europe and India
Viral genes and antigens. The genome of HIV contains the three structural genes (gag, pol and env) characteristic of all retroviruses, as well as other nonstructural and regulatory genes specific for the virus. The products of these genes, both structural and nonstructural, act as antigens. Sera of infected persons contain antibodies to them. Detection of these antigenes and antibodies is ofgreat value in the diagnosis and prognosis of HIV infections.
Virus travels through Bloodstream HIV attacks t-cells Killer t-cells destroy affected cells AIDS virus attaches to a CD4 receptor Transcription Reverse Transcription Proteins cut and packaged with RNA Possible Infections Budding new viruses
The pathogenesis of AIDS is dependent on the biology of HIV, e.g: 'Trojan horse' mechanism - virus escapes recognition by replication inside monocytes, from where it can spread to other tissues and other hosts. Latency - Lentiviruses do not show true latency (unlike Herpes viruses or lambda) but do have the capacity to control the expression of their genome by means of virus-encoded trans-acting regulatory proteins (tat and rev). Antigenic variation - new variants continually arise. In other Lentiviruses such as CAEV, each new antigenic variant results in a flare up of disease. May also occur in HIV and contribute to decline of immune system - 'ratcheting' mechanism due to increasing virus load?
Some of the immune abnormalities in HIV infection include: Altered cytokine expression Decreased CTL and NK cell function Decreased humoral and proliferative response to antigens and mitogens Decreased MHC-II expression Decreased monocyte chemotaxis Depletion of CD4+ cells Impaired DTH reactions Lymphopenia Polyclonal B-cell activation It is not clear how much of the pathology of AIDS is directly due to the virus and how much is caused by the immune system itself. There are numerous models which have been suggested to explain how HIV causes immune deficiency:
Evolution of Antibodies Window Period
Window Period • Time from initial infection with HIV until antibodies are detected by a single test • Usually 3-8 weeks before antibodies are detected • May test false-negative for HIV antibodies during this time period • Can still pass the virus to others during this period
Disease Progression • Severity of illness is determined by amount of virus in the body (increasing viral load) and the degree of immune suppression (decreasing CD4+ counts) • As the CD4 count declines, the immune function decreases.
-blood -semen -vaginal fluid -breast milk What body fluids transmit HIV?
ACQUIRED DEFICIENCY SYNDICOME (AIDS) Clinical features of HIVinfection. AIDS is only the last stage in the divide spectrum of clinica features in HIV infection. The natural evolution of HIV infection can be considered in the following stages: I. Acute HIV infection. Within a few weeks of infection with HIV, about 10-15 per cent of persons experience low grade fever, malaise, headache, 1ymphadenopathy, sometimes with rash and arthropathy resembling glandular fever.
2. Asymptomatic infection. All persons infected with HIV, whether they experience seroconversion illness or not, pass through a phase of symptom1ess infection; lasting for several months or years. They show positive HIV antibody tests during this phase and are infectious. In some, the infection may not progress any further, while in others it may lead to full brown AIDS, either directly or through cytopenias, minor opportunistic infection, persistent generalised lympnadenopathy or AIDS related complex (ARC) as described below.
3. Persistant Generalised Liphadenopathy (PGL). This has been defined as the presence of enlarged lymph nodes, at least 1,0 cm, in diameter, in two or more noncontiguous extrainguinal sites, that persist for at least three months, in the absence of any current illness or medication that may cause lymphadenopathy. This by itself is benign but a proportion of the cases may progress to ARC or AIDS.
4. AIDS Related Complex (ARC). This group inc1udes patients with considerable immunodeficiency, suffering from various constitutional symptoms or having minor opportunistic infections. The typical constitutional symptoms are fatigue, unexplained fever, persistent diarrhea and parked weight loss of more than 10 per cent of body weight. The common opportunistic infections are oral candidiasis, herpes zoster, salmonellosis or tuberculosis. Generalized lyrnphadenopathy and splenomegaly are usually present. ARC patients are usually severely ill and many of them progress to AIDS in a few months.
5. AIDS. This is the end stage disease representing the irreversible breakdown of immune defense mechanisms, leaving the patient a prey to progressive opportunistic infections and malignancies. The clinical severity of AIDS varies with the type of infection or malignancy present. In early AIDS, many patients are ill only during episodes of infection which may respond to treatment. Between episodes they may be relatively well and able to resume normal life.
WHO HIV/AIDS Classification System Stage I Asymptomatic Stage II Minor Symptoms Stage III Moderate Symptoms Stage IV AIDS
According to the system most affected patients present with various complaints, some of which are as follows: A. The commonest presentation is with increasing dry cough, dyspnea and fever. In the USA and other Western countries, the characteristic pathogen initially was P. carinii but now M. tuberculosis or an atypical mycobacterium such as M. avium-intracellulare is more often responsible. In the developing countries, the most important pathogen is M. tuberculosis, with many strains being multidrug resistant. In fact the poor nations are facing a double epidemic, jointly with HIV and tuberculosis. Pneumonia may be viral (CMV) or fungal (cryptococcus, histoplasma). Recurrent pneumonia is considered to be indicative of AIDS.
B. Gastrointestinal system. The mouth is often involved in AIDS, with thrush, herpetic stomatitis, gingivitis, Kaposi's sarcoma. Dysphagia may be due to esophageal candidiasis. A characteristic intestinal pathogen in AIDS is cryptosporidium. Salmonellae, mycobacteria, CMV or adenoviruses also frequently cause intestinal infections. Systemic strongyloidosis may occur. Chronic colitis is common in male homosexuals («gay bowel syndrome»), from which ameba, lamblia and a host of diarrheagenic bacteria have been reported.
Central nervous system: The typical CNS opportunistic infections are toxoplasmosis and cryptococcosis. Infections are also seen with CMV, herpes simplex, papovaviruses, mycobacteria, aspergillus and Candida. Lymphomas of the central nervous system are common. D. Malignancies: Kaposi's sarcoma is the characteristic lesion seen in male homosexuals. It is an indolent multifocal nonmetastasising is mucosal or cutaneous tumor, probably of endothelial origin. The other tumors commonly seen are lymphomas, both the Hodgkin and non Hodgkin types.
