1.INTRODUCTION
In June 1981, the centers for The Disease Control of the United States reported that five young homosexual men in the Los Angels area had contracted Pneumocystis Carinii pneumonia( a kind of pneumonia that is particularly found in AIDS patient). 2 of the patients had died. This report signalled the begninning of an epidemic of a viral disease characterized by immunosuppression associated with opportunistic infection( an infection caused by a microrganism that does not normally produce disease in human; it occurs in persons with abnomality functioning immune system), secondary neoplasms( any abnormal growth of new tissue, benign or malignant) and neurologic mainfestation, which has come to be known as AIDS.
Though Aids was first discovered in U.S.A, AIDS has been reported from more than 163 countries around the world and an estimated 10 million people are infected worldwide. Worsestill, the pool of HIV- infected persons in Africa is large and expanding.
2.RISK GROUP AND MODE OF TRANSMISSION
Studies in the U.S.A. have retentified five groups of adults at risk for developing AIDS. The case distribution in these groups are as follows:
(1). Homosexuals or bisexual males constitute the largest group, about 60% of the reported cases. This includes 5% who were intravenuous drug as well.
(2). Intravenous drug users with no previous history of homosexuality compose the next largest group, about 23% of all patients.
(3). Hemophiliacs (the people who have inborn disease characterized by excesssive bleeding and occuring only in males) especially those who received factor VIII concentrate before 1985, about 1% of all patients.
(4).Recipents of blood and blood components who are not hemophiliacs but who received tranfusions of HIV-infected whole blood components (e.g. platelet, plasma) account for 2 %.
(5). Other high risk groups: 86% of patients acquire disease through heterosexual contacts with members of other high risk groups. 80% of children with AIDS have a HIV-infected parents and suffer from transplacental or perinatal transmission.
Thus from the preceding discussion, it should be aparent that transmission of HIV occurs under conditions that facilitate exchange of blood fluids containing the virus-infected cells. Hence, the three major routes of transmission are sexual contact , parenteral routes( ie adminstration of a substance not through the digestive system) and the passage of the virus from infected mothers to their new borns where are mainly by three routes: in the womb by transplacental spread, during delivery through a infected birth canal, and after birth by ingestion of breast milk.
3. CAUSES
It is little doubt that AIDS is caused by HIV-I, a human type C retrovirus ( RNA virus the contains the enzyme, reverse transcriptase , to replicate its RNA genome to DNA) in the same family as the animal lentivirus family. It is also closely related to HIV- II, which cause a similiar disease, primarily in Africa.
3.1 Biology of HIV-I ( please refer to fig. 1)
HIV is a retrovirus inducing immunodeficiency by destruction of target T cells. Like most C-type retrovirus, it is spherical and contains a electron-dense core surrounded by a lipid envelop derived from the host cell membrane. The virus core contains four core proteins, including p24 and p18, two strands of genomic RNA and the enzyme reverse transcriptase. Studding the envelope are two glycoprotein gp120 and gp41 and the former one is important in binding the host CD4+ molecules to cause viral infection. And the proviral genome contains several genes that are not present in the other retrovirus. Many genes such as tat and rev regulate the HIV propagation and hence may be targeted for therapy.
3.2 The Development of AIDS
There are two major targets of HIV: the immune system and the central nervous system (CNS). The effects of HIV infection on each of these will be discussed seperately.
3.2.1HIV infection of lymphocyte & Monocytes -- the immune system (fig. 2 & fig.3)
Central to the pathogenesis of AIDS is the depletion of CD4+ helper T cells. The CD4 antigen is the high affinity receptor to the gp120 protein on HIV-I. After binding to the host cell, the virus is internalized and the genome undergoes reverse transcription; the proviral DNA is then integrated in to the genome of host. Transcription or translation and viral propagation may subsequently occur only with T-cell activation (e.g. antigenic stimulation). In the absence of T-cell activation, the infection enters a latent phase.
For the infected monocytes and macrophages they are refractory to cell breakdown caused by virus and thus they either act as reservioirs for HIV or as vehicles for viral transport, expecially to the central nervous system.
In addition to T-cell depletion, there are also qualitative defects in T-cell functions with a selcetive loss of T-cell memory early in the cause of disease.
3.2.2 Central nervous system involvement by HIV
The CNS is a major target in HIV infection. This occurs predominantly, if not exclusively via monocytes. Infected monocytes circulate to the brain and are somehow activated either to release toxic cytokines directly or to recruit other nervous damaging inflammatory cells.
4. NATURAL HISTORY OF HIV INFECTION (fig. 4)
Generally, the interactions of HIV with the host immune system can be divided into 3 phase. The early ,acute phase, is characterized by the presenceof viremia(virus in the blood), a fall in CD4+ Cells and a rise of CD8+ cells. Clinically, patient may have self-limited acute illnesses with sore throat, nonspecific muscle pain and aseptic meningitis . Recovery occur within 6-12 weeks. Then the middle, chronic phase, characterized by clinical latency with low-level viral replication and a gradual decline of CD4+ counts, may last from 7 to 10 years. Patients may develop persistent generalized lymph node enlargement with no constitutional symptoms. Toward the end of this phase, fever, rash, fatigue, and viremia appear. The final, crisis phase, characterized by a rapid decline in host defenses manifested by low CD4+ counts, is also recognized as full brown AIDS which include features of loss of weight, diarrhea, opportunistic infections, spectrum of bacterial infections, secondary neoplasm and neurologic inv
olvement. With AIDS, the 5-year mortality rate is 85% and with longer intervals the rate approaches 100%. Anyone with HIV infections and CD4+ t-cell count less than 200 cells/ ul may also consider having AIDS even if no clinical features are present.
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