A Case Study in Physiology - Essay Example

A Case Study in Physiology Case: Andy is a 30-year-old intravenous drug user. In recent months he has suffered a succession of infections, which have been difficult to shake off. In desperation, he visits his GP, who takes a blood sample and sends it to the local hospital for tests. Tasks: Four questions have been generated in relation to this above case. They are all physiology related and this essay requires to answer these four questions adequately. Question 1: 1) How could the blood sample be used to diagnose (a) human immunodeficiency virus (HIV) infection, and (b) acquired immune deficiency syndrome (AIDS)? Answer 1: (a): As per 'New York State Department of Health, 2005, guidelines, whichh are taken to be exemplary here, blood samples are to be tested for presence of human Immunodeficiency virus (HIV) either using the enzyme-linked immunosorbent assay (ELISA) or rapid testing. Positive results should be subjected to Western Blot analysis. It is notable that the subject here is a high risk patient (NIH, 2008) and NIH, 2008, recommendations advise a screening test for HIV Infection. In lieu of this the blood sample should be prepared for the initial ELISA screening test and any positive results would require the next test - the Western Blot analysis - to confirm an infection. It Is also recommended that even If this combination of tests prove negative HIV infection cannot be ruled out (it may be at primary or acute stage) as there is a latent period between the presence of the virus in the body and appearance of HIV antibodies (NIH, 2008). This latent period Is known as the 'window period' (NIH, 2008). In lieu of this, other tests to assay HIV viral load is recommended (NIH, 2008). It is also notable that positive results may also not prove HIV infection because conditions like Lyme disease, syphilis and lupus often initiate such positive results (NIH, 2008). It is also notable that most enzyme-linked immunoabsorbent assays (EIAs) target the most common form of the lentivirus - the HIV-1 group M type - and does not prove effective against the HIV-1 group N and O and HIV-2 type infections (Rambaut et al, 2004). Thus, progressive improvement is being sought to develop an EIA that works universally in detecting as many types of the viral infection as is possible. Question 2: What symptoms are associated with AIDS? Answer 2: Most people who are infected with the human immunodeficiency virus do not manifest any symptoms. Instead, often, within a few days or weeks after exposure to the virus some people develop a flu-like illness and complain of fever, headache, tiredness and enlarged lymph glands in the neck (Sharma, 2004). Thereafter, these symptoms may disappear. The initial infection does not have any overtly pathological effect on many patients. The disease may progress variously for patients from the acute stage to the chronic one for a period ranging from several months to over 10 years (Sharma, 2004). Once the disease has progressed to the most advanced stage it becomes defined as AIDS (acquired immune deficiency disease) (Sharma, 2004). AIDS is a pathological condition that becomes definable when the patient is diagnosed with less than 200 CD4+ T-cells per microlitre of blood (Sharma, 2004). The disease progressively destroys the body's ability to fight infections and certain cancers by seriously compromising its immune system (NIH, 2003). The U.S. Center for Disease Control and Prevention (CDC) defines AIDS in an adult or adolescent 13 years or above as the presence of one of 26 conditions indicative of severe immunosuppression associated with HIV infection (NIH, 2003). It is significant that, aside from common infective conditions caused by pathological agents like bacteria, virus and other groups of microbes, extremely rare pathological conditions, against which the healthy human body has adequate protection, such as Pneumocystis carinii pneumonia (PCP), Kaposi's sarcoma and disseminated infection with the Mycobacterium avium complex (MAC) (NIH, 2003) has become common after the universal prevalence of AIDS. Thus, these associative pathologies, called 'opportunistic infections' are indirectly construed as symptomatic of AIDS as the disease itself has no other definitely indicative symptoms (NIH, 2003). Physical symptoms that may also be construed as being indicative of AIDS may be as follows: cough and shortness of breath; seizures and lack of coordination; difficult or painful swallowing; mental symptoms such as confusion and forgetfulness; severe and persistent diarrhea; fever; vision loss; nausea, abdominal cramps, and vomiting; weight loss and extreme fatigue; severe headaches with neck stiffness and coma (Sharma, 2004). Question 3: How is HIV thought to cause AIDS? Answer 3: The human immunodeficiency virus type 1 and 2 evolved from two separate groups of simian immunodeficiency lentivirus (SIV). HIV-1 is most closely related to SIV.cpz, a group of lentivirus most commonly prevalent in a subspecies of chimpanzee found in equatorial western and central Africa. HIV-2, in contrast, has probably evolved from a species of sooty mangabey monkeys (Cercocebus atys) found in regions of West Africa (Rambaut et al, 2004). The SIVs have a phylogeny that seems incompatible with the evolutionary trends of host primates (Rambaut et al, 2004). There is evidence that co-divergence is a recent phenomenon with transfer among different host species of sub-species traceable within decades of present times. Since it is conjectured that such host transfers take place only among species or subspecies living in adjacent areas and among closely-related host species SIV co-divergence can be easily from host and virus phylogeny trees. It has been found, though, that such phylogenic trees are mismatched suggesting that the co-divergence is accounted for by transfer among species and subspecies existing in present times (Rambaut et al, 2004). Tapping the molecular clocks within the lentivirus it has been found that the RNA virus has mutation and substitution rates that produce a time scale within the 20th century. The HIV-1 M group viruses have evolved as recently as the 1930s (Rambaut et al, 2004). What is alarming about all this is that fast mutation and substitution rates produce innumerable recombinant and mutant varieties, even within particular HIV group strians, that defy effective therapeutic preventive and curative measures (Rambaut et al, 2004). HIV-1 has three major groups - M, N and O - with the commonly prevalent M type having 9 subtypes and 15 circulating recombinant forms (Rambaut et al, 2004). The HIV-2 type has 7 subtypes (Rambaut et al, 2004). Though both HIV 1 and 2 were once wholly transmitted through homosexual activities today both are transmitted through heterosexual activities and passed on from mother to child (Rambaut et al, 2004). HIV does affect a number of cell types In the human body but its mainstay is the CD4+ T helper lymphocyte cells of the human Immune system. The viral envelope proteins find copies on the T-cell surface and bind to them as well as to chemokine coreceptors and gradually the viral core inserts itself into the cell (Rambaut et al, 2004). Reverse transcription of the viral DNA allows import into the T-cell nucleus and integration with the cellular genomic DNA. The viral DNA takes command and copies of viral proteins are built up to create a viral prototype with viral RNAs transcripting viral DNA materials (Rambaut et al, 2004). Subsequently, the virus buds out of the destroyed or debilitated cell and escapes into the host's body, ready to infect other CD4+ T-cells (Rambaut et al, 2004). Fig. 1, p. 53,Rambaut et al, 2004, perfectly illustrates this viral life cycle. Destruction of too many such T-cell types may result in the infected person becoming classified as an AIDS victim. Question 4: What treatments for HIV/AIDS are currently used, and how are they thought to work? Answer 4: The principal strategy most retroviral drugs adopt to combat HIV Infection is to affect replication of the virus in patient's body to a point where the inherent immunosuppressive properties of the human T-cell lymphocytes can attack and contain the virus (Re et al, 2001). This preservation of the T-cell immunosuppressive properties is mostly seriously compromised by the virus' abilities to mutate. The retroviral proteases that allow the virus to replicate so fast has similarity with certain endogenous viral proteases in primates, including proteases in other species. These proteases, as in the HIV ones, are encoded by the pol gene that lies between the gag gene, that encodes structural proteins, and other genes that encode enzymes like reverse transcriptase and integrase (Dunn et al, 2002). The reverse transcriptase of the HIV virus that allows it to replicate through the intermediate DNA stage (as in Answer 3) is an error-prone enzyme that has no proof-reading function (Dunn et al, 2002). Nucleotide substitution occurs frequently and almost every round of replication is prone to such mutative forms of the virus (Dunn et al, 2002). This is probably a survival strategy of the virus that can escape host cell immunity strategies and survive. The consequent result is extreme variance in HIV-1 isolates in individuals and among individuals and high resistance to existing drugs (Dunn et al, 2002). New retroviral drug strategy for inhibiting HIV is to selectively target viral proteins exclusively without affecting the T-cell ones. One such novel anti-retroviral drug may be generated from thiopurine groups that alter the DNA-RNA substrates for HIV RNaseH, substantially inhibiting HIV replication at its early stages within introducing cytotoxicity into the host T-cells (Krynetskaia et al, 2001). There is another strategy that proves effective against both wild-type and drug-resistant HIV strains (Lau et al, 2005). In the process of HIV replication the host cell DNA damage response is essential to integrate the viral and host cell nuclear components (Lau et al, 2005). On such agent - ataxia-telangiectasia-mutated (ATM) kinase can be targeted by a small molecule KU-55933 that can inhibit this damage response agent for both wild-type and drug resistant HIV, thus sensitivising the host cell to DNA damage and cell death during viral replication and possibly inducing cellular responses to combat this and, thus, inhibit such replication. Since ATM kinase is effective only for ionised-r4adiation Induced damage and the small molecule does not affect any of the other DNA damage response agents this strategy is hoped to be successful (Lau et al, 2005). The mutative and recombinant hypervariable HIV strains do not become amenable to any suitable vaccines (Azizi et al, 2006). Vaccines targeting the gag, pol and nef gene products in macrophages that transcribe for various essential T-cell activation processes (Swingler et al, 1999) have proved ineffective, in some cases inducing patient proneness to HIV infection (Roehr, 2007). Other novel techniques include targeting mucosal immune system, including entire GI tract elements, elements that do not recover like peripheral blood elements upon treatment of HIV and cause transmission of the disease (Mehandru et al, 2006). There is a variety of therapy options but none to date has proved effective enough to produce comprehensive results. The paper believes that delving into the phylogeny of the SIVs may elicit effective information on how the RT action of the viral replication process can be more Intently targeted for complete HIV-1 and 2 therapy. Reference: Azizi, Ali, et al, Immunogenecity of a polyvalent HIV-1 candidate vaccine based on fourteen wild-type gp120 proteins in golden hamsters, BMC Immunology, 2006; 7:25. Dunn, Ben M., et al, Protein family review, Retroviral Proteases, Genome Biology 2002. http://www.niaid.nih.gov/factsheets/evidhiv.htm Krynetskaia, Natalia F., et al, Deoxythioguanosine triphosphate impairs HIV replication: a new mechanism for an old drug, The FASEB Journal, 2001; 15; 1902-1908. Lau, Alan, et al, Suppression of HIV-1 by a small molecule inhibitor of the ATM kinase, Nature Cell Biology 7; 493-500; 2005. Mehandru, Saurabh, et al, Lack of Mucosal Immune Reconstitution During Prolonged Treatment of Acute and Early HIV-1 Infection, PLoS Medicine, Dec 2006. Accessed on 11th March, 2008, at: National Institutes of Health, US Department of Health and Human Services, 2008. Accessed on 6th March, 2008, at: http://www.nlm.nih.gov/medlineplus/ency/article/003538.htm New York State Department of Health, Diagnostic, monitoring and resistance tests for HIV, May 2005, p. 12. Accessed on 6th March, 2008, at: http://www.guideline.gov/summary/summary.aspx?view_id=1&doc_id=7408 Rambaut, Andrew, et al, The Causes and Consequences of HIV Evolution, Nature Review, Genetics, Vol. 5, January 2004, p. 52-61. Re, Maria Carla, et al, Analysis of HIV-1 drug resistant mutations by line probe assay and direct sequencing in a cohort of therapy naïve HIV-1 infected Italian patients, BMC Microbiology 2001; 1:30. Roehr, Bob, Future of HIV Vaccine Research Remains Uncertain, Medscape Medical News, 2007. Accessed on 11th March, 2008, at: http://www.medscape.com/viewarticle/567505 Sharma, Sat, HIV/AIDS, Emedicine, 2004. Accessed on 6th March, 2008, at: http://www.emedicine.com/aaem/topic252.htm Swingler, S., et al, HIV-1 Nef mediates lymphocyte chemotaxis and activation by infected macrophages, Nature Medicine, 5; 997-1003 (1999). Read More