AIDS

Microbial DiseasesEtiology, Prevention and CureDiseases Caused By VIRUSES with Special Reference to AIDS : Microbial DiseasesEtiology, Prevention and CureDiseases Caused By VIRUSES with Special Reference to AIDS

: Epidemiology Is the study of health-event, health-characteristic, or health-determinant patterns in a society. Etiology The study of causes or origins ;the branch of medicine that deals with the causes or origins of disease. Prevention The act of preventing or hindering; obstruction of action, access, or approach. Cure Act of healing or state of being healed; restoration to health from disease, or to soundness after injury.

Introduction: : AIDS was first recognized in United States in 1981 in Los Angeles,Newyork and San Francisco when a group of patients displayed Pneumocystis carinii. Pneumonia(PCP),caused by opportunistic fungal pathogen Pneumocystis carinii and Kaposi sarcoma, an extremely rare skin tumor. A more complete evaluation of the patients showed that they had in common a mark deficiency in cellular immune responses and a significant decrease in the sub-population of T-cells that carry the CD4 marker(55KD protein found in T-lymphocytes) AIDS is the first great Pandemic of the second half of the twentieth century. The disease appears to have begun in Central Africa in early 1950s. Introduction:

AIDS - Acquired Immune Deficiency Syndrome : Etiologic agent of AIDS is Human Immunodeficiency Virus(HIV).It was discovered by Luc Montagnier(in Paris) and Robert Gallo(in Bethesda)in year 1983 from a patient suffering from lymphadenopathy. HIV belongs to the Family of human retrovirus and Sub family of Lentivirus. HIV progressively reduces the effectiveness of the immune system and leaves individuals susceptible to Opportunistic infections and Tumors. The peculiar fact of HIV is its capacity to quickly mutate. Therefore is a highly variable virus and there are many different strains of HIV, even within the body of a single infected person. At the present time HIV is classified on the bases of its genetic differences and similarities into types, groups and subtypes. HIV TYPES       There are two types of HIV :  HIV-1 and HIV-2 AIDS - Acquired Immune Deficiency Syndrome

Slide 5 : HIV-1 Virus:- is related to viruses found in chimpanzees and gorillas living in western Africa, It is the first in the class of human retroviruses and accounts for more than 95% of the world's HIV infections. Its origin can be traced back to a Simian Immunodeficiency Virus (SIV) isolated from a Chimpanzee (Cpz) sub-species,. Both HIV-1 and SIVcpz have a unique Vpu gene in their respective genomic structures. HIV-2 Viruses are largely confined to West Africa. Its closest relative is a monkey, sooty manage(Sm) SIVsm. A unique Vpx gene characterizes both viruses gene structures. However, HIV-2 and HIV-1/HIV2 co-infections have also been documented outside West Africa . HIV-1 and HIV-2 are closely related viruses with nucleotide sequence homology of 58%, 59% and 39% in the group specific antigen (Gag), Pol and Env genes encoding the viral nucleocapsid, polymerase enzymes and envelope glycoproteins, respectively. HIV-1 viruses may be further divided into groups. The HIV-1 group M viruses predominate and generally when people refer to HIV without specifying the type of virus they will be referring to HIV-1. HIV – 1 GROUPS   There are three groups of HIV based on their genetic materials  HIV-O  the"outlier"group (appears to be restricted to west-central Africa )  HIV-N   the"new" group  (discovered in 1998 in Cameroon and is extremely rare) HIV-M  the "major" group (the most common of the three)

HIV SUBTYPES : Within group M there are known to be at least nine genetically distinct subtypes (or clades) of HIV-1. These are subtypes A, B, C, D, F, G, H, J and K.    Occasionally, two viruses of different subtypes can meet in the cell of an infected person and mix together their genetic material to create a new hybrid virus (a process similar to sexual reproduction, and sometimes called "viral sex").  Many of these new strains do not survive for long, but those that infect more than one person are known as “Circulating Recombinant Forms" or CRFs.  For example, the CRF A/B is a mixture of subtypes A and B. HIV SUBTYPES

Slide 7 : SIGNS AND SYMPTOMS: The symptoms of AIDS are primarily the result of conditions that do not normally develop in individuals with healthy immune systems. Steady decline in number of the CD4+ T cells. Depression of the T4:T8 cell Ratio to less than 0.9(1.5 Normal) Functional Impairment of Monocytes and Macrophages. Decreased Natural Killer cell Activity. Allergy to recall antigens in Skin Tests. Opportunistic Infections Flourish(An opportunistic infection is an infection caused by pathogens, particularly opportunistic pathogens(bacterial, viral, fungal or protozoan) that usually do not cause disease in a healthy host, i.e. one with a healthy immune system. A compromised immune system, however, presents an "opportunity" for the pathogen to infect.)Examples Burkitt`s Lymphoma Candidiasis of Respiratory Tree/ viral (herpes simplex-1or cytomegalovirus) Crytococcal Meningitis Histoplasmosis Recurrent Pneumonia Salmonella sp.Septicemia Wasting disease, Multidrug Resistance Esophagitis(inflammation of the lining of the lower end of the esophagus (gullet or swallowing tube leading to the stomach

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Kaposi's sarcoma (KS) is the most common tumor in HIV-infected patients. The appearance of this tumor in young homosexual men in 1981 was one of the first signals of the AIDS epidemic. Caused by a gammaherpes virus called Kaposi's sarcoma-associated herpes virus (KSHV). : Kaposi's sarcoma (KS) is the most common tumor in HIV-infected patients. The appearance of this tumor in young homosexual men in 1981 was one of the first signals of the AIDS epidemic. Caused by a gammaherpes virus called Kaposi's sarcoma-associated herpes virus (KSHV).

Slide 10 : Scanning Electron Microscope of HIV-1, colored green, budding from a cultured Lymphocyte.

Etiology – Causes Of AIDS : AIDS is the ultimate clinical consequence of infection with HIV. HIV is a retrovirus that primarily infects vital organs of the human immune system such as CD4+ T cells (a subset of T cells),Macrophages and dendritic cells. It directly and indirectly destroys CD4+ T cells. Once the number of CD4+ T cells per microliter (µL) of blood drops below 200, cellular immunity is lost. HIV is transmitted through direct contact of a mucous membrane or the bloodstream with a bodily fluid containing HIV, such as blood, semen, vaginal fluid, preseminal fluid, and breast milk.  This transmission can involve Anal, Vaginal or Oral Sex, Blood transfusion, contaminated hypodermic needles, exchange between mother and baby during Pregnancy, childbirth, Breastfeeding or other exposure to one of the above bodily fluids. Etiology – Causes Of AIDS

HIV is not CONTAGIOUS and normal Social,Non Sexual Contact poses no Threat. : From 2008-2010,new cases of HIV in UNITED STATES were Heterosexual Contact(18%) Homosexual Contact (48%) Intravenous Drug Use(32%) Transfusions or Mother to Infant Transmission(2%) HIV is not CONTAGIOUS and normal Social,Non Sexual Contact poses no Threat.

Major Risk Groups(Descending Order) : Indiscriminate Homosexual/Bisexual Men Prostitutes(Sex Trade Workers) and Bisexuals Intravenous (IV)Drug Users Heterosexuals who have Intercourse with Drug Users Transfusion Patients or Hemophiliacs who must receive clotting factor preparations made from donated blood Children born of Infected Mothers People who give and receive tattoos and piercings Individuals with ulcerative STD`s example:syphilis,chancroid,genital herpes. Epidemiologically AIDS occur World-Wide, and the mortality rates from it is extremely high. Major Risk Groups(Descending Order)

Epidemiology Of AIDS : Despite recent improved access to antiretroviral treatment and care in many regions of the world, in 2007 the AIDS pandemic killed an estimated 2.1 million people, including 330,000 children. As of 2009, it is estimated that there are 33.3 million people worldwide living with HIV/AIDS, with 2.6 million new HIV infections per year and 1.8 million annual deaths due to AIDS. This has been attributed to lack of access to antiretroviral treatment in huge areas such as the continent of Africa AIDS is not homogeneous within regions, with some countries more afflicted than others. Even at the country level, there are wide variations in infection levels between different areas. The number of people infected with HIV continues to rise in most parts of the world, despite the implementation of prevention strategies. Sub-Saharan Africa being by far the worst-affected region, with an estimated 22.5 million at the end of 2007, 68% of the global total. South & South East Asia have an estimated 12% of the global total. Epidemiology Of AIDS

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HIV-AIDS In India : In 1986, the first known case of HIV was diagnosed by Dr. Suniti Solmon amongst female sex workers in Chennai. Later that year, sex workers began showing signs of this deadly disease. At that time, foreigners in India were traveling in and out of the country. It is thought that these foreigners were the ones responsible for the first infections. As per UNDP`s 2010 report, India had 2.39 million (23.95 lakh) people living with HIV at the end of 2009, up from 2.27 million (22.7 lakh) in 2008. Adult prevalence also rose from 0.29% in 2008 to 0.31% in 2009 . The adult HIV prevalence in India is declining from estimated level of 0.41% in 2000 through 0.36% in 2006 to 0.31% in 2009. Adult HIV prevalence at a national level has declined notably in many states, but variations still exist across the states. A decreasing trend is also evident in HIV prevalence among the young population of 15–24 years. The estimated number of new annual HIV infections has declined by more than 50% over the past decade HIV statistics, 2009 In 2009, the average HIV prevalence among women attending Antenatal clinics in India was 0.48%. STD clinics (3.6%), Female sex workers (5.1%), Injecting drug users (7.2%) and Men who have sex with men (7.4%). HIV-AIDS In India

Slide 18 : Government Schemes In 1986, HIV started its epidemic in India, attacking sex workers in Chennai, Tamil Nadu. Setting up HIV screening centres was the first step taken by the government to screen its citizens and the blood bank. To control the spread of the virus, the Indian government set up the National AIDS Control Programme in 1987 to co-ordinate national responses such as blood screening and health education. In 1992, the government set up the National AIDS Control Organisation (NACO) to oversee policies and prevention and control programmes relating to HIV and AIDS and the National AIDS Control Programme (NACP) for HIV prevention. The State AIDS Control Societies (SACS) was set up in 25 societies and 7 union territories to improving blood safety. Besides government bodies at the Centre and the State level, a large number of NGOs are involved in spreading information. Many international NGOs and organizations run by the United Nations are also involved in spreading information about AIDS. Some of these international NGOs are: Action Aid, AVERT, AIDS Care Education and Training (ACET), Family Health International(FHI),  International Red Cross and the Panos AIDS Programme

PEOPLE OF SUB SAHARAN REGION SUFFERING FROM AIDS…… : The sharp rise is due to a number of factors Barbarism and Forced Mismatched Blood Tranfusion,Poverty, Migratory Sex workers. High levels of rape linked to the very low status of women, rising sexually transmitted disease and Civil war. Along with ineffective leadership and the unwillingness of governments to accept the problem. Heterosexual transmission is by far the most common way of getting infected with the virus in this region. African women are being infected at a much younger age then infected men, Women and girls are at greater risk of HIV/AIDS due to gender inequality, discrimination, and stigma.  Women and girls often are unable to talk with their sexual partners about abstinence, faithfulness, and Condom use. Many face sexual or physical violence, or the threat of violence. They are often blamed for causing AIDS and other sexually transmitted infections (STIs) and shunned once they do have the disease Pregnant women have no choice but to pass the virus onto their unborn child – they just don’t have the medication to prevent it. PEOPLE OF SUB SAHARAN REGION SUFFERING FROM AIDS……

HIV Genome : HIV-1 is a Retrovirus. It contains two copies of plus single stranded RNA genome(+ssRna ).It contains Nine different genes in its 9kb RNA genome. Flanking these genes are the long Terminal Repeats (LTR),which contain regulatory element involved in gene expression. Gene Function of encoded Protein gag Nucleocapsid proteins Pol Enzymes like Reverse Transcriptase ,Protease,Integrase,Ribonuclease Env Envelope glycoprotein Vif Promotes infectivity of Viral Particle Vpu Required for efficient viral assembly and budding Vpr Weakly activates transcription of Proviral DNA Tat Strongly activates transcription of Proviral DNA Rev Allows export of unspliced and singly spliced mRNAs from nucleus Nef Increases viral replication down-regulates hot cell CD4 HIV Genome

Process of Viral Entry into Target Cell : Process of Viral Entry into Target Cell The env gene of HIV is transcribed, translated, and glycosylated to form a single polyprotein product, glycoprotein 160 (gp160), which is subsequently cleaved into glycoprotein 120 (gp120 N-terminal extracellular protein)and gp41(C-terminal transmembrane protein). These two glycoproteins non-covalently associate at the membrane surface: each subunit of the trimeric, normally hidden gp41 associates in a non-covalent manner with a trimeric spikes of gp120, thereby anchoring gp120 in the viral membrane as the outermost receptor of HIV. Steps Involved: Infection Of Target Cell/Adsorption Uncoating and Production of a Provirus/Activation of Provirus Translation: Once viral mRNA is transcribed from the DNA provirus inserted in the host genome, it is transported through the nuclear pore into the cytoplasm where it uses the host cell’s ribosome's to translate its genetic information into protein-form. Translation of viral structural proteins, glycoproteins, enzymes, and regulatory proteins is carried out in ribosome's of the infected host cell, contributing to the assembly and egress of new viral particles.

Slide 22 : ICOSAHEDRAL STRUCTURE OF HIV VIRUS

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Prevention……. : Prevention……. HIV counseling and testing are fundamental for HIV prevention. People living with HIV are less likely to transmit the virus to others if they know they are infected and if they have received counseling about safer behaviour. Risk of becoming HIV infected during sex is minimized by: Abstain from sex or delay of first sex. Be faithful to one partner or have fewer partners. Condomise, which means using Male condoms (Latex without Oil lubricants such as Petroleum jelly etc.)or Female condoms(polyurethane ,nitrile and Latex) consistently and correctly. Comprehensive sex education for young people is an essential part of HIV prevention.

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Slide 27 : There is now very strong evidence that male circumcision and Female genital cutting reduces the risk of HIV transmission from women to men by around 50%, which is enough to justify its promotion as an HIV prevention measure in some high-prevalence areas. However, studies of Circumcision and HIV suggest that the procedure does not reduce the likelihood of male-to-female transmission, and the effect on male-to-male transmission is unknown. Some sexually transmitted infections - most notably Genital herpes ,syphilis, have been found to facilitate HIV transmission during sex. Treating these other infections may therefore contribute to HIV prevention. Further research is ongoing. Needle Exchange programmes have been shown to reduce the number of new HIV infections without encouraging drug use. These programmes distribute clean needles and safely dispose of used ones, and also offer related services such as referrals to drug treatment centres and HIV testing. Needle exchanges are a necessary part of HIV prevention in any community that contains injecting drug users. The safety of medical procedures and other activities that involve contact with blood, such as Tattooing and circumcision, can be improved by routinely sterilizing equipment. Health care workers can reduce exposure to HIV by employing precautions to reduce the risk of exposure to contaminated blood. These precautions include barriers such as gloves, masks, protective eyeware or shields, and gowns or aprons which prevent exposure of the skin or mucous membranes to blood borne pathogens.

Slide 28 : Mother To Child HIV prevention A course of antiretroviral drugs given to her during pregnancy and labour as well as to her newborn baby can greatly reduce the chances of the child becoming infected. A caesarean section is an operation to deliver a baby through its mother’s abdominal wall, which reduces the baby’s exposure to its mother’s body fluids. This procedure lowers the risk of HIV transmission, but is likely to be recommended only if the mother has a high level of HIV in her blood. The World Health Organization advises mothers with HIV not to breastfeed whenever the use of replacements is acceptable, feasible, affordable, sustainable and safe. An HIV positive mother should be counselled on the risks and benefits of different infant feeding. Transfusion of infected blood and HIV infection greatly reduced by screening all blood supplies for the virus, and by heat-treating blood products where possible. Because screening is not quite 100% accurate, it is sensible to place some restrictions on who is eligible to donate, justified by epidemiological evidence Reducing the number of unnecessary transfusions also helps to minimise risk.

Cure : Cure Treatment of HIV: Antiretrovirals Antiretroviral medications have completely revolutionized the prognosis and life expectancy of those living with HIV. Antiretroviral extremely effective when taken as prescribed. Research scientists are constantly on the lookout for new ways to target the virus, and thus new Antiretrovirals are constantly being reviewed for release to the general public. Delta 32 The delta 32 mutation is a mutation that involves the deletion of 32 base pairs in the CCR5 protein that is present on the surface of macrophages, rendering the protein non-functional. Individuals who are homozygous for this mutation are therefore relatively resistant to infection by CCR5-tropic HIV. Individuals who are heterozygous for this mutation are shown to still be able to get infected with R5 tropic HIV, but their infection and overall viral replication progresses much more slowly than normal HIV positive individuals without this mutation.

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Vaccines for HIV : Vaccines for HIV Recently, an adenovirus-vector HIV vaccine candidate was tested in clinical trials and was found to actually increase recipient's susceptibility to contracting HIV. No current vaccine is available to prevent against HIV infection of any subtype. However, a vaccine is available to protect cats against Feline Leukemia Virus. There are a number of factors that cause development of an HIV vaccine to differ from the development of other classic vaccines: Classic vaccines mimic natural immunity against reinfection generally seen in individuals recovered from infection; there are almost no recovered AIDS patients. Most vaccines protect against disease, not against infection; HIV infection may remain latent for long periods before causing AIDS. Most effective vaccines are whole-killed or live-attenuated organisms; killed HIV-1 does not retain antigenicity and the use of a live retrovirus vaccine raises safety issues. Most vaccines protect against infections that are infrequently encountered; HIV may be encountered daily by individuals at high risk.

Slide 32 : Most vaccines protect against infections through mucosal surfaces of the respiratory or gastrointestinal tract; the great majority of HIV infection is through the genital tract. The epitopes of the viral envelope are more variable, those of many other viruses. Furthermore, the functionally important epitopes of the gp120 protein are masked by glycosylation,trimerisationand receptor-induced conformational changes making it difficult to block with neutralizing antibodies. The ineffectiveness of previously developed vaccines primarily stems from two related factors. First, HIV is highly mutable. Because of the virus' ability to rapidly respond to selective pressures imposed by the immune system, the population of virus in an infected individual typically evolves so that it can evade the two major arms of the adaptive immune system; humoral (antibody-mediated) and cellular (mediated by T cells) immunity. Second, HIV isolates are themselves highly variable. HIV can be categorized into multiple clades and subtypes with a high degree of genetic divergence. Therefore, the immune responses raised by any vaccine need to be broad enough to account for this variability. Any vaccine that lacks this breadth is unlikely to be effective.

THANKYOU……………. : THANKYOU…………….

Circumcision…….how cud prevent Infection : Circumcision…….how cud prevent Infection The foreskin creates a moist environment in which HIV can survive for longer in contact with the most delicate parts of the penis, and the inner surface of the foreskin contains cells that are especially vulnerable to infection by HIV. A study of Ugandan men before and after circumcision concluded that observed decreases in anaerobic bacteria may play a role in reducing the risk of HIV acquisition. Removing the foreskin also means that the skin on the head of the penis tends to become tougher and more resistant to infection. In addition, any small tears in the foreskin that occur during sex make it much easier for the virus to enter the body. The protective effect conferred by male circumcision was approximately 60% when compared with the controls. This intervention, as studied thus far, did not result in any noticeable changes in sexual behavior.