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Sexually transmitted infections (HIV and HPV).docx

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Natural Science
NATS 1670
Motti Anafi

HIV and AIDS: History of an Infectious Agent -Early transmission of HIV in Africa was from prostitutes to truck drives which helped the virus spread throughout the continent Brazzaville, Congo ◦ 1929 ◦ Happened when hunters killed monkey and was contaminated by its blood ◦ HIV & AIDS – Reduction of the immune system January 10, 1981, Dr. Gottlieb office @ UCLA Medical Center, Los Angeles Dr Gottlieb( immunologist) in Los Angeles met the 5 patient with HIV/AIDS . Patient was looking for a job in New York city but couldn’t get one because he has Labial herpes virus (Cold Sore) on his lips- lasted for half a year. ◦ He had no acquired immunity ◦ Helper T-cells extremely low & antibody production low ◦ 2 weeks later Michael had pneumocystis carinii ( fungal pathogen) pneumonia (PCP) ◦ In Los Angeles (1967-1978): only 2 cases of PCP in immunocompromised patients ( taking chemotherapy) 1981, Los Angeles – 5 cases of PCP ◦ All Young ◦ All Homosexual male Early 1970s: 5 cases/ a year of Kaposi’s sarcoma (KS) in elderly of Mediterranean background 1981 – 26 cases of Kaposi’s sarcoma ◦ San Francisco and New York ◦ Young ◦ Homosexual male ◦ Aggressive cancer ◦ can move to internal organs Epidemiology of a New Disease ◦ Two rare diseases: ◦ Opportunistic infection (PCP) ◦ Rare cancer (KS) ◦ Other conditions linked to immunosuppression Clusters of infected gay men Concentration within sexually interactive groups Suggests an infectious agent Sexually transmitted within the gays The original name of the disease: Gay-Related Immune Deficiency (GRID) Gaetan Dugas ◦ was a common partner to many patients ◦ Had over 2500 sexual partners ◦ All were part of the homosexual community ◦ He had slept with 250 partners per year ◦ was a flight attendant Epidemiology of a new disease Not just in the gay community ◦ Other ways of getting a similar syndrome ◦ Intravenous drug use could also get HEP from it as well, that why it’s important to use clean syringe & needles. ◦ Blood transfusions Druggies would sell their blood to hospitals in order to get money for daily fix, the blood bank was completely contaminated this way. ◦ Hemophilia A (coagulation factor VIII) The blood from blood banks and use it to isolate factor VIII to supplement for the patient who does not have enough (hemophiliacs) ◦ Female sex partners of AIDS-positive, IV drug users and hemophiliacs A New Name for the Disease: Acquired Immune Deficiency Syndrome (AIDS) AIDS Statistics (2010) Sub-Saharan Africa ◦ About 1.9 million new cases of HIV infection per year ◦ 350 000 are children ◦ 1.2 million deaths every year ◦ Approximately 23 million people are infected right now with HIV ◦ 3.1 million are children below the age of 15 ◦ Several countries in sub Saharan Africa report infection rates of 20-35% ◦ Significant decrease in life expectancy in African countries in 1995 even though there was an increase when vaccines were brought to the countries before Only part of world where females (13 million) are infected almost 20% more than males (10 million) Females are infected earlier in life (at around age 20, 1/5 of women are infected) This is because of gender power, cultural norms, and rape being highly prevalent. The "gogo" (Zoolo word for grandmother) The gogo's are left to take care of several children who have become orphans due to their parents being infected with the disease. No room in orphanage so gogo's take care of the children. Friday, 24th January, 2014. Tutorial: Most children infected with AIDS are infected via sexual activity. Anti-viral drugs given to mother and baby during and directly after birth reduces the chance of the baby being infected by 90%. However, the baby can still be infected through breast milk as anti-viral drugs cannot be given to the baby for an extended period. Low income mothers will choose to expose their babies to AIDS through breast milk rather than let them starve. January 27 monday (SIDE NOTE: above is JANUARY 22nd wednesday notes, friday january 24th hasnt been added, i cannot upload them as i was not here for the class, so if someone has them put them above this)Aids/HIV in western counties (the US as example) ◦ Over a million ppl diagnosed with aids in US since 81, At least 600 000 of them died. ◦ Estimated 1.3 million US ppl are infected & 27% are unaware of it ◦ HIV carriers are going up but aids and death from aids is going down. ◦ In US more males infected with aids but in Africa more females, and at an earlier age. How are people getting it?
Women: 75% from opposite gender sex and 25% from injections/blood Men: 67% same gender sex, 11% opposite gender sex, 14%injections, 8% ?
Gay community and aids: In US men who have sex with men (MSM) accounted for approx 2/3 of all HIV infections among men even though only about 7% identify as msm HIV in body fluid: 18000 blood, 11 000 semen, 7000 vaginal fluid, 4000 amniotic fluid, 1 saliva HIV transmission: blood to blood, unprotected sex, mother to child HIV is NOT transmitted by: physical contact, sneezing/coughing, saliva, toilet, insect bites. Safer Sex ◦ The best way to stop HIV being passed on is to use condoms during vaginal, oral or anal sex if there is any possibility that either partner could have the virus ◦ It can take only a single episode of unprotected sex (ie. not using a condom) with an infected partner for HIV to be passed on ◦ However HIV is not always passed on the first time ◦ Hence its never too late to start practicing safer sex ◦ It is never too late to get tested for the virus Drug, Alcohol and HIV ◦ Significantly reduced protection if a person is drunk or high on drugs ◦ Persons under the influence of alcohol and other recreational drugs are more likely not to use condoms or they don't use them correctly Approached to HIV Prevention ◦ Education and behavior modification ◦ Safer sex ◦ Condom » Choose your sexual partners wisely and responsibly when you can make decisions. - Avoid mixing drugs/alcohol with sex. Wednesday January 29 Diagnostic Tests for HIV ◦ If you have antibodies against HIV, it means you have previously been exposed to HIV ◦ Today: antibody tests are used for screening ◦ It's a quick process - nearly 20 minutes ◦ Old days: many people missed their positive diagnosis because they never returned for their test results -Apart from diagnosis (leading to treatment), these tests are a means of prevention as well (as people diagnosed with the infection are expected to take precaution and minimize the spread of disease) From HIV infection to AIDS There are kind of like two stage: when the infection is chronically subclinical and when infection become AIDS (Below is an explanation of what happens during the course of the disease; derived from the graph shown in class) ◦ Acute infection flu-like detected when one has infection at the chronically subclinical stage. After firs 6 months (approximately) only do antibodies against HIV develop. Before that, you can't use antibody (serology tests) to detect the disease even though the virus is transmittable during the time. ◦ Stage of Chronic infection can last very long ◦ T- Cell production is not stable (up and down) as the t-cells are being killed by HIV and then reproducing. Overall, T-cell production declines over the course of the disease. ◦ When T-cells reach the amount of 200 cell/ mm3, the person has AIDS. HIV Antibodies (serology) Tests ◦ Detect antibodies for HIV ◦ False negative results during the window period ◦ An infected person can transmit HIV to others, without their HIV infection being detectable using an antibodies test ◦ False positive- cross reaction. Not very common. ◦ Both directions of false negative and and false positive are possible ◦ Confirmation by virus tests (in detail in next section) - will guarantee your results, much more reliable. A little more expensive but worth it. Antibodies tests were common in the past but not so much now. Antibodies tests detect after some time has passed, virus test can tell right away. Sometimes people with HIV are well treated so that they get negative on the virus test. - Many cases the diagnosis of HIV is happening cause of the symptoms (which usually occur after the infection has developed into AIDS), can have certain symptoms that suggested low immunity which can suggest HIV/AIDS. About 27% ppl with HIV wont have symptoms and wont know, but usually there are symptoms to help tell ex pneumonia (PCP one), long-lasting herpes virus or other unusual conditions. ◦ Antibodies go down as immune system breaks down HIV (virus) Tests ◦ Viral Antigen Test ◦ The test detects the presence of viral proteins (these are simply in the serum and unattached to anything else) ◦ Nucleic Acid (PCR) Test ◦ Amplify and detect HIV genome sequence ◦ It is important to know the HIV status of the mom: reduces mother newborn transmission. ◦ When the child is born the child is exposed to the mothers blood and this is when the child can be infected. ◦ The mother can take certain drugs before birth and it can reduce the child from getting infected by 50%. ◦ Also as soon as the child is born, give them medication against HIV as well Mother – Newborn Transmission ◦ The transmission rate from mother to newborn is around 15-50% ◦ May occur during transplacentally route ◦ May occur during the birth process (most cases) ◦ May occur postnatally through breast milk ◦ Greatly reduced by one dose of anti HIV drugs to the mother just before giving birth and to the newborn, up to 72 hours after birth ◦ Knowing the HIV status of the mom is critical *prevention if better then having to give treatment!
- It is illegal to give HIV drugs without the permission of the mother ◦ HIV is directly related to certain types of cancer ◦ HIV mutates more than any other virus ◦ Huge amount of variability - for this reason people can't take just ONE drug, must take MANY at once Side effects of drugs: changing distribution of fat in the body, diarrhea, nausea etc. Friday. January 31 The structure of HIV: nucleic acid genome: Rna (Diploid)The virus enters the cell with several enzymes: reverse transcriptase, integrase, and protease. Protein coatLipid envelopGP120 attachment protein ◦ Drugs for AIDS Treatment ◦ Existing and potential drugs for AIDS are based on unique enzymatic activities of the HIV in HIV infected cells. ◦ Drugs can inhibit; ◦ 1. Fusion of viral cells with healthy cells ◦ 2. Integrase activity ◦ 3. Reverse transcriptase ◦ 4. Protease activity HIV flow of info: DNA >(transcription)>RNA >(translation)>Protein . This is the normal wayReverse transcriptase (RT) Is Rna>Dna.VIDEO(Missed a lot of the info): HIV enters helper T-cells by binding its gp120 to the glycoprotein CD4 of the helper T-cell. The binding to CD4 causes CCR5 to change. The virus must bind to both before entering the host cell. Reverse transcriptase creates single stranded DNA from RNA. The single stranded DNA is then picked up by host cell polymerase which forms the double stranded DNA. Due to the lack of proof reading mechanism, the DNA contains a high amount of mutation. We can try to stop the interaction between virus and co-receptor, several drugs that can bind to co-receptor and cover it so virus cant bind to it so it cant get in the cell. Sometimes the virus is enveloped and when its membrane fuses with cell membrane the virus gets in, there are drugs to stop this.. Integrase enables integration of viral dna into cellular dna. There are drugs that can inhibit the integrase which are very useful drugs.Virus is present in genome. Memory cells can stay in your system for a lifetime. When the memory cells replicate, the daughter cells will contain viral genome. That's why people with hiv have it for life because somewhere in our body, there are infected memory cells. They just haven't been activated.Virus makes mRNAs which leaves nucleus and is translated(not a good stage to make drugs against, because we will be fighting our own ribosome). A single genome codes for a long protein chain which consists of several enzymes. It is activated when the protein is separated into the corresponding enzymes. Protease is the enzyme responsible for cleaving polypeptides into functional protein. . Anti HIV chemotherapy HAART: highly active anti retroviral therapy ◦ Not only one drug against HIV. In order to use drugs against a virus which is mutated so much we need to use several drugs which stop the virus at different stages. HAART : use of drug combos. Often 2 reverse transcriptase inhibitors and 1 protease inhibitor which both are inhibitors of viral enzymes.Animation: Substates molecules bind to the active site of a molecule. Enzyme substrate- complex occurs, catalyses occur which releases the product(substrate molecule). Substrates need to fit the enzyme binding site. ◦ Competitive inhibitors: a substrate that binds to enzyme, preventing other substrates to use the enzyme. ◦ Non competitive inhibitors: a substrate that binds to allosteric sites, changing the enzyme and preventing/ slowing the enzyme from catalyzing.AZT: an inhibitor for HIV replicationAZT is similar to thymidine except difference is no OH.Acts as chain terminator. As a result, RT often will confuse Thymidine with AZT. Viral reverse transcriptase is 100 times more susceptible in inhibition by AZT than pst cellular dna polymeraseAnimations(maybe wrong, was trying to type quick):Treatment of Hiv: reverse transcriptase binds to Hiv RNA, you add azt and integrates in the dna. When azt integrates into the virus dna strand that will be the end of the dna, no more nucleotides can be added to dnaNucleotide-like competitive RT inhibitors: thymidine, azt, and 3tc. ◦ 3tc made as a drug against hiv and a modification of azt, also ended up being a drug successful against hepatitis b. works better on hep then hiv. Nevirapine: an AIDS drug Non-nucleoside Non-competitive RT inhibitors ◦ Good blocker of mother to child transmission ◦ Single dose before delivery to the mom and by 72 hours after delivery to the newborn reduced HIV transmission by 50% ◦ Combination therapy with AZT Resistance mutations are not likely to be at multiple sites Works at very low concentrations Minimal toxicity Protease Inhibitors Retrovirus: HIV Drug Design
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