Lecture 17 INTRO-STD and Chlamydia-ELMS

Lecture 17 INTRO-STD and Chlamydia-ELMS - What is a...

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Unformatted text preview: What is a Sexually Transmitted Disease (STD)? Disease Diseases you can get by having sex – vaginal, oral, or anal – with someone who is already infected. Caused by bacteria, viruses, fungi or protozoa that are spread through blood, semen, and vaginal fluids. Also, spread simply by touching infected skin for certain STDs, like herpes and genital warts. STD Facts STD Estimated Annual Cases 1 out of 4 people between ages 15 and 55 will contract an STD. 2/3 of all STD cases occur in ages 25 or younger. 333 Million Worldwide ~16 Million new cases in the United States this year alone Common STDs Common Estimated U.S. Annual Incidences Human Papilloma Virus Trichomoniasis (protozoal pathogen) 6,500,000 Chlamydia Herpes Gonorrhea Hepatitis B Syphilis HIV Total 5,000,000 3,000,000 1,000,000 650,000 77,000 70,000 40,000 16,337,000 Most common sexually transmitted infection About 40 HPV types Causes genital warts and cervical cancer Condoms do not completely protect ~50% of all men or women acquire HPV at some time in their lives Most people do NOT develop symptoms after infection Treatment for warts available Prevention in women by HPV vaccine!! HPV HPV Genital Herpes: Overview Genital Caused by Herpes Simplex Viruses Both symptomatic & asymptomatic infections are common Asymptomatic shedding is well documented Genital Herpes Genital About 1/5 of adult Americans have HSV 2 Most do not recognize or get symptoms New type­specific blood tests can accurately diagnose HSV 2 infection even when no symptoms are present Treatment to control symptoms and lessen the chance of transmission are available Most dangerous cases involve babies infected during delivery (C­section to avoid infection) Genital Herpes Genital Transmission υ Major routes: sexual & mother­to­infant Most sexual transmission probably occurs when index case is asymptomatic υ Genital Herpes Genital Treatment Options Treatment of symptoms (blisters) Suppression of symptoms by daily medication Vaccine in development Daily medication to lessen chance of transmission Experimental drugs HIV: etiologic agent (cause) of AIDS HIV: Frequency of occurrence: Pandemic: >100 million worldwide inf. Reservoir: HIV-infected people Transmission: Direct: sexual contacts, childbirth, blood transfusions Indirect: via fomites (non­living objects involved in spread of infection) e.g. contaminated syringes Mechanism of Path.: kills TH cells HIV: Mechanism of Pathogenesis HIV: Mechanism of Pathogenesis HIV kills TH cells Depleted Immune System Infections by Microbial Pathogens Bacteria Fungi Viruses Protozoa Why is HIV so devastating? Why is HIV so devastating? 1. 2. 3. 4. The host cells are crucial to the immune response generally responsible for fighting viral infections The virus genome “hides” as a provirus within the host cell The virus genome mutates readily making treatment a challenge The only host is humans making research a challenge . 10 Reverse Transcriptase Inhibitors Nucleotide analogs Non-nucleotide RT inhibitors Protease Inhibitors Anti­HIV Drugs Anti­HIV Drugs HIV Inhibitors of HIV Protease Block Viral Replication by Preventing Cleavage of gag Polyprotein. Cleavage gag ‘polyprotein’ Protease Inhibitor HIV protease inactive RT Inhibitors HIV Protease Inhibitors HAART Combinations of RT Inhibitors Combinations and Protease Inhibitors and 10 - 16 pills / day → "one a day" 10 Adverse side-effects >$10,000 per year Anti­HIV Drugs Anti­HIV Drugs HAART drug cocktails have helped to lengthen asymptomatic stage & prolong life of HIV-infected individuals HAART in U.S. Chlamydia Infections Chlamydia Most common reportable disease in the U.S. Estimated 3million cases annually caused by bacterium Chlamydia trachomatis Most infections are asymptomatic Leading cause of preventable infertility in women Direct and indirect costs estimated at $1.7 billion annually Babies exposed to C. trachomatis in the birth canal during delivery may develop an eye infection or pneumonia Incidence is highest among sexually active adolescents and young adults Chlamydia Rates: U. S., 1984– Chlamydia 2002 Rate (per 100,000 population) 300 240 180 120 60 0 1984 86 88 90 92 94 96 98 2000 02 Almost 3% of college age women will get a chlamydial infection each year. chlamydial Gonorrhea Gonorrhea Caused by Neisseria gonorrhoeae Overall rates falling, but incidence in certain groups remains high Most common in young adults and adolescents Chlamydia trachomatis co­infection with gonorrhea cases remains at about 40% Cofactor for HIV infection Resistance to medication is an spreading problem Gonorrhea Rates: U.S. 1970–2002 and the Healthy People 2010 objective objective Rate (per 100,000 population) 500 400 300 200 100 0 1970 73 76 79 82 85 88 91 94 97 2000 Gonorrhea 2010 Objective Note: The Healthy People 2010 objective for gonorrhea is 19.0 cases per 100,000 population. Syphilis Syphilis Incidence had been steadily declining in the Incidence U.S. since 1990 U.S. 28 U.S. counties account for 50% of the 28 reported cases reported In 1999, the CDC initiated a nation-wide In Syphilis Elimination Effort, targeting these areas areas Chlamydiaceae Lecture 17 Classification Classification Family Genera Species Chlamydiaceae Chlamydia Chlamydophila C. trachomatis C. pneumoniae C. psittaci General Characteristics General Characteristics Very small (<0.45um) Gram­neg. rod No peptidoglycan cell wall (Penicillin Resistance!!) Strict intracellular growth!! Unique developmental cycle (EB­RB) LPS and outer membrane proteins for serum ID Energy parasites C. psittaci C. psittaci Zoonotic disease (birds) Human infections Rare (mostly professionals handling birds) and if so mostly benign In some cases severe disease may develop ­fever, chills, vomiting, diarrhea, (persist for more than 2 weeks without improvement) ­encephalitis, high fever, death if untreated Tetracyclines and macrolides (not Penicillin) C. pneumoniae C. pneumoniae Strict human pathogen ~200,000 cases of pneumonia annually (in adults) Most cases are mild Tetracyclines or macrolides (~2 weeks) Epidemiology C.trachomatis ~ 500 million infections in underdeveloped countries 7­9million people blind/yr In USA most common STD (~900,000 reported cases per year) Chlamydia — Rates: United States, Chlamydia — Rates: United States, 1984–2004 Rate (per 100,000 population) 350 280 210 140 70 0 1984 86 88 90 92 94 96 98 2000 02 04 Note: As of January 2000, all 50 states and the District of Columbia had regulations requiring the reporting of chlamydia cases. Epidemiology Epidemiology USA MMWR Oct 2010 Epidemiology Epidemiology Transmission Can be transmitted via vaginal , anal or oral sex Eye­hand­eye transmission of eye infections Clinical Manifestation “Silent Epidemic” Urogenital Infections: Urogenital Infections: 80% women asymptomatic Most infections in men a symptomatic ­but up to 25% may remain asymptomatic Clinical Manifestation In Women: ­vaginal discharge or bleeding ­abdominal cramps ­painful urination, intercourse ­fever In Men: ­discharge (white, watery) from penis ­painful urination ­swollen testicles ­fever Clinical Manifestation “Silent Epidemic” Untreated infections may lead to: Untreated infections may lead to: In women: Pelvic Inflammatory disease (PID): ­generic term for infection of uterus, fallopian tubes and/or ovaries ­can cause scarring of tissues and thus lead to infertility ­250,000­500,000 cases of PID per year in USA Clinical Manifestation “Silent Epidemic” Untreated infections may lead to: Untreated infections may lead to: In men: Epididymitis (inflammation of epididymis of testicles): ­can lead to sterility ­250,000 cases of epididymitis per year in USA Clinical Manifestation Clinical Manifestation Conjunctivitis: Adult: caused by strain associated with STD, may lead to chronic infection, blindness Neonatal: woman carrier, exposure at birth, eyelids swell, purulent discharge, (up to 12month), blindness Clinical Manifestation Clinical Manifestation Ocular Trachoma: Chronic, inflammatory process of eye surface, ulceration,eyelids turn inward scarring, blindness Transmitted via infectious droplets (eye­hand­ eye) Treatment/Prevention Treatment/Prevention Ocular and genital infections: Tetracyclines Neonatal conjunctivitis or pneumonia: Macrolides No vaccine available Safe sex practice Screening of sexually active women (to detect asymptomatic infections) Prompt treatment helps spread disease George Gray : HeLa cell line ~1950 (Johns Hopkins University) Laboratory diagnosis Laboratory diagnosis No culture media or plate media available! Use of specific human cell line for intracellular growth (e.g. HeLa); followed by iodine staining for inclusion bodies Stain bacteria with antibodies (Immunofluorescence, ELISA) Use molecular biology techniques (DNA­ probes/ PCR) biochemical tests serology Lifecycle of Chlamydia Bacteria exist in two forms (“Lifecycle”) Bacteria exist in two forms (“Lifecycle”) Elementary Body (EB): ­metabolically inactive, extra­and intracellular, infectious (adhesins) Reticulate Body (RB): ­metabolically active, intracellular, non­ infectious Chlamydia infected cell Chlamydia infected cell Lifecycle of Chlamydia Lifecycle of Chlamydia Diff. into RB Inside cell “Zipper”­like induced phagocytosis •TTSS •Tarp Pathogenesis Pathogenesis Pathogenesis mechanisms little understood (no animal model, no genetic tools, no in vitro growth) Inhibit phagosome­lysosome fusion (outer membrane protein/lipid?) Inhibit host cell death (programmed cell death=apoptosis) Cell Death: Apoptosis vs. Necrosis Cell Death: Apoptosis vs. Necrosis NECROSIS APOPTOSIS/ Programmed Cell death Apoptosis Pathways Caspase Independent Lysosome mediated Caspase Dependent EXTRINSIC Death Receptor (Fas; TNF­R1) (Intracell. Stress; Cytokine deprivation) INTRINSIC Mitochondria Lysosomal stress Lysosomes Cathepsin B Cathepsin D Generalized proteolysis Receptor Ligation Intracellular stress Caspase-8 Caspase-3/6/7 Caspase-9 APOPTOSIS How to die How to die Chlamydia mediated inhibition of Chlamydia mediated inhibition of host cell apoptosis ...
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