Lec#23 .pptx

Lecture #23- STD Chapter 30-Person to Person Bacterial Diseases Chlamydia Gonorrheae Syphilis Lecture Overview In this lecture we will investigate three of the commonest sexually transmitted diseases (STD) or infections (STI). Lecture Objectives After this lecture you should be able to: • descri...

Lecture #23- STD Chapter 30-Person to Person Bacterial Diseases Chlamydia Gonorrheae Syphilis Lecture Overview In this lecture we will investigate three of the commonest sexually transmitted diseases (STD) or infections (STI). Lecture Objectives After this lecture you should be able to: • describe chlamydial infections and the life cycle of this bacterium • describe gonorrhea and syphilis as well as the historical roles of these bacteria • describe the virulence factors of STD’s. Microorganisms and Concepts Chlamydia trachomatis Neisseria gonorrhea Neisseria meningitidis Treponema pallidum • obligate pathogen • elementary body and reticulate body • pathogenesis and virulence factors Sexually Transmitted Diseases • major worldwide public health problem (~300 M new cases/year) • some also transmitted by nonsexual means • some cured easily, others difficult or impossible to cure • most frequent in 15–30-year age group but also others sexually active 4 Chlamydia "Chlamydia is a very common STI spread by having unprotected vaginal, anal or oral sex. Often there are not obvious symptoms so you may not know you have it. Testing is quick, simple and painless, and it can easily treated" Chlamydia is caused by the bacterium Chlamydia trachomatis. The word chlamys is Greek for "cloak draped around the shoulder." This describes how the intracytoplasmic inclusions caused by the bacterium are "draped" around the infected cell's nucleus. Because the symptoms of the disease resemble other pathologies, chlamydia was not recognized as a sexually transmitted disease until recently. Intracellular Inclusions of C. trachomatis • obligate parasitic bacteria • distinct lineage of bacteria • small ca. 1 micron in diameter • gram- and have RNA and DNA • limited biosynthetic capabilities • 1 mB chromosome •Chlamydia is the most prevalent sexually transmitted disease in the United States. •There are roughly four million cases annually, most occurring in men and women under the age of 25. Direct and indirect costs of chlamydia (mainly costs for complications) total $24 billion a year. Life Cycle • The life cycle of C. trachomatis consists of two stages: elementary body (EB) and reticulate body (RB). • The EB is the dispersal form and is analogous to a spore. It is approximately 0.3 um in diameter and induces its own endocytosis upon exposure to target cells. • Once inside the endosome, the glycogen produced causes the elementary body to "germinate" into the vegetative form, the reticulate body (RB). • the RB divides by binary fission at 2-3 hours per generation. It has an incubation period of 7-21 days in the host. • contains no cell wall and (when stained with iodine) is detected as an inclusion in the cell. After division, the RB transforms back to the EB and is released by the cell by exocytosis. One phagolysosome usually produces 100-1000 elementary bodies. In these structures the chlamydial genome is transcribed into RNA, proteins are synthesized, and the DNA is replicated. The reticulate body divides by binary fission. Chlamydia trachomatis elementary bodies infect the columnar epithelial cells of the cervix, which often causes few or no clinical symptoms. The bacteria can ascend to infect the endometrium and the fallopian tubes, causing pelvic inflammatory disease, tubal inflammation (also known as salpingitis), scarring and occlusion, which can lead to infertility or ectopic pregnancy. The inflammatory reaction is characterized by an influx of macrophages and neutrophils and the formation of immune inductive sites in the submucosa. These inductive sites, which contain B cells, T cells, dendritic cells and macrophages, coordinate the initiation of an acquired immune response. •Symptoms in men may include discharge from the penis, burning when urinating and burning around the opening of the penis. • Many men will have no noticeable symptoms, or symptoms so mild they go unnoticed. • For women any vaginal discharge, chronic abdominal pain, bleeding between menstrual periods and low-grade fever may be later symptoms of infection. • 80% of women have no noticeable symptoms until complications set in. • treatment: tetracyclines, Doxycycline, azithromycin, erythromycin, sulfisoxazole, Amoxicillin In the past, reemergence of symptoms was blamed on continued intercourse with infected partners, a believable theory considering the infection is usually asymptomatic in men. Many times, a person treated for chlamydia will see symptoms clear up, only to reemerge later. A review published in Infection and Immunity has found the culprit: your gut. In a recent study, coauthor and Arkansas colleague Laxmi Yeruva showed in mice that azithromycin eradicated the genital infection, but not the gastrointestinal (GI) infection. Gonorrheae • The family Neisseriaceae consists of Gram-negative aerobic bacteria in the genera Neisseria, Moraxella, Kingella, and Acinetobacter. The genus Neisseria contains two important human pathogens, N. gonorrhoeae and N. meningitidis. • N. gonorrhoeae causes gonorrhea, and N. meningitidis is a significant a cause of acute bacterial meningitis. • N. gonorrhoeae infections have a high prevalence and low mortality, whereas N. meningitidis infections have a low prevalence and high mortality. 19 Infections caused by N. gonorrhoeae • The disease gonorrhea is a specific type of urethritis that, in adults, practically always involves mucous membranes of the urethra, resulting in a copious discharge of pus, more obvious in the male than the female. •The first usage of the term gonorrhea, by Galen in the second century, implied a "flow of seed". • For centuries thereafter, gonorrhea and syphilis were confused, resulting from the fact that the two diseases were often present together in infected individuals. Pus-containing discharge from the urethra of a male with an acute case of gonorrhea. Intracellar gramdiplococci Gram-stained smear of urethral discharge Note the Neisseria gonorrhoeae (gram-negative diplococci) inside the white blood cells. Neisseria gonorrhoeae is a Gram-negative coccus, 0.6 to 1.0 µm in dia., usually seen in pairs with adjacent flattened sides The organism is frequently found intracellularly in polymorphonuclear leukocytes (neutrophils) of the gonorrhea pustular exudate. Fimbriae, which play a major role in adherence, extend several micrometers from the cell surface. • Paracelsus (1530) thought that gonorrhea was an early symptom of syphilis. •The confusion was further heightened by the classic blunder of English physician John Hunter, in 1767. Hunter intentionally inoculated himself with pus from a patient with symptoms of gonorrhea and wound up giving himself syphilis! • The causative agent of gonorrhea, Neisseria gonorrhoeae, was first described by A. Neisser in 1879 in the pustular exudate of a case of gonorrhea. •The organism was grown in pure culture in 1885, and its etiological relationship to human disease was later established using human volunteers (??) in order to fulfill the experimental requirements of Koch's postulates. Pathogenesis • Gonorrhea in adults is almost invariably transmitted by sexual intercourse. • The bacteria adhere to columnar epithelial cells, penetrate them, and multiply on the basement membrane. • Adherence is mediated through fimbriae and opa (P.II) proteins. although nonspecific factors such as surface charge and hydrophobicity may play a role. Virulence Factors • Neisseria gonorrhoeae has a wide range of virulence determinants, although it does not produce any exotoxins. • The first stages of infection, involving adherence and invasion, are mediated by surface components of the "gonococci" • N. gonorrhoeae first attaches to epithelial cells by means of its fimbriae. • After initial attachment, the bacteria enter a second stage of binding mediated by the outer membrane protein P.II (also known as Opa) which is needed for tight binding and invasion of epithelial cells. • construction of a microcolony and involvement of protease that could play a role in the colonization stage. Gonorrhea… • diagnosis – culture of bacterium followed by gram stain, oxidase test, and determination of cell and colony morphology; DNA probe test • treatment, prevention, and control – antibiotic therapy • penicillin resistance common – public education, diagnosis and treatment of asymptomatic individuals, condom use, and quick diagnosis and treatment of infected individuals 29 Syphilis •Treponemes are helically coiled, corkscrew-shaped organisms 6 to 15 µm long and 0.1 to 0.2 µm wide. • Treponema pallidum subspecies pallidum is the causative agent of syphilis; sexual contact accounts for virtually all cases of the disease. •Despite the availability of effective therapy (penicillin), syphilis remains a commonly sexually transmitted disease worldwide (over 100,000 cases were reported in the United States in 1992). •Untreated syphilis can result in significant neurological and cardiovascular disease. Penile chancre of primary syphilis. Hutchinson’s incisors: oral manifestation of congenital syphilis Syphilis and history The first unquestionable epidemic of syphilis occurred in Europe at the end of the 15th century. With this first epidemic, came the first chorus of blames. Travelers were blamed, prostitutes were blamed, soldiers were blamed, and of course Columbus was blamed. The Muscuvites called syphilis the Polish sickness. The Poles called it the German sickness. By most historical accounts, it does seem that France was the likely starting point of the European epidemic. In the beginning syphilis had many names in Europe. It was called the German disease, The Naples disease, the French disease, the Italian disease, and the Spanish disease. During Charles the VIII's Italian campaign in 1495, his mercenaries returned home with this new sickness. It spread quickly and viciously. The city of Lyons became so 'contaminated' with diseased people that in March of 1496 the infected people were expelled outside of the city walls. By 1497, the disease had spread throughout France. Less then a decade later, nearly all corners of Europe were already infected as well. Oral syphilis 40 Syphilis has three stages. • (1) a painless sore may appear at the spot where the bacteria first entered the body (usually from 10 to 90 days after sexual contact with an infected person). This sore may appear around or in the vagina, on the penis, or inside the mouth or anus. • (2) The second stage occurs from 3 weeks to 3 months after the primary stage and includes flu-like symptoms and possible hair loss. Some people experience a rash on the palms of the hands and soles of the feet, as well as over the entire body. • (3)Although extremely rare, tertiary syphilis can appear 3 to 10 years or more after the first and second stages. Symptoms of this stage may include skin lesions, mental deterioration, loss of balance and vision, loss of sensation, shooting pains in the legs, and heart disease. 42 Pathogenesis • Humans are the only natural host for T. pallidum, and infection occurs through sexual contact. • organisms penetrate mucous membranes or enter minuscule breaks in the skin. Less than 10 organisms are capable of producing infection. • other target tissues include lymph nodes, skin, mucous membranes, liver, spleen, kidneys, heart, bones, joints, larynx, and eyes. It is generally believed that the motility of the organisms contributes to the invasiveness of these bacteria. Syphilis… • diagnosis – clinical history, microscopic examination, and serology • treatment, prevention, and control – antibiotic therapy most effective in early stages – public education, prompt treatment of new cases, follow-up on sources and contacts, sexual hygiene, and use of condoms 45