Microbiology of Urogenital System

Microbiology of Urogenital system Lecture 6 Sexually transmitted diseases In this slide we’ll cover ulcerative genital lesions, genital warts and pelvic inflammatory disease. Things that’ll be covered: • Chancroid • Syphilis • Genital herpes • Genital warts Note: anything bolded, highlighted or added in green is what the doctor emphasized, added or focused on. Ulcerative genital infections • Genital ulceration reflects a set of important STIs, most of these ulcers sharply increase the risk of sexual acquisition and shedding of HIV. • PCR testing of ulcer specimens demonstrated herpes simplex virus HSV in 62% of patients, Treponema pallidum (the cause of syphilis chancers) in 13%, and Haemophilus ducreyi (the cause of chancroid) in 12–20%. ✓ major cause of ulcers is HSV2 followed by T. pallidum (syphilitic chancers) followed by H. ducreyi (chancroids) • In Asia and Africa (developing countries), chancroid was once considered the most common type of genital ulcer, PCR testing of genital ulcers now clearly implicates genital herpes was by far the most common cause of genital ulceration. Lympho granuloma venereum: It’s caused by serotypes L1,L2,L3 of chlamydia. Other than the non-ghonococcal urethritis caused by chlamydia, some serotypes can cause LGV, which starts first as an ulcer that goes unnoticed most of the time, then the ulcer disappears and the lymph nodes enlarge (inguinal and femoral LNs) Notice how the enlargement is grooved by a tendon The most common cause of ulcerations in the genitals (HSV) Chancroids present as multiples painful ulcers Ulcerative genital infections / Genital herpes / epidemiology • Genital herpes is a common sexually transmitted disease, affecting more than 400 million persons worldwide • In the United States, nearly one in five adults (approximately 50 million persons) has HSV-2 infection, with 1 million new infections occurring each year. ✓ HSV-2 is the most common cause of genital herpes (but type one can cause it too!) ✓ HSV has a double stranded linear DNA genome, these viruses are usually characterized by: • Lifelong infection and periodic reactivation Ulcerative genital infections / Genital herpes / pathophysiology HSV manages to find a break in the skin (even microabrasions) during sexual contact and it gets inoculated into the epidermis. It starts its cytopathic effects by causing swelling and apoptosis in epidermal cells, this draws in inflammatory cells. Inflammation then ensues to cause blisters within the skin. later on the blisters rupture and lead to release of viruses, forming an ulcer behind which would heal with time. However, The story doesn’t end here … Ulcerative genital infections / Genital herpes / pathophysiology The virus would then move from the epithelial cells in the periphery (skin) through the peripheral nervous system to lay dormant within the dorsal ganglia neurons, So after causing the initial pathology within the epithelial layers, the virus would sit dormant in the peripheral NS. Very rarely, HSV can spread to the CNS causing meningitis or encephalitis. But the more common route is reactivation every once in a while within the epithelial cells and causing the same pathological presentation It’s been noted that reactivation is usually less symptomatic than the primary infection Ulcerative genital infections / Genital herpes/ signs and symptoms • A visible outbreak consists of single or clustered vesicles (a cluster of blisters) on the genitalia that rupture and ulcerate before resolving. ✓ This is the effect of epithelial damage ✓ If a genital ulcer is preceded by a blister: suspect herpes • Primary infections may cause malaise, fever, or localized adenopathy, Subsequent outbreaks are usually milder and are caused by reactivation of latent virus. • Patients with HSV-1 infection average zero to one recurrence per year, whereas HSV-2 recurs four to five times annually • Asymptomatic viral shedding is common, occurring on 10% to 20% of all days, and facilitates viral transmission. ✓ Even if the patient doesn’t have blisters or ulcers they can still be spreading it. Ulcerative genital infections / Genital herpes/ Diagnosis and treatment ✓ We previously mentioned that clinically it can be diagnosed by the presence of an ulcer preceded by a blister with a history of recurrence. • Viral culture from vesicular fluid and ulcerated lesions are useful for definitive diagnosis • PCR- based viral detection (the gold standard) is rapid and specific. And so is Viral antigen detection. ✓ The infection is lifelong, it reactivates and can’t be eradicated but: • Systemic antiviral drugs especially acyclovir, valacyclovir, and famciclovir can partially control the signs and symptoms of genital herpes when used to treat first clinical and recurrent episodes or when used as daily suppressive therapy.  These drugs do not eradicate latent virus nor affect/reduce the risk, frequency, or severity of recurrences after the drug is discontinued. • Symptomatic treatment— saline bathing, analgesia, and topical local anaesthetic agents (e.g. 5% lidocaine) ointment especially for painful micturition. Ulcerative genital infections / Chancroid • Chancroid is a sexually transmitted disease (STD) caused by the Gram negative bacterium Haemophilus ducreyi and is characterised by necrotising genital ulceration ✓ H. Ducreyi is still a leading cause of genital ulceration in developing countries • Painful, erythematous papules develop on the external genitalia then advance into pustules, and then erode into sloughy, non- indurated haemorrhagic ulcers • To treat chancroids, Single oral dose of azithromycin or ciprofloxacin and intramuscular ceftriaxone regimens offer advantages in terms of improved patient compliance. ✓ Chancroids are similar to chancres (syphilitic ulcers), but they can be differentiated by some characteristics: ✓ Chancroids are painful and they have a ragged edge whereas chancres have raised, circular edges and are painless. You start here by taking the complaint At this point the DDX includes: Chancres Chancroids Genital herpes Ulcers of LGV The patient has mistaken a papule for an ulcer • WHO recommended syndromic management for genital ulceration includes therapy for both chancroid and syphilis. Check whether it’s syphilis Genital herpes Primary syphilis Chancroid LGV Diagnostic clue Painful vesicular Painless indurated Extremely painful deep lesions → multi- border superficial ulcer ulceration, ragged edges Painless ulcer, heals within few days ‘ Groove sign’ Treatment Acyclovir Doxycycline Erythromycin Benzathine pen G Alternatives Doxycycline Tetracycline Eryhtomycin Ceftriaxone Ciprofloxacin Erythromycin azithromycin Genital warts/ etiology and epidemiology • Genital warts are a sexually transmitted infection caused by certain types of human papillomavirus (HPV) • Genital warts are a common cause of morbidity, with estimates of up to 50% of the population (US) HPV at some point in their lifetime ✓ In some cases HPV can manage to cause life long infections • 90% of cases are related to HPV subtypes 6 and 11. • HPV Subtypes 16 and 18 are associated with squamous cell carcinoma. ✓ Especially in the cervix • Women tend to be affected more than men in most settings. Genital warts/ pathophysiology  The wart goes away and the epithelial physiology is restored. However, in types associated with cancer, the virus would insert its DNA within the genome of the epithelial cells, this takes a long period of time (10-30 years) in the case of warts there’s no DNA insertion.  Within  During sexual contact We try to screen early for any changes within the epithelium of the cervix, and if the changes look malignant we should worry about cancerous transformation in the future  The virus replicates and causes the upper layers of the epithelium to keep dividing (we know that normally there’s no division as cells go to the surface). It’s a mitogenic virus. Appreciation: The clinician that discovered the HPV genome within cervical cancer patients (the association between HPV and cervical cancer) was awarded the noble prize in 2008 Hopefully in 20 years, medical students would be appreciating YOU for some grand discovery. Genital warts/ Signs and symptoms • On average, physical symptoms begin approximately 2 to 3 months after initial contact, Many studies estimate the rate of subclinical HPV infection to be as high as 40% • Within few weeks of the initial contact we can start seeing those fleshy outgrowths, around the genitals or anus • Approximately 30 percent of all warts will regress within the first four months of infection. • Significant risk factors for long-term wart persistence include host immunosuppression, infection with high-risk HPV subtypes, and an older patient age • Lesions are rarely considered to be painful; however, they are often associated with severe discomfort, burning, and pruritis and they may bleed. Genital warts/ diagnosis and prevention • Diagnosis is mostly made through clinical examination or through PCR of DNA or antigens tests to determine the type of HPV. • A vaccine known as Gardasil protects against four strains of HPV that cause cancer, and is used to prevent genital warts (against HPV 6,11,16,18) • These vaccines are most effective if given to children before they become sexually active • Pap tests, can help detect vaginal and cervical changes caused by genital warts or the early signs of cervical cancer, some advocate that it should be performed annually after the age of 21, or after one’s sexually active. ✓ A pap test is performed by opening up of the vagina, taking specimens from the cervix and examining them under the microscope to see if there’re changes within the epithelial layers. Genital warts/ treatment ✓ Imiquimod is a newer modality of therapy, it activates innate immunity by activating toll like receptor 7 and it helps in activation of adaptive immunity. ✓ podophyllotoxin, works on continuously dividing cells or viruses, (antimitotic drug) ✓ Cryotherapy: application of liquid nitrogen to the warts to help in eliminating them ✓ Trichloroacetic acid: can help in “melting” the warts 90% go on their own within 2 years If it isn’t severe Pelvic inflammatory disease (PID) • • The term pelvic inflammatory disease usually refers to infection that ascends from the cervix or vagina to involve the endometrium and/ or fallopian tubes and ovaries. Infection can extend beyond the reproductive tract to cause peritonitis or pelvic abscesses. ✓ Most of the time it’s caused by an STI like chlamydia or gonorrhea because they’re commonly asymptomatic in females and they remain in the vagina for awhile then ascend upwards to cause PID, but it can result from infections other than STIs like bacterial vaginosis. • Other than primary infections from STDs, infection can also be secondary to invasive intrauterine surgical procedures (e.g. termination of pregnancy). Rarely, infection is not related to specific sexually transmitted pathogens, and originates from another focus of infection. (the infection can originate from the peritoneum then extend to the reproductive organs) Pelvic inflammatory disease (PID) Suspect STIs Introduction of foreign pathogens, Iatrogenic infection. Slow development → suspect villains that grow slowly Pelvic inflammatory disease/ Signs and symptoms • The hallmark of the diagnosis is pelvic tenderness (cervical motion tenderness, adnexal tenderness, or uterine compression tenderness) combined with inflammation of the lower genital tract; women with pelvic inflammatory disease often have very subtle symptoms and signs • Fever can occur, but systemic manifestations are not a prominent feature of PID. • The abrupt onset of severe lower abdominal pain during or shortly after menses has been the classic symptom used to identify acute PID. • Clinical diagnosis is often imprecise and more tests are needed to confirm diagnosis. Pelvic inflammatory disease/ Diagnosis • Although laparoscopy has been considered the standard for the diagnosis of pelvic inflammatory disease, it has high interobserver variability and is invasive. ✓ Diagnostic differences among doctors observing such cases • Transcervical endometrial aspiration with histopathological findings of increased WBCs is more commonly used to confirm the diagnosis of pelvic inflammatory disease. Laparoscopy image and close-up image of same patient show sausage-shape dilated right fallopian tube (arrow) • Imaging: MRI has high sensitivity, reveals Nucleic acid thickened, fluid-filled tubes. amplification test • All patients with suspected PID should undergo cervical or vaginal NAATs for N. gonorrhoeae and C. trachomatis infection increased numbers of white cells (≥1 per vaginal epithelial cell) Pelvic inflammatory disease/ Sequalae • Infection results in fibrinous or suppurative inflammatory damage along the epithelial surface of the fallopian tubes and the peritoneal surface of the fallopian tubes and ovaries, which leads to scarring, adhesions with surrounding organs, and possibly partial or total obstruction of the fallopian tubes • This can result in long-term reproductive disability, including infertility, ectopic pregnancy, and chronic pelvic pain. Pelvic inflammatory disease/ Treatment ✓ Treatment depends mainly on eradication of the primary causative agent • The treatment of pelvic inflammatory disease is empirical and involves the use of broadspectrum combination regimens of antimicrobial agents to cover likely pathogens. To cover chlamydia we give doxycycline, Metronidazole to cover trichomoniasis or Bacteroides that cause bacterial vaginosis, ceftriaxone and other third generation cephalosporins to cover Neisseria gonorrhoea. And hopefully with antimicrobial treatment the inflammation subsides.