Reproductive Tract Infections Dr. Belay R. (Asst. Professor) 1 Introduction • Reproductive tract infections are infections that are spread by sexual activity, especially vaginal intercourse, anal sex, and oral sex • Sexually transmitted disease (STD) refers to a recognizable disease state that has developed from an STIs (sexually transmitted infections) • STIs can be caused by a number of microorganisms that vary widely in size, life cycle, susceptibility to available treatments and the diseases and symptoms they cause Dr. Belay R. (Asst Professor) 2 Introduction… • More than 30 different bacteria, viruses and parasites are known to be transmitted through sexual contact, including vaginal, anal and oral sex • Endogenous infections are caused by an overgrowth of organisms that are normally present in the genital tract. – E.g.endogenous infection is bacterial vaginosis • Iatrogenic infections may be introduced into the reproductive tract by medical procedures – Examples of such medical procedures are dilation and curettage (D&C) or Cesarean sections Dr. Belay R. (Asst Professor) 3 Introduction… Dr. Belay R. (Asst Professor) 4 Introduction… • STIs have a profound impact on sexual and reproductive health worldwide • More than 1 million STIs are acquired every day • In 2020, WHO estimated 374 million new infections with 1 of 4 STIs: – chlamydia (129 million), gonorrhoea (82 million), syphilis (7.1 million) and trichomoniasis (156 million) Dr. Belay R. (Asst Professor) 5 Classification • STDs can be divided into two general categories, those that can be cured and those that currently cannot • curable STDs – Syphilis, chancroid, gonorrhea, chlamydial infection, and trichomoniasis are the most common • Incurable STDs are viral. – The most dangerous viral STD is human immunodeficiency virus (HIV), which leads to AIDS. – Other incurable viral STDs include human papilloma virus (HPV), hepatitis B and genital herpes • In addition, emerging outbreaks of new infections that can be acquired by sexual contact such as monkeypox, Shigella sonnei, Neisseria meningitidis, Ebola and Zika, as well as re-emergence of neglected STIs such as lymphogranuloma venereum Dr. Belay R. (Asst Professor) 6 Impact • STIs can have serious consequences beyond the immediate impact of the infection itself – STIs like herpes, gonorrhoea and syphilis can increase the risk of HIV acquisition – Mother-to-child transmission of STIs can result in stillbirth, neonatal death, low-birth weight and prematurity, sepsis, neonatal conjunctivitis and congenital deformities – HPV infection causes cervical and other cancers – Hepatitis B resulted in an estimated 820 000 deaths in 2019, mostly from cirrhosis and hepatocellular carcinoma – STIs such as gonorrhoea and chlamydia are major causes of pelvic inflammatory disease and infertility in women Dr. Belay R. (Asst Professor) 7 Syphilis • Syphilis is caused by T. pallidum, a spirochete that cannot survive for long outside the human body • T. pallidum enters through the mucous membranes or skin, reaches the regional lymph nodes within hours, and rapidly spreads throughout the body • Syphilis occurs in 3 stages: – Primary – Secondary – Tertiary • There are long latent periods between the stages • Infected people are contagious during the first 2 stages Dr. Belay R. (Asst Professor) 8 • Infection is usually transmitted by – sexual contact (including genital, orogenital, and anogenital) – by skin contact or transplacentally, causing congenital syphilis • Infection does not lead to immunity against reinfection • After an incubation period of 3 to 4 weeks (range 1 to 13 weeks), Dr. Belay R. (Asst Professor) 9 Primary syphilis • Primary lesion (chancre) develops at the site of inoculation • Chancres can occur anywhere but are most common on the following: – Penis, anus, and rectum in men – Vulva, cervix, rectum, and perineum in women – Lips or mouth • The chancre usually heals in 3 to 12 weeks. Then, people appear to be completely healthy Dr. Belay R. (Asst Professor) 10 Secondary syphilis • Symptoms typically begin 6 to 12 weeks after the chancre appears – Fever, loss of appetite, nausea, and fatigue are common • Condyloma lata are hypertrophic, flattened, dull pink or gray papules at mucocutaneous junctions and in moist areas of the skin (eg, in the perianal area, under the breasts) • Syphilitic dermatitis lesions are round, often scale, and may coalesce to produce larger lesions in palms and soles • Secondary syphilis can affect many other organs – lymphadenopathy, hepatosplenomegaly, eyes (uveitis), bones (periostitis), joints, meninges, kidneys (glomerulitis), liver (hepatitis), or spleen Dr. Belay R. (Asst Professor) 11 Dr. Belay R. (Asst Professor) 12 Late or tertiary syphilis • About one third of untreated people develop late syphilis, although not until years to decades after the initial infection • Lesions may be clinically classified as – Benign tertiary syphilis – Cardiovascular syphilis – Neurosyphilis • Benign tertiary gummatous syphilis usually develops within 3 to 10 years of infection and may involve the skin, bones, and internal organs. • Gummas are soft, destructive, inflammatory masses that are typically localized but may diffusely infiltrate an organ or tissue; they grow and heal slowly and leave scars Dr. Belay R. (Asst Professor) 13 Dr. Belay R. (Asst Professor) 14 Diagnosis of Syphilis • Tests include serologic tests for syphilis (STS), which consist of – Screening (a reaginic, or nontreponemal) tests – Confirmatory (treponemal) tests – Darkfield microscopy • Serologic reaginic tests (rapid plasma reagin [RPR] or Venereal Disease Research Laboratory [VDRL]) for screening blood and diagnosing central nervous system infections • Serologic treponemal tests (eg, fluorescent treponemal antibody absorption or microhemagglutination assay for antibodies to T. pallidum) Dr. Belay R. (Asst Professor) 15 Treatment of Syphilis – Benzathine penicillin G for most infections – Aqueous penicillin for ocular syphilis or neurosyphilis – Treatment of sex partners • The treatment of choice in all stages of syphilis and during pregnancy is – The sustained-release penicillin benzathine penicillin (Bicillin L-A) • Jarisch-Herxheimer reaction – Starts generally during the first 24 hours of antibiotic treatment – Increase in temperature, decrease in blood pressure; rigors, leukopenia – May occur during treatment of any of the spirochete diseases • Prevention:- benzathine penicillin is given to contacts; no vaccine is available. Dr. Belay R. (Asst Professor) 16 Chancroid • Chancroid is infection of the genital skin or mucous membranes caused by Haemophilus ducreyi – characterized by papules, painful ulcers, and enlargement of the inguinal lymph nodes leading to suppuration • Chancroid is a rare sexually transmitted infection (STI) in the US and other resource-rich countries, occurring primarily in occasional, local epidemics • Chancroid is a common cause of genital ulcers in resource-poor areas of Asia, Africa, and the Caribbean • Like other STIs causing genital ulcers, chancroid increases risk of HIV transmission Dr. Belay R. (Asst Professor) 17 • After an incubation period of 3 to 7 days, small, painful papules appear on the genitals and rapidly break down into shallow, soft, painful ulcers with ragged, undermined edges (ie, with overhanging tissue) and a red border • Deeper erosion occasionally leads to marked tissue destruction • Slow to heal without treatment • The inguinal lymph nodes form a bubo (enlarged and tender group of regional lymph nodes) Dr. Belay R. (Asst Professor) 18 • Diagnosis of Chancroid – History and physical examination – Sometimes culture • H. ducreyi is a small, fastidious, gram-negative rod that requires an enriched growth medium containing hemin and usually serum for successful cultivation (Chocolate agar) • Incubated at 33° to 35°C in high humidity with CO2 enrichment – polymerase chain reaction (PCR) • Treatment of Chancroid – A single-dose of azithromycin 1 g orally or ceftriaxone 250 mg IM – Erythromycin 500 mg orally 3 times a day for 7 days – Ciprofloxacin 500 mg orally twice a day for 3 days Dr. Belay R. (Asst Professor) 19 Gonorrhea • N. gonorrhoeae is a gram-negative diplococcus that occurs only in humans and is almost always transmitted by sexual contact • Urethral and cervical infections are most common, but infection in the pharynx or rectum can occur after oral or anal intercourse, and conjunctivitis may follow contamination of the eye • Dissemination to skin and joints, which is uncommon, causes sores on the skin, fever, and migratory polyarthritis or pauciarticular septic arthritis • Neonates can acquire conjunctival infection (Ophthalmia neonatorum) during passage through the birth canal (rapidly leads to blindness if untreated) Dr. Belay R. (Asst Professor) 20 • About 10 to 20% of infected women and very few infected men are asymptomatic • Male urethritis has an incubation period from 2 to 14 days – Onset is usually marked by mild discomfort in the urethra, followed by more severe penile tenderness and pain, dysuria, and a purulent discharge • Pelvic inflammatory disease may include salpingitis, pelvic peritonitis, and pelvic abscesses and may cause lower abdominal discomfort (typically bilateral), dyspareunia, and marked tenderness on palpation of the abdomen, adnexa, or cervix • Cervicitis usually has an incubation period of > 10 days – Symptoms range from mild to severe and include dysuria and vaginal discharge Dr. Belay R. (Asst Professor) 21 purulent discharge Dr. Belay R. (Asst Professor) 22 • Diagnosis of Gonorrhea – Gram stain is sensitive and specific for gonorrhea in men with urethral discharge; gram-negative intracellular diplococci typically are seen – Culture using chocolate agar or Thayer-Martin Medium – Nucleic acid amplification tests (NAATs) may be done on genital, rectal, or oral swabs and can detect both gonorrhea and chlamydial infection • Treatment of Gonorrhea – Uncomplicated gonococcal infection : A single dose of ceftriaxone 500 mg IM (1 g IM for patients weighing ≥ 150 kg) – Concomitant treatment for chlamydial infection – Treatment of sex partners • Prevention – Adult forms: no vaccine; condoms – Neonatal: silver nitrate or erythromycin ointment in eyes at birth Dr. Belay R. (Asst Professor) 23 Fig:- Colonies of Neisseria gonorrhoeae on chocolate (A) and blood agar plates (B) after a 2-day incubation Dr. Belay R. (Asst Professor) 24 Chlamydiae • Chlamydiae are obligate intracellular bacteria – C. trachomatis, C. psittaci, C. pneumoniae • Chlamydia alternates between two morphological forms, the elementary body (EB) and the reticulate body (RB) • Sexually transmitted urethritis, cervicitis, proctitis, and pharyngitis (that are not due to gonorrhea) are caused predominantly by chlamydiae and less frequently by mycoplasmas • Chlamydiae may also cause salpingitis, epididymitis, perihepatitis, neonatal conjunctivitis, and infant pneumonia • Chlamydia trachomatis causes – lymphogranuloma venereum – about 50% of nongonococcal urethritis cases – most cases of mucopurulent cervicitis Dr. Belay R. (Asst Professor) 25 • Men develop symptomatic urethritis after a 7- to 28-day incubation period, usually beginning with mild dysuria, discomfort in the urethra, and a clear to mucopurulent discharge • Women are usually asymptomatic, although vaginal discharge, dysuria, increased urinary frequency and urgency, pelvic pain, dyspareunia, and symptoms of urethritis may occur – Cervicitis with yellow, mucopurulent exudate and cervical ectopy (expansion of the red endocervical epithelium onto the vaginal surfaces of the cervix) are characteristic • Chlamydiae may be transferred to the eye, causing acute conjunctivitis • Infants born to women with chlamydial cervicitis may develop chlamydial pneumonia or ophthalmia neonatorum (neonatal conjunctivitis) Dr. Belay R. (Asst Professor) 26 Dr. Belay R. (Asst Professor) 27 • LGV is caused by serotypes L1, L2, and L3 of the bacteria Chlamydia trachomatis. They can invade and reproduce in regional lymph nodes • Lymphogranuloma venereum occurs in 3 stages. – The 1st stage begins after an incubation period of about 3 days with a small skin lesion at the site of entry – The 2nd stage usually begins in men after about 2 to 4 weeks, with the inguinal lymph nodes on one or both sides enlarging and forming large, tender, sometimes fluctuant masses or abscesses (buboes) – In the 3rd stage, lesions heal with scarring, but sinus tracts can persist or recur Dr. Belay R. (Asst Professor) 28 Dr. Belay R. (Asst Professor) 29 • Diagnosis of Chlamydia – Nucleic acid–based tests of cervical, urethral, pharyngeal, or rectal exudate or urine – Chlamydial or mycoplasmal infection is suspected in patients with symptoms of urethritis, salpingitis, cervicitis, or unexplained proctitis, but similar symptoms can also result from gonococcal infection. • Treatment of Chlamydia – Oral antibiotics (preferably azithromycin) – Empiric treatment for gonorrhea if it has not been excluded – Treatment of sex partners Dr. Belay R. (Asst Professor) 30 Trichomoniasis • Trichomoniasis is infection of the vagina or male genital tract with Trichomonas vaginalis. It can be asymptomatic or cause urethritis, vaginitis, or occasionally cystitis, epididymitis, or prostatitis. • Trichomonas vaginalis is a flagellated, sexually transmitted protozoan • Coinfection with gonorrhea and other sexually transmitted infections (STIs) is common Dr. Belay R. (Asst Professor) 31 • In women, range from none to copious, yellow-green, frothy vaginal discharge with a fishy odor, and soreness of the vulva and perineum, dyspareunia, and dysuria • Men are usually asymptomatic; however, sometimes urethritis results in a discharge that may be transient, frothy, or purulent Dr. Belay R. (Asst Professor) 32 • Diagnosis of Trichomoniasis – Wet-mount microscopic examination for flagella – Vaginal testing with nucleic acid amplification tests (NAATs) – rapid-antigen dipstick tests – Culture of urine or urethral swabs from men • Treatment of Trichomoniasis – Oral metronidazole or tinidazole – Treatment of sex partners Dr. Belay R. (Asst Professor) 33 Human papillomavirus (HPV) • HPV consists of a family of small, double-stranded DNA viruses that infect the epithelium. • More than 200 distinct types have been identified; they are differentiated by their genomic sequence. • Virtually all cervical cancer is caused by HPV – about 70% is caused by types 16 and 18 – many of the rest result from types 31, 33, 45, 52, and 58 Dr. Belay R. (Asst Professor) 34 • Most of the > 100 subtypes infect cutaneous epithelium and cause skin warts • some types infect mucosal epithelium and cause anogenital warts – Condylomata acuminata are benign anogenital warts • Some types that infect mucosal epithelium can lead to anogenital or oropharyngeal cancer Dr. Belay R. (Asst Professor) 35 • In men, warts occur most commonly under the foreskin, on the coronal sulcus, within the urethral meatus, and on the penile shaft – They may occur around the anus and in the rectum, especially in men who have sex with men • In women, warts occur most commonly on the vulva, vaginal wall, cervix, and perineum; the urethra and anal region may be affected • HPV types 16 and 18 usually cause endocervical or anal intraepithelial lesions that are difficult to see Dr. Belay R. (Asst Professor) 36 Dr. Belay R. (Asst Professor) 37 • Diagnosis of HPV Infection – Physical examination – HPV testing: Nucleic acid amplification tests (NAATs) for oncogenic HPV subtypes are used as part of routine cervical cancer screening in women – Cervical cytology (Pap smear test) – Vinegar (acetic acid) solution test. A vinegar solution applied to HPV infected genital areas turns them white • Treatment of HPV Infection – Cytodestructive therapy or excision (eg, by caustics/(eg, trichloroacetic acid/, cryotherapy, electrocauterization, laser, or surgical excision) – Topical medications (eg, with antimitotics/eg, podophyllotoxin, podophyllin, 5-fluorouracil or interferon inducers/eg, interferon alfa2b, interferon alfa-n3) – No treatment of anogenital warts is completely satisfactory, and relapses are frequent and require retreatment Dr. Belay R. (Asst Professor) 38 Pap smear Dr. Belay R. (Asst Professor) 39 Human immunodeficiency virus (HIV) • HIV infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cellmediated immunity • Initial infection may cause nonspecific febrile illness. Risk of subsequent manifestations—related to immunodeficiency—is proportional to the level of CD4+ lymphocyte depletion • HIV can directly damage the brain, gonads, kidneys, and heart, causing cognitive impairment, hypogonadism, renal insufficiency, and cardiomyopathy • Manifestations range from asymptomatic carriage to acquired immune deficiency syndrome (AIDS), which is defined by serious opportunistic infections or cancers or a CD4 count of < 200/mcL Dr. Belay R. (Asst Professor) 40 • HIV-1 causes most HIV infections worldwide, but HIV-2 causes a substantial proportion of infections in parts of West Africa • In some areas of West Africa, both viruses are prevalent and may coinfect patients • HIV-2 appears to be less virulent than HIV-1 • The normal CD4 count is about 750/mcL, and immunity is minimally affected if the count is > 350/mcL – If the count drops below about 200/mcL, loss of cell-mediated immunity allows a variety of opportunistic pathogens to reactivate from latent states and cause clinical disease • WHO estimates that in 2019, about 38 million people, including 1.8 million children (< 15 years), were living with HIV worldwide Dr. Belay R. (Asst Professor) 41 • AIDS is defined as one or more of the following: – HIV infection that leads to any of certain AIDS-defining illnesses – A CD4+ T lymphocyte (helper cell) count of < 200/mcL – A CD4+ cell percentage of ≤ 14% of the total lymphocyte count • AIDS-defining illnesses are – Serious opportunistic infections – Certain cancers (eg, Kaposi sarcoma, non-Hodgkin lymphoma) to which defective cell-mediated immunity predisposes – Neurologic dysfunction Dr. Belay R. (Asst Professor) 42 • Transmission is usually – Sexual: Direct transmission through sexual intercourse – Needle- or instrument-related: Sharing of blood-contaminated needles or exposure to contaminated instruments – Maternal: Childbirth or breastfeeding – Transfusion- or transplant-related • HIV attaches to and penetrates host T cells via CD4+ molecules and chemokine receptors (see figure below HIV life cycle). After attachment, HIV RNA and several HIVencoded enzymes are released into the host cell • In moderate to heavy HIV infection, about 108 to 109 virions are created and removed daily Dr. Belay R. (Asst Professor) 43 Life cycle of HIV Dr. Belay R. (Asst Professor) 44 • Initial HIV infection – Initially, primary HIV infection may be asymptomatic or cause transient nonspecific symptoms (acute retroviral syndrome) • include fever, malaise, fatigue, several types of dermatitis, sore throat, arthralgias, generalized lymphadenopathy, and septic meningitis. • Worsening HIV infection – When the CD4 count drops to < 200/mcL, nonspecific symptoms may worsen and a succession of AIDSdefining illnesses develop Dr. Belay R. (Asst Professor) 45 • There are three stages of HIV infection: • Acute HIV Infection – Acute HIV infection is the earliest stage of HIV infection, and it generally develops within 2 to 4 weeks after infection with HIV. – During this time, some people have flu-like symptoms, such as fever, headache, and rash. – In the acute stage of infection, HIV multiplies rapidly and spreads throughout the body. – The virus attacks and destroys the infection-fighting CD4 cells (CD4 T lymphocyte) of the immune system. – During the acute HIV infection stage, the level of HIV in the blood is very high, which greatly increases the risk of HIV transmission Dr. Belay R. (Asst Professor) 46 • Chronic HIV Infection – The second stage of HIV infection is chronic HIV infection (also called asymptomatic HIV infection or clinical latency). – During this stage, HIV continues to multiply in the body but at very low levels. – People with chronic HIV infection may not have any HIVrelated symptoms. – Without ART, chronic HIV infection usually advances to AIDS in 10 years or longer, though in some people it may advance faster. – People who are taking ART may be in this stage for several decades. Dr. Belay R. (Asst Professor) 47 • AIDS – AIDS is the final, most severe stage of HIV infection. – Because HIV has severely damaged the immune system, the body cannot fight off opportunistic infections – Opportunistic infections are infections and infectionrelated cancers that occur more frequently or are more severe in people with weakened immune systems than in people with healthy immune systems – People with HIV are diagnosed with AIDS if they have a CD4 count of less than 200 cells/mm3 or if they have certain opportunistic infections Dr. Belay R. (Asst Professor) 48 WHO clinical stages of HIV/AIDS • Stage 1 – Patients who are asymptomatic or have persistent generalized lymphadenopathy (lymphadenopathy of at least two sites [not including inguinal] for longer than 6 months) • Stage 2 (mildly symptomatic stage) – unexplained weight loss of less than 10 percent of total body weight and recurrent respiratory infections (such as sinusitis, bronchitis, otitis media, and pharyngitis), as well as a range of dermatological conditions including herpes zoster flares, angular cheilitis, recurrent oral ulcerations, papular pruritic eruptions, seborrhoeic dermatitis, and fungal nail infections Dr. Belay R. (Asst Professor) 49 • Stage 3 (the moderately symptomatic stage) – weight loss of greater than 10 percent of total body weight, prolonged (more than 1 month) unexplained diarrhea, pulmonary tuberculosis, and severe systemic bacterial infections including pneumonia, pyelonephritis, empyema, pyomyositis, meningitis, bone and joint infections, and bacteremia – Mucocutaneous conditions, including recurrent oral candidiasis, oral hairy leukoplakia, and acute necrotizing ulcerative stomatitis, gingivitis, or periodontitis • Stage 4 (the severely symptomatic stage) – includes all of the AIDS-defining illnesses – Clinical manifestations for stage 4 disease that allow presumptive diagnosis of AIDS to be made based on clinical findings alone are: • HIV wasting syndrome, Pneumocystis pneumonia (PCP), recurrent severe or radiological bacterial pneumonia, extrapulmonary tuberculosis, • HIV encephalopathy, CNS toxoplasmosis, chronic (more than 1 month) or orolabial herpes simplex infection, esophageal candidiasis, and Kaposi’s sarcoma Dr. Belay R. (Asst Professor) 50 Dr. Belay R. (Asst Professor) 51 Diagnosis of HIV Infection • Diagnosis of HIV Infection – HIV antibody testing with or without HIV P24 antigen tests (ELISA, Western blot…) • Newer point-of-care tests using blood or saliva (eg, particle agglutination, immunoconcentration, immunochromatography) can be done quickly and simply, allowing testing in a variety of settings and immediate reporting to patients. – Nucleic acid amplification assays to determine HIV RNA level (viral load) Dr. Belay R. (Asst Professor) 52 Treatment of HIV Infection • Treatment – Combinations of antiretroviral drugs (antiretroviral therapy [ART], sometimes called highly active ART [HAART] or combined ART [cART]) – Chemoprophylaxis for opportunistic infections in patients at high risk • ART aims to – Reduce the plasma HIV RNA level to undetectable (ie, < 20 to 50 copies/mL) – Restore the CD4 count to a normal level (immune restoration or reconstitution) Dr. Belay R. (Asst Professor) 53 • Two drugs from one class, plus a third drug from a second class, are typically used • The classes of anti-HIV drugs include:• Non-nucleoside reverse transcriptase inhibitors (NNRTIs) turn off a protein needed by HIV to make copies of itself – Examples include efavirenz (Sustiva), rilpivirine (Edurant) and doravirine (Pifeltro). • Nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) are faulty versions of the building blocks that HIV needs to make copies of itself – Examples include abacavir (Ziagen), tenofovir disoproxil fumarate (Viread), emtricitabine (Emtriva), lamivudine (Epivir) and zidovudine (Retrovir). – Combination drugs also are available, such as emtricitabine/tenofovir disoproxil fumarate (Truvada) and emtricitabine/tenofovir alafenamide fumarate (Descovy). Dr. Belay R. (Asst Professor) 54 • Protease inhibitors (PIs) inactivate HIV protease, another protein that HIV needs to make copies of itself – Examples include atazanavir (Reyataz), darunavir (Prezista) and lopinavir/ritonavir (Kaletra) • Integrase inhibitors work by disabling a protein called integrase, which HIV uses to insert its genetic material into CD4 T cells – Examples include bictegravir sodium/emtricitabine/tenofovir alafenamide fumarate (Biktarvy), raltegravir (Isentress), dolutegravir (Tivicay) and cabotegravir (Vocabria) • Entry or fusion inhibitors block HIV's entry into CD4 T cells. – Examples include enfuvirtide (Fuzeon) and maraviroc (Selzentry) Dr. Belay R. (Asst Professor) 55 Herpes simplex viruses • Eight types of herpesviruses infect humans, two of which are herpes simplex viruses (HSV) • HSV is double stranded DNA virus • Both types of herpes simplex virus, HSV-1 and HSV-2, can cause oral or genital infection • Most often, HSV-1 causes gingivostomatitis, herpes labialis, and herpes keratitis • HSV-2 usually causes genital lesions • Transmission results from close personal contact (i.e., kissing, sexual contact) • After the initial infection, HSV remains dormant in nerve ganglia, from which it can periodically emerge, causing symptoms Dr. Belay R. (Asst Professor) 56 • Diseases include – Mucocutaneous infection (most common), including genital herpes – Ocular infection (including herpes keratitis) – Central nervous system (CNS) infection – Neonatal herpes • Eczema herpeticum is a complication of HSV infection in which severe herpetic disease develops in skin regions with eczema • HSV outbreaks may be followed by erythema multiforme • Herpetic whitlow, a swollen, painful, erythematous lesion of the finger, results from inoculation of HSV through the skin and is most common among health care practitioners Dr. Belay R. (Asst Professor) 57 Fig:- Genital herpes Dr. Belay R. (Asst Professor) 58 • Diagnosis of Herpes Simplex Virus – Clinical evaluation – Sometimes laboratory confirmation – Polymerase chain reaction (PCR) of cerebrospinal fluid (CSF) and MRI for HSV encephalitis • Laboratory confirmation can be helpful – A Tzanck test (a superficial scraping from the base of a freshly ruptured vesicle stained with Wright-Giemsa stain) often reveals multinucleate giant cells in HSV or varicella-zoster virus infection • Treatment of Herpes Simplex Virus – Usually acyclovir, valacyclovir, or famciclovir – For keratitis, topical trifluridine (typically in consultation with an ophthalmologist) Dr. Belay R. (Asst Professor) 59 Viral hepatitis • Acute viral hepatitis is a common, worldwide disease that has different causes; each type shares clinical, biochemical, and morphologic features • The term acute viral hepatitis often refers to infection of the liver by one of the hepatitis viruses • At least 5 specific viruses appear to be responsible for acute viral hepatitis: – – – – – Hepatitis A (HAV) Hepatitis B (HBV) Hepatitis C (HCV) Hepatitis D (HDV) Hepatitis E (HEV) Dr. Belay R. (Asst Professor) 60 • Blood and other body fluids (eg, saliva, semen) of patients with acute HBV and HCV infection and stool of patients with HAV infection are considered infectious • HBV and HCV are double stranded DNA virus that causes cirrhosis and hepatocellular carcinoma which is fatal • Some manifestations of acute hepatitis are virus-specific, but in general, acute infection tends to develop in predictable phases: – Incubation period: The virus multiplies and spreads without causing symptoms – Prodromal (pre-icteric) phase: Nonspecific symptoms occur; they include profound anorexia, malaise, nausea and vomiting – Icteric phase: After 3 to 10 days, the urine darkens, followed by jaundice • The liver is usually enlarged and tender, but the edge of the liver remains soft and smooth • Mild splenomegaly occurs in 15 to 20% of patients • Jaundice usually peaks within 1 to 2 weeks – Recovery phase: During this 2- to 4-week period, jaundice fades Dr. Belay R. (Asst Professor) 61 Dr. Belay R. (Asst Professor) 62 Dr. Belay R. (Asst Professor) 63 Dr. Belay R. (Asst Professor) 64 Dr. Belay R. (Asst Professor) 65 Dr. Belay R. (Asst Professor) 66 • Diagnosis of Acute Viral Hepatitis – Liver tests (aspartate aminotransferase [AST] and alanine aminotransferase [ALT] elevated out of proportion to alkaline phosphatase, usually with hyperbilirubinemia) – Viral serologic testing e.g. HBsAg test • Treatment – chronic hepatitis B:- entecavir (Baraclude), tenofovir (Viread), lamivudine (Epivir), adefovir (Hepsera) and telbivudine – Hepatitis C is treated using direct-acting antiviral (DAA) tablets:- a combination of ledipasvir and sofosbuvira combination of ombitasvir, paritaprevir and ritonavir, taken with or without dasabuvira combination of elbasvir and grazoprevir…etc • Immunoprophylaxis – Immunoprophylaxis can involve active immunization using vaccines and passive immunization – Vaccines for hepatitis A and hepatitis B are available Dr. Belay R. (Asst Professor) 67