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Reproductive Tract Infections

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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)
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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)
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• 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)
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• 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)
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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)
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Dr. Belay R. (Asst Professor)
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• 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)
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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)
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• 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)
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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)
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• 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
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• 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
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