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🌱 來自: Huppert’s Notes
Sexually Transmitted Infections (STIs)🚧 施工中
Sexually Transmitted Infections (STIs)
Chlamydia & gonorrhea
• Pathogens: Chlamydia trachomatis & Neisseria gonorrhoeae. Most common bacterial STIs
• Clinical features: Purulent urethral discharge, scrotal pain or pelvic pain, dysuria, intermenstrual bleeding
• Diagnosis:
- Vaginal or urinary nucleic acid amplification test (NAAT)
- Obtain pharyngeal and/or rectal swabs for NAAT in patients with a history of oral sex or receptive anal intercourse
• Treatment:
- Chlamydia: Azithromycin (1000 mg oral dose) alone
- Gonorrhea: ceftriaxone 250 mg IM ×1 + 1000 mg azithromycin
- Sexual partners should be referred for evaluation and presumptive therapy
Disseminated gonococcal infection (DGI)
• Pathophysiology: A systemic infection caused by N. gonorrhoeae that develops when genital infection spreads to the blood stream
• Clinical features: There are two classic clinical syndromes of DGI:
- Tenosynovitis, dermatitis, and polyarthralgias. A pustular or vesiculopustular rash is present in about ~75% of cases, but the absence of a rash does not rule out DGI.
- Acute, purulent arthritis of one or multiple joints. Common joints = wrists, knees, ankles.
• Diagnosis:
- Blood cultures may return positive for N. gonorrhoeae
- Positive NAAT testing of mucosal sites (genitals, rectum, or oropharynx)
- Synovial fluid analysis (in patients with an acute arthritis)
• Treatment:
- Ceftriaxone 1 g IV daily in all patients + azithromycin 1 g PO ×1 +/– surgical joint drainage in patients with an acute arthritis who are not responding to therapy
Herpes simplex virus (HSV)
• Subtypes:
- HSV-1 (oropharynx or genital ulcers): Adults are often asymptomatic with HSV-1 primary infection, but the virus can remain dormant in the trigeminal ganglia and later reactivate to cause lesions near the mouth/lips (grouped vesicles on an erythematous base). Treatment: Acyclovir.
- HSV-2 (recurrent genital ulcers): Painful genital ulcers, prodrome burning/pruritus, lymphadenopathy. Treatment: Acyclovir (chronic suppressive therapy if ≥6 outbreaks/yr or to prevent transmission to a seronegative partner, or episodic therapy for those with fewer outbreaks)
• Complications**:**
- Disseminated HSV: Can cause encephalitis, meningitis, keratitis, and chorioretinitis, typically in immunocompromised individuals
- Ocular disease: HSV-1 or HSV-2 can cause keratitis, blepharitis, keratoconjunctivitis
- Herpetic whitlow: HSV-1 or HSV-2 on the hand, which causes a throbbing pain in the distal pulp space
• Diagnosis: PCR (most sensitive, if available) or viral culture
Syphilis (T. pallidum spirochete)
• Microbiology & pathogenesis:
- A slender spirochete with rotary-type movements. Can be seen with darkfield microscopy.
- Transmission of syphilis occurs due to direct contact with an open lesion (chancre or condyloma lata) infected with organisms during intercourse or other physical or sexual contact.
- During initial infection, two paradoxical events happen:
• The host immune response controls the local infection, leading to resolution of the chancre. During this time, antibodies to T. pallidum develop and the infection can progress into its latent, asymptomatic phase.
• However, even with local control of the infection and resolution of the chancre, the spirochetes disseminate widely throughout the body, which can lead to the systemic manifestations of secondary and tertiary syphilis.
• Phases:
- Primary: Painless ulcerated lesion with raised and indurated edges. Often accompanied by regional lymphadenopathy. It usually resolves spontaneously within two weeks, with or without treatment.
- Secondary: A syndrome characterized by systemic symptoms (e.g., fevers, chills, malaise) and multiple potential manifestations, including:
• Rash: A diffuse macular rash of the trunk, extremities, palms, and soles. The absence of palm and sole involvement does not decrease the likelihood of syphilis
• Mucous patches: White, erosive lesions of the oral mucosa or tongue
• Condyloma lata: Raised lesions that can arise in the perineal or oral areas
• Alopecia: Patchy, scattered, “moth-eaten” alopecia. It is often irreversible
- Latent: Asymptomatic phase of infection between symptomatic phases. Patients will have positive syphilis tests.
• Early latent syphilis: Infection known to occur in the last 12 months.
• Late latent syphilis: Infection occurred at an unknown time or >12 months ago.
- Tertiary: Late manifestations of untreated syphilis. Rare in the antibiotic era, but still present given rising rates of syphilis worldwide. Primarily affects the cardiac and neurologic systems.
• Cardiovascular manifestations include a large vessel vasculitis that can cause aortitis or aortopathy (e.g., aortic insufficiency)
• Neurologic manifestations include:
- General paresis: A dementia syndrome characterized by memory deficits and eventual psychosis
- Tabes dorsalis: Disease of the posterior columns of the spinal cord, which causes lancinating pains of the extremities, back or face, sensory ataxia, and pupillary defects (Argyll-Robertson pupil, which does not react to light but accommodates when light is shown in the contralateral eye)
- Neurosyphilis: Can develop at any phase of disease because the spirochetes quickly disseminate after initial inoculation. Symptoms include meningitis, uveitis (ocular syphilis), hearing loss or tinnitus (otosyphilis), and, rarely, a CNS vasculitis.
• Diagnosis:
- Direct visualization with darkfield microscopy after samples from skin lesions with high organism burden (chancre, mucous patch, or condyloma lata)
- Serologic testing, which uses:
• Non-treponemal tests: These monitor disease activity but are not specific to syphilis. Non-treponemal test titers wane with time or treatment. Non-treponemal tests include:
- Rapid plasma reagin (RPR)
- Venereal Disease Research Laboratory (VDRL)
• Treponemal test: These test for antibodies to T. pallidum. They will remain positive even after treatment. Treponemal tests include:
- Fluorescent treponemal antibody absorption (FTA-ABS)
- T. pallidum particle agglutination assay (TPPA)
- T. pallidum enzyme immunoassay (TP-EIA)
- Chemiluminescence immunoassay (CIA)
• Interpretation of serologic tests: Serologic tests for syphilis include an algorithm that starts with either a treponemal (reverse algorithm) or non-treponemal test (traditional algorithm). The interpretation of the test results depend on the testing algorithm used.
• Diagnosis of neurosyphilis: Positive CSF analysis for neurosyphilis or symptoms consistent with ocular or otosyphilis
• Treatment:
• Primary, secondary, early latent: Penicillin G 2.4 million units IM ×1 dose
• Tertiary or late latent: Penicillin G 2.4 million units IM once weekly ×3 weeks
• Neuro: Penicillin G 3–4 million units IV q4 hours ×10–14 days
• For all: See IDSA guidelines and follow post-treatment monitoring recommendations
Chancroid (H. ducreyi)
• Clinical features: Painful genital ulcer(s) with a ragged border and unilateral painful inguinal lymphadenopathy (buboes) that occurs at the same time as the ulcer(s)
• Diagnosis: No serologic tests available; rule out syphilis and HSV-2
• Treatment: Azithromycin (oral, one dose) OR ceftriaxone (IM, one dose)
Lymphogranuloma venereum (C. trachomatis)
• Clinical features: Painless anal or genital lesion(s) that often go unnoticed. This is followed by tender lymphadenopathy weeks later. The third phase is a genital/anal/rectal syndrome with pelvic lymphadenopathy, diarrhea, proctitis, and, in severe cases, abscesses or fistulas.
• Diagnosis: C. trachomatis NAAT (urine, rectal), antibody testing (LGV is caused by serovars L1–L3)
• Treatment: Doxycycline 100 mg PO BID ×21 days
Genital warts (HPV 6 and 11)
• Clinical features: Painless flesh-colored, exophytic lesions
• Treatment: Podophyllin, TCA, cryotherapy, surgery. Treatment of genital warts does not prevent HPV transmission.
HIV/AIDS
• Pathogenesis: See Figure 8.1. The 4 main steps in HIV infection include:
- Viral entry: The HIV virus enters host cells by binding its gp120 viral envelope protein to the CD4 protein on the host’s CD4+ T cell surface. gp120 then interacts with a second surface protein, a chemokine receptor, and then the gp41 protein mediates fusion of the viral envelope with the host’s CD4+ T-cell membrane, allowing the virion core to enter the cytoplasm.
• Medications that impact this step include the entry/fusion inhibitors:
- Enfuvirtide: Binds to the viral envelope protein GP41 to prevent fusion
- Maraviroc: Binds to the chemokine co-receptor 5 (CCR5) to prevent entry
- Ibalizumab: Binds to the domain 2 of CD4+ T cells, to prevent entry
- Transcription of the viral RNA into double stranded DNA by the reverse transcriptase: Once in the cytoplasm, the virus’s reverse transcriptase transcribes the HIV RNA genome into double-stranded DNA.
• Medications that impact this step include the NRTIs and NNRTIs:
- NRTIs include lamivudine, tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), emtricitabine, and abacavir
- NNRTIs include efavirenz, rilpivirine, etravirine, doravirine, and nevirapine
- Integration of the viral DNA with the host DNA: The double-stranded DNA then migrates into the nucleus and integrates into the host DNA via a virus-encoded integrase.
• Medications that block this step are integrase inhibitors: Dolutegravir, raltegravir, bictegravir
- Cleavage of the viral RNA into large polyproteins by proteases: The viral mRNA is then transcribed by the host RNA polymerase, translated, and then cleaved by proteases into several large polyproteins.
• Medications that impact this step include the protease inhibitors, ritonavir and atazanavir
• Transmission: HIV infection occurs via sexual intercourse (oral, vaginal, or anal), exposure to infected blood (injection drug use, or, rarely, needlestick), or perinatal transmission
FIGURE 8.1: Life cycle of the HIV virus and mechanisms of anti-retroviral medications. Shown are the steps of the HIV life cycle and relevant medications that act on each step of viral replication.
FIGURE 8.2: Changes in serum markers of HIV infection during the early phase of HIV infection in untreated patients.
• Stages: These stages of HIV infections are based on the CDC’s updated staging system:
- Stage 0: If the individual had a negative HIV test within 6 months (180 days) of the diagnosis of HIV infection, they are classified as Stage 0, which reflects early infection. The criteria for Stage 0 supersede criteria for other stages and individuals diagnosed at stage 0 remain stage 0 for the first 180 days after diagnosis.
- Stage 1: CD4 T-lymphocyte cell count ≥500 cells/µL or ≥26%*
- Stage 2: CD4 T-lymphocyte cell count of 200–499 cells/µL or 14–25%*
- Stage 3: CD4 T-lymphocyte cell count of <200 cells/µL or <14%* or the presence of any Stage-3 defining opportunistic infection.# Individuals in this stage have AIDS.
*Cell count takes precedence over %. Use the % only if the absolute count is missing.
#Examples of stage-3 defining illnesses include PJP pneumonia, esophageal candidiasis, TB infection of any site, Kaposi sarcoma, CMV retinitis, extrapulmonary cryptococcosis, extrapulmonary or disseminated coccidioidomycosis or histoplasmosis
• Diagnosis:
- There are three markers for HIV infection, and each turns positive at different phases (Figure 8.2):
• The HIV RNA viral load (turns positive ~10 days after infection)
• The HIV p24 antigen (turns positive ~15–20 days after infection)
• The HIV antibody (turns positive ~20–30 days after infection)
- These differential times to positivity means that there is a “window period” during which the fourth-generation HIV test (which tests for the p24 Ag and the HIV Ab) can be negative. During this time period, the HIV RNA test is needed to detect acute infection
• Treatment:
- Antiretroviral therapy (ART):
• All patients with HIV should be offered ART at the time of diagnosis. Early treatment improves long-term outcomes and retention in care.
• In certain patients with specific opportunistic infections, ART initiation should be delayed. The decision to initiate or delay ART in the setting of OIs should be made with the assistance of an ID consultant. OIs that prompt delayed ART start include:
- Cryptococcal meningitis (CM): Induction of ART may precipitate immune reconstitution inflammatory syndrome (IRIS). This can be fatal in cryptococcal meningitis due to the inflammatory response of IRIS in the closed space of the CNS.
- Tuberculous meningitis
- CNS infection other than CM or TB meningitis with evidence of brain edema or mass effect
- CMV retinitis
- Patients who are intubated or hypotensive as a result of non-CNS or non-ocular OI or bacterial infection
• Vaccinations in individuals with HIV: Regular and strict adherence to vaccination schedules is a key component of HIV management. See IDSA and CDC guidelines.
• Opportunistic infections & prophylaxis: Table 8.23 reviews the different opportunistic infections in individuals living with HIV, as well as prophylaxis regimens for each infection
TABLE 8.23 • Opportunistic Infections and Prophylaxis Regimens in Individuals Living with HIV
• HIV Prevention:
- Post-exposure prophylaxis (PEP): This approach to HIV prevention can be used in individuals who had a high-risk exposure to HIV (e.g., receptive or penetrative vaginal or anal intercourse without condom use or percutaneous exposure to blood). Obtain a baseline HIV test and start therapy with tenofovir disoproxil fumarate/emtricitabine + dolutegravir or raltegravir.
- Pre-exposure prophylaxis (PrEP): This approach to HIV prevention is used for certain populations who have a high risk of HIV exposure, and thus take an antiretroviral medication daily to reduce the risk of getting HIV if they are exposed to the virus. See CDC guidelines for indications for PrEP, recommended testing prior to starting PrEP, possible regimens, and monitoring recommendations.