Herpes Simplex Virus (HSV) Infections PDF

2.3.4. Herpes Simplex Virus (HSV) Infections Herpes Simplex Virus 1 (HSV-1) and Herpes Simplex Virus 2 (HSV-2) infections are members of the alpha herpesvirus sub-family. They are characterized by infections of the skin, the mucous membranes, the central nervous system, sometimes even viscer...

2.3.4. Herpes Simplex Virus (HSV) Infections Herpes Simplex Virus 1 (HSV-1) and Herpes Simplex Virus 2 (HSV-2) infections are members of the alpha herpesvirus sub-family. They are characterized by infections of the skin, the mucous membranes, the central nervous system, sometimes even visceral complications may develop. Although HSV-1 most commonly causes infections at the level of the cephalic extremity, while HSV-2 at the level of the genitals, both viruses can develop infections with oro-facial and/or genital localization. Epidemiology. Ubiquitous distribution. HSV-1 is one of the most widespread infections worldwide. Studies regarding HSV-2 seroprevalence indicate that 70-90% of adults have anti-HSV-1 IgG antibodies, primary infection being most commonly seen in childhood. HSV-2 is rarely found before puberty; 15-20% of adults are infected with this virus. Risk factors related to HSV-2 infection are linked to sexual behavior - multiple partners, prostitution. The prevalence of HSV-2 infection among this population category can reach 90%. Humans are the exclusive reservoir of the infection – individuals with clinically manifest infections, but also those with subclinical infections (asymptomatic, but eliminating the virus through saliva / genital secretions), whether it is primary infection or the reactivations of a latent infection. Way of transmission: contact with oral secrections (eg: kiss, shared-used dishes) / genital secretions (sexual contact, oral sex) or mucocutaneous lesions, as well as maternal-fetal transmission (mother-to-child transmission). Immune response: humoral – initially IgM antibodies, later IgG - and cellular ones. The infection is reactivated due to immunodepression, especially cellular one. Pathogenesis. The mucosal surfaces or labraded skin sites are the main portals through which Herpes Simplex Virus (HSV) infections enter the human body. After an initial replication at the the gateway, the virus infects the sensory / autonomic nerve endings and is transported intra-axonally to nerve cell bodies in ganglia, where replication continues. From this level, the virus spreads to other mucosal skin surfaces by centrifugal migration through sensory nerve endings, where the characteristic lesions are developed. The virus invades the central nervous system, causing herpes simplex encephalitis through the axonal pathway. Viremia is more intense in immunocompromised patients or newborn infants. HSV resides in a latent state in the sensory ganglia. The infection may be reactivated as a result of low immunity - clinically or subclinically manifest. Clinical picture  Incubation: 2-12 days. Early infection may be asymptomatic or may be manifested by cutaneous and mucosal lesions, sometimes accompanied by systemic manifestations: fever, poor (altered) general condition, myalgia. Gingivostomatitis / Herpetic pharyngitis. Most commonly associated with early infection, they occur in children or young adults. They are mainly caused by HSV-1, rarely by HSV-2 (transmitted through oral sexual contact). The patient presents with fever, alteration of the general condition, myalgia, pretragian and subangulomandibular adenopathies, dysphagia, odynophagia, sometimes even impossibility of feeding. Aphthous ulcers are present in the oropharyngeal mucosa: lips, tongue, palate, pharyngeal pillars. Bacterial overinfection is possible. Oro-Labial Herpes (herpes labialis) –the most frequent clinical manifestation of recurrent herpes infection - vesicles at the mucocutaneous junction of the lip, accompanied / preceded by discrete pruritus or local burning sensation. Similar lesions can be located at the level of the nasal pyramid or chin. Herpetic whitlow (herpes panaritium). Vesicles on a finger or thumb – most commonly the index finger of the dominant hand, accompanied by edema, erythema, local pain, regional adenopathy. Autoinoculation to different areas of the body can happen by touching an open lesion on a finger that comes in contact with sores or blisters around your face or genital area. Herpes gladiatorum ("Mat Herpes"). Frequent among those who practice contact sports (Greek-Roman fights); inoculation of the virus through microabrasions in the skin. Vesicles can be located anywhere- face, limbs, thorax. Eczema herpeticum - diffuse herpes lesions as a result of eczema. Ocular manifestations. Herpetic keratitis, potential cause of blindness, starts suddenly, unilaterally, with local pain, foreign body sensation, hyperlacrimation, photophobia, erythema, chemozis. The local examination reveals dendritic/ geographic corneal ulcers. Bacterial superinfection is possible. Other ocular manifestations include acute retinal necrosis or uveitis, with a poor prognosis. Herpes simplex encephalitis – hemorrhagic, necrotizing encephalitis, affecting mainly the temporal and frontal lobes. It can be caused by HSV-1 (children / adults) or HSV-2 (newborns from mothers with genital infection), even in the absence of cutaneous and mucosal lesions. The patient presents with fever, intracranial hypertension syndrome, seizures, outbreaks of neurological diseases, impaired consciousness, behavioral and memory disorders, sometimes visual / auditory hallucinations. Mortality rate is high- 80% in the absence of treatment, and sequelae are common among survivors. Visceral herpes infections – pneumonia, hepatitis, esophagitis, more commonly in the immunocompromised patients.  Genital herpes – most commonly caused by HSV-2, rarely by HSV-1 (oral sex). Early infection can be accompanied by systemic manifestations such as: fever, alteration of the general condition. The patient complains of itching or local pain, dysuria, leukorrhea, vesicles on an erythematous base with evolution towards ulcerations, located at genital / urethral level, inguinal adenopathy. Reactivations of the infection are usually less severe, sometimes even asymptomatic, but the patient is contagious through the HSV secretions in the genital discharge. Anal and perianal herpes, most commonly caused by HSV-2, transmitted by anal sexual contact, it develops with local pain, tenesmus, inguinal adenopathy, sometimes constipation; the endoscopic examination reveals the presence of vesicles / ulceration. It can be complicated by bacterial superinfection. Neonatal herpes simplex virus infection – most frequently caused by HSV-2. It is transmitted during delivery, the newborn’s direct contact with the mother's infected vaginal secretions; rarely transplacental or postpartum transmission. When primary HSV-2 infection onset during late pregnancy the risk is elevated, but transmission is also possible in case of a reactivation, even asymptomatic of the maternal infection. The clinical picture is of particular severity, with encephalitis, pneumonia with respiratory distress, keratitis, esophagitis, necrotizing enterocolitis, infectious necrotic hepatitis, thrombocytopenia and hemorrhagic syndrome, vesicular or necrotic exanthema (possibly absent). Mortality is high - 65-80%, and survivors develop significant neurological sequelae. Congenital HSV infection –in case of primary maternal infection it rarely occurs before the 28th week of gestation, leading to spontaneous abortion, delay in intrauterine fetal growth development, malformations of the central nervous system or the sensory organs - microcephaly, chorioretinitis, microphthalmia, intracranial calcifications, cataract. Positive diagnosis Diagnosis is usually determined by clinical data. Tzanck smears from vesicular lesions show giant cells with intranuclear inclusions. Serum HSV-1 and 2 IgM are present in case of primary infection or reactivation. IgG antibodies indicate chronic infection, but their simple determination can not confirm a reactivation. HSV can be grown in cell cultures with cytopathic effect. The viral DNA genome can be detected from the vesicular fluid by polymerase chain reaction (PCR). The examination of the cerebrospinal fluid (CSF) for the diagnosis of HSV encephalitis reveals lymphocytic pleocytosis - several hundred cells/mm3, sometimes with the presence of red blood cells, the diagnosis being hemorrhagic encephalitis. Proteinuria is moderately increased while the levels of glucose in the CSF are normal. One week after onset anti-HSV antibodies are detected in the CSF. The electroencephalogram can detect focal lesions and brain MRI scan - lesions located in the temporal sometimes frontal lobes. Treatment Primary HSV infection benefits from etiological treatment with Acyclovir 5x200 mg / day p.o. (oral) or 3x5mg/kg / day i.v. or Valaciclovir 2x500 mg / day p.o. (oral) for 10 days. The mechanism of action consists in inhibiting viral DNA polymerase. Renal function monitoring is required. Valaciclovir 2x500 mg / day p.o. (oral) for 5 days it is also recommended for severe skin and mucosa reactivations. Topical treatment with Acyclovir- cream is usually sufficient in case of reactivations with decreased severity - eg herpes labialis. Visual impairment requires topical administration of Acyclovir for 5-10 days, as an ophthalmic ointment, and if the condition is severe (deep keratitis, uveitis, necrotic retinitis) intravenous acyclovir is needed. For herpes simplex encephalitis, intravenous acyclovir should be administered at 3x10 mg / kg / day for 2-3 weeks; associated - corticosteroids, depletives, neuroroborants. Profilaxis Up to date, there is no HSV vaccine. The prevention of HSV transmission is based on the education of patients and contacts on avoiding contact with skin lesions, saliva, genital secretions, condom use in the case of genital infections. Long-term administration (months) of Valaciclovir or Famciclovir (chemoprophylaxis) is aimed at patients with more than 6 infectious reactivations / year, respectively in immunocompromised patients with multiple recurrences. In case of primary maternal genital HSV infection, if it occurred in the last month of pregnancy or if the mother shows a clinically manifest reactivation at the beginning of labor, a caesarean delivery is recommended. Valaciclovir prescribed to the mother in case of a primary infection or reactivation during the last month of pregnancy reduces the risk of neonatal infection. SECTION Denumirea cartii | 7 8 | Denumirea cartii sau a sectiunii/capitolului