Approach
The goal of medical management of herpes B virus exposure is to prevent progression to infection, to document infection if it has occurred, and to manage infection to prevent a potentially fatal encephalitis. Infection control is critical for the management of all patients confirmed or suspected to be infected with B virus.
Cleansing the exposed area
If a potential B virus exposure occurs, the immediate response should aim at preventing exposure from progressing to infection. Thus, the critical first step is immediate and thorough cleansing of the exposed area. The area should be cleansed on presentation for medical evaluation regardless of whether or not it was previously cleansed. The exposed area should be thoroughly washed and gently scrubbed with soap, povidone-iodine, or detergent for 15 minutes, followed by irrigating the area with running water for 15 to 20 minutes.[42] Mucosal exposure (nose, eyes, mouth) should be flushed with sterile saline solution or water for 15 minutes.
Post-exposure prophylaxis
If herpes B virus exposure is suspected and the patient presents for medical evaluation within 5 days of potential exposure, post-exposure prophylaxis (PEP) with a high-dose oral antiviral should be considered while diagnostic tests are being carried out to confirm infection. As the goal of prophylactic antivirals is to prevent exposure from progressing to infection, and because animal models of B virus infection show that antivirals prevented disease if given within 5 days after infection, antiviral prophylaxis is not recommended for patients who present for medical evaluation more than 5 days after exposure.[45][46]
The recommended first-line antiviral for B virus prophylaxis is high-dose oral valaciclovir. The alternative is high-dose oral aciclovir.[4] In one animal study, aciclovir administered within 24 hours after infection with B virus prevented mortality.[45] High-dose aciclovir administered to humans within hours after exposure may prevent progression to infection or may modify symptomatic B virus disease.[4]
Prophylactic administration of antibiotics or rabies vaccine and rabies immune globulin may also be considered depending on the cause and severity of exposure and the risk that exposure presents for infections other than B virus. Non-human primates housed outside can be exposed to rabies-infected animals and transmit rabies. Non-human primate bites carry similar risks of bacterial infections as bites inflicted by humans. If the animal associated with exposure has been used in research, specific infections that may have occurred during the research history may be clinically relevant (e.g., simian immunodeficiency virus [SIV], HIV) and should be investigated.
All patients who have experienced B virus exposure should be monitored for changes in serological titres and onset of clinical signs and symptoms suggestive of B virus infection. Patients who present more than 5 days after exposure should be followed with monitoring alone.
Infection control measures
In order to protect healthcare personnel and family members from exposure to potentially infectious tissue or body fluids, anyone treating or attending to patients with B virus infection must follow standard precautions.[53] Infection control practitioners should be consulted for further instruction. Observance of these standard precautions should occur regardless of whether the patient is receiving antiviral treatment. B virus has been isolated from skin lesions and buccal mucosa of patients actively receiving high-dose intravenous aciclovir.[34] The number of well documented human infections is too small to confidently predict what findings are atypical based on case reports or what findings are more likely to be common for most human infections. Asymptomatic human infection with B virus has never been documented. The one documented case of human-to-human transmission of B virus occurred in a spouse who treated a skin lesion on her B virus-infected husband prior to his diagnosis. She used the same cream to treat her dermatitis. He succumbed to B virus disease. She developed a pruritic rash subsequently laboratory confirmed as B virus, but responded to aciclovir treatment with no subsequent recurrences.[24]
Treatment of infection
Patients who develop signs and/or symptoms consistent with B virus disease after exposure must be treated with high-dose intravenous antiviral therapy. Patients already receiving an oral antiviral as PEP who have onset of symptomatic disease compatible with B virus should be switched to high-dose intravenous antiviral therapy immediately. Treatment should continue until B virus infection has resolved or can be excluded.
If central nervous system (CNS) disease is present, high-dose intravenous ganciclovir is the recommended first-line treatment.[4] High-dose intravenous aciclovir is the recommended first-line treatment for B virus disease in the absence of CNS disease. High-dose intravenous ganciclovir can be used as an alternative to aciclovir, and should be preferred in any patient who appears to progress on aciclovir or who develops signs and symptoms of CNS disease.[4] Higher antiviral doses than those used to treat HSV infection are required to ensure effectiveness against B virus, because B virus is less sensitive to aciclovir than HSV in vitro.
Patients receiving aciclovir should be well hydrated to prevent precipitation of the drug in the renal tubules and renal insufficiency. Creatinine levels also need to be monitored, and dosage adjusted accordingly. If patients develop additional symptoms while being treated with aciclovir clinical evaluation is needed to consider whether treatment should be switched to ganciclovir.
B virus is more susceptible to ganciclovir compared with aciclovir, both in vitro and in animal models. Ganciclovir was used in the only case documenting complete recovery of B virus infection with brainstem encephalitis.[34] While ganciclovir is more toxic than aciclovir, the decision whether or not to use ganciclovir should be balanced against its potential benefit. As is the case with aciclovir, the dosage of ganciclovir needs to be adjusted for renal insufficiency. White blood cell and platelet counts should be monitored closely due to the myelosuppressive effects of ganciclovir.
Valganciclovir has been used successfully to manage a B virus patient with recurrent ocular lesions.[38]
The routine use of antivirals for prophylaxis following potential exposure and for the treatment of early-stage B virus disease, including those with early symptoms associated with CNS involvement, may have prevented infections and improved survival rates among infected patients over recent decades.[24][34] Recognition of the importance of non-injury associated exposures of mucous membranes or non-intact skin, along with improvements in routine use of protective equipment and practices, combined with efforts to develop B virus-free macaque colonies have also likely contributed to the rarity of B virus cases in recent decades.
Supportive care
Beyond the described recommendations for antiviral therapy and diagnostic testing, management of B virus-infected people is largely supportive: for example, adequate hydration, use of antipyretics for fever, anti-emetics for vomiting, and analgesia for headaches.
Intensive care (ICU) is usually indicated for patients with encephalitis. Death is often associated with respiratory failure. However, management decisions must be made at the bedside based on clinical judgement of the treating physician in association with engaged infectious disease specialists.
Some people who were laboratory confirmed to be infected with B virus survived the acute illness. For these patients, long-term supportive and rehabilitative care has contributed to restoration of mobility and recovery following acute, ascending paralysis. However, recovery from this stage of disease remains an uncommon event and is usually incomplete.[32][38]
Pregnant women
Fairly extensive clinical experience suggests that administering aciclovir during pregnancy is reasonably safe. A registry of women who received the drug during pregnancy showed no increase in congenital abnormalities, although numbers were limited and insufficiently powered to detect low-incidence adverse outcomes.[54][55][56] Aciclovir is the antiviral therapy against herpesvirus with the most evidence for safety during pregnancy. If a woman of childbearing age presents with suspected B virus exposure or known B virus infection, a pregnancy test should be carried out to aid in the decision of which antiviral to choose. The relative safety of treatment with aciclovir compared with ganciclovir for the fetus must be weighed against the risk of B virus encephalitis for the mother during clinical decision making. Ganciclovir is indicated in any CNS infection.
Children
Potential B virus exposures of children and infants have occurred.[6] The social hierarchy among macaques, based on establishment of dominance by attacks against subordinates, may put children at increased risk of attack when in the vicinity of free-ranging macaques. Specific recommendations for treating B virus exposures and disease for children do not exist. Management of potential B virus exposures or disease suggestive of B virus infection should involve an infectious disease specialist who can provide advice on adaptation of existing guidelines in adults and antiviral dosing in children. Because valaciclovir is recommended for the treatment of varicella in children aged 2 to 18 years, and one study of the pharmacokinetics and safety of valaciclovir oral suspension showed that the drug was well tolerated and safe in children aged 3 months and older, valaciclovir may be considered for prophylaxis of children exposed to B virus.[57]
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