Primary prevention
There are no vaccines available for B virus. The most effective preventative measures against B virus infection are to avoid contact (feeding or petting) in settings where macaques are permitted to roam freely and, in the laboratory setting, to establish a safe laboratory and animal care environment using appropriate personal protective equipment (PPE).
Prevention in the natural setting:
Macaques should not be kept as pets.
Close contact with free-roaming macaques in public settings, such as parks or temples, should be avoided both domestically and internationally.
Prevention in the laboratory setting:
B virus is classified as a biosafety level-4 (BSL-4) biological agent; therefore, laboratory workers handling B virus either directly or indirectly (via infected materials) should do so in facilities with BSL-4 capabilities in order to prevent infection.
Macaques housed in research facilities may have very high rates of B virus infection. A survey of monkeys in one such colony revealed a B virus seroprevalence of 97%.[40]
Direct handling of animals should be minimised. Workers should not attempt to handle fully conscious macaques; procedures should be conducted using appropriate physical and chemical restraining methods.
Macaque handlers should remove physically active animals from cages using arm-length reinforced leather gloves. A long-sleeved garment and face shield are also recommended to protect against scratches. Cages and other potentially contaminated equipment should be free of sharp edges and corners that could cut or scratch animal workers. Areas where macaques are housed should have access limited to properly trained personnel.
Macaques with lesions consistent with B virus infection should be quarantined until the lesions have healed, reducing transmission risk to both humans and other macaques.
Workers handling macaques must be trained in proper methods of restraint and in the use of appropriate PPE.
Personnel handling macaques should be educated about B virus, the risks of exposure, the nature of illness due to B virus infection, and appropriate first aid procedures.
The occurrence of an eye splash without cutaneous injury leading to a B virus fatality resulted in the additional recommendation that protective eyewear (goggles or glasses with solid side shields) and a mask, or a chin-length wrap-around face shield and a mask should be used to protect mucous membranes in area where macaques are kept. Face shields or glasses must be able to prevent splashes from running or dripping down into the eyes.[41]
Guidelines for the prevention of B virus exposure have been published.[3][4][41] The guidelines recommend that, while exposure involving unpredictable, aggressive animals is not completely preventable, adherence to appropriate laboratory and animal facility protocols will greatly reduce the risk of infection. The following recommendations are published by the US Centers for Disease Control and Prevention:[4]
Handling B virus-susceptible monkeys should be done using humane restraint methods to reduce the potential for bites and scratches
Proper PPE, including a laboratory coat, gloves, and a face shield, must be used when working with macaque monkeys
All bites, scratches, or exposure to the tissues or secretions of macaques must be cleansed immediately. The first few minutes after an exposure are considered the most critical period for reducing the risk of infection. For skin exposure, the exposed area should be thoroughly cleansed by washing and scrubbing with soap, concentrated solution of detergent, povidone-iodine, 0.25% hypochlorite, or chlorhexidine and water for 15 minutes. The exposed area should then be irrigated with running water for 15 to 20 minutes. Mucosal exposed areas (nose, eyes, mouth) should be flushed with sterile saline solution or water for 15 minutes
The cleansed wound should be evaluated by a third party for adequacy of washing, and repeated if necessary. The date, time, location, nature, and site of injury, and the type of fluid or tissue exposure should also be recorded.
Following exposure, acute and convalescent serum specimens from the exposed human should be sent for serological testing to evaluate for B virus infection. Sending serum specimens from the implicated macaque can also be considered if safe to do so, and if the outcome of testing will affect how that macaque or the colony is managed. Results of macaque testing will not impact management of the exposed human.
In humans, collection of wound specimens at the time of exposure is not recommended; collection of PCR or viral culture specimens from the site of exposure may be considered only after it has been thoroughly cleansed to prevent risk of driving the virus into the wound and increasing the risk of infection.
Secondary prevention
Preventing human-to-human transmission:
Human-to-human transmission of B virus is rare. B virus has been transmitted from human to human in one documented report. Transmission occurred from husband to wife following the repeated use of lotion that the wife used for both her husband's open herpetic lesions and her own dermatitis.[24] The husband's herpetic lesions were subsequently confirmed to have been shedding B virus.
Patients confirmed or suspected to be infected with B virus should be assumed to be shedding virus from open wounds at the site of virus inoculation, any herpetic-like lesions, and possibly oral and genital mucosa. Serial PCR testing of these sites should guide infection control practices, which should be determined in consultation with infectious disease and infection control specialists. Positive cultures taken from the conjunctiva and buccal mucosa of a patient with B virus infection receiving intravenous aciclovir treatment has shown that shedding of infectious B virus can occur for up to 11 weeks following treatment initiation.[4][24]
Those who are infected with B virus should avoid exposing their body fluids or skin lesions to others during the incubation period. Standard precautions should be practiced for all humans infected with B virus until absence of shedding of virus has been confirmed.
Post-exposure prophylaxis (PEP):
If B virus exposure is suspected, PEP can be instituted. The following diagram outlines when PEP should be considered in patients with suspected B virus exposure:[Figure caption and citation for the preceding image starts]: Guidelines for post-exposure prophylaxis for suspected B virus infectionCDC [Citation ends].
Fatal B virus infections have occurred in people who recall no exposure or who had minimal exposures. For this reason, ranking the risk of exposure is discouraged. All potential exposures should be assumed to present risk and managed appropriately. However, it is not feasible or recommended to provide antiviral prophylaxis for every possible exposure.
Antiviral prophylaxis is recommended for exposures that present for medical evaluation within 5 days of exposure. Prophylaxis is not recommended for those who present more than 5 days after exposure. The following factors should be considered in determining the advisability of providing prophylaxis:[4]
Source of the exposure
Timeliness and adequacy of first aid for wounds or splashes
Type of wound or exposure
Evaluation of exposure to materials that were in contact with macaques.
The severity and the nature of the wound and the area affected by the splash or other exposure are relevant. Bites or scratches that break the skin, and especially deep puncture wounds such as from a severe bite or an accidental stick from a contaminated needle, that are difficult to cleanse are assumed to result in a higher risk than superficial injuries that are more easily cleansed. Wounds and exposures of the head, neck, or torso are at risk for rapid transport of virus to the central nervous system (reasoning by analogy from rabies virus experience) and should thus be regarded as high-risk exposures. Prophylaxis for potential exposures to these parts of the body is recommended, regardless of the severity of the wound or the extent of the exposure to fluids. Antiviral prophylaxis should be administered immediately once the wound or exposure site on the head, neck, or torso has been thoroughly cleansed, and specimens have been taken for serology, PCR, and/or culture.[4]
Superficial wounds to the extremities that have been immediately and properly cleansed are presumed to be less likely to lead to fatal disease. Scratches from cages in which macaques are housed are also considered to carry a lower level of risk, again assuming that the wound has been properly cleansed. For these exposures, antiviral prophylaxis should be considered on a case-by-case basis.[4]
Bites and other exposures involving non-macaque primates that have not been housed with macaques are regarded as having no risk for B virus transmission. However, such wounds should be evaluated for bacterial infection as well as for other viruses of concern, such as rabies.
It should be stressed, however, that in none of the potential exposures mentioned can the risk of infection be regarded as zero. As such, the decision to initiate prophylaxis or treat a patient with anti-herpes antivirals should be made at the physician’s discretion, with consideration of the patient’s wishes and concerns. Decision tools for evaluating the need for antiviral prophylaxis in laboratory workers are in development.[61]
Oral antivirals (aciclovir, valaciclovir, famciclovir) are recommended for PEP. In the US, none of these antivirals have been approved by the Food and Drug Administration (FDA) for treatment of B virus infections. Valaciclovir and famciclovir are oral pro-drugs; each is metabolised in the liver and intestine to aciclovir and penciclovir, respectively. Both drugs have substantially higher bioavailability than oral aciclovir.[62][63] The preferred antiviral drug for post-exposure B virus prophylaxis is oral valaciclovir (in adults, including non-pregnant women) due to the superior bioavailability compared with aciclovir.[4][24] However, aciclovir can be used as an alternative. There are no available studies (animal or in vitro) for the efficacy of famciclovir at inhibiting B virus replication. However, famciclovir and valaciclovir have comparable efficacy for the treatment of herpes simplex and herpes zoster, and might also be expected to be similarly efficacious against B virus.[4]
PEP should be started within a few hours and no later than 5 days after exposure, but only after the completion of the first aid protocol. Prophylaxis should be continued for 14 days.[4] If the patient is asymptomatic at the end of 14 days of prophylaxis, antiviral treatment can be stopped, but careful follow-up of the patient is necessary to observe for late onset of symptoms. If symptoms of B virus disease develop, PEP should stop and treatment for B virus disease should be started.[4]
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