Zoster Immune Globulin Research Articles

Live Vaccine and Varicella Postexposure Prophylaxis in Pediatric Liver Transplant Recipients: A Survey of Practice in Australia and New Zealand.

Administration of live vaccines following liver transplant (LT) has historically not been recommended due to concerns regarding risk of vaccine-attenuated disease. However, there is evidence suggesting that in select transplant recipients live vaccinations can be administered safely. Studies in other regions have indicated that despite this evidence many clinicians remain hesitant to administer live vaccinations. A REDCap survey was distributed to gastroenterologists, pediatricians, and infectious diseases physicians at pediatric centers across Australia and New Zealand via email between September and November 2023. The survey included a series of questions regarding live vaccine and varicella postexposure prophylaxis (PEP) practices in pediatric LT recipients and barriers to live vaccine administration in this cohort. There was a total of 16 responses to the survey, from 10 different pediatric centers, including 10/11 pediatric gastroenterology centers and all four pediatric LT centers in the region. Only 31% (5/16) of respondents (from 3/10 different centers) offer live vaccines. The main barrier to live vaccine administration was clinician reluctance and the main reason for not offering live vaccines was insufficient safety data. Sixty-nine percent (11/16) of respondents take vaccination status and/or serology into account when deciding whether to offer varicella PEP to this cohort. Respondents universally offer varicella zoster immunoglobulin as PEP, though 31% (5/16) also offer antiviral medication. Many clinicians in our region remain hesitant to provide live vaccines to pediatric LT recipients, with concerns regarding insufficient safety data. Updated local guidelines may help to address this.

Management of a major varicella zoster exposure in a pediatric oncology population

Management of the exposure of pediatric oncology patients to varicella zoster virus (VZV) is controversial. We report the exposure of 56 patients to a single child with chicken pox at a pediatric cancer housing facility and describe our strategic approach for their management. We reviewed the immune and clinical status of 56 children with cancer receiving ongoing treatment at Memorial Sloan Kettering Cancer Center (MSK) who, while living at a pediatric cancer housing facility, were exposed to the index patient. The management of patients exposed included: (1) determination of immune status, (2) availability of vaccination history or VZV disease prophylaxis, (3) exposure status and subsequent isolation during the period of incubation, and (4) VZV disease prophylaxis. In addition to the 56 patients exposed to the index case, eight children with cancer treated at other facilities and 11 healthy siblings living in the facility were exposed. Of the 56 MSK patients, 21 were classified as immunosuppressed and received varicella zoster immune globulin (human), intravenous standard immune globulin, or acyclovir based on serostatus and immune function. The cohort was followed for 4 weeks after the exposure and no secondary infections were diagnosed. We performed a risk assessment and created a management plan to control and prevent further exposure and development of disease. No secondary cases developed. This strategic approach could serve as a model for the management of VZV exposure for other pediatric oncology centers.

Chickenpox in pregnancy

Varicella, the number one contamination with varicella-zoster virus (VZV; human herpes virus) in pregnancy, might also cause maternal mortality or extreme morbidity. It may also be the cause of fetal varicella syndrome (FVS) and varicella contamination in new children, which incorporates congenital varicella syndrome (CVS) and neonatal varicella. This guiding principle addresses the role of varicella vaccination in women of reproductive ages. The rule also assesses evidence concerning the maternal and fetal risks of VZV contamination in pregnancy and whether these headaches may be prevented or changed beneficially with the aid of the management of varicella-zoster immunoglobulin (VZIG) or with the aid of a remedy for infected people with acyclovir. This fact should manual the prudent use of VZIG, which is made of the plasma of human blood donors and is consequently a restricted and costly aid. The control of neonates is outdoor the scope of this tenet. Guidance on neonatal publicity and disorder is to be had from other sources [1-2]

PEPtalk 3: oral aciclovir is equivalent to varicella zoster immunoglobulin as postexposure prophylaxis against chickenpox in children with cancer – results of a multicentre UK evaluation

ObjectiveTo compare the occurrence of chickenpox in children with cancer who received varicella immunoglobulin (VZIG) or aciclovir as postexposure prophylaxis (PEP).DesignProspective multicentre service evaluation of children with cancer who received...

Varicella Pneumonia in an Elderly Patient

Varicella pneumonia is a common complication in adults, while it is a mild and self-limiting disease inchildren. Elderly patients may have severe manifestations compared to adults due to the weakening oftheir immune system in clearing the virus. Treatment with intravenous acyclovir and varicella-zosterimmunoglobulin (VZIG) offers a good prognosis, while the use of steroids is still debated. Despite standardmanagement, our case presents a fatality in an older woman with varicella pneumonia.

Case Report: Neonatal Varicella Acquired From Maternal Zoster

The incidence of neonatal varicella has decreased dramatically since the introduction of the varicella vaccination. Although the varicella zoster virus is often associated with a mild infection, it may cause severe morbidity and mortality, particularly in the neonatal period and immunocompromised hosts. We report a case of neonatal varicella acquired from maternal zoster in a mother on biological immunosuppressive therapy. Following the diagnosis, the baby improved on antiviral therapy without any neurological sequelae. This case highlights the limited published data on neonatal varicella following herpes zoster reactivation to inform practice. This includes the role of varicella zoster immunoglobulin in neonates exposed to maternal zoster, the degree of trans-placental immunity and optimum antiviral dosing and duration.

Varicella Zoster in pregnancy

Chickenpox during pregnancy can cause serious complications for both mother and fetus. This includes varicella pneumonia in the mother, fetal varicella syndrome and varicella of newborn. Primary prevention includes vaccination against varicella infection and is part of standard childhood immunisation programme in many countries. Timely post-exposure prophylaxis of susceptible pregnant women with varicella zoster immunoglobulin is key to preventing chickenpox during pregnancy and its adverse fetomaternal sequelae. Antiviral therapy and appropriate supportive treatment improve maternal and neonatal outcomes

Varicella zoster immune globulin (human) (VARIZIG) in immunocompromised patients: a subgroup analysis for safety and outcomes from a large, expanded-access program

BackgroundImmunocompromised children and adults are at increased risk for severe disease and death following varicella zoster virus infection. Varicella zoster immune globulin (human) (VARIZIG) is recommended for post-exposure prophylaxis to prevent or attenuate varicella infection in high-risk individuals.MethodsAn open-label, expanded-access program provided VARIZIG to high-risk individuals exposed to varicella or herpes zoster. Immunocompromised participants were stratified by type of immunocompromising condition (“oncologic immunodeficiency”, “primary immunodeficiency”, “solid organ transplant” [SOT], “hematopoietic cell transplant” [HCT], and “other”). Patient characteristics, type of exposure and varicella outcome, and safety data were assessed.ResultsThis analysis included 40 adults (primary [n = 6] or oncologic [n = 10] immunodeficiencies, history of SOT [n = 5] or HCT [n = 6], and other [n = 13]), and 263 children (primary [n = 13] or oncologic [n = 152] immunodeficiencies, history of SOT [n = 36] or HCT [n = 17], and other [n = 45]). Among adults and children, 48% vs 72% were exposed to varicella, 38% vs 16% were exposed to herpes zoster, and 15% vs 12% had an unspecified exposure. Overall incidence of varicella infection in adults after VARIZIG use was 6%; incidence of varicella infection in children after VARIZIG use was 7%. Similar rates were noted in each subgroup. Most cases of varicella were mild, with two children developing > 100 lesions and no cases of varicella-related pneumonia or encephalitis. Varicella-related hospitalizations occurred primarily in children with oncologic immunodeficiencies. One serious adverse event (serum sickness) was considered related to VARIZIG and occurred in a child with oncologic immunodeficiency. There were no varicella- or VARIZIG-related deaths.ConclusionsThese data indicate that VARIZIG may reduce severity of varicella in immunocompromised children and adults.Trial registrationThis study was retrospectively registered with the public clinical trial identification NCT00338442 at https://www.clinicaltrials.gov on 20 June 2006.

Preventing Transmission of Vaccine-Associated Viral Infections from a Patient With Severe Combined Immune Deficiency

Background: The transmissibility of vaccine-strain viruses from immunocompromised patients, such as those with severe combined immune deficiency (SCID) is unknown. The infection control management of a patient diagnosed with SCID and infected with vaccine-strain varicella zoster virus (VZV) and measles virus is described below. A previously healthy, full-term boy was vaccinated at 14 months with measles mumps rubella varicella (MMR) vaccine. He had received prior vaccinations, including rotavirus, without adverse effects. During the 6 weeks after vaccination, the patient developed signs and symptoms clinically consistent with chicken pox and measles. An immune work-up revealed SCID. Methods: The Alberta Health Services (AHS) SCID protocol was followed to manage the patient upon admission at 17 months of age. Multiple meetings with various stakeholders were held to ensure appropriate precautions were followed to minimize the risk of pathogen transmission. Results: The patient was placed on airborne and contact precautions in a negative-pressure room. The pressure differential of the room to the corridor was continually monitored and displayed at the entry to the room. Staff known to be immune to VZV or measles were not required to wear an N95 respirator. All intrahospital movement of the patient was coordinated with the respective care teams and departments, including infection prevention and control, facilities maintenance and engineering, respiratory therapy, and diagnostic imaging. A mask was placed on the patient when movement outside the room was required. VZV testing was positive for the Oka/vaccine strain on all samples tested (ie, nasopharyngeal, skin, blood, and cerebrospinal fluid). Nasopharyngeal swabs and blood were PCR positive for measles genotype A/vaccine strain virus. Both viruses were persistently positive in spite of treatment with acyclovir, valganciclovir, varicella zoster immune globulin, and intravenous immune globulin. Conclusions: There is currently no documented transmission of measles vaccine-strain virus, and transmission of VZV vaccine-strain virus is rare. According to the AHS SCID protocol, the use of airborne and contact precautions for a patient identified with measles and/or VZV supersedes the use of a positive-pressure room for patients identified with SCID. Newborn screening for SCID was implemented in Alberta in June 2019. As a result, more SCID patients will be diagnosed earlier in their course, and therefore prior to most routine vaccinations. However, newborn screening will not pick up some types of combined immune deficiencies. Some children may still be at risk of vaccine-associated illnesses due to undiagnosed underlying immune deficiencies.Funding: NoneDisclosures: None

Chickenpox in Pregnancy

AbstractPregnant women in the tropics like India are more susceptible to varicella zoster infection due to the lower seroprevalence of varicella as compared to temperate regions. Seronegative pregnant women are highly susceptible following a significant exposure owing to the high secondary attack rate of the virus. Fetal transmission could happen transplacentally while neonatal transmission occurs through close contact post partum. Maternal VZV infection could be severe (particularly varicella pneumonia) with high mortality if untreated. Congenital varicella syndrome has an incidence of about 1–2% and is more likely if maternal symptoms occur between 5th and 24th week of pregnancy. Susceptible pregnant women with a significant contact should be administered VZIG not later than 10 days of exposure. Women presenting with the typical rash of VZV infection should be prescribed oral aciclovir. The mainstay of diagnosis of fetal varicella syndrome is detailed ultrasound scanning starting 4 weeks after the onset of maternal rash. Prenatal diagnosis of varicella can be achieved by varicella PCR of the amniotic fluid at least 6 weeks after maternal infection. However, presence of the virus in the amniotic fluid does not necessarily imply progression to fetal varicella syndrome. If the mother contracts primary infection at term, her delivery should be delayed by at least 5–7 days after the onset of the rash if possible. Neonatal varicella zoster immunoglobulin should be administered to prevent neonatal infection if delivery cannot be postponed. Obstetrician should be aware of the prophylactic and treatment strategies in the event of exposure/infection.

Safety and Varicella Outcomes in In Utero-Exposed Newborns and Preterm Infants Treated With Varicella Zoster Immune Globulin (VARIZIG): A Subgroup Analysis of an Expanded-Access Program.

BackgroundInfants exposed to varicella zoster virus (VZV) in utero ≤5 days before or ≤48 hours after delivery and preterm infants are at high risk for varicella complications. An expanded-access program assessed varicella outcomes after administration of varicella zoster immune globulin (human) (VARIZIG) in a real-world setting.MethodsIn this open-label, expanded-access program, high-risk infants received ≤125 IU/10 kg of VARIZIG (NCT00338442). VZV outcomes and safety were assessed.ResultsThere were 43 newborns exposed to VZV in utero and 80 preterm infants exposed to VZV; >80% received VARIZIG within 96 hours of reported exposure. When varicella outcomes were available, varicella occurred in 7 of 38 (18%) in utero–exposed newborns and zero of 65 preterm infants. Varicella-related complications were reported in 3 in utero–exposed newborns (3 with >100 lesions, 1 each with encephalitis and pneumonia). Adverse events were reported for 16% of in utero–exposed newborns and 25% of preterm infants, but few were considered related to VARIZIG. There were no deaths attributable to varicella or VARIZIG.ConclusionsVaricella incidence and morbidity were low in in utero–exposed infants and zero in preterm infants who received prophylactic VARIZIG. There were few VARIZIG-related safety concerns.

A fatal case of severe systemic varicella zoster infection in a patient with chronic use of immunosuppressive agents for cutaneous vasculitis.

Acute varicella zoster virus (VZV) infection is a common condition in children, which is considered a mild, self-limited disease with diffuse skin vesicular rash. However, disseminated VZV infection with multiple organ involvement can occur in immunocompromised patients with impaired T cell immunity including solid or hematopoietic stem cell transplant recipients, receiving immunosuppressive therapy, leukemia, lymphoma, and HIV infection. Prompt antiviral therapy is mandatory in those immunocompromised persons. A 52 year-old man receiving chronic immunosuppressive drugs for his underlying leukocytoclastic vasculitis visited emergency department for diffuse skin vesicular rash that developed 4 days after contact with varicella zoster patients at his office. Despite prompt initiation of oral antiviral agents had been prescribed, rapid progression with septic shock, lactate acidosis, and disseminated intravascular coagulopathy occurred. The patient died within 24 h of intensive care unit admission. Varicella zoster infection commonly causes severe complications in adults receiving chronic immunosuppressive therapy. Post exposure prophylaxis varicella zoster immune globulin and early parenteral antiviral agents use after acute varicella virus infection may be mandatory in immunocompromised patients.

Varicella-zoster virus post-exposure management and prophylaxis: A review.

Varicella-zoster virus causes both varicella (chickenpox) and herpes zoster (shingles). Although varicella incidence has dramatically declined since introduction of the live-attenuated varicella vaccine, vaccination rates are suboptimal, and outbreaks still occur. Additionally, herpes zoster incidence continues to rise. Severe or fatal complications may result from varicella transmission to at-risk individuals who are exposed to either varicella or herpes zoster. An increasing number of children and adults are receiving immunosuppressive therapies and are at high risk for severe varicella and other complications if exposed to the virus. Clinical management of individuals exposed to varicella-zoster virus should take into consideration the type of exposure, evidence of immunity, and host-immune status with regard to ability to receive varicella vaccination safely. Post-exposure varicella vaccination may prevent infection or mitigate disease severity in persons eligible for vaccination. Post-exposure prophylaxis with varicella zoster immune globulin is indicated for populations ineligible for vaccination, including immunocompromised children and adults, pregnant women, newborns of mothers with varicella shortly before or after delivery, and premature infants. Appropriate post-exposure management of individuals exposed to either varicella or herpes zoster-including assessment of immune status and rapid provision of optimal prophylaxis-can help avoid potentially devastating complications of varicella-zoster virus infection.

Varicella zoster immune globulin (VARIZIG) administration up to 10 days after varicella exposure in pregnant women, immunocompromised participants, and infants: Varicella outcomes and safety results from a large, open-label, expanded-access program

IntroductionDespite vaccination, there were more than 100,000 annual cases of varicella in the United States in 2013–2014. Individuals at highest risk of developing severe or complicated varicella include immunocompromised people, preterm infants, and pregnant women. Varicella zoster immune globulin (human) (VARIZIG) is recommended by the CDC for postexposure prophylaxis to prevent or attenuate varicella-zoster virus infection in high-risk individuals. Contemporary information on administration of VARIZIG is limited.MethodsThis open-label, expanded-access program provided VARIZIG to physician-identified, high-risk participants exposed to varicella. Participants included immunocompromised children/adults, infants (preterm, newborns whose mothers had varicella onset within 5 days before or 2 days after delivery, and those aged <1 year), and pregnant women. VARIZIG (125 IU/10 kg [up to 625 IU]) was administered intramuscularly, ideally within 96 hours, but up to 10 days, postexposure. Incidence of varicella rash and severity (>100 pox, pneumonia, or encephalitis) were assessed up to 42 days after administration.ResultsThe varicella outcome population (n = 507) included 263 immunocompromised participants (32 adults, 231 children), 137 pregnant women, 105 infants, and 2 healthy adults with no history of varicella. Varicella incidence was 4.5% in immunocompromised participants, 7.3% in pregnant women, and 11.5% in infants. The incidence of varicella was similar when comparing VARIZIG administration ≤ 96 hours vs > 96 hours (up to 10 days) postexposure in the entire population (6.2% vs. 9.4%, respectively), and also in each subgroup. Of 34 participants with varicella, 5 developed > 100 pox and 1 developed pneumonia and encephalitis. There were no product-related deaths and only 1 serious adverse event (serum sickness) considered probably related to VARIZIG.ConclusionPostexposure administration of VARIZIG was associated with low rates of varicella in high-risk participants, regardless of when administered within 10 days postexposure. VARIZIG was well-tolerated and safe in high-risk participants.

Retrospective and prospective evaluation of chickenpox post-exposure prophylaxis (PEP) in at-risk groups before and after the change in PEP guidelines

Background Public Health England (PHE) chickenpox post-exposure prophylaxis (PEP) guidelines were updated in August 2018. Varicella Zoster Immunoglobulin (VZIg) was replaced with oral aciclovir or valaciclovir in specific settings. Method We retrospectively examined issues of VZIg between August 1 2017 and July 31 2018 at a transplantation centre that also had a large maternity service. In addition, since September 2018, information has been collected prospectively. Additional data were collected on exposure incident, patient risk group and any clinical or serological follow up. Results Thirty issues of VZIg were identified retrospectively over 12 months. These included 9 pregnant women and 21 immunosuppressed patients, average age was 7.6 years (median 4.4 years, SD 11.1). Prospective outcome data were collected since September 4 2018 involving 2 pregnant women and 6 immunosuppressed individuals. Clinical follow-up information was available for 2 pregnant women and 16 immunosuppressed patients. One pregnant woman exposed to her own child with chickenpox and 2 immunosuppressed patients developed clinical varicella at an average of 15.3 days post VZIg. Five immunosuppressed patients were VZV IgG negative post-exposure. Follow-up available to date for 2 of 8 exposure incidents after the change in guidance has shown no clinical or serological evidence of varicella infection. Discussion Where follow up information was available, 19 % developed attenuated VZV around 2 weeks after receiving VZIg. Given the new guidance on using aciclovir prophylaxis, prospective outcome data are being collected and no VZV infections have been noted to date.

Epidemiology, management and outcome of varicella in pregnancy: a 20-year experience at the Tuscany Reference Centre for Infectious Diseases in Pregnancy.

Data from 215 pregnant women exposed to varicella and 276 with varicella observed at the Tuscany Reference Center for Infectious Diseases in Pregnancy, Florence, Italy, in the period 1997-2016 were retrospectively collected. The risk of developing varicella was lower in exposed women who received varicella zoster immunoglobulin compared with those who did not receive it [42% (21 of 50) vs 72% (13 of 18); p = 0.0263]. Typical congenital varicella syndrome was observed in 1.56% of fetuses/neonates born from pregnant women with varicella.

PEPtalk2: results of a pilot randomised controlled trial to compare VZIG and aciclovir as postexposure prophylaxis (PEP) against chickenpox in children with cancer

ObjectiveTo determine the likely rate of patient randomisation and to facilitate sample size calculation for a full-scale phase III trial of varicella zoster immunoglobulin (VZIG) and aciclovir as postexposure prophylaxis...

Cutaneous manifestations of systemic viral diseases in neonates: an update.

Dermatologic findings may be the first signs of a neonatal viral infection. This review provides an update of the diagnostic features and therapies for selected viral illnesses [herpes simplex virus (HSV), varicella zoster virus, enterovirus, and Zika virus] that present with cutaneous manifestations in the neonate. HSV DNA polymerase chain reaction of plasma and cerebrospinal fluid, routinely used in the diagnosis of neonatal HSV, may have expanded utility in assessing prognosis and acyclovir therapeutic efficacy. Maternal antiviral suppressive therapy may alter the clinical appearance of congenital HSV, resulting in delayed diagnosis and treatment. VariZIG, a varicella zoster immune globulin, is a US Food and Drug Administration approved form of prophylaxis for varicella. The Centers for Disease Control and Prevention has expanded the period of VariZIG eligibility for preterm infants, a group particularly susceptible to severe varicella infection. For severe neonatal enterovirus sepsis, the results of a randomized, double-blind, placebo-controlled trial of pleconaril, a viral capsid inhibitor, suggest that this compound is an effective therapy. Human Parechovirus type 3, a strain within a newly formed viral genus, has a similar, and potentially underestimated, clinical presentation to enterovirus sepsis. However, a distinctive erythematous palmoplantar rash may be specific to human Parechovirus type 3 infection. Perinatal Zika virus infection in the neonate may present with a nonspecific macular and papular rash. As this rash is not specific, obtaining a maternal travel history and, if appropriate, requesting additional diagnostic testing are critical for early diagnosis. Neonatal rashes may be harmless and transient, whereas others may reflect the presence of a severe systemic illness. Recognizing key cutaneous features of viral-associated rashes may aid in the prompt and accurate diagnosis and treatment of neonatal viral illnesses.

Varicella-zoster immunoglobulin treatment in pregnant women in Denmark from 2005 to 2015: descriptive epidemiology and follow-up.

Primary infection with varicella-zoster virus in pregnancy poses a risk of severe infection and embryopathies. Upon exposure, seronegative women are candidates for varicella-zoster immunoglobulin (VZIG). The aim of this paper was to describe risk factors for VZIG treatment including sources of varicella exposure and to study how many women developed clinical infection and received postpartum vaccination. We identified all pregnant women who received VZIG from December 2005 to March 2015. Additional information was obtained from Danish registers and a follow-up questionnaire. A total of 104 women were included and 88 completed the questionnaire. Significantly more women had 'other country of origin' than Denmark. They were more often second para (57%) and had most commonly been exposed to varicella by their own child (58%). Five women developed clinical varicella infection, and only 26·5% were vaccinated after delivery. The study concludes that few women developed infection after VZIG and none developed pneumonia. General practitioners should be particularly aware of obtaining varicella anamnesis in parous women from non-temperate countries in order to perform selective vaccination prior to pregnancy. In case of varicella exposure during pregnancy in a seronegative woman, postpartum vaccination is crucial.

Efficacy of varicella (VZV) vaccination: an update for the clinician.

Varicella-zoster virus (VZV) infection causes two distinct clinical conditions. Primary varicella infection results in chickenpox, a contagious rash illness typically seen among children. VZV can reactivate years after the initial infection to cause herpes zoster (HZ) and lead to post-herpetic neuralgia, a common complication resulting in persistent pain that may last for years after the zoster rash resolves. A person's risk of having longer lasting and more severe pain associated with HZ increases with age. Since the introduction of VZV vaccines, the rates of infection, hospitalizations, and mortality have declined. In this review, we discuss in detail current VZV vaccines available for the prevention of VZV and HZ infections. Varilrix (GSK Biologicals, UK), Varivax (Merck, USA) and the combined measles, mumps, rubella, and varicella (MMRV) vaccine contain the live attenuated Oka strain of VZV for routine varicella vaccination. While Zostavax is the only HZ vaccine currently approved for use in the United States and the European Union [EMEA, 2011], a subunit vaccine candidate called HZ/su has recently shown improved efficacy for zoster prevention in two clinical trial phase III studies. VariZIG, a post-exposure prophylactic, uses zoster immune globulin to prevent VZV infection in those who have recently been in contact with VZV but lack evidence of varicella immunity and are contraindicated to receive the varicella vaccine. Further, we discuss the skin tropic and neurotropic factor VZV ORF7 gene and its involvement in varicella infection, reactivation and latency in ganglia. Ultimately, these studies can contribute to the development of a neuroattenuated vaccine candidate against varicella or a vector for delivery of other virus antigens.