Primary Varicella Research Articles

The Use of Antibiotics in the Treatment of Pediatric Varicella Patients: Evidence from the multi-country MARVEL study

Background: Varicella is a common infectious disease in childhood that can result in bacterial complications such as skin and soft tissue infections and pneumonias, among others. Although well-tolerated and effective varicella vaccines have been available for >20 years, only 40 countries around the world have implemented universal varicella vaccination (UVV) programmes. The objective of this study was to examine empiric data on the appropriate and inappropriate use of antibiotics in the treatment of pediatric varicella patients, based on data collected in five countries (Argentina, Hungary, Mexico, Peru, and Poland). Methods & Materials: Five primary data collection studies were conducted between 2014-2017 as part of MARVEL (Multi-country economic and epidemiological burden of varicella study). Detailed data were obtained on the treatment of primary varicella in both inpatients and outpatients aged 1-14 years between 2009-2016. We descriptively analyzed data on the type of complications, severity of disease (measured by number of lesions), and dosage and duration of both prescription and non-prescription antibiotic use, together with data on whether or not a confirmation of the presence of bacterial infections was available. These results were contrasted within countries to treatment guidelines for varicella and the use of antibiotics to assess appropriate and inappropriate use, and between countries to compare utilization patterns. Results: Across the 5 countries, 787 patient records were included (401 outpatients, 386 inpatients). The average number of antibiotics used per inpatient ranged from 0.9 in Poland to 1.9 in Peru, with an average duration of use of 7.2 days (Hungary) to 15.8 days (Mexico) among users. Among outpatients, this ranged from 0.03 antibiotics in Hungary to 0.4 antibiotics in Argentina, with an average duration of antibiotics used of 6.5 days (Peru) to 9.5 days (Argentina). The proportion of antibiotics prescribed without a probable or confirmed diagnosis of bacterial infection ranged from 44.3% (Hungary) to 89.9% (Peru). Conclusion: UVV could substantially reduce both inappropriate and appropriate use of antibiotics in pediatric varicella patients, and could be a valuable tool in an arsenal to combat antimicrobial resistance. Further studies on the gap between appropriate and inappropriate use of antibiotics in the treatment of varicella may be warranted.

Live zoster vaccination in an immunocompromised patient leading to death secondary to disseminated varicella zoster virus infection

In 2016, the live attenuated zoster vaccine (Zostavax, Merck and Co, USA) was introduced into the Australian National Immunisation Program for people aged 70 years who are not significantly immunocompromised. We report the administration of Zostavax in an immunocompromised patient with chronic lymphocytic leukaemia and no evidence of primary varicella zoster virus (VZV) infection. The patient presented with a bilateral vesicular facial rash 22 days after receiving Zostavax and was initially managed as an outpatient with oral acyclovir. He re-presented three days later and was diagnosed with disseminated VZV infection complicated by meningoencephalitis. The patient died following cardiac arrest on day 10 of hospitalisation. This unfortunate case highlights the challenge of safely implementing a high titre live vaccine in a population where contraindications are prevalent. The non-live recombinant herpes zoster subunit vaccine (Shingrix, GSK) may provide a safe and effective option to protect immunocompromised patients from shingles and post-herpetic neuralgia.

Spontaneous splenic rupture complicating primary varicella zoster infection: a case report

BackgroundPrimary varicella zoster virus (VZV) infection is a common illness, predominantly affecting children. Its course is typically benign, although severe complications have been described. Splenic rupture is an extremely rare and potentially fatal complication of primary VZV infection, with only a handful of cases reported in the literature.Case PresentationA 32-year-old Romanian man with no significant past medical history, presented with a 2 day history of sudden onset, worsening generalised abdominal pain and a 1 day history of vomiting. The following day he developed fevers and a generalised widespread erythematous rash consisting of clusters of macules, papules and vesicles at different stages of development. There was no history of sore throat, coryza, arthralgia, myalgia, cough, shortness of breath, weight loss, or night sweats. There was no recent illness and no history of trauma. CT abdomen showed splenic rupture with intra-abdominal haemorrhage. Admission bloods showed anaemia and thrombocytopenia, with haemoglobin 110 g/l and platelets 78 × 109/l. Viral PCR of vesicle fluid from the rash was positive for VZV DNA confirming the clinical diagnosis of primary varicella zoster infection. Viral serology also confirmed recent infection. He was haemodynamically resuscitated, and underwent laparotomy and splenectomy. He was commenced on IV acyclovir and completed a 5 day course. Prior to discharge he was commenced on recommended splenectomy secondary prevention treatment.ConclusionThere are several reported complications of varicella infection, more commonly in the immunocompromised population. Spontaneous splenic rupture is an unusual complication of primary VZV infection. Here we report the sixth known case in the literature. Splenic rupture should be considered in cases of primary varicella in young adults presenting with abdominal pain.

PIN30 - The Economic Burden of Varicella in Mexico

To assess the clinical and economic burden of varicella in Mexico, where the varicella vaccine is not publicly available, except in children undergoing bone marrow transplantation. Annual societal costs were estimated for a base scenario by multiplying per-patient costs with varicella incidence from the Mexican epidemiological surveillance system (SUIVE), adjusted for the estimated proportion of public healthcare centers who do not regularly report. In a sensitivity analysis where cost calculations remained stable, epidemiological estimates ranged between raw SUIVE varicella rates (lower bound), and a 25% additive increment to reflect the estimated proportion of public sector patients who utilize private services (upper bound). Outcome Measures Clinical complications; health care resource utilization (HCRU)(frequency and type) including outpatient visits, allied healthcare contacts, doctor’s visits, tests/procedures performed, prescription and over-the-counter (OTC) medications, hospitalizations, and Emergency Room (ER) and Intensive Care Unit(ICU) visits/stays. Charts of 152 varicella patients were included, of which 75 and 77 were outpatients and inpatients [mean (SD) age=3.0 (3.2) and 2.6 (3.5) years, respectively]. Inpatients reported higher complication rates (inpatients vs. outpatients: 84.4% vs. 6.7%), prescription medication use (94.8% vs. 80.0%), over-the-counter medications use (71.4% vs. 80.0%), tests/procedures (87.0% vs. 5.3%), and allied health professional consultations (61.0% vs. 12.0%). Direct/indirect costs per case were $198/$42 (outpatients), and $5,633/$175 (inpatients). Estimated societal costs related to varicella ranged from $77-$218 million. Substantial clinical and associated public health and economic burden were observed among children with primary varicella infection in Mexico. These results highlight the need for implementation of a childhood varicella vaccination program.

905 Anti-VZV-IgM antibody is more frequently induced in herpes zoster patients with systemic dissemination

(Background) Although herpes zoster is an internal reactivation of latently infected varicella zoster virus (VZV), some zoster patients become anti-VZV-immunogloburin (Ig) M antibody positive. We have previously reported that anti-VZV specific IgM antibody is observed in 12% in patients with acute herpes zoster. (Purpose) To find out whether these IgM patients had specific clinical features. (Method) Medical records of patients with varicella or herpes zoster were sought in the database of Fukuoka University hospital from 2010 to 2016, and their skin symptom, time lapse from onset to the first visit, as well as serum titers of anti-VZV-IgM and IgG were retrospectively extracted and analyzed. (Result) Total of 94 patients with acute herpes zoster (n=79) or varicella (n=15) were tested with both anti-VZV-IgM and IgG antibodies in the database. Anti-VZV-IgM were positive positive (VZV-IgM> 1.0 by enzyme linked immuno-sorbent assay, ELISA) in 8/79 (10%) patients, in 4/6 (67%) primary varicella in young patients, and in 6/7 (86%) secondary varicella infection in old subjects. Interestingly, 5/8 (63%) IgM-positive subjects had disseminative eruption, while only 5/60 (8%) IgM-negative patients had dissemination (p=0.0172, Fishers exact test). When stratified by titer, 4/5 (80%) of zoster patients had relatively low titer (ELISA reading between 1.0 to 4.0), while most patients with primary or secondary VZV infection had higher titers (>4.0). (Conclusion) Resistance against herpes zoster may be controlled by both systemic and local immunity, and loss/attenuation of systemic immunity may allow systemic dissemination of VZV and induce anti-VZV-IgM de novo, like primary varicella.

Primary varicella presenting with coexistent features of PLEVA

Primary varicella presenting with coexistent features of PLEVA

Economic burden of varicella in children 1–12 years of age in Argentina, 2009–2014

Background: In Argentina, varicella vaccination was included in the national schedule for mandatory immunizations in 2015. The vaccine has been shown to substantially reduce the morbidity and mortality associated with the virus. The purpose of this study was to evaluate the clinical and economic burden associated with varicella in Argentina prior to vaccine introduction.Methods: This was a multi-center, retrospective chart review study among patients aged 1–12 years with a primary varicella diagnosis in 2009–2014 in Argentina. Healthcare resource utilization (HCRU) associated with varicella and its complications, unit costs, and work loss were used to estimate direct and indirect costs. All costs are presented in 2015 United States dollars (USD).Results: One hundred and fifty children with varicella were included (75 outpatients, 75 inpatients), with a mean age of 3.8 (SD = 2.4) and 2.9 (SD = 2.2) years, respectively. One or more complications were experienced by 28.0% of outpatients and 98.7% of inpatients, the most common being skin and soft tissue infections, pneumonia, sepsis, cerebellitis, and febrile seizure. HCRU estimates included use of over-the-counter (OTC) medications (58.7% outpatients, 94.7% inpatients), prescription medications (26.7% outpatients, 77.3% inpatients), tests/procedures (13.3% outpatients, 70.7% inpatients), and consultation with allied health professionals (1.3% outpatients, 32.0% inpatients). The average duration of hospital stay was 4.9 (95% CI = 4.2–5.7) days, and the average duration of ICU stay was 4.8 (95% CI = 1.6–14.1) days. The total combined direct and indirect cost per varicella case was 2947.7 USD (inpatients) and 322.7 USD (outpatients). The overall annual cost of varicella in Argentina for children aged ≤14 years in 2015 was estimated at 40,054,378.0 USD.Conclusion: The clinical burden of varicella in Argentina was associated with utilization of significant amounts of healthcare resources, resulting in substantial economic costs. These costs should be reduced with the recent implementation of routine vaccination of children.

BET 2: NSAIs and chickenpox

A shortcut review was carried out to establish whether non-steroidal anti-inflammatory drugs (NSAIDs) is safe to prescribe in patients with chicken pox. 66 unique papers were found in CINAHL, Medline,...

The Case Files

The Case Files

Seroprevalence of Varicella Zoster Infection at Provincial Level in Iranian Adolescents: The CASPIAN-III Study

Background: Although primary varicella zoster virus (VZV) infection (chicken pox) is a mild childhood disease, it can cause severe infection with complications in adults. As the disease is preventable by effective vaccination, it is important to determine the level of immunity to VZV in every region to implement proper vaccination strategies. Objectives: The aim of this study was to investigate the seroprevalence of VZV infection in adolescents living in different provinces of Iran. Methods: In a cross-sectional multicentre study, serum samples from 2315 students, aged 10 - 18 years, were examined for VZV antibodies (IgM/IgG). Students were selected by multistage cluster sampling during a national surveillance program. Results: Prevalence of VZV antibodies was statistically different in various provinces of Iran (P = 0.001); it ranged from 82.4% in Isfahan, Center of Iran, to 98.5% in Mazandaran, North of the country. The VZV seroprevalence was not significantly different by gender, except for Khuzestan, South of Iran, where antibodies were much more prevalent in girls (92.7%) than in boys (78.3%, P = 0.004). Seroprevalence was not significantly different according to the living area (urban/rural). Conclusions: VZV seroprevalence is different in various provinces of Iran; the susceptibility of adult population to VZV infection is suggested to be high in Ardabil, Isfahan, and Kermanshah; and low in Kerman and Mazandaran. Therefore, different strategies should be implemented in each province to protect high-risk adults from severe varicella infection.

Post-Varicella Acute In ammatory Demyelinating Polyradiculoneuropathy in a 51-year old Filipino Male: A Case Report

Primary varicella zoster infection is commonly observed in school-aged children. There are increasing reports of adults being affected. Varicella zoster infection has a myriad of clinical complication. The rarer of these complications is GuillanBarre syndrome (GBS) or acute inflammatory demyelinatimgpolyradiculoneuropathy, with less than 50 cases in reported literature. Keywords: varicella, acute inflammatory demyelinating polyradiculoneuropathy, GuillanBarre Syndrome

Zoster vaccine-associated primary varicella infection in an immunocompetent host

A 64-year-old immunocompetent man developed a widespread pruritic and vesicular rash 2 weeks after receiving the zoster vaccine (Zostavax). He had fever, bandaemia with normal total white blood cell count...

Economic burden of varicella in children 1\u201312\xa0Years of age in Hungary, 2011\u20132015

BackgroundAlthough live-attenuated varicella-zoster virus (VZV) vaccines have been proven to be safe and effective in preventing varicella and real-word evidence shows routine childhood immunization programs are effective in dramatically reducing varicella associated morbidity and mortality, varicella vaccine is not included in the National Immunization Program (NIP) in Hungary. The purpose of this study was to evaluate the clinical and economic burden associated with varicella in Hungary.MethodsThis was a multicenter, retrospective, chart review study of patients aged 1–12 years with a primary varicella diagnosis between 2011 and 2015. Healthcare resource utilization (HCRU) associated with varicella, unit costs, and work loss were used to estimate direct and indirect costs. All costs are presented in 2015 HUF / Euros (€).Results156 children with varicella were included (75 outpatients, 81 inpatients), with a mean age of 4.4 (SD: 2.0) and 3.7 (SD: 2.1) years, respectively. One or more complications were reported by 12.0% of outpatients and 92.6% of inpatients, the most common being dehydration, skin and soft tissue infections, pneumonia, keratoconjunctivitis, and cerebellitis. HCRU estimates included use of over-the-counter (OTC) medications (96.0% outpatients, 53.1% inpatients), prescription medications (9.3% outpatients, 70.4% inpatients), tests/procedures (4.0% outpatients, 97.5% inpatients), and consultation with allied health professionals (2.7% outpatients, 30.9% inpatients). The average duration of hospital stay (inpatients) was 3.6 (95% CI: 3.2, 4.1) days. The total combined direct and indirect cost per varicella case was 228,146.7 Hungarian Forint (HUF)/€ 736.0 for inpatients and 49,790.6 HUF/€ 106.6 for outpatients. The overall annual cost of varicella in Hungary for children aged <15 years in 2015 was estimated at 1,903,332,524.3 HUF/ € 6,139,980.4.ConclusionVaricella is associated with substantial clinical burden in Hungary, resulting in the utilization of a significant amount of healthcare resources. These results support the need for routine vaccination of all healthy children to reduce the varicella-associated disease burden.

Öncesinde Sağlıklı Olan Herpes Zosterli Çocuklarda Primer Varisella Zoster Virüs Enfeksiyonunun Zamanı: Önemli mi?

Öncesinde Sağlıklı Olan Herpes Zosterli Çocuklarda Primer Varisella Zoster Virüs Enfeksiyonunun Zamanı: Önemli mi?

The Time of the Primary Varicella Zoster Virus Infection in Previously Healthy Children with Herpes Zoster: Is It Important?

The Time of the Primary Varicella Zoster Virus Infection in Previously Healthy Children with Herpes Zoster: Is It Important?

Olgu sunumu: 83 yaşındaki bir hastada primer varisella enfeksiyonu

Varicella is a common and highly contagious disease of childhood which is caused by varicella zoster virus (VZV). A 83 year old man consulted our clinic with black crusted lesions without ichting on his trunk for one week. Dermatological examination showed multipl necrotic ulcerations on his trunk, scalp and upper parts of extremities and a few vesicles on his left femoral area. He has hypertension for 45 years, diabetes mellitus for 10 years, chronic kidney failure for one year and because of those diseases he’s been using a lot of medicines. He had a heart attack and coronary bypass surgery six months ago. He had many infections in different times and had given many antibiyotics. The patient consulted Dermatolgy for skin lesions. Skin biopsy showed VZV infection. We reported this case due to its rarity in older ages and to emphasize that the possibilty of primary varicella infection should be kept in mind as an entity for differential diagnosis during the clinical evolutions vesiculobullous diseases in older ages.

Primary Varicella Zoster Virus Infection in an Eritrean Male Refugee in Denmark

Primary infection with varicella zoster virus (VZV) in neonates, adults and in pregnancy may lead to severe disease and embryopathy. On the Northern hemisphere varicella is a mild childhood disease, but in tropical regions it typically occurs at later age and is more frequently observed among adolescents and adults. Disease presents with fever, malaise and a characteristic vesiculopapular rash (chickenpox) after an incubation period of 14 days on average. VZV is very contagious and transmission occurs mainly airborne. After infection, virus persists latent and prompts herpes zoster on reactivation. Severe complications include bacterial sepsis, pneumonia, encephalitis, haemorrhage, congenital varicella syndrome and others.

Cost-effectiveness of Varicella Vaccination Program in Iran.

Background:Varicella zoster virus is the etiologic agent of primary varicella (chickenpox) during childhood, and varicella vaccination has not been introduced in Iran. The aim of this study is to estimate cost-effectiveness of one- and two-dose Varicella Vaccination Program in Iran.Methods:A decision-tree model was conducted to evaluate the cost-effectiveness of the Varicella Vaccination Program in a cohort of 12 months children in Iran. Epidemiologic parameters of varicella were extracted from local and international sources, and cost of disease was estimated based on societal prospective in 2015 US$. Incremental cost per disability-adjusted life years (DALY) averted calculated as final outcome. Sensitivity analysis was also performed for lower and upper estimate of incidence, DALY, and vaccine efficacy.Results:Considering the vaccine efficacy of 95%, for the two-dose and 85% for the one-dose vaccination, incremental cost-effectiveness ratio (ICER) per DALYs averted were US$41,531 and US$17,280, respectively. ICER has changed between (US$ 6,177–US$167,047) in lower and upper base estimate of epidemiological burden parameters in sensitivity analysis.Conclusions:Varicella vaccination is not cost-effective in Iran in one-dose and two-dose scenario under the assumptions of this study in base case scenario according to the threshold of incremental cost per DALY averted less than three time of GDP per capita in Iran = US$ 14,292. One-dose vaccination program might be cost-effective in upper scenario of epidemiological burden of varicella in sensitivity analysis.

Primary varicella infection in children with systemic juvenile idiopathic arthritis under tocilizumab therapy

We report the clinical course and outcome of primary varicella infection in six children with systemic juvenile idiopathic arthritis (sJIA) receiving tocilizumab. None had disseminated or fatal varicella infection, but one patient developed macrophage activation syndrome (MAS) and another had an arthritis relapse. All patients had a significant elevation of serum IL-6 levels, and the two children who developed MAS or arthritis relapse showed high serum IL-18 levels, which could cause a sJIA flare-up.

Primary varicella zoster virus infection in renal transplant recipients

L’accès à la greffe rénale pour les patients insuffisants rénaux chroniques terminaux est un enjeu majeur en France. L’inscription sur liste d’attente de greffe est une étape obligatoire pour pouvoir accéder à cette technique. La Haute Autorité de santé a mis à jour, en 2015, les contre-indications à l’accès à cette liste. Dans ce contexte, nous avons voulu réaliser un état des lieux des motifs de non-inscription sur la liste d’attente de greffe rénale chez les patients dialysés depuis au moins un an, âgés de moins de 80 ans, en France. Tous les patients inclus dans le registre d’épidémiologie et d’information en néphrologie (REIN), devant avoir leur point annuel de suivi du 1er août au 30 novembre 2016 répondant aux critères, ont été inclus et un questionnaire dédié a été rempli par leur centre de dialyse. Ainsi, 3172 patients ont été analysés : 2302 (73 %) avaient une contre-indication médicale à la greffe, le plus souvent (33 %) vasculaire, 458 (14 %) refusaient d’être inscrits, avec proportionnellement plus de femmes dans cette catégorie et enfin, chez 412 patients (13 %), on ne retrouvait pas de motif renseigné dans notre questionnaire. Néanmoins, pour 65 % des patients de cette dernière catégorie, un bilan en vue d’une inscription était débuté. Il y avait donc, dans notre cohorte, seulement 144 patients (4,5 %) sans explication à la non-inscription. Cette étude nationale est la première à donner à un état des lieux des motifs de non-inscription sur liste de greffe rénale en France. Sans surprise, la contre-indication médicale est le premier motif de non-inscription dans cette population de patients chroniques. Le fort taux de refus doit être souligné et analysé plus précisément, notamment avec le ressenti du patient. Et enfin, très peu de patients n’ont pas de motif renseigné ou de bilan en cours.Access to kidney transplants for patients with end-stage chronic renal disease is a major challenge in France. Registration on the transplant waiting list is a mandatory step to be able to access this technique. The Haute Autorité de santé (HAS) updated, in 2015, the contraindications to access this list. In this context, we wanted to make an inventory of the reasons for non-registration on the renal transplant waiting list in patients on dialysis for at least a year, aged less than 80 years, in France. All patients included in the Epidemiology and Nephrology Information Register (REIN), who were supposed to have their annual monitoring point from August 1 to November 30, 2016 meeting the criteria, were included and a dedicated questionnaire was completed by their dialysis center. Thus, 3172 patients were analyzed: 2302 (73%) had a medical contraindication to transplant, most often (33%) vascular, 458 (14%) refused to be registered, with proportionately more women in this category, and finally in 412 patients (13%), there was no reason given in our questionnaire. However, for 65% of patients in the latter category, an assessment for registration had started. There were therefore, in our cohort, only 144 patients (4.5%) without explanation for the non-registration. This national study is the first to give a view of the reasons for non-registration on the renal transplant list in France. Unsurprisingly, medical contraindication is the primary reason in this population of chronic patients. The high refusal rate should be emphasized and analyzed more precisely, in particular with the patient's point of view. And finally, very few patients have no informed reason or current assessment.