Varicella in the 21st Century.

Varicella is a highly contagious disease caused by the varicella-zoster virus and has a wide range of clinical presentations. Varicella can cause mild disease in infants born to infected persons who are immunized as a result of previous vaccination or previous clinical or subclinical infection. However, varicella can also lead to severe life-threatening disease in infants, particularly for those born to nonimmunized persons. In this review, we will summarize the natural history of varicella-zoster infection in pregnant persons, infants with congenital varicella syndrome, and infants with postnatal varicella infection. We will also provide guidance about isolation recommendations and chemoprophylaxis for exposed hospitalized infants. Finally, we will describe risk factors for developing disseminated disease and review the approach to treatment of infected infants.

An Autopsy Case of Disseminated Varicella Zoster Virus Infection during the Treatment of Nephrotic Syndrome.

A 68-year-old woman developed systemic blisters while receiving treatment for nephrotic syndrome. As she also developed marked liver dysfunction and disseminated intravascular coagulation, she was admitted to our hospital. She was diagnosed with varicella zoster virus (VZV) infection. Treatment was administered in the intensive-care unit, but the patient died on day 24 post-admission after severe VZV infection. A post-mortem examination showed micro-abscesses and necrosis caused by varicella zoster infection in multiple organs, including the liver, kidneys, and gastrointestinal tract. Because VZV infection can become severe in immunocompromised patients, careful consideration is needed for the prevention and treatment of the viral infection.

Caracterización clínica y de costos de la hospitalización asociada a varicela en niños de la Región Metropolitana y de Valparaíso, Chile / Clinical and cost characterization of hospitalization associated with varicella in children from the Metropolitan Region and Valparaíso, Chile

INTRODUCCIÓN: La varicela es una infección relevante en la salud pública de Chile, pudiendo causar en algunas ocasiones complicaciones graves e incluso la muerte, lo que se asocia a un significativo gasto en salud. En Chile sólo se realiza vigilancia centinela a nivel ambulatorio, sin conocerse el impacto de la varicela en casos más graves que determinan hospitalización. OBJETIVOS: Realizar una descripción clínica y de los costos asociados a la atención de niños hospitalizados con diagnóstico de varicela, en años previos a la introducción de la vacuna en el Programa Nacional de Inmunización en Chile. MATERIALES Y MÉTODOS: Estudio multicéntrico, observacional y retrospectivo, en todos los casos de niños hospitalizados (0-15 años) con diagnóstico de varicela, entre enero de 2011 y diciembre de 2015 en cinco hospitales de Chile. Se realizó revisión de fichas para evaluar características clínicas de la enfermedad y los costos asociados a la hospitalización por varicela. RESULTADOS: Un total de 685 hospitalizaciones por varicela fueron incluidas en el estudio. La mediana de edad fue de 3 años (RIC:1-5), siendo la mayoría de los niños con edades comprendidas entre los 1 y 4 años (52% del total de casos). El 56% fueron hombres y sólo 7 niño s (1%) tuvieron antecedente de vacuna varicela. La mediana de días de hospitalización fue de 3 días en cada episodio (RIC: 2-5). El 13% de los casos requirió hospitalización en unidades de mayor complejidad, 7% de los niños ingresó a Unidad de Tratamiento Intensivo y 6% ingresó a Intermedio, ambos con una mediana de 3 días de hospitalización. Las principales complicaciones fueron: infección de piel y tejidos blandos (42%), alteraciones neurológicas (8%) y shock séptico/tóxico (4%). La letalidad fue de 0,4%. El costo de un caso de varicela considerando los costos directos fue de US$417, el costo indirecto fue de US$224 y los costos proporcionales de una muerte de US$3.575. Se estima que el costo total de un caso de varicela hospitalizado en Chile, considerando todos los factores anteriores, fue de US$4.216. CONCLUSIONES: La varicela es una enfermedad inmunoprevenible frecuente. Se observaron casos con una mediana de 3 días de hospitalización por complicaciones, con 13% de los casos requiriendo hospitalización en unidades de mayor complejidad, con un alto costo asociado, que se estima podría disminuir significativamente con la reciente incorporación de la vacuna al Programa Nacional de Inmunizaciones.

BACKGROUND: Varicella is a relevant infection in Chile and may cause serious complications and death, which could be associated with significant health care resource utilization and associated costs. In Chile, sentinel surveillance is carried out only on an outpatient basis, without knowing the impact of varicella in serious cases who need to be hospitalized. AIM: To describe the clinical characteristics and the costs associated with hospitalized children with diagnosis of varicella prior to the vaccine introduction in the National Immunization Program in Chile. PATIENTS AND METHODS: A multicenter, observational, and retrospective study in hospitalized children (0-15 years) with a diagnosis of varicella, were conducted in five hospitals in Chile between January 2011 and December 2015. A review of the clinical records was performed to evaluate the clinical characteristics of the disease and costs associated with hospitalization episodes for varicella. RESULTS: A total of 685 hospitalized children for varicella were included in this study. The median age was 3 years (IQR: 1-5), most children were between 1 and 4 years of age (52% of total cases). 56% were male, and only 7 patients (1%) had a history of previous varicella vaccination. The median lenght of days of hospitalization was 3 days (IQR: 2-5). 13% of the cases required hospitalization in a more complex care unit, 6% in the intermediate unit and 7% in the pediatric intensive treatment unit, both with a median stay of 3 days. The main complications were: skin and soft tissue infections (42%), neurologic (8%) and septic or toxic shock (4%). There were 3 cases of death (0.4%). The direct cost of a varicella case was US $ 417, the indirect cost was US $ 224 and the proportional cost of a case of death was US $ 3,575. It is estimated that the total cost of a hospitalized varicella case in Chile was US $ 4,216. CONCLUSIONS: Varicella is associated with a significant burden of disease in Chile. The median hospital stay was three days with 13% of cases requiring medical care in a complex unit, with high associated costs which could be significantly reduced with the recently incorporation of the varicella vaccine into the National Immunization Program.

Emerging and Re-emerging Infections in Children: COVID/ MIS-C, Zika, Ebola, Measles, Varicella, Pertussis ... Immunizations.

The role of the emergency provider lies at the forefront of recognition and treatment of novel and re-emerging infectious diseases in children. Familiarity with disease presentations that might be considered rare, such as vaccine-preventable and non-endemic illnesses, is essential in identifying and controlling outbreaks. As we have seen thus far in the novel coronavirus pandemic, susceptibility, severity, transmission, and disease presentation can all have unique patterns in children. Emergency providers also have the potential to play a public health role by using lessons learned from the phenomena of vaccine hesitancy and refusal.

Use of health care resources for varicella in the paediatric population, Jordan.

BACKGROUND: The exact burden of varicella is not well quantified in Jordan. AIMS: This study aimed to estimate the varicella burden in paediatric patients in Jordan who sought care in a hospital-based setting. METHODS: This was a multicentre, retrospective review of medical records of patients aged 0-14 years with a primary varicella diagnosis in Jordan between 2013 and 2018. The data assessed were: use of health care resources for varicella (outpatient and inpatient visits, tests and procedures, and medication use), and clinical complications of the infection. Estimated costs were based on health care resources used (direct costs) and lost revenue to the child's caregiver (indirect costs) for outpatients and inpatients. RESULTS: In total, 140 children with varicella were included: 78 outpatients, mean age (standard deviation) 4.4 (3.2) years, and 62 inpatients, mean age 4.0 (3.8) years. No outpatients had varicella-related complications, while 32 (52%) inpatients had ≥ 1 complication. The use of health care resources was higher for inpatients than outpatients, including prescription medication use - 94% of inpatients versus 6% of outpatients. Total costs of varicella were estimated at US$ 66.1 (95% CI: 64.1-68.1) per outpatient and US$ 914.7 (95% CI: 455.6-1373.9) per inpatient. CONCLUSIONS: Varicella is associated with considerable use of health care resources in Jordan and may be responsible for annual costs of US$ 11.5 million. These results support universal varicella vaccination in Jordan.

Efficacy of plasma exchange with a high dose of acyclovir for disseminated varicella infection.

In individuals treated with immunosuppressive therapies, the varicella-zoster virus (VZV) infection can become disseminated and lead to a life-threatening condition. There is currently no established treatment strategy for this life-threatening condition. Here, we describe a case where plasma exchange (PE) with a high dose of acyclovir (ACV) ameliorated the severe effects, including VZV-hemophagocytic lymphohistiocytosis (VZV-HLH) and disseminated intravascular coagulation (DIC), in a 9-year-old girl with steroid-dependent nephrotic syndrome. This 9-year-old girl experienced frequent relapse steroid-dependent nephrotic syndrome. She had been treated with steroids, tacrolimus, mizoribine, and rituximab. She had not previously received a varicella vaccine. She was admitted with only one vesicular rash. At admission, a serum test revealed 1.6 × 106 copies/mL of VZV DNA. The patient rapidly developed VZV-HLH and DIC. A combination of a high dose of ACV, immunoglobulin, and steroid pulse therapy could not improve these severe complications. Therefore, PE was applied. PE with a high dose of ACV successfully reduced serum VZV DNA from 7.5 × 106 to 2.8 × 104 copies/mL. This reduction in the VZV DNA copy number suggested that the combination of PE and a high dose of ACV was effective in treating a disseminated VZV infection. To the best of our knowledge, this is the first report showing that PE with a high dose of ACV ameliorated the severe complications of disseminated VZV by reducing the VZV DNA copy number.

Epidemiological and clinical characteristics and the approach to infant chickenpox in primary care.

Chickenpox is not common in the first year of life (infant varicella) and there is a lack of data on its presentation, especially in primary care. A year-long observational study (July 2015-2016) carried out by a research network of primary care pediatricians throughout Spain.Two hundred and sixty-four pediatricians gathered data from 358 cases of clinically diagnosed chickenpox in infants. The illness was considered mild in 78% of infants < 7 months compared to 65% in those aged 7 to 12 months (p = 0.0144). Fever (46%) was present in 35% of children ≤ 6 months compared to 55% in older children (p = 0.0005). The number of skin lesions was > 50 in 35% of children ≤ 6 months old compared to 47% in > 7 months (p = 0.0273). From the 2% of hospitalized children 86% were younger than 7 months. Oral antiviral treatment was given in 33% of cases ≤ 6 months compared to 18% in older patients (p = 0.0023). Doubts about administering the chickenpox vaccine at a later date were expressed by 18% of pediatricians.Conclusion: Chickenpox is considered benign, having a mild effect on most infants. There is less clinical effect in infants ≤ 6 months although this age group is hospitalized more and is prescribed more antiviral treatment. There are doubts among pediatricians about the subsequent need for vaccination. What is Known: • Chickenpox is uncommon and of uncertain evolution in the first year of life • Hospital admissions for chickenpox are more frequent in the first year of life What is New: • The course of chickenpox in the first year of life is mild, especially in infants younger than 7 months despite the fact they are hospitalized more and are treated more frequently with antivirals. Antivirals are prescribed to 1 in 4 children with chickenpox under 12 months of age. • Almost 50% of pediatricians recommend a subsequent vaccination against chickenpox especially if it occurs in the first 6 months of life.

How to manage chickenpox during pregnancy: case reports.

Chickenpox is a human infection that occurs mainly during childhood. Infection during pregnancy is therefore rare but may cause a congenital infection with malformation in less than 1% of cases. A specific management should be proposed at diagnosis in order to reduce materno-fetal transmission and morbimortality. Three cases were herein presented focusing on the main at-risk situations for pregnant women, whom immunological status against varicella was unknown. The first case focused on a varicella eruption during early pregnancy that leads to a lethal outcome. The second one described the management of varicella contact during early pregnancy. This woman was treated by specific immunoglobulins, leading to a positive outcome. The third case focused on another varicella contact, at the end of pregnancy. The woman was treated by acyclovir, before and after delivery, to limit materno-fetal consequences. In conclusion, after a suspicious contact, a serology assay has to be performed to know the immune status of the pregnant woman against varicella. In case of seronegativity, prevention against varicella infection should be carried out using specific immunoglobulins or valacyclovir. Clinical varicella does not require virology confirmation but requires immediate treatment with valacyclovir especially when it occurs during the first trimester.

Case Report: Delayed Diagnosis of Congenital Malaria by Plasmodium vivax in a Newborn of an Eritrean Woman with Varicella Infection.

Congenital malaria (CM) is uncommon in both malaria-endemic and non-endemic countries. It may be caused by any Plasmodium spp., although Plasmodium falciparum and Plasmodium vivax are the more frequent etiologic agents. We report a case of delayed diagnosis of CM by P. vivax in a newborn of an Eritrean primigravida. The mother developed pregnancy-related immunodepression and varicella-zoster viral infection 9 days before natural delivery; therefore, the child was admitted in the neonatal intensive care unit (NICU) to administer specific varicella-zoster immunoglobulin prophylaxis and for clinical monitoring. During the NICU stay, the newborn presented a febrile syndrome with vomiting, anemia, and thrombocytopenia. A P. vivax severe malaria diagnosis was made by detecting trophozoites in the thick and thin blood smears. The infant was successfully treated with intravenous artesunate and clindamycin. Our experience suggests that malaria diagnostic tests need to be included in routine blood analyses in newborns with febrile syndrome from mothers with an epidemiologic link to malaria-endemic areas.

Lessons From an Outbreak of Varicella Infection in Pediatric Hemato-oncology Patients.

BACKGROUND: Immunocompromised patients exposed to varicella may experience significant morbidity and a 7% mortality rate. Management and outcome of an outbreak of varicella infection among hospitalized pediatric hemato-oncology patients using the guidelines of the American Academy of Pediatrics Committee on Infectious Diseases are presented. METHODS: This retrospective study describes an outbreak of varicella infection between February 2011 and June 2011. Data were retrieved from the patients' files. Positive polymerase chain reaction results for varicella zoster virus from vesicular skin lesions were used for the diagnosis of varicella infection. RESULTS: Twelve pediatric hemato-oncology patients experienced 13 episodes of varicella infection, 11 underwent 1 episode each and 1 patient had 2 episodes. All exposed patients without immunity received varicella zoster immune globulins or intravenous immunoglobulin and were isolated as recommended by the guidelines. Infected patients received intravenous acyclovir. One patient with acute lymphoblastic leukemia at induction chemotherapy died. All the other patients survived. CONCLUSIONS: Our experience in the management of hospitalized immunocompromised patients exposed to varicella was that a positive IgG serology did not confer protection after exposure to varicella infection and thus can not serve as a marker for immunity. Unlike the isolation period sufficient for immunocompetent patients, crusted lesions can be contagious and thus require extended isolation for immunocompromised patients. Patients receiving rituximab are at greater risk of having persistent or recurrent disease. Studies with a larger sample size should be performed to better assess the management of immunocompromized patients exposed to varicella.

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.

Economic burden of varicella in children 1-12 Years of age in Hungary, 2011-2015.

BACKGROUND: Although 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. METHODS: This 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 (€). RESULTS: 156 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. CONCLUSION: Varicella 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.

Varicella associated pneumoniae in a pediatric population.

BACKGROUND: Varicella pneumonia has been studied extensively in adults; it may also affect children and may require hospitalization. METHODS: We examined pneumonia complications in children hospitalized for varicella, over a 13 year period. RESULTS: Pneumonia occurred in 8.2% of children hospitalized for varicella. The median length of hospitalization was 6 days. No statistically significant difference in length of stay was detected between immunodepressed children and previously healthy children. The hospitalization was on average shorter in patients who started antiviral therapy within 24 h of varicella onset. None of the included patients had been previously immunized for varicella. CONCLUSIONS: Our results support the need for increased awareness of current varicella prevention recommendations among both immunocompetent and immunodepressed individuals. In children affected by varicella, prompt antiviral therapy may be indicated to reduce the number of days of hospitalization.

Chicken pox infection in patients undergoing chemotherapy: A retrospective analysis from a tertiary care center in India.

There is paucity of data on the incidence, severity and management of chicken pox in patients receiving active chemotherapy for cancer. From October 2010 to October 2011, patients were included in this study if they developed a chicken pox infection during their chemotherapy. The details of patients' cancer diagnosis and treatment along with clinical and epidemiological data of the chicken pox infections were assessed from a prospectively maintained database. Twenty-four patients had a chicken pox infection while receiving chemotherapy and/or radiotherapy. The median age of the patients was 21 years, and two-thirds of the patients had solid tumor malignancies. Overall, eight (33%) patients had complications, six (25%) patients had febrile neutropenia, four (17%) had diarrhea/mucositis, and four (17%) had pneumonia. The median time for recovery of the infection and complications in the patients was 9.5 days (5-29 days), whereas for neutropenic patients, it was 6.5 days (3-14 days). The median time for recovery from chicken pox infections in neutropenic patients was 10 days (5-21 days), compared with 8.5 days (0-29 days) in non-neutropenic patients (P=0.84). The median time for recovery from infections was 8.5 days in patients with comorbidities (N=4), which was the same for patients with no comorbidities. The clinical presentation and complication rates of chicken pox in cancer patients, who were on active chemotherapy, are similar to the normal population. The recovery from a varicella infection and complications may be delayed in patients with neutropenia. The varicella infection causes a therapy delay in 70% of patients. Aggressive antiviral therapy, supportive care and isolation of the index cases remain the backbone of treatment.

[Perinatal varicella: fetal and neonatal risks and management]. / La varicelle périnatale: risques et prise en charge fœtale et néonatale.

The occurrence of clinical varicella during pregnancy is rare but it may pose maternal and fetal risks. Perinatal maternal varicella may result in potentially severe neonatal varicella, especially when maternal eruptions occur between 5 days before and 2 days after delivery. We report eight cases of newborns of mothers with varicella in the peri-partum period in order to synthesize the current state of knowledge on the risk of contracting virus as well as to develop treatment protocol. We conducted a descriptive study at the Maternity and Neonatology Center, Sousse, over a period of 10 years. Eight newborns were included in the study. Prenatal diagnosis was made in 7 mothers. Only a woman developed varicella 3 days after delivery. Five newborns were symptomatic on admission. All newborns had typical varicella skin lesions, three of them had respiratory distress associated. Treatment was based on newborn isolation, local skin care and Acyclovir therapy. Patients evolution was favorable. The occurrence of varicella infection during pregnancy remains possible in the countries where vaccination is still not accessible to all. The risk of maternal and fetal complications justifies specific and well codified treatment.

[Epidemiology and prophylaxis of varicella in military units].

Epidemiology and prophylaxis of varicella in military units. Topical issues in military units varicella epidemiology and prevention, as one of the most important infections, potentially controlled by means of immunization. As a result of the retrospective epidemiological analysis of the incidence of varicella personnel- in one of the military districts found that the risk category for the disease are conscripts from the young recruits. The main riskfactors for introduction and spread of the infection: violation of statutory requirements to placement and life conditions of young recruits, delays in army of observation in epidemic outbreaks of varicella. The connection of the skid in a military collective agents of varicella with disabilities in the diagnostic work of the medical service and the organization of sanitary and anti-epidemic regime in. infectious wards of military hospitals. The possibilities of improving the selective immunization against varicella soldiers of the young recruits.