Clinical Chickenpox Research Articles

Long-Term Varicella Zoster Virus Immunity in Paediatric Liver Transplant Patients Can Be Achieved by Booster Vaccinations-A Single-Centre, Retrospective, Observational Analysis.

Varicella is one of the most common vaccine-preventable infections after paediatric solid organ transplantation; thus, vaccination offers simple and cheap protection. However, children with liver disease often progress to liver transplantation (LT) before they reach the recommended vaccination age. As a live vaccine, varicella zoster virus (VZV) vaccination after transplantation is controversial; however, many case series demonstrate that vaccination may be safe and effective in paediatric liver transplant recipients. Only limited data exists describing long-term vaccination response in such immunocompromised patients. We investigated retrospectively vaccination response in paediatric patients before and after transplantation and describe long-term immunity over ten years, including the influence of booster-vaccinations. In this retrospective, single-centre study, 458 LT recipients were analysed between September 2004 and June 2021. Of these, 53 were re-transplantations. Patients with no available vaccination records and with a history of post-transplant lymphoproliferative disease, after hematopoietic stem cell transplantation and clinical chickenpox were excluded from this analysis (n = 198). In total, data on 207 children with a median annual follow-up of 6.2 years was available: 95 patients (45.9%) were unvaccinated prior to LT. Compared to healthy children, the response to vaccination, measured by seroconversion, is weaker in children with liver disease: almost 70% after one vaccination and 93% after two vaccinations. One year after transplantation, the mean titres and the number of children with protective antibody levels (VZV IgG ≥ 50 IU/L) decreased from 77.5% to 41.3%. Neither diagnosis, gender, nor age were predictors of vaccination response. Booster-vaccination was recommended for children after seroreversion using annual titre measurements and led to a significant increase in mean titre and number of protected children. Response to vaccination shows no difference from monotherapy with a calcineurin inhibitor to intensified immunosuppression by adding prednisolone or mycophenolate mofetil. Children with liver disease show weaker seroconversion rates to VZV vaccination compared to healthy children. Therefore, VZV-naïve children should receive basic immunization with two vaccine doses as well as those vaccinated only once before transplantation. An average of 2–3 vaccine doses are required in order to achieve a long-term seroconversion and protective antibody levels in 95% of children.

Trend of chickenpox incident cases through absent vaccination in Najaf Governorate-Iraq from January 2009 to May 2014

Background: Chickenpox infection is a common and highly contagious viral disease caused by the varicella zoster virus. It is highly endemic disease with increasing annual incidence in absence of varicella immunization program in Iraq. The predominance of uncomplicated cases in children tends to overshadow the morbidity associated with social and economic burden of families in addition to risk of complication in younger age groups. Chickenpox now has been considered one of the most common vaccine-preventable diseases in many countries including Iraq.Amis of the study: Describing the epidemiology of registered clinical cases of chickenpox in Najaf governorate of January 2009 to May 2014. More over verifying the increasing number of incident cases of chickenpox for future need of varicella vaccine in Iraq.Methodology: A descriptive cross sectional study was conducted of January 2009 to May 2014, and the data was collected of the public health department of the existing anonymous surveillance of chickenpox. Those monthly records were sent of corresponding surveillance units of six districts in Najaf governorate including north of Najaf, south of Najaf, Al-Kufa, Al-manathera, Al-abbassiya and Al-mishkhab districts. The variables included age groups, gender, and district distributions in this study were based on a classification used in the surveillance system in Iraq.Results: The frequency of chickenpox cases in Najaf Governorate revealed an obvious rise of (1076) in 2009 and (2563) in 2010 to (4692) in 2o13. The incidence rate of occurrence of clinical chickenpox cases also shows an obvious rise in 2011 was 408/100000 population. Most often cases occurred in age group 5-14 years (75 %) and only (3.05 %) in those over 45 years. According to gender distribution, there was sustained non-significant preponderance for the male over female. All registered cases had shown the same seasonal distribution with two peaks of infection per year; spring (March, April and May) and early winter (November, December and January) seasons. Median Endemic Index of chickenpox cases in Najaf in May of 2009-2013 was 633 and the number of cases during January through May 2014 was 558.Conclusion: chickenpox is still increasing in incident cases in Najaf governorate which necessitate thinking of varicella vaccine recommendation.

Chickenpox and Risk of Stroke: A Self-controlled Case Series Analysis

There is good evidence that respiratory and other infections that cause systemic inflammation can trigger strokes; however, the role of specific infections is unclear. Case reports have highlighted chickenpox as a possible risk factor for arterial ischemic stroke, particularly in children, but rigorous studies are needed to determine and quantify any increased risk. We used anonymized electronic health records totaling >100 million person-years of observation from 4 UK primary care databases to identify individuals who had documented clinical chickenpox and a stroke or transient ischemic attack (TIA). Self-controlled case series methods were used to quantify any increased risk of first stroke or TIA in the 0-6 and 7-12 months following chickenpox compared to other observed time periods. We analyzed data within each database, and performed meta-analyses to obtain summary age-adjusted incidence ratios (IRs) separately for adults and children. Five hundred sixty eligible individuals (including 60 children) were identified who experienced chickenpox and a stroke or TIA during follow-up. Among children, there was a 4-fold increased risk of stroke in the 0-6 months after chickenpox (summary IR = 4.07; 95% confidence interval [CI], 1.96-8.45; I(2) = 0%). Among adults, there was a less marked increased risk with moderate between-database heterogeneity (random-effects summary IR = 2.13; 95% CI, 1.05-4.36; I(2) = 51%). There was no significant increased risk of stroke in the 7-12 months after chickenpox in children or adults, nor was there evidence of increased risk of TIA in either time period. Our study provides new evidence that children who experience chickenpox are at increased risk of stroke in the subsequent 6 months.

Clinical Epidemiology of Chickenpox in Iraq from 2007-2011

Varicella zoster (chickenpox) infection is an acute common disease caused by the varicella zoster virus (VZV). Children are most susceptible to infection. In non-vaccinated populations, primary infection tends to occur at a younger age. In 1998, the World Health Organization (WHO) recommended that routine childhood varicella vaccination be considered in countries where the disease is a relatively important public health and socioeconomic problem, and where high (85 to 90%) and sustained vaccine coverage can be achieved.Aim:1- To determine the trend (occurrence, age and gender distribution, seasonal variation) of registered clinical cases of chickenpox in Iraq from 2007-2011.2- To determine the need for the use of chicken pox vaccine in Iraq and putting a plan for its use accordingly.Methods:Retrospective descriptive study.Results:Frequency of clinical cases shows an obvious rise in the registration of chickenpox cases from 21798 case in 2007 through 59681 in 2008 to 74195 in 2011 with possible outbreaks occurred in 2008 and 2011. Rate of occurrence of clinical chickenpox cases also shows an obvious rise in the occurrence that ranges from 73.41/100000 in 2007 to 222.61/100000 in 2011. The rate in 2008 and 2011 is suggestive of a possible outbreak. Although the total number of chickenpox varies from 2007-2011 but all have shown the same seasonal distribution, being highest in spring (April, May) season. The largest no. recorded was in 2011 (14000 cases in April and May). The lowest no. recorded was in 2007 (4000 cases in April and May).The highest registered number of chickenpox cases was in provinces of Ninawa, Baghdad/russafa, Dihok, Baghdad/karkh, Al-Basrah, As-Sulaymaniyah. Regarding gender distribution there was sustained preponderance for the males over females with nearly the same percentage over the years. Age distribution of the registered cases had shown that most of the cases occurred in those of age 5-14 years (65%), only 1% occur in those >45 years with statistical significance p=0.001.Conclusions:1- There is a rising trend in the registration of clinical chickenpox cases.2- Most cases occur in the age group of less than 15 years. Males are a little bit higher than females.3- The highest frequencies were reported in March, April, and May.4- Most of the cases were registered in Baghdad, Ninawa, Dihok and Al-Basrah.

The immunology of chickenpox: A review prepared for the UK Advisory Group on Chickenpox on behalf of the British Society for the Study of Infection

Despite the 42 years that have elapsed since the isolation of the varicella-zoster virus (VZV), our understanding of the immunology of chickenpox remains incomplete. Major hurdles to a fuller understanding of the immunological events that take place on contact with VZV have been the absence of a generally accepted animal model 1 and the incomplete nature of the immunity induced. 2 The absence of an animal model has led to the extrapolation from related models. While deriving a plausible model of pathogenesis, 3 related models have not proven useful in analysing the immune response to VZV. Incomplete immunity in 15% of the population is associated with the occurrence of zoster in individuals previously infected with the VZV and the much rarer occurrence of chickenpox in individuals with documented immunity. 4' 5 An understanding of the relative importance of the humoral versus the cellular immune system has been both informed and complicated by a number of 'experiments of nature'. The importance of the cellular immune system is highlighted by the relatively benign nature of clinical chickenpox in children with 'pure' humoral defects such as agammaglobulinaemia, contrasted with the life-threatening nature of the illness in individuals with compromised cell-mediated immunity. 6 Antibodies alone cannot prevent chickenpox or zoster, and reinfection with VZV has been documented in antibody-positive individuals. In contrast, anti-VZV antibodies derived from immune donors and contained in zoster immune globulin are able to modify the natural history of VZV infection and even prevent clinical infection when given to susceptible VZV contacts. The lack of clarity regarding the immunology of VZV infection has been further hampered by the absence of a 'gold standard' in vitro correlate of

Multiple sclerosis in India: a case-control study of environmental exposures.

To compare the rate of prior environmental exposures between Indian multiple sclerosis (MS) patients and controls in order to identify potential disease triggering factors. A standard self-administered questionnaire regarding prior exposures was presented to 56 Indian MS patients and 147 other neural disease and healthy controls at two large medical centers in India. The rate of prior foreign travel, surgeries, blood transfusions, clinical chicken pox and mumps infections and exposure to cats and farm animals was not significantly different between MS patients and controls. However, clinical measles infection and dog exposure occurred significantly more often in the MS patients. These findings are consistent with but do not prove an association between prior measles infection, dog exposure and MS.

Viral serology after bone marrow transplantation.

Bone marrow transplantation (BMT) may change the recipient's pretransplant serostatus for herpes group viruses. We reviewed 68 patient records (1 year's transplants) to determine how frequently this occurs. Only 7 had data on serostatus before as well as at days 20 to 35 and greater than 100 after BMT. Serostatus was assessed by complement fixation and ELISA. All patients received a variety of blood-product support after BMT. One patient converted from anti-varicella zoster virus (VZV) positive to negative after BMT and developed clinical chickenpox; an additional patient converted from anti-VZV negative to positive after BMT but reverted to seronegative by day 102. One patient converted from anti-cytomegalovirus (CMV) positive pre-BMT to persistently anti-CMV negative post-BMT (donor: anti-CMV negative). Two patients had a greater than 4-fold fall in anti-herpes simplex (HSV) antibody post-BMT, and both shed HSV after BMT. Most seronegative recipients of marrow from seropositive donors developed herpesvirus antibodies. We conclude that the herpesvirus serostatus of BMT recipients should be determined again after BMT to aid in decisions about antiviral prophylaxis and diagnosis of clinical disease.

Live attenuated varicella vaccine: Evidence that the virus is attenuated and the importance of skin lesions in transmission of varicella-zoster virus

To examine whether the live varicella vaccine virus is attenuated, we analyzed varicella vaccine-induced contact cases of clinical chickenpox in healthy siblings of immunized children with leukemia. A rash developed approximately 1 month later in 156 children with leukemia who had been vaccinated. Vaccine-type virus was isolated from 25 of these children. Of 88 known susceptible healthy siblings who were exposed to a vaccine with a rash and from whom follow-up information was available, there was evidence of infection in 15 (17%). Of 15 siblings with seroconversion, 11 (73%) also acquired a mild rash with an average of 38 lesions and no accompanying systemic symptoms. Vaccine-type virus was isolated from four of the contact siblings. Tertiary transmission was documented once. Contact siblings with seroconversion were protected during future household exposure to chickenpox, which occurred in four instances. There was a direct relationship between transmission from vaccinees to varicella-susceptible close contacts and the presence and number of skin lesions in children with leukemia after vaccination. We conclude that in the transmission of varicella, the virus probably originates from skin lesions of infected persons and reaches the respiratory tract of those with secondary cases by the airborne route. On the basis of the mildness of the contact illness, the higher-than-normal rate of subclinical primary infection with varicella-zoster virus in contacts, and the lower-than-normal rate of spread of the vaccine virus to susceptible children in the household, we further conclude that the vaccine virus is attenuated. There was no evidence of reversion of the vaccine virus to virulence.

Comments on vaccines, August 1987

Because of latency and infectious recurrences, eradication of herpes simplex and herpes zoster from the world by vaccines is likely to be much more difficult to accomplish than eradication of smallpox. For some time we may have to settle for control of these diseases rather than their eradication. The live, attenuated varicella vaccine protects immunocompromised and normal persons against clinical chickenpox but it does not completely prevent subsequent infection with natural chickenpox virus or latency. With herpes simplex vaccines we may have to be satisfied with amelioration or control of clinical infections and diminution of latency and recurrent disease. Varicella zoster immune globulin plays a useful role in attenuation of varicella in immunocompromised or special-risk persons exposed to varicella zoster virus. Passive immunization for herpes simplex (herpes simplex immune globulin or other antibody preparations) has been studied very little. Maybe passive immunization will have a place in future therapies, especially for serious herpes simplex virus infections in immunocompromised hosts.

Mucosal cell-mediated immunity to varicella zoster virus: Role in protection against disease

By indirect immunofluorescence, enzyme-linked immunosorbent assay, and in vitro lymphocyte proliferation, we studied the antibody and cell-mediated immune response to varicella zoster virus (VZV) in serum, peripheral blood lymphocytes, and tonsillar lymphocytes in 49 children before and after tonsillectomy and adenoidectomy. Among the naturally infected patients seropositive for VZV antibody, most demonstrated VZV-specific proliferation in the peripheral blood and tonsillar lymphocytes, with activity consistently higher in the tonsillar lymphocytes. Several patients seronegative for VZV antibody and without a prior history of clinical chickenpox also manifested VZV-specific proliferation in the tonsillar lymphocytes, and less frequently in peripheral blood lymphocytes. Of these, six children with high levels of activity in tonsillar lymphocytes, with or without high levels in the peripheral blood lymphocytes, failed to develop disease after intimate exposure to VZV in family settings. On the other hand, three other subjects with little or no VZV-specific proliferative activity in the tonsillar lymphocytes developed disease after similar exposure to VZV. These observations suggest the development of VZV-specific mucosal cellular immunity after overt or inapparent exposure to VZV. The appearance of such immunity appears to have a protective role against reinfection even in the absence of detectable serum antibody.

Expanded Guidelines for Use of Varicella-Zoster Immune Globulin

I. BACKGROUND INFORMATION 1. Zoster Immune Globulin Zoster immune globulin (ZIG) can prevent clinical chickenpox in exposed, susceptible, normal children.1 In a collaborative study2 in which 15 susceptible children at high risk received ZIG within three days following exposure, there were no deaths and only one child developed progressive varicella. At that time, a mortality of 7% and a rate of progressive varicella of 30% were reported in similar children who failed to receive prophylaxis.3 At the present time, varicella may be even more hazardous for children with leukemia, possibly because of the use of more intensive therapy. 2. Varicella-Zoster Immune Globulin The use of plasma obtained from patients convalescing from zoster to prepare ZIG resulted in a limited supply of this material. The finding that plasma from normal donors with high varicella-zoster (V-Z) antibody could be used to prepare a globulin of similar potency, referred to as varicella-zoster immune globulin (VZIG),4 now assures ample supply. The availability of this material, through the American Red Cross, permits us to recommend it for additional indications. The major deterrent to the use of VZIG is its cost, which in August 1983 was approximately $75 per 125 units (approximately 1.25 mL), the dose for a 10-kg child. The recommended adult dose of 625 units costs about $375. 3. Morbidity from Varicella in Adults Adults suffer greater morbidity from chickenpox than do children. Although less than 2% of reported cases occur in individuals after the second decade, nearly one quarter of all the reported mortality occurs in this group.5 Of particular concern are pregnant women who develop chickenpox.