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.

Treatment of chickenpox in immunocompromised children.

In Hungary since 1981, 98 immunocompromised children have been treated with intravenous acyclovir for varicella zoster virus infections. They were treated in an open study or a double-blind study. Results of both are discussed briefly. Overall, five of 74 patients with varicella died, whereas all 24 patients with herpes zoster recovered. Treatment failures occurred in patients in whom treatment started late and in those with severe lymphocytopenia. In some children, varicella zoster virus-specific antibodies failed to develop by the end of treatment, and a proportion of these suffered recurrent episodes of varicella.

Epidemiological studies on drug resistance in Streptococcus pneumoniae in Hungary: an update for the 1990s.

The aim of this study was to give an overview about the epidemiological features of pneumococcal resistance in Hungary in the 1990s, and to assess the clinical relevance of drug resistance in Streptococcus pneumoniae primarily in upper respiratory tract infections and the role of risk factors in the acquisition of resistant strains. In Hungary, resistance in S. pneumoniae decreased slightly in recent years, but is still highly prevalent (around 40% to penicillin) compared to the prevalence in western and northern neighboring countries. The prevalent serogroup among resistant strains is 19A, as it was several years ago. In 76 case histories studies, chronic underlying diseases associated with long hospitalization, episodes of earlier hospitalization, and antibiotic therapy were found more frequently if the patient was infected with a resistant strain than with a susceptible one, indicating that these factors promote the acquisition of drug-resistant S. pneumoniae. Resistant S. pneumoniae modified the course of infection by prolonging the duration of hospitalization, making more courses of antibiotics necessary, including parenteral drugs, as well as more invasive interventions such as myringotomy and sinus puncture. These data justify the clinical relevance of resistance, particularly in the upper respiratory tract infections.

Oral acyclovir to prevent dissemination of varicella in immunocompromised children.

Twenty-five immunocompromised children with varicella were treated with oral acyclovir 800 mg, five times daily for 7 days. Two patients were transferred from the oral to the intravenous route: one had signs of varicella pneumonitis on routine X-ray, the other had continuing new lesion formation on day 4 of oral treatment. The disease healed in all patients, with no other evidence of dissemination. In an historical placebo treated group, 12 of 25 patients were transferred to intravenous acyclovir. The reduction to two of 25 is statistically significant (P < 0.01). The mean peak plasma acyclovir concentration in these patients was 6.56 mumol/l. Mild, self-limiting diarrhoea in nine patients was the only adverse event considered to be related to acyclovir. It is concluded that immunocompromised children with varicella can be treated safely and effectively with oral acyclovir. All patients should be observed closely by a physician.

[Incidence and characteristics of childhood suppurative meningitis in Hungary in 1983-87]. / A gyermekkori gennyes meningitis magyarországi elöfordulása és néhány jellemzöje az 1983-87. években.

Data of 1208 infants and children hospitalized for purulent meningitis were analysed. The incidence of the disease was closely age related: morbidity calculated for 100,000 children was found 97.5 under one year of age; 15.6 in 1 to 5 and 2.2 in 6 to 14 years of age. Incidence of newborn meningitis cases was 3.7 per 10,000 live-borns. The disease was caused by N. meningitidis in 278 (23%), H. influenzae in 171 (14%), S. pneumoniae in 157 (13%), E. coli in 74 (6%), B-group streptococcus in 61 (5%), other bacteria (altogether 17 species) in 107 (9%) cases, while in 360 cases (30%) the etiology remained unknown. Overall case fatality was 19.6 per cent. When compared to international data mortality was especially high among the newborns (53%) and in meningitis cases due to S. pneumoniae (29%), E. coli (48%), B-group streptococcus (37%) and "other bacteria" (41%). Neurologic sequelae were found in 17 per cent of the patients at discharge however, in newborns it was 54 per cent. Since the antibacterial therapy was appropriate in all cases, authors try to reveal the possible causes of the relatively high mortality and make recommendations for reducing it.

[Chronic granulomatous disease (CGD): dysfunction of the neutrophil granulocyte NADPH-oxidase enzyme system]. / Krónikus granulomatózus betegség (CGD): a neutrofil granulocita NADPH-oxidáz enzimrendszerének múködésképtelensége.

Dysfunction of NADPH oxidase results in chronic granulomatous disease (CGD), a syndrome characterized by severe bacterial and fungal infections. Phagocytes of the patients are unable to kill ingested microorganisms which leads to the formation of granulomas and abscesses. Predominant pathogens are the catalase-positive bacteriae (Staphylococcus aureus) and some fungi (Aspergillus species). Infections of these patients should be treated by antimicrobial agents, which penetrate cells and kill pathogens inside. The aim of this study was to give a short description of the structure and function of the NADPH oxidase enzyme and to summarize the results obtained during the diagnostic of 10 patients with chronic granulomatous disease. Characterization of the disease was confirmed by mutation analyses.

The diagnostic value of varicella-zoster virus (VZV)-specific antibodies in the early phase of varicella in immunocompromized children.

Varicella-zoster virus (VZV)-specific antibodies were tested by indirect membrane immunofluorescent technique in sera of 32 immunocompromized children during the first week after onset of varicella. VZV-specific IgM antibodies were found in sera of all but four patients. Three of the four IgM negative patients were followed up, and it was demonstrated that all of them gave a retarded antibody response. They had severe leukopenia and had several relapses of their VZV-infection. The results indicate (a) that the demonstration of VZV-specific IgM antibodies is of diagnostic value even in atypical varicella of immunocompromized patients; and (b) that in cases with retarded antibody response relapses can be expected.

Acyclovir prevents dissemination of varicella in immunocompromised children.

Fifty immunocompromised children with varicella who exhibited no signs of dissemination were treated with intravenous acyclovir or placebo in a double-blind, randomized study. Twelve of 25 placebo recipients were withdrawn from treatment because of their deteriorating condition and were given open acyclovir therapy; only one of 25 recipients of acyclovir was similarly withdrawn (P less than .001). Among those patients who did not receive open treatment, acyclovir significantly reduced time to full crusting (P = .01). Overall, acyclovir, as judged by the physician, significantly improved the patients' condition.

Congenital varicella syndrome.

The authors are reporting a typical case of congenital varicella syndrome following maternal varicella during the 17th week of pregnancy. At birth, the newborn showed necrotic bullae on the skin that healed later with characteristic scars. Other typical anomalies, i.e. hypoplastic limbs with muscular atrophy and clubfoot, intrauterine atrophy, dysphagia and anisocoria were also found. In view of the risk of serious malformations following intrauterine varicella infection attempts should be made to prevent varicella zoster virus infection during pregnancy.

Early relapses of varicella-zoster virus infection in immunocompromised children treated with acyclovir.

Authors observed one or more early VZV relapses in 8 out of 98 Acyclovir treated immunocompromised children with varicella. None of the 8 children developed VZV antibodies by the end of the 5-day ACV treatment. All VZV relapses were successfully treated with ACV or Vidarabine, but were stopped only after the appearance of VZV antibodies in the patients' sera. The possible role of ACV treatment in pathogenesis of early VZV relapses could be excluded by comparing the VZV antibody production of patients treated with ACV from the first day of varicella on with the antibody response of those, who received ACV as late as on the 5th day of varicella. By prolonging the ACV treatment till the appearance of VZV antibodies, early relapses could be avoided.