The incidence of varicella and herpes zoster in Massachusetts as measured by the Behavioral Risk Factor Surveillance System (BRFSS) during a period of increasing varicella vaccine coverage, 1998–2003

BACKGROUND: The authors sought to monitor the impact of widespread varicella vaccination on the epidemiology of varicella and herpes zoster. While varicella incidence would be expected to decrease, mathematical models predict an initial increase in herpes zoster incidence if re-exposure to varicella protects against reactivation of the varicella zoster virus. METHODS: In 1998–2003, as varicella vaccine uptake increased, incidence of varicella and herpes zoster in Massachusetts was monitored using the random-digit-dial Behavioral Risk Factor Surveillance System. RESULTS: Between 1998 and 2003, varicella incidence declined from 16.5/1,000 to 3.5/1,000 (79%) overall with ≥66% decreases for all age groups except adults (27% decrease). Age-standardized estimates of overall herpes zoster occurrence increased from 2.77/1,000 to 5.25/1,000 (90%) in the period 1999–2003, and the trend in both crude and adjusted rates was highly significant (p < 0.001). Annual age-specific rates were somewhat unstable, but all increased, and the trend was significant for the 25–44 year and 65+ year age groups. CONCLUSION: As varicella vaccine coverage in children increased, the incidence of varicella decreased and the occurrence of herpes zoster increased. If the observed increase in herpes zoster incidence is real, widespread vaccination of children is only one of several possible explanations. Further studies are needed to understand secular trends in herpes zoster before and after use of varicella vaccine in the United States and other countries

Varicella Viruses Inhibit Interferon-Stimulated JAK-STAT Signaling through Multiple Mechanisms

Varicella zoster virus (VZV) causes chickenpox in humans and, subsequently, establishes latency in the sensory ganglia from where it reactivates to cause herpes zoster. Infection of rhesus macaques with simian varicella virus (SVV) recapitulates VZV pathogenesis in humans thus representing a suitable animal model for VZV infection. While the type I interferon (IFN) response has been shown to affect VZV replication, the virus employs counter mechanisms to prevent the induction of anti-viral IFN stimulated genes (ISG). Here, we demonstrate that SVV inhibits type I IFN-activated signal transduction via the JAK-STAT pathway. SVV-infected rhesus fibroblasts were refractory to IFN stimulation displaying reduced protein levels of IRF9 and lacking STAT2 phosphorylation. Since previous work implicated involvement of the VZV immediate early gene product ORF63 in preventing ISG-induction we studied the role of SVV ORF63 in generating resistance to IFN treatment. Interestingly, SVV ORF63 did not affect STAT2 phosphorylation but caused IRF9 degradation in a proteasome-dependent manner, suggesting that SVV employs multiple mechanisms to counteract the effect of IFN. Control of SVV ORF63 protein levels via fusion to a dihydrofolate reductase (DHFR)-degradation domain additionally confirmed its requirement for viral replication. Our results also show a prominent reduction of IRF9 and inhibition of STAT2 phosphorylation in VZV-infected cells. In addition, cells expressing VZV ORF63 blocked IFN-stimulation and displayed reduced levels of the IRF9 protein. Taken together, our data suggest that varicella ORF63 prevents ISG-induction both directly via IRF9 degradation and indirectly via transcriptional control of viral proteins that interfere with STAT2 phosphorylation. SVV and VZV thus encode multiple viral gene products that tightly control IFN-induced anti-viral responses

Managing Medicare’s HIV Caseload in the Era of Suppressive Therapy

Objectives. The 1996 introduction of antiretroviral medications changed Medicare’s role in providing HIV care. We analyzed Medicare’s patient database in an effort to document the new HIV therapies’ effects on expenditures and outcomes

Injury Prevalence Among Children and Adolescents With Mental Retardation

Childhood injuries lead to increased morbidity and result in significant costs to public insurance programs. People with mental retardation, most of whom are covered by Medicaid, are at high risk for injury, which has implications for community inclusion, a central policy goal. Medicaid data from inpatient, outpatient, and long-term care settings represent an important new resource for injury surveillance in this population. Injury prevalence for 8.4 million Medicaid-eligible children in 26 states was measured using 1999 eligibility and claims data; 36.9% Medicaid beneficiaries ages 1 to 20 with mental retardation had at least one injury claim as compared with 23.5% of those without mental retardation. Prevalence rates are reported by gender and age for a variety of injury types

Changes in Drug Coverage Generosity and Untreated Serious Mental Illness

Importance More than 1 in 5 disabled people with dual Medicare-Medicaid enrollment have schizophrenia or a bipolar disorder (ie, a serious mental illness). The effect of their transition from Medicaid drug coverage, which varies in generosity across states, to the Medicare Part D drug benefit is unknown. Many thousands make this transition annually. Objectives To determine the effect of transitioning from Medicaid drug benefits to Medicare Part D on medication use by patients with a serious mental illness and to determine the influence of Medicaid drug caps. Design, Setting, and Participants In time-series analysis of continuously enrolled patient cohorts (2004-2007), we estimated changes in medication use before and after transitioning to Part D, comparing states that capped monthly prescription fills with states with no prescription limits. We used Medicaid and Medicare claims from a 5% national sample of community-dwelling, nonelderly disabled dual enrollees with schizophrenia (n = 5554) or bipolar disorder (n = 3675). Main Outcomes and Measures Psychotropic treatments included antipsychotics for schizophrenia and antipsychotics, anticonvulsants, and lithium for bipolar disorder. We measured monthly rates of untreated illness, intensity of treatment, and overall prescription medication use. Results Prior to Part D, the prevalence of untreated illness among patients with a bipolar disorder was 30.0% in strict-cap states and 23.8% in no-cap states. In strict-cap states, the proportion of untreated patients decreased by 17.2% (relatively) 1 year after Part D, whereas there was no change in the proportion of untreated patients in no-cap states. For patients with schizophrenia, the untreated rate (20.6%) did not change in strict-cap states, yet it increased by 23.3% (from 11.6%) in no-cap states. Overall medication use increased substantially after Part D in strict-cap states: prescription fills were 35.5% higher among patients with a bipolar disorder and 17.7% higher than predicted among schizophrenic patients; overall use in no-cap states was unchanged in both cohorts. Conclusions and Relevance The effects of transitioning from Medicaid to Medicare Part D on essential treatment of serious mental illness vary by state. Transition to Part D in states with strict drug benefit limits may reduce rates of untreated illness among patients with bipolar disorders, who have high levels of overall medication use. Access to antipsychotic treatment may decrease after Part D for patients with a serious mental illness living in states with relatively generous uncapped Medicaid coverage

Lyme Neuroborreliosis - Diagnosis and Treatment

Lyme neuroborreliosis, the infection of the nervous system by the tick-borne bacterium Borrelia burgdorferi, is a common infection in the temperate parts of the Northern hemisphere. Manifestations of the disease include facial palsy, radicular pain, sensory disturbances, and occasionally CNS symptoms such as confusion and paraparesis. The diagnosis of Lyme neuroborreliosis is based on medical history, clinical examination and cerebrospinal fluid (CSF) analysis. Recommended antibiotic treatment is oral doxycycline or intravenous ceftriaxone. The overall aims of this thesis were to improve the diagnosis and treatment of Lyme neuroborreliosis. In paper I, 102 patients with peripheral facial palsy were studied. Onset of symptoms in July to October, additional neurological symptoms and CSF pleocytosis were factors that discriminate patients with peripheral facial palsy caused by Lyme neuroborreliosis from patients with Bell’s palsy. In paper II, it was shown that CSF levels of the chemokine CXCL13 are highly elevated in Lyme neuroborreliosis and that levels decline after treatment, but high and overlapping CXCL13 levels were also seen in patients with asymptomatic HIV-infection and the decrease in CXCL13 is correlated to the decrease in CSF cell count. The additional diagnostic value of CXCL13 analysis is therefore limited. In paper III, new reference ranges for CSF cell counts when analyzed with automatic cell counters were determined, based on CSF sampling of 80 healthy volunteers. The differentiation of mononuclear cells into lymphocytes and monocytes was shown to be of limited value in the discrimination between Lyme neuroborreliosis and viral CNS infections. In paper IV, it was shown that treatment with oral doxycycline resulted in a similar decrease in CSF mononuclear cell counts in patients with Lyme neuroborreliosis with CNS symptoms compared with patients with peripheral nervous systems symptoms, and that all patients with CNS symptoms improved on treatment with no need for retreatment. Oral doxycycline can therefore be considered an effective treatment for Lyme neuroborreliosis, irrespective of the severity of symptoms