Trends in the incidence, mortality, and cost of neonatal herpes simplex virus hospitalizations in the United States from 2003 to 2014.

OBJECTIVE: To examine the temporal trends in the incidence and outcomes of neonatal herpes simplex infections (NHSV) in the United States. STUDY DESIGN: We conducted a retrospective study using the National Inpatient Sample (NIS). Neonates ≤28 days old with ICD-9 codes for NHSV (054.xx) from 2003 to 2014 were included. Trends in the incidence, mortality, length of stay (LOS), and hospital cost were analyzed using Jonckheere-Terpstra test. RESULTS: NHSV increased from 7.9 to 10 per 100,000 live births from 2003-05 to 2012-14 (P = 0.04). Hospital costs increased from $21,650 to $27,843; P < 0.001). The overall mortality rate and median LOS were 7.9% and 20 days, respectively and there were no significant variations across years during the study period. CONCLUSIONS: The incidence of NHSV in the United States increased between 2003 and 2014 without a significant change in mortality. NHSV remains a serious health threat and new and effective strategies to prevent NHSV are needed.

Recognizing Common Skin and Soft Tissue Infections in the Nephrology Clinic.

Renal failure patients have an increased risk of infection, including skin and soft tissue infections. This increased susceptibility is multifactorial, due to the conditions causing the renal failure as well as complications of treatment and renal failure's innate effects on patient health. These infections have a significant impact on patient morbidity, increased hospital and procedural demands, and the cost of health care. Many renal failure patients are seen regularly by their nephrology clinic caregivers due to the need for frequent dialysis and transplant monitoring. Familiarity with common skin and soft tissue infections by these caregivers allowing enhanced patient education, optimal infection prevention, and early recognition could significantly reduce the morbidity and cost of these disorders, such as diabetic foot syndrome, necrotizing fasciitis, and herpetic infections.

Hospitalization cost per case of neonatal herpes simplex virus infection from claims data.

The purpose of this study was to estimate the average excess inpatient cost of neonatal herpes simplex virus (NHSV) infection from 2005 to 2009 insurance claims data. The estimated adjusted average excess inpatient cost for neonate admissions with HSV diagnosis and >7 days of hospitalization was $40,044 [95% confidence interval (CI), $33,529-$47,775]. When disaggregated by the days of admission, cost estimates were: 8-13 days, $23,918 [CI, $19,490-$29,282]; 14-21 days, $44,358 [CI, $34,654-$56,673]; >21 days, $68,916 [CI, $49,905-$94,967]). Although these estimates are not representative of the entire US, they can inform future economic evaluation studies on NHSV interventions.

A flexible and low-cost polypropylene pouch for naked-eye detection of herpes simplex viruses.

Effective viral detection is a key goal in the development of point of care (POC) diagnostic devices. Loop-mediated isothermal amplification (LAMP) could potentially be a valuable tool for rapid viral detection and diagnosis in commercial and hospital laboratories and resource limited settings. Here, we present a novel polypropylene pouch (PP) for detection of HSV-1 and HSV-2. With this plastic pouch we could detect up to 6.08 × 10(1) copies per µL of HSV-1 DNA and 0.598 copies per µL of HSV-2 DNA within 45 minutes. Since LAMP itself is less sensitive to inhibitory substances present in the real sample, we could also detect viral DNA without the need for viral DNA extraction and purification. The result from LAMP could be evaluated by naked eye due to the addition of hydroxy naphthol blue (HNB) dye in the reaction mixture. Since this proposed device is easy to handle, portable, user friendly and low cost, it offers a tremendous potential to be a perfect candidate for POC diagnostic device for use in resource limited settings.

Projected cost-savings with herpes simplex virus screening in pregnancy: towards a new screening paradigm.

OBJECTIVES: Herpes simplex virus (HSV) infections in newborns are an uncommon but potentially devastating consequence of genital HSV infection in women. Current practice focuses on preventing perinatal transmission by women with prevalent HSV, but transmission risk is greatest when genital HSV is acquired for the first time late in pregnancy. The objective of this study was to assess the effectiveness and cost effectiveness of identifying pregnant women at risk of de novo HSV acquisition as a means of preventing vertical HSV transmission. METHODS: A Bayesian decision tree model was parameterized using the best available health and economic data relating to HSV in pregnancy and was used to evaluate the cost effectiveness of screening to identify individuals susceptible to HSV infection in a hypothetical cohort of 100,000 pregnant women in their second trimester of pregnancy. Final outcomes were the projected incidence of maternal and neonatal HSV, quality-adjusted life expectancy and life-time costs associated with neonatal HSV. RESULTS: In the absence of testing, model projected incidence of neonatal HSV was 34 cases per 100,000 births, similar to available surveillance data. Screening pregnant women and their partners was projected to decrease the incidence of HSV-1 and HSV-2 infections in women and infants and to save costs. These findings were robust under alternative assumptions and in wide-ranging sensitivity analyses. CONCLUSIONS: The use of accurate and relatively inexpensive serological tests for HSV to identify women vulnerable to incident HSV infection in pregnancy has the potential to reduce neonatal HSV incidence and reduce health-related costs.

Impact of congenital anomalies and treatment location on the outcomes of infants hospitalized with herpes simplex virus (HSV).

BACKGROUND: Herpes simplex virus (HSV) is a rare but costly reason for hospitalization in infants under 60 days of age. The impact of coexisting comorbid conditions and treatment location on hospital outcome is poorly understood. OBJECTIVE: Determine patient and hospital factors associated with poor outcomes or death in infants hospitalized with HSV. DESIGN: : Retrospective cohort study using the 2003 Kids' Inpatient Database (KID). SETTING: U.S. hospitals. PATIENTS: Infants under 60 days of age with a diagnosis of HSV. INTERVENTION: Treatment at different types of hospitals, younger age at admission, and presence of congenital anomalies. MEASUREMENTS: Serious complications, in-hospital death. RESULTS: A total of 10% of the 1587 identified HSV hospitalizations had a concurrent congenital anomaly. A total of 267 infants had a serious complication and 50 died. After controlling for clinical and hospital characteristics, concurrent congenital anomalies were associated with higher odds of a serious complication (adjusted odds ratio [OR], 3.34; 95% confidence interval [CI], 2.00-5.56) and higher odds of death (adjusted OR, 4.17; 95% CI, 1.74-10.0). Similar results were found for infants admitted under 7 days of age. Although different hospital types had statistically similar clinical outcomes after controlling for case-mix differences, treatment at a children's hospital was associated with an 18% reduction in length of stay (LOS). CONCLUSIONS: Infants with concurrent congenital anomalies infected with HSV were at increased risk for serious complications or death. Health resource use may be improved through identification and adoption of care practiced at children's hospitals.

Herpes simplex virus testing and hospital length of stay in neonates and young infants.

OBJECTIVE: To examine whether ordering testing of cerebrospinal fluid (CSF) for herpes simplex virus (HSV) by polymerase chain reaction (PCR) in neonates and young infants is associated with increased hospital length of stay (LOS) or increased hospital charges. STUDY DESIGN: This retrospective cohort study enrolled infants age

Congenital anomalies and resource utilization in neonates infected with herpes simplex virus.

BACKGROUND: Neonatal herpes simplex virus (HSV) infection, while uncommon, is associated with substantial morbidity and mortality. However, there is little nationally representative data describing resource utilization. METHODS: This retrospective cohort study was conducted using the Pediatric Health Information System, an administrative database that contains discharge diagnosis and resource utilization data from 35 free-standing children's hospitals. Patients

Upstairs and downstairs: socio-economic and gender interactions in herpes simplex virus type 2 seroprevalence in australia.

BACKGROUND: This study investigates socio-economic differentials in herpes simplex virus type 2 (HSV-2) seroprevalence in Australian men and women using individual and geographic measures of socio-economic status. METHODS: HSV-2 seropositivity among men and women aged over 25 years was investigated by levels of individual and area-based measures of socio-economic status (SES) in a series of Poisson regression models, variously adjusting for age, country of birth, marital status, indigenous status, and urban/rural residence as potential confounders. Serum and socio-demographics were collected during 1999 and 2000 in a population-based Australia-wide prevalence survey. RESULTS: HSV-2 seroprevalence was significantly lower in areas of low SES than in high SES areas among both men (P for trend <0.001) and women (P for trend = 0.004) for all ages. A similar pattern was evident for individual education level for men with lower rates of HSV-2 in respondents with lower educational achievement (relative risk = 0.77, 95% CI 0.61-0.97, P = 0.024). In contrast, HSV-2 prevalence was higher for women with lower individual levels of education for all ages (relative risk = 1.22, 95% CI 1.04-1.44, P = 0.017). Analyses stratifying HSV-2 prevalence for individual education level by area-based SES showed the highest prevalence of HSV-2 in women with the lowest education level residing in the highest SES areas. This pattern was not evident in men, with a greater concordance between individual and area-based SES. CONCLUSION: HSV-2 seroprevalence is not consistently distributed across individual and area measures of SES, suggesting that upward and downward mixing between social strata in men and women is an important mode of HSV-2 transmission.

Cost-effectiveness analysis of herpes simplex virus testing and treatment strategies in febrile neonates.

OBJECTIVE: To determine the clinical effectiveness and cost-effectiveness of testing for and empirically treating herpes simplex virus (HSV) infection in neonates with fever aged from birth to 28 days. DESIGN: Cost-effectiveness analysis. SETTING: Decision model. PATIENTS: Neonates with fever with no other symptoms and neonates with fever with cerebrospinal fluid (CSF) pleocytosis. INTERVENTIONS: Four clinical strategies: (1) HSV testing and empirical treatment while awaiting test results; (2) HSV testing and treatment if test results were positive for HSV or the patient had symptoms of HSV; (3) treatment alone without testing; or (4) no HSV testing or treatment unless the patient exhibited symptoms. The 2 HSV testing methods used were CSF HSV polymerase chain reaction (PCR) and comprehensive evaluation with blood HSV PCR, CSF HSV PCR, and multiple viral cultures. MAIN OUTCOME MEASURES: Twelve-month survival and quality-adjusted life expectancy with a cost-effectiveness threshold of $100,000 per quality-adjusted life year (QALY) gained. RESULTS: Clinical strategy 1, when applied in febrile neonates with CSF pleocytosis, saved 17 lives per 10,000 neonates and was cost-effective using CSF HSV PCR testing ($55,652/QALY gained). The cost-effectiveness of applying clinical strategy 1 in all febrile neonates depended on the cost of the CSF HSV PCR, prevalence of disease, and parental preferences for neurodevelopmental outcomes. Clinical strategies using comprehensive HSV testing were not cost-effective in febrile neonates ($368,411/QALY gained) or febrile neonates with CSF pleocytosis ($110,190/QALY gained). CONCLUSIONS: Testing with CSF HSV PCR and empirically treating with acyclovir sodium saves lives and is cost-effective in febrile neonates with CSF pleocytosis. It is not a cost-effective use of health care resources in all febrile neonates.

Burden of infection and fat mass in healthy middle-aged men.

OBJECTIVE: Our aim was to study the effect of exposure to four infections on fat mass. RESEARCH METHODS AND PROCEDURES: This was a cross-sectional study of healthy middle-aged men from the general population (n = 74). Each study subject's serum was tested for specific IgG class antibodies against herpes simplex virus (HSV)-1, HSV-2, enteroviruses, and Chlamydia pneumoniae through the use of quantitative in vitro enzyme-linked immunosorbent assays (ELISAs). A total pathogen burden score based on these seropositivities [Quantitative Seropositivity Index (QSI)] was constructed. Fat mass was measured by bioelectrical impedance. RESULTS: We observed significant relationships between the HSV-1 titer and fat mass and percentage fat mass. The associations were stronger when considering the infection burden. The QSI was significantly associated with fat mass (r = 0.30, p = 0.009) and percentage fat mass (r = 0.27, p = 0.01). Those subjects in the highest tertile of fat mass showed significantly higher QSI (259.5 +/- 74.1 vs. 206.9 +/- 78.2, p = 0.007). In subjects that were seropositive for Enteroviruses, the relationship between the QSI and fat mass was strengthened (r = 0.51, p = 0.02). In a multivariate regression analysis, the QSI, independently of age and C-reactive protein, contributed to 9% of fat mass variance. DISCUSSION: Pathogen burden showed an association with fat mass. Subjects with increased fat mass could be more susceptible to developing multiple infections resulting in a chronic low-grade inflammation. We can not exclude the possibility that exposure to multiple infections leads to increased fat mass.

Burden of infection and insulin resistance in healthy middle-aged men.

OBJECTIVE: We hypothesized that burden of infection could be associated with chronic low-grade inflammation, resulting in insulin resistance. We aimed to study the effect of exposure to four infections on insulin sensitivity in apparently healthy middle-aged men (n = 124). RESEARCH DESIGN AND METHODS: By inclusion criteria, all subjects were hepatitis C virus antibody seronegative. Each study subject's serum was tested for specific IgG class antibodies against herpes simplex virus (HSV)-1, HSV-2, enteroviruses, and Chlamydia pneumoniae through the use of quantitative in vitro enzyme-linked immunosorbent assays. Insulin sensitivity was evaluated using minimal model analysis. RESULTS: The HSV-2 titer was negatively associated with insulin sensitivity even after controlling for BMI, age, and C-reactive protein (CRP). The associations were stronger when considering the infection burden. In particular, in those subjects who were seropositive for C. pneumoniae, the relationship between the quantitative seropositivity index (a measure of the exposure to various pathogens) and insulin sensitivity was strengthened (r = -0.50, P < 0.0001). We also observed decreasing mean insulin sensitivity index with increasing seropositivity score in subjects positive for enteroviruses. In the latter, the relationship between insulin sensitivity and seropositivity was especially significant (r = -0.71, P < 0.0001). In a multivariate regression analysis, both BMI and quantitative seropositivity index (7%) independently predicted insulin sensitivity variance in subjects with C. pneumoniae seropositivity. When controlling for CRP, this association was no longer significant. CONCLUSIONS: Pathogen burden showed the strongest association with insulin resistance, especially with enteroviruses and C. pneumoniae seropositivity. We hypothesize that exposure to multiple pathogens could cause a chronic low-grade inflammation, resulting in insulin resistance.

Real-time polymerase chain reaction detection of herpes simplex virus in cerebrospinal fluid and cost savings from earlier hospital discharge.

Neonatal herpes simplex virus (HSV) can be a devastating illness and may be difficult to diagnose in those cases without a typical skin rash. As a result, physicians often rely on HSV polymerase chain reaction of cerebrospinal fluid to rule out HSV encephalitis. We developed a real-time polymerase chain reaction assay for HSV using the SmartCycler II (Cepheid, Sunnyvale, CA). End point dilution studies showed sensitivity comparable to that of two national reference laboratories that use LightCycler. In-house turnaround time was approximately 1.5 days versus approximately 5.2 days for sending the test to a reference laboratory. We hypothesized that the rapid availability of a negative test result would allow physicians to discharge appropriate patients earlier. Six months after implementation, clinical case analysis identified 12 pediatric patients who were discharged earlier based on more rapid test results, with a projected savings of approximately 55.2 hospital days throughout the first year. Actual length of stay for patients tested in-house was significantly less than that of historical controls and was projected to save approximately 70.2 hospital days in the first year. Including projected annual laboratory cost/test savings of approximately $11,000, a total savings of $38,000 to $43,000 was estimated for the first year of implementation, more than offsetting startup instrument and development cost.

Neonatal herpes should be a reportable disease.

Neonatal herpes is a devastating disease, the most serious complication of genital herpes, one of the most common serious congenital or perinatal infections, and the most frequent complication of sexually transmitted infections among children. Nevertheless, neonatal herpes is not reportable to health authorities in most states. The potential for prevention has been enhanced by recent diagnostic and therapeutic advances, and the disease meets widely accepted criteria for reporting, including incidence rates that exceed those of comparable conditions, epidemiologic instability, disease severity, direct and indirect socioeconomic costs, concern by persons at risk, the potential for prevention by public health interventions, and the prospect that the resulting data would influence public health policy. The absence of national surveillance contributes to beliefs by healthcare providers and the public health community that genital and neonatal herpes are uncommon conditions that affect small segments of society, beliefs that directly interfere with prevention. Neonatal herpes should be a reportable condition.

Genital herpes in pregnancy: is screening cost-effective?

We investigated the cost-effectiveness of strategies for screening pregnant women for herpes simplex virus (HSV) genital infection. The cost of performing tests for HSV-1 antibody and for HSV-2 antibody on each serum was likely to average approximately 10 pounds sterling per sample and the total cost of screening 37,500 pregnancies in Manchester would be between 0.4 pounds sterling and 0.5 pounds sterling million per year. This estimated cost might prevent the development of neonatal herpes due to a primary HSV infection. However, initial HSV-2 infection is also associated with neonatal herpes and therefore the above cost-estimates might be a gross underestimate.

Antiviral therapy for neonatal herpes simplex virus: a cost-effectiveness analysis.

Each year, about 1,600 infants in the United States are infected with neonatal herpes simplex virus. We conducted a cost-effectiveness analysis of antiviral drug therapy (acyclovir) for three forms of herpes simplex virus infection: skin, ear, and mouth (SEM), central nervous system (CNS), and disseminated multiorgan (DIS) disease. Five levels of patient outcomes were examined (normal, mild, moderate, severe, dead). We obtained information on disease occurrence and survival from clinical trials and historical reviews of untreated newborns. We considered approaches for treating all or any of the forms of the disease and compared them with no use of antiviral drugs. The main measure of effectiveness was lives saved, including those of descendants of survivors. Costs were measured from a societal perspective and included direct medical costs, institutional care, and special education. We used a discount rate of 3% and valued dollars at 1995 levels. We also considered the perspective of a managed care organization. From a societal viewpoint relative to no treatment, antiviral therapy for SEM resulted in a gain of 0.8 lives and a cost reduction of $78,601 per case. For the treatment of CNS and DIS disease, antiviral therapy saved more lives but at increased cost, with respective marginal costs per additional life saved of $75,125 and $46,619. From a managed care perspective, antiviral therapy is more cost-effective than from a societal viewpoint because costs of institutional care and special education are not the responsibility of managed care organizations. Development of at-home therapies will further improve the cost-effectiveness of antiviral therapy for neonatal herpes simplex virus infection.