A Phase 1, Open-Label Assessment of a Dengue Virus-1 Live Virus Human Challenge Strain.

BACKGROUND: Dengue human infection models (DHIM) have been used as a safe means to test the viability of prophylaxis and therapeutics. METHODS: A phase 1 study of 12 healthy adult volunteers using a challenge virus, DENV-1-LVHC strain 45AZ5, was performed. A dose escalating design was used to determine the safety and performance profile of the challenge virus. Subjects were evaluated extensively until 28 days and then out to 6 months. RESULTS: Twelve subjects received the challenge virus: 6 with 0.5 mL of 6.5 × 103 plaque-forming units (PFU)/mL (low-dose group) and 6 with 0.5 mL of 6.5 × 104 PFU/mL (mid-dose group). All except 1 in the low-dose group developed detectable viremia. For all subjects the mean incubation period was 5.9 days (range 5-9 days) and mean time of viremia was 6.8 days (range 3-9 days). Mean peak for all subjects was 1.6 × 107 genome equivalents (GE)/mL (range 4.6 × 103 to 5 × 107 GE/mL). There were no serious adverse events or long-term safety signals noted. CONCLUSIONS: We conclude that DENV-1-LVHC was well-tolerated, resulted in an uncomplicated dengue illness, and may be a suitable DHIM for therapeutic and prophylactic product testing. CLINICAL TRIALS REGISTRATION: NCT02372175.

Novel Poxvirus Infection in an Immune Suppressed Patient.

BACKGROUND: Human and animal poxvirus infections are being reported with increasing frequency. We describe a challenging case history and treatment of a previously unknown poxvirus rash illness in a renal transplant patient. METHODS: A combination of classical microbiology techniques, including viral culture and electron microscopy, were used to provide initial clinical diagnosis. Subsequent standard polymerase chain reaction assays available in 2001 were noncontributory. Next generation sequencing was used to provide definitive diagnosis. RESULTS: Retrospectively, next generation sequencing methods were used to ultimately provide the definitive diagnosis of a novel poxvirus infection initially identified by electron microscopy. The closest relative of this poxvirus, identified in North America, is a poxvirus collected from a mosquito pool from Central Africa in 1972. CONCLUSIONS: This diagnostic quandary was ultimately solved using next generation DNA sequencing. This article describes the use of classical and next generation diagnostic strategies to identify etiologic agents of emerging infectious diseases and once again demonstrates the susceptibility of immunossupressed patients to novel pathogens. The virus identified is closely related to Yoka virus; these viruses appear to have independently diverged from a common ancestor of all known orthopoxviruses.

A university hospital's 10-year experience with tuberculin testing: value of the 2-step tuberculin skin test.

BACKGROUND: The usefulness of the 2-step tuberculin skin test as a tool for monitoring tuberculosis exposure among health care workers is controversial. OBJECTIVES: We aimed to determine the cost-effectiveness and influence of initiation of a preemployment, 2-step tuberculin skin-testing program on the annual tuberculin skin conversion rate among a university hospital's health care workers. METHODS: The tuberculin skin test conversion rates among the recipients of 31,729 tuberculin skin tests over 10 years were retrospectively analyzed. Data from the first 6 years of this study were generated when a single preemployment tuberculin skin test was utilized. Data from the last 4 years were gathered after the advent of a preemployment 2-step program. A cost analysis of the 2-step tuberculin skin test process was performed to determine the annual cost of this program. RESULTS: Relative risk of a conversion was 8.43 times less during the 2-step period when compared with the years when a single tuberculin skin test was given at the start of employment (P < .001). A cost analysis showed that the annual added cost of the 2-step program was approximately 9,565 US dollars. CONCLUSION: A greater than 8-fold reduction in the number of annual tuberculin skin test conversion coincided with, but could not be attributed solely to, the initiation of a 2-step program in our hospital. The Infection Control Committee concluded that the 2-step testing program is essential to achieve the hospital's goal of a 0% annual tuberculin skin test conversion rate and that the annual cost is justified.

Preemptive antiretroviral therapy modifications for the management of potential clinically significant drug interactions with direct acting hepatitis C therapies.

We report a case series of HIV/HCV co-infected patients who underwent preemptive antiretroviral therapy modifications to manage clinically significant drug interactions with HCV therapy. Among the 15 patients reviewed, all changed to a raltegravir-based regimen and none experienced a loss of virologic suppression or increase in HIV-RNA.

The tale of infective endocarditis: fatal then curable but rarely preventable.

The story of infective endocarditis (IE) is a miracle of medical progress. In retrospect, it seems as a logical and orderly progression of remarkable events leading to the nearly complete conquest of the disease. IE was almost uniformly fatal until the 1st cures by surgery, followed by frequent cures with antibiotics, further improved when combined with valve surgery. Most recently, it has become almost a new disease with a change in the offending organisms, a change in the type of afflicted patients and the infection of implanted medical devices. Despite therapeutic success, prevention of IE has been elusive. In this review, the authors tell the story by highlighting major events, illustrating interconnections among branches of science that brought the authors to their present state and describing some well-known patients. For this summary, the authors are indebted to the more detailed descriptions of the IE history readily available for interested readers.

Medication adherence in HIV-infected smokers: the mediating role of depressive symptoms.

Strict medication adherence is integral to the success of highly active antiretroviral therapies (HAART) in patients with HIV. Research has examined several predictors of adherence, but few studies have examined the association between current smoking, which is highly prevalent among people living with HIV, and medication adherence; moreover, no study has examined the mediating role of depressive symptoms, which may influence both smoking and adherence. Therefore, we recruited 168 patients who were prescribed HAART and assessed viral load, CD4+ count, cigarette smoking, past week and 3-month medication adherence, and depressive symptoms. Results showed that 70% smoked at least one cigarette per day. As predicted, smoking was associated with poorer past week and 3-month adherence, and more depressive symptoms. Regression analyses provided partial support for the hypothesis that depressive symptoms mediated nonadherence among smokers. We conclude that future smoking cessation interventions with this population should target medical adherence and depression as intervention components.

The association of benefit finding to psychosocial and health behavior adaptation among HIV+ men and women.

Psychological and behavioral adaptation to HIV is integral to long-term survival. Although most research on coping with HIV has focused on factors associated with poor adaptation, recent research has expanded to include positive concomitants of adaptation, such as benefit finding. This study examined the occurrence of benefit finding among HIV+ men and women and evaluated the potential relevance of benefit finding to positive health behavior and psychosocial adaptation. HIV+ participants (N = 221) recruited during outpatient care completed self-report assessments of benefit finding, social support, depression, HAART adherence, substance use, and physical activity. In a series of multivariate analyses that controlled for demographic and health status variables, benefit finding was associated with lower depression scores, greater social support, and more physical activity, but showed no association to HAART adherence or substance use. The association of benefit finding to depression was partially mediated by differences in social support. Thus, benefit finding may improve psychological adjustment by motivating patients who experience stress-related growth to seek social support.

Cigarette smoking among HIV+ men and women: examining health, substance use, and psychosocial correlates across the smoking spectrum.

The prevalence of cigarette smoking among HIV+ individuals is greater than that found in the general population. However, factors related to smoking within this population are not well understood. This study examined the associations between smoking and demographic, medical, substance use, and psychosocial factors in a clinic-based sample of HIV+ men and women. Two hundred twelve participants completed self-report measures of tobacco use, HIV-related symptoms, viral load, CD4, alcohol and illicit drug use, depression, and social support. Multinomial logistic regression (MLR) analyses modeled the independent associations of the cross-sectional set of predictors with smoking status. Results indicated that 74% of the sample smoked at least one cigarette per day; using standard definitions, 23% of the sample were light smokers, 22% were moderate smokers, and 29% smoked heavily. Smoking was associated with more HIV-related symptoms, greater alcohol and marijuana use, and less social support. Light smoking was related to minority race/ethnicity and less income; moderate smoking was associated with less education; and heavy smoking was related to less education and younger age. Viral load, CD4 count, and depression were not associated with smoking status. Psychosocial interventions targeting this population should consider the relationships between biopsychosocial factors and smoking behavior.

Impact of HIV-related stigma on health behaviors and psychological adjustment among HIV-positive men and women.

HIV-related stigmatization remains a potent stressor for HIV-positive people. This study examined the relationships among stigma-related experiences and depression, medication adherence, serostatus disclosure, and sexual risk among 221 HIV-positive men and women. In bivariate analyses that controlled for background characteristics, stigma was associated with depressive symptoms, receiving recent psychiatric care, and greater HIV-related symptoms. Stigma was also associated with poorer adherence and more frequent serostatus disclosure to people other than sexual partners, but showed no association to sexual risk behavior. In a multivariate analysis that controlled for all correlates, depression, poor adherence, and serostatus disclosure remained as independent correlates of stigma-related experiences. Findings confirm that stigma is associated with psychological adjustment and adherence difficulties and is experienced more commonly among people who disclose their HIV status to a broad range of social contacts. Stigma should be addressed in stress management, health promotion, and medication adherence interventions for HIV-positive people.

Smallpox: clinical features, prevention, and management.

OBJECTIVE: To describe a general overview of smallpox, clinical presentation, diagnosis, adverse events, and management of both pre- and postexposure vaccination. DATA SOURCES: Literature was identified by search of MEDLINE (1966-June 2003) and International Pharmaceutical Abstracts (1966-May 2003) databases using the key terms smallpox, bioterrorism, biological warfare, and smallpox vaccine. STUDY SELECTION AND DATA EXTRACTION: Articles identified from data sources were evaluated, and relevant information was included in this review. DATA SYNTHESIS: Smallpox is spread by human-to-human contact with an infected host and therefore can be contagious. The mortality rate for smallpox is approximately 30%. While the disease was completely eradicated by 1980 with successful use of smallpox vaccine, concern has been raised that smallpox may emerge as a tool of bioterrorism. This concern, combined with the reality of current smallpox vaccination programs in the military and selected civilian populations, mandates a clear understanding of vaccination-related adverse events and contraindications by all healthcare professionals. The vaccine may cause moderate to severe adverse events such as eczema vaccinatum, progressive vaccinia, and generalized vaccinia. CONCLUSIONS: The balance between the risks and benefits of mass vaccination in prevention of an epidemic is not clear. The Centers for Disease Control and Prevention has established a guideline for appropriate use of smallpox vaccine in the civilian population.