Meningococcal conjugate vaccines: optimizing global impact

Meningococcal conjugate vaccines have several advantages over polysaccharide vaccines, including the ability to induce greater antibody persistence, avidity, immunologic memory, and herd immunity. Since 1999, meningococcal conjugate vaccine programs have been established across the globe. Many of these vaccination programs have resulted in significant decline in meningococcal disease in several countries. Recent introduction of serogroup A conjugate vaccine in Africa offers the potential to eliminate meningococcal disease as a public health problem in Africa. However, the duration of immune response and the development of widespread herd immunity in the population remain important questions for meningococcal vaccine programs. Because of the unique epidemiology of meningococcal disease around the world, the optimal vaccination strategy for long-term disease prevention will vary by country

Menthol tobacco use is correlated with mental health symptoms in a national sample of young adults: implications for future health risks and policy recommendations

Introduction Depression and anxiety are correlated with greater nicotine dependence, smoking persistence, and relapse back to smoking after a quit attempt. Menthol cigarette smoking, which is prevalent in young adults, is associated with nicotine dependence, progression to regular smoking, and worse cessation outcomes than non-menthol smoking. Few have established a link between menthol tobacco use, beyond just smoking, with mental health in this high-risk age group. This study examined the association of menthol tobacco use to anxiety and depression in a national sample of young adults. Material and Methods Data were from Waves 1 through 7 (n = 9720, weighted) of the Truth Initiative Young Adult Cohort, a national sample of men and women aged 18 to 34 assessed every 6-months. Demographics, past 30-day use of non-menthol and menthol tobacco products, and current alcohol, marijuana, and other drug use were assessed among those with depression and anxiety. Results Thirty nine percent of current tobacco users used menthol as their preferred brand. Using a cross-sectional analysis (collapsed across waves), past 30-day menthol tobacco was uniquely associated with greater odds of both depression and anxiety, beyond the effects of demographic and substance correlates and non-menthol tobacco product use. Conclusions Menthol is disproportionately used among young adults tobacco users with mental health problems, above and beyond the impact of a variety of other mental health and tobacco use risk factors. Findings suggest a strong link between menthol tobacco use and poor health outcomes. Policies should be developed to deter menthol tobacco use in vulnerable groups

Invasive Haemophilus influenzae Disease in Adults ≥65 Years, United States, 2011.

BackgroundSince the introduction of the Haemophilus influenzae serotype b vaccine, H influenzae epidemiology has shifted. In the United States, the largest burden of disease is now in adults aged ≥65 years. However, few data exist on risk factors for disease severity and outcome in this age group.MethodsA retrospective case-series review of invasive H influenzae infections in patients aged ≥65 years was conducted for hospitalized cases reported to Active Bacterial Core surveillance in 2011.ResultsThere were 299 hospitalized cases included in the analysis. The majority of cases were caused by nontypeable H influenzae, and the overall case fatality ratio (CFR) was 19.5%. Three or more underlying conditions were present in 63% of cases; 94% of cases had at least 1. Patients with chronic heart conditions (congestive heart failure, coronary artery disease, and/or atrial fibrillation) (odds ratio [OR], 3.27; 95% confidence interval [CI], 1.65-6.46), patients from private residences (OR, 8.75; 95% CI, 2.13-35.95), and patients who were not resuscitate status (OR, 2.72; 95% CI, 1.31-5.66) were more likely to be admitted to the intensive care unit (ICU). Intensive care unit admission (OR, 3.75; 95% CI, 1.71-8.22) and do not resuscitate status (OR, 12.94; 95% CI, 4.84-34.55) were significantly associated with death.ConclusionsWithin this age group, burden of disease and CFR both increased significantly as age increased. Using ICU admission as a proxy for disease severity, our findings suggest several conditions increased risk of disease severity and patients with severe disease were more likely to die. Further research is needed to determine the most effective approach to prevent H influenzae disease and mortality in older adults

Penicillin Use in Meningococcal Disease Management: Active Bacterial Core Surveillance Sites, 2009.

In 2009, in the Active Bacterial Core surveillance sites, penicillin was not commonly used to treat meningococcal disease. This is likely because of inconsistent availability of antimicrobial susceptibility testing and ease of use of third-generation cephalosporins. Consideration of current practices may inform future meningococcal disease management guidelines

Optimising text messaging to improve adherence to web-based smoking cessation treatment: a randomised control trial protocol

Introduction Millions of smokers use the Internet for smoking cessation assistance each year; however, most smokers engage minimally with even the best designed websites. The ubiquity of mobile devices and their effectiveness in promoting adherence in other areas of health behaviour change make them a promising tool to address adherence in Internet smoking cessation interventions. Text messaging is used by most adults, and messages can proactively encourage use of a web-based intervention. Text messaging can also be integrated with an Internet intervention to facilitate the use of core Internet intervention components. Methods and analysis We identified four aspects of a text message intervention that may enhance its effectiveness in promoting adherence to a web-based smoking cessation programme: personalisation, integration, dynamic tailoring and message intensity. Phase I will use a two-level full factorial design to test the impact of these four experimental features on adherence to a web-based intervention. The primary outcome is a composite metric of adherence that incorporates general utilisation metrics (eg, logins, page views) and specific feature utilisation shown to predict abstinence. Participants will be N=860 adult smokers who register on an established Internet cessation programme and enrol in its text message programme. Phase II will be a two-arm randomised trial to compare the efficacy of the web-based cessation programme alone and in conjunction with the optimised text messaging intervention on 30-day point prevalence abstinence at 9 months. Phase II participants will be N=600 adult smokers who register to use an established Internet cessation programme and enrol in text messaging. Secondary analyses will explore whether adherence mediates the effect of treatment condition on outcome. Ethics and dissemination This protocol was approved by Chesapeake IRB. We will disseminate study results through peer-reviewed manuscripts and conference presentations related to the methods and design, outcomes and exploratory analyses. Trial registration number NCT02585206

Meningococcal Disease in Patients With Human Immunodeficiency Virus Infection: A Review of Cases Reported Through Active Surveillance in the United States, 2000-2008.

BackgroundAlthough human immunodeficiency virus (HIV) infection is an established risk factor for several bacterial infections, the association between HIV infection and meningococcal disease remains unclear.MethodsExpanded chart reviews were completed on persons with meningococcal disease and HIV infection reported from 2000 through 2008 from 9 US sites participating in an active population-based surveillance system for meningococcal disease. The incidence of meningococcal disease among patients meeting Centers for Disease Control and Prevention acquired immune deficiency syndrome (AIDS) surveillance criteria was estimated using data from the National HIV Surveillance System for the participating sites.ResultsThirty-three cases of meningococcal disease in individuals with HIV infection were reported from participating sites, representing 2.0% of all reported meningococcal disease cases. Most (75.8%) persons with HIV infection were adult males aged 25 to 64 years old. Among all meningococcal disease cases aged 25 to 64 years old, case fatality ratios were similar among HIV-infected and HIV-uninfected persons (13.3% vs 10.6%; P = .6). The cumulative, mean incidence of meningococcal disease among patients aged 25 to 64 years old with HIV infection ever classified as AIDS was 3.5 cases per 100000 person years (95% confidence interval [CI], 2.1-5.6), compared with 0.3 cases per 100000 person years (95% CI, 0.3-0.3) for persons of the same age group not reported to have AIDS (relative risk = 12.9; 95% CI, 7.9-20.9).ConclusionsIndividuals with HIV infection meeting the AIDS surveillance case definition have a higher incidence of meningococcal disease compared with the general adult population

ATYPICAL REVERSE REACTION IN A MULTIBACILLARY PATIENT

A hanseníase é uma doença infectocontagiosa causada pelo Mycobacterium leprae que atinge preferen- cialmente pele e/ou nervos periféricos. Pode apresentar períodos de agudização denominados reações. Os dois tipos de reações hansênicas, tipo1 ou reversa e tipo 2 ou eritema nodoso, refletem o processo inflamatório imunomediado, envolvendo distintos mecanismos de hipersensibilidade. A reação tipo 1 corresponde a um súbito aumento da imuni- dade mediada por células sendo mais comum nas formas paucibacilares da doença e a reação tipo 2 é reconhecida como alteração na imunidade humoral, sendo mais comum nas formas multibacilares. O presente artigo tem o objetivo de demonstrar um caso de reação reversa, ou seja, tipo 1 em um paciente compro- vadamente multibacilar. PALAVRAS-CHAVE – Lepra; Mycobacterium leprae. Leprosy is an infectious disease caused by Mycobacterium leprae that primarily affects the skin and/or peripheral nerves. It can have periods of acute reactions known as type 1 or reverse and type 2 or erythema nodosum. These reactions reflect the immune-mediated inflammatory process involving different mechanisms of hypersensitivity. The type 1 reaction corresponds to a sudden increase in cell-mediated immunity is more common in paucibacillary forms of the disease and type 2 reaction is recognized as changes in humoral immunity, is more common in multibacillary. This article aims to demonstrate a case of reverse reaction in a multibacillary patient. KEYWORDS – Leprosy, multibacillary; Mycobacterium leprae.

Persistence of serogroup C antibody responses following quadrivalent meningococcal conjugate vaccination in United States military personnel

AbstractSerogroup C meningococcal (MenC) disease accounts for one-third of all meningococcal cases and causes meningococcal outbreaks in the U.S. Quadrivalent meningococcal vaccine conjugated to diphtheria toxoid (MenACYWD) was recommended in 2005 for adolescents and high risk groups such as military recruits. We evaluated anti-MenC antibody persistence in U.S. military personnel vaccinated with either MenACYWD or meningococcal polysaccharide vaccine (MPSV4). Twelve hundred subjects vaccinated with MenACYWD from 2006 to 2008 or MPSV4 from 2002 to 2004 were randomly selected from the Defense Medical Surveillance System. Baseline serologic responses to MenC were assessed in all subjects; 100 subjects per vaccine group were tested during one of the following six post-vaccination time-points: 5–7, 11–13, 17–19, 23–25, 29–31, or 35–37 months. Anti-MenC geometric mean titers (GMT) were measured by rabbit complement serum bactericidal assay (rSBA) and geometric mean concentrations (GMC) by enzyme-linked immunosorbent assay (ELISA). Continuous variables were compared using the Wilcoxon rank sum test and the proportion of subjects with an rSBA titer ≥8 by chi-square. Pre-vaccination rSBA GMT was <8 for the MenACWYD group. rSBA GMT increased to 703 at 5–7 months post-vaccination and decreased by 94% to 43 at 3 years post-vaccination. GMT was significantly lower in the MenACWYD group at 5–7 months post-vaccination compared to the MPSV4 group. The percentage of MenACWYD recipients achieving an rSBA titer of ≥8 decreased from 87% at 5–7 months to 54% at 3 years. There were no significant differences between vaccine groups in the proportion of subjects with a titer of ≥8 at any time-point. GMC for the MenACWYD group was 0.14μg/mL at baseline, 1.07μg/mL at 5–7 months, and 0.66μg/mL at 3 years, and significantly lower than the MPSV4 group at all time-points. Anti-MenC responses wane following vaccination with MenACYWD; a booster dose is needed to maintain protective levels of circulating antibody

ABCC Multidrug Transporters in Childhood Neuroblastoma: Clinical and Biological Effects Independent of Cytotoxic Drug Efflux

Background Although the prognostic value of the ATP-binding cassette, subfamily C (ABCC) transporters in childhood neuroblastoma is usually attributed to their role in cytotoxic drug efflux, certain observations have suggested that these multidrug transporters might contribute to the malignant phenotype independent of cytotoxic drug efflux. Methods A v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (MYCN)-driven transgenic mouse neuroblastoma model was crossed with an Abcc1-deficient mouse strain (658 hMYCN1/−, 205 hMYCN+/1 mice) or, alternatively, treated with the ABCC1 inhibitor, Reversan (n = 20). ABCC genes were suppressed using short interfering RNA or overexpressed by stable transfection in neuroblastoma cell lines BE(2)-C, SH-EP, and SH-SY5Y, which were then assessed for wound closure ability, clonogenic capacity, morphological differentiation, and cell growth. Real-time quantitative polymerase chain reaction was used to examine the clinical significance of ABCC family gene expression in a large prospectively accrued cohort of patients (n = 209) with primary neuroblastomas. Kaplan-Meier survival analysis and Cox regression were used to test for associations with event-free and overall survival. Except where noted, all statistical tests were two-sided. Results Inhibition of ABCC1 statistically significantly inhibited neuroblastoma development in hMYCN transgenic mice (mean age for palpable tumor: treated mice, 47.2 days; control mice, 41.9 days; hazard ratio [HR] = 9.3, 95% confidence interval [CI] = 2.65 to 32; P < .001). Suppression of ABCC1 in vitro inhibited wound closure (P < .001) and clonogenicity (P = .006); suppression of ABCC4 enhanced morphological differentiation (P < .001) and inhibited cell growth (P < .001). Analysis of 209 neuroblastoma patient tumors revealed that, in contrast with ABCC1 and ABCC4, low rather than high ABCC3 expression was associated with reduced event-free survival (HR of recurrence or death = 2.4, 95% CI = 1.4 to 4.2; P = .001), with 23 of 53 patients with low ABCC3 expression experiencing recurrence or death compared with 31 of 155 patients with high ABCC3. Moreover, overexpression of ABCC3 in vitro inhibited neuroblastoma cell migration (P < .001) and clonogenicity (P = .03). The combined expression of ABCC1, ABCC3, and ABCC4 was associated with patients having an adverse event, such that of the 12 patients with the "poor prognosis” expression pattern, 10 experienced recurrence or death (HR of recurrence or death = 12.3, 95% CI = 6 to 27; P < .001). Conclusion ABCC transporters can affect neuroblastoma biology independently of their role in chemotherapeutic drug efflux, enhancing their potential as targets for therapeutic interventio