Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
- Being Prepared: Bioterrorism and Mass Prophylaxis: Part II. [JOURNAL ARTICLE]
- Adv Emerg Nurs J 2014 October/December; 36(4):307-317.
Although several biological agents have been recognized as presenting a significant threat to public health if used in a bioterrorist attack, those that are of greatest importance are known as the Category A agents: Bacillus anthracis (anthrax); variola major (smallpox); Yersinia pestis (plague); Francisella tularensis (tularemia); ribonucleic acid viruses (hemorrhagic fevers); and Clostridium botulinum (botulism toxin). In the previous issue, Part I of this review focused on the clinical presentation and treatment of anthrax, plague, and tularemia. In this second part of this 2-part review of these agents, the focus is on the clinical presentation and treatment of smallpox, viral hemorrhagic fevers, and botulism toxin. The utilization of mass prophylaxis to limit the morbidity and mortality associated with all these agents is also discussed along with the role emergency care personnel play in its implementation.
- Detecting Differential Transmissibilities That Affect the Size of Self-Limited Outbreaks. [JOURNAL ARTICLE]
- PLoS Pathog 2014 Oct; 10(10):e1004452.
Our ability to respond appropriately to infectious diseases is enhanced by identifying differences in the potential for transmitting infection between individuals. Here, we identify epidemiological traits of self-limited infections (i.e. infections with an effective reproduction number satisfying [Formula: see text]) that correlate with transmissibility. Our analysis is based on a branching process model that permits statistical comparison of both the strength and heterogeneity of transmission for two distinct types of cases. Our approach provides insight into a variety of scenarios, including the transmission of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the Arabian peninsula, measles in North America, pre-eradication smallpox in Europe, and human monkeypox in the Democratic Republic of the Congo. When applied to chain size data for MERS-CoV transmission before 2014, our method indicates that despite an apparent trend towards improved control, there is not enough statistical evidence to indicate that [Formula: see text] has declined with time. Meanwhile, chain size data for measles in the United States and Canada reveal statistically significant geographic variation in [Formula: see text], suggesting that the timing and coverage of national vaccination programs, as well as contact tracing procedures, may shape the size distribution of observed infection clusters. Infection source data for smallpox suggests that primary cases transmitted more than secondary cases, and provides a quantitative assessment of the effectiveness of control interventions. Human monkeypox, on the other hand, does not show evidence of differential transmission between animals in contact with humans, primary cases, or secondary cases, which assuages the concern that social mixing can amplify transmission by secondary cases. Lastly, we evaluate surveillance requirements for detecting a change in the human-to-human transmission of monkeypox since the cessation of cross-protective smallpox vaccination. Our studies lay the foundation for future investigations regarding how infection source, vaccination status or other putative transmissibility traits may affect self-limited transmission.
- CD4+ T cell help is dispensable for protective CD8+ T cell memory against mousepox following vaccinia virus immunization. [JOURNAL ARTICLE]
- J Virol 2014 Oct 29.
It has been shown in various infection models that CD4(+) T cell help (TH) is necessary for the conditioning, maintenance and/or recall responses of memory CD8(+) T cells (CD8M). Yet, in the case of vaccinia virus (VACV), which constitutes the vaccine used to eradicate smallpox and is a candidate vector for other infectious diseases, the issue is controversial because different groups have shown either TH dependence or independence of CD8M conditioning, maintenance and or recall response. In agreement with some of these groups, we show that TH plays a role but is not essential for the maintenance, proliferation and effector differentiation of polyclonal memory CD8(+) T cells after infection with wild type VACV WR. More important, we show that un-helped and helped anti-VACV memory CD8(+) T cells are similarly efficient at protecting susceptible mice from lethal mousepox, the mouse equivalent of human smallpox. Thus, TH is not essential for the conditioning and maintenance of memory CD8(+) T cells capable of mounting a recall response strong enough to protect from a lethal natural pathogen. Our results may partly explain why the VACV vaccine is so effective.We used vaccinia virus (VACV) -a gold standard vaccine - as the immunogen, and ectromelia virus (ECTV) as the pathogen to demonstrate that the conditioning and maintenance of anti-VACV memory CD8(+) T cells and their ability to protect against an Orthopoxvirus (OPV) infection in its natural host can develop in the absence of CD4(+) T cell help. Our results provide important insight to our basic knowledge of the immune system. Further, because VACV is used as a vaccine in humans, our results may help us understand how this vaccine induces protective immunity in this species. In addition, this work may partly explain why VACV is so effective as a vaccine.
- 'Forgotten' NIH smallpox virus languishes on death row. [News]
- Nature 2014 Oct 28; 514(7524):544.
- TLR3 and TLR9 Agonists Improve Postexposure Vaccination Efficacy of Live Smallpox Vaccines. [JOURNAL ARTICLE]
- PLoS One 2014; 9(10):e110545.
Eradication of smallpox and discontinuation of the vaccination campaign resulted in an increase in the percentage of unvaccinated individuals, highlighting the need for postexposure efficient countermeasures in case of accidental or deliberate viral release. Intranasal infection of mice with ectromelia virus (ECTV), a model for human smallpox, is curable by vaccination with a high vaccine dose given up to 3 days postexposure. To further extend this protective window and to reduce morbidity, mice were vaccinated postexposure with Vaccinia-Lister, the conventional smallpox vaccine or Modified Vaccinia Ankara, a highly attenuated vaccine in conjunction with TLR3 or TLR9 agonists. We show that co-administration of the TLR3 agonist poly(I:C) even 5 days postexposure conferred protection, avoiding the need to increase the vaccination dose. Efficacious treatments prevented death, ameliorated disease symptoms, reduced viral load and maintained tissue integrity of target organs. Protection was associated with significant elevation of serum IFNα and anti-vaccinia IgM antibodies, modulation of IFNγ response, and balanced activation of NK and T cells. TLR9 agonists (CpG ODNs) were less protective than the TLR3 agonist poly(I:C). We show that activation of type 1 IFN by poly(I:C) and protection is achievable even without co-vaccination, requiring sufficient amount of the viral antigens of the infective agent or the vaccine. This study demonstrated the therapeutic potential of postexposure immune modulation by TLR activation, allowing to alleviate the disease symptoms and to further extend the protective window of postexposure vaccination.
- [Squamous cell carcinoma in ulcer after bacille Calmette-Guérin vaccination.] [JOURNAL ARTICLE]
- Ugeskr Laeger 2014 Oct 13; 176(42)
Marjolin's ulcer is an aggressive squamous cell carcinoma (SCC) found in chronically inflamed skin. SCC has been reported in smallpox vaccination sites, whereas basal cell carcinomas are more common in scar after bacille Calmette-Guérin (BCG) vaccination. A 72-year-old man presented with a chronic ulcer at the site of his childhood BCG vaccination. At the time of examination, a 3 × 1.5 cm fleshy and secreting ulcer was found on the shoulder. Biopsy revealed SCC, and the tumour was surgically removed. In conclusion, chronic ulcers, especially those originating in chronically inflamed skin, should be regularly biopsied to assure that malignant transformation has not occurred.
- Interwoven support: An historical survey of US federal programs enabling immunization. [JOURNAL ARTICLE]
- Vaccine 2014 Oct 7.
The US Government (USG) can date its involvement with immunization to military and civilian efforts in 1777 and 1813 to prevent smallpox. USG involvement began accelerating with federal licensing of vaccine and antibody manufacturers in 1903. In addition to ongoing regulation of manufacturing and product quality, military and civilian arms of the USG have led research efforts into new or improved vaccines. These efforts have included diseases endemic in the United States, as well as medical countermeasures targeted against biological weapons, influenza pandemics, and emerging infectious diseases. Especially since the 1950s, the USG has provided increasing levels of funding to purchase vaccines and conduct vaccination programs. These programs have focused largely on children, although vaccination programs for adults have been expanded somewhat in recent years. Multiple agencies of the USG have convened various panels of accomplished external experts who have generated widely regarded recommendations on vaccine safety and efficacy and optimal immunization practices. USG programs for safety assessment, injury compensation, liability protection, and disease surveillance have been developed to assess needs, evaluate safety questions, ensure vaccine supply, and foster confidence in vaccination efforts. Debates on the extent of government involvement date back to the 1890s and continue today. Several pivotal expansions of government involvement followed disease outbreaks or manufacturing accidents. This historical survey describes each of the major US federal programs in these categories, including references to applicable law.
- Improved estimation of the initial number of susceptible individuals in the general stochastic epidemic model using penalized likelihood. [Journal Article]
- ScientificWorldJournal 2014.:241687.
The initial size of a completely susceptible population in a group of individuals plays a key role in drawing inferences for epidemic models. However, this can be difficult to obtain in practice because, in any population, there might be individuals who may not transmit the disease during the epidemic. This short note describes how to improve the maximum likelihood estimators of the infection rate and the initial number of susceptible individuals and provides their approximate Hessian matrix for the general stochastic epidemic model by using the concept of the penalized likelihood function. The simulations of major epidemics show significant improvements in performance in averages and coverage ratios for the suggested estimator of the initial number in comparison to existing methods. We applied the proposed method to the Abakaliki smallpox data.
- From Crescent to Mature Virion: Vaccinia Virus Assembly and Maturation. [REVIEW]
- Viruses 2014; 6(10):3787-3808.
Vaccinia virus (VACV) has achieved unprecedented success as a live viral vaccine for smallpox which mitigated eradication of the disease. Vaccinia virus has a complex virion morphology and recent advances have been made to answer some of the key outstanding questions, in particular, the origin and biogenesis of the virion membrane, the transformation from immature virion (IV) to mature virus (MV), and the role of several novel genes, which were previously uncharacterized, but have now been shown to be essential for VACV virion formation. This new knowledge will undoubtedly contribute to the rational design of safe, immunogenic vaccine candidates, or effective antivirals in the future. This review endeavors to provide an update on our current knowledge of the VACV maturation processes with a specific focus on the initiation of VACV replication through to the formation of mature virions.
- Serial intervals of respiratory infectious diseases: a systematic review and analysis. [Journal Article]
- Am J Epidemiol 2014 Nov 1; 180(9):865-75.
The serial interval of an infectious disease represents the duration between symptom onset of a primary case and symptom onset of its secondary cases. A good evidence base for such values is essential, because they allow investigators to identify epidemiologic links between cases and serve as an important parameter in epidemic transmission models used to design infection control strategies. We reviewed the literature for available data sets containing serial intervals and for reported values of serial intervals. We were able to collect data on outbreaks within households, which we reanalyzed to infer a mean serial interval using a common statistical method. We estimated the mean serial intervals for influenza A(H3N2) (2.2 days), pandemic influenza A(H1N1)pdm09 (2.8 days), respiratory syncytial virus (7.5 days), measles (11.7 days), varicella (14.0 days), smallpox (17.7 days), mumps (18.0 days), rubella (18.3 days), and pertussis (22.8 days). For varicella, we found an evidence-based value that deviates substantially from the 21 days commonly used in transmission models. This value of the serial interval for pertussis is, to the best of our knowledge, the first that is based on observations. Our review reveals that, for most infectious diseases, there is very limited evidence to support the serial intervals that are often cited.