pestis fulminans [keywords]
- A Recombinant Trivalent Fusion Protein F1-LcrV-HSP70(II) Augments Humoral and Cellular Immune Responses and Imparts Full Protection against Yersinia pestis. [Journal Article]
- Front Microbiol 2016.:1053.
Plague is one of the most dangerous infections in humans caused by Yersinia pestis, a Gram-negative bacterium. Despite of an overwhelming research success, no ideal vaccine against plague is available yet. It is well established that F1/LcrV based vaccine requires a strong cellular immune response for complete protection against plague. In our earlier study, we demonstrated that HSP70(II) of Mycobacterium tuberculosis modulates the humoral and cellular immunity of F1/LcrV vaccine candidates individually as well as in combinations in a mouse model. Here, we made two recombinant constructs caf1-lcrV and caf1-lcrV-hsp70(II). The caf1 and lcrV genes of Y. pestis and hsp70 domain II of M. tuberculosis were amplified by polymerase chain reaction. Both the recombinant constructs caf1-lcrV and caf1-lcrV-hsp70(II) were cloned in pET28a vector and expressed in Escherichia coli. The recombinant fusion proteins F1-LcrV and F1-LcrV-HSP70(II) were purified using Ni-NTA columns and formulated with alum to evaluate the humoral and cell mediated immune responses in mice. The protective efficacies of F1-LcrV and F1-LcrV-HSP70(II) were determined following challenge of immunized mice with 100 LD50 of Y. pestis through intraperitoneal route. Significant differences were noticed in the titers of IgG and it's isotypes, i.e., IgG1, IgG2b, and IgG3 in anti- F1-LcrV-HSP70(II) sera in comparison to anti-F1-LcrV sera. Similarly, significant differences were also noticed in the expression levels of IL-2, IFN-γ and TNF-α in splenocytes of F1-LcrV-HSP(II) immunized mice in comparison to F1-LcrV. Both F1-LcrV and F1-LcrV-HSP70(II) provided 100% protection. Our research findings suggest that F1-LcrV fused with HSP70 domain II of M. tuberculosis significantly enhanced the humoral and cellular immune responses in mouse model.
- Plague in Iran: past and current situation. [JOURNAL ARTICLE]
- Epidemiol Health 2016 Jul 24.
Plague remains a public health concern worldwide, particularly in old foci. Multiple epidemics of this disease have been registered in Iran's history. Despite the long-standing history of human plague in Iran, it is difficult to get a historical and current overview of the general situation.In this review, available data and reports on human plague occurrences in the past and present in Iran and in neighboring countries are collected and information is compiled on when, where and how many cases occurred.This paper considers the history of plague in Persia (predecessor of today's Iran) and has a brief review on countries in the WHO Eastern Mediterranean Region, consisting of some of the countries in the Middle East and North Africa.Considering that Iran has experienced outbreaks of plague for several centuries, neighboring countries have reported the disease in recent years, the disease can be silent for decades, and the reports of the circulation of Y. pestis among rodents and dogs in western Iran, more attention should be paid to disease monitoring in areas with previously reported human cases and high-risk regions with previous epizootic and enzootic activities.
- Cross-Species Antiviral Activity of Goose Interferons against Duck Plague Virus Is Related to Its Positive Self-Feedback Regulation and Subsequent Interferon Stimulated Genes Induction. [Journal Article]
- Viruses 2016; 8(7)
Interferons are a group of antiviral cytokines acting as the first line of defense in the antiviral immunity. Here, we describe the antiviral activity of goose type I interferon (IFNα) and type II interferon (IFNγ) against duck plague virus (DPV). Recombinant goose IFNα and IFNγ proteins of approximately 20 kDa and 18 kDa, respectively, were expressed. Following DPV-enhanced green fluorescent protein (EGFP) infection of duck embryo fibroblast cells (DEFs) with IFNα and IFNγ pre-treatment, the number of viral gene copies decreased more than 100-fold, with viral titers dropping approximately 100-fold. Compared to the control, DPV-EGFP cell positivity was decreased by goose IFNα and IFNγ at 36 hpi (3.89%; 0.79%) and 48 hpi (17.05%; 5.58%). In accordance with interferon-stimulated genes being the "workhorse" of IFN activity, the expression of duck myxovirus resistance (Mx) and oligoadenylate synthetases-like (OASL) was significantly upregulated (p < 0.001) by IFN treatment for 24 h. Interestingly, duck cells and goose cells showed a similar trend of increased ISG expression after goose IFNα and IFNγ pretreatment. Another interesting observation is that the positive feedback regulation of type I IFN and type II IFN by goose IFNα and IFNγ was confirmed in waterfowl for the first time. These results suggest that the antiviral activities of goose IFNα and IFNγ can likely be attributed to the potency with which downstream genes are induced by interferon. These findings will contribute to our understanding of the functional significance of the interferon antiviral system in aquatic birds and to the development of interferon-based prophylactic and therapeutic approaches against viral disease.
- A one-step duplex rRT-PCR assay for the simultaneous detection of duck hepatitis A virus genotypes 1 and 3. [JOURNAL ARTICLE]
- J Virol Methods 2016 Jul 16.
Duck hepatitis A virus (DHAV) is a highly infectious pathogen that causes significant bleeding lesions in the viscera of ducklings less than 3 weeks old. There are three serotypes of DHAV: serotype 1 (DHAV-1), serotype 2 (DHAV-2) and serotype 3 (DHAV-3). These serotypes have no cross-antigenicity with each other. To establish an rRT-PCR assay for the rapid detection of a mixed infection of DHAV-1 and DHAV-3, two pairs of primers and a pair of matching TaqMan probes were designed based on conserved regions of DHAV-1 VP0 and DHAV-3 VP3. Finally, we established a one-step duplex rRT-PCR assay with high specificity and sensitivity for the simultaneous detection of DHAV-1 and DHAV-3. This method showed no cross-antigenicity with the other pathogens tested, including duck plague virus, Muscovy duck parvovirus, Riemerella anatipestifer, and pathogenic E. coli from ducks. Sensitivity tests identified the minimum detection limits of this method as 98 (DHAV-1) and 10 (DHAV-3) copies/reaction. To validate the method, thirty-eight clinical samples and thirty artificially infected samples collected from dead duck embryos were studied. Thirty-seven samples were positive for DHAV-1, seventeen samples were positive for DHAV-3, and fourteen samples were positive for a mixed infection using the duplex rRT-PCR method. The method established in this study is specific, sensitive, convenient and timesaving and is a powerful tool for detecting DHAV-1, DHAV-3, and their mixed infection and for conducting surveys of pandemic virus strains.
- Effects of Nitric Oxide on Carotid Intima Media Thickness: A Pilot Study. [Journal Article]
- Altern Ther Health Med 2016 Jun.:32-4.
Cardiovascular disease is among the leading causes of morbidity and mortality worldwide. Preventive treatment of high-risk asymptomatic individuals depends on accurate prediction of a person's risk to develop a cardiovascular event. Currently, cardiovascular risk prediction in asymptomatic individuals is based on the level of cardiovascular risk factors incorporated in scoring equations. Improvement in cardiovascular risk prediction is needed because atherosclerosis underlies the occurrence of cardiovascular events, develops over decades, and has a prolonged asymptomatic phase during which it is possible to modify the course of the disease. The carotid intima media thickness test (CIMT) is a measure used to diagnose the extent of carotid atherosclerotic vascular disease. The test measures the thickness of the inner 2 layers of the carotid artery-the intima and media-and alerts physicians to any thickening when patients are still asymptomatic. Early detection may indicate the need for a more aggressive approach to managing the risk factors associated with heart disease and stroke. The role of nitric oxide (NO) in maintaining the integrity of the cardiovascular system is well established. Utilizing a dietary supplement that restores NO production, the author conducted a pilot study involving 10 patients with stable plague. Six months of treatment with the NO lozenge resulted in a statistically significant 10.9% reduction in CIMT. This pilot study suggests this approach may be a safe and effective strategy for patients with early stages of atherosclerotic vascular disease.
- Serotonin transporter polymorphism moderates the effects of caregiver intrusiveness on ADHD symptoms among institutionalized preschoolers. [JOURNAL ARTICLE]
- Eur Child Adolesc Psychiatry 2016 Jul 18.
Research consistently chronicles a variety of mental health difficulties that plague institutionally reared children, including attention-deficit/hyperactivity disorder (ADHD), even if not all institutionalized children evince such problems. In seeking to extend work in this area, this research on gene × environment (GXE) interplay investigated whether the effect of the quality of institutional care-most notably, caregiver intrusiveness-on ADHD symptoms is moderated by the serotonin transporter (5-HTTLPR) polymorphism. One hundred and twenty-seven institutionalized preschoolers were evaluated using the Child Behavior Checklist. Caregiver-rated attention problems and hyperactivity were unrelated to both 5-HTTLPR polymorphism and caregiver intrusiveness. A significant GXE effect, independent of age at placement or duration of institutionalization, emerged, however, consistent with the differential-susceptibility hypothesis: s/s homozygotes manifest the most and least ADHD symptoms when they experienced, respectively, more and less intrusive caregiving. These results provide new insight into the reasons why some institutionalized children, but not others, exhibit ADHD symptoms.
- Impact of Twitter intensity, time, and location on message lapse of bluebird's pursuit of fleas in Madagascar. [JOURNAL ARTICLE]
- J Infect Public Health 2016 Jul 13.
The recent outbreak of bubonic plague in Madagascar reminds us of the continuing public health challenges posed by such deadly diseases in various parts of the world years after their eradication. This study examines the role of Twitter in public health disease surveillance with special focus on how Twitter intensity, time, and location issues explain Twitter plague message delay.We retrospectively analyzed the Twitter feeds of the 2014 bubonic plague outbreak in Madagascar. The analyses are based on the plague-related data available in the public domain between November 19th and 27th 2014. The data were compiled in March 2015. We calculated the time differential between the tweets and retweets, and analyzed various characteristics of the Tweets including Twitter intensity of the users.A total of 6873 Twitter users were included in the study, of which 52% tweeted plague-related information during the morning hours (before mid-day), and 87% of the tweets came from the west of the epicenter of the plague. More importantly, while session of tweet lease and relative location had effect on message lapse, absolute location did not. Additionally, we found no evidence of differential effect of location on message lapse based on relative location i.e. tweets from west or east nor number of following. However, there is evidence that more intense Twitter use appears to have significant effect on message lapse such that as the number of tweets became more intense, time differential between the tweets and retweets increased while higher number of retweets diminished message lapse.This study affirms that Twitter can play an important role in ongoing disease surveillance and the timely dissemination of information during public health emergencies independent of the time and space restrictions. Further ways should be explored to embed social media channels in routine public health practice.
- Classic Spotlight: Studies on the Low-Calcium Response of Yersinia pestis Reveal the Secrets of Plague Pathogenesis. [Editorial]
- J Bacteriol 2016 Aug 1; 198(15):2018.
- Adjunctive Corticosteroid Treatment Against Yersinia pestis Improves Bacterial Clearance, Immunopathology and Survival in the Mouse Model of Bubonic Plague. [JOURNAL ARTICLE]
- J Infect Dis 2016 Jul 11.
Plague is initiated by Yersinia pestis, a highly virulent bacterial pathogen. In late stages of the infection, bacteria proliferate extensively in the internal organs despite the massive infiltration of neutrophils. The ineffective inflammatory response associated with tissue damage may contribute to the low efficacy of anti-plague therapies during late stages of the infection. In the present study, we address the possibility of improving therapeutic efficacy by combining corticosteroid administration with antibody therapy in the mouse model of bubonic plague. M&M: Mice were subcutaneously infected with a fully virulent Y. pestis strain and treated at progressive stages of the disease with anti-plague antibodies alone or in combination with the corticosteroid methylprednisolone. The addition of methylprednisolone to antibody therapy correlated with improved mouse survival, a significant decrease in the amount of neutrophils and matrix metalloproteinase-9 in the tissues and the mitigation of tissue damage. Interestingly, the combined treatment led to a decrease in the bacterial loads in infected organs. Corticosteroids induce an unexpectedly effective anti-bacterial response apart from their anti-inflammatory properties, thereby improving treatment efficacy.
- [Sympatric Speciation of the Plague Microbe Yersinia pestis: Monohostal Specialization in the Host-Parasite Marmot-Flea (Marmota sibirica-Oropsylla silantiewi) System]. [English Abstract, Journal Article]
- Izv Akad Nauk Ser Biol 2016 Mar-Apr; (2):117-27.
An ecological scenario of the origin of the plague microbe that is interpreted in the light of modern Darwinism (synthetic theory of evolution) is presented. It is shown that the plague microbe emerged from a clone of the psychrophilic saprozoonotic pseudotuberculosis microbe Yersinia pseudotuberculosis O:1b in the mountain steppe landscapes of Central Asia in the Sartan time, 22000-15000 years ago, in the monohostal Mongolian marmot (Marmota sibirica)-flea (Oropsylla silantiewi) host-parasite system. It was noted that the evolutionary process described corresponds to the sympatric form of speciation by transition ofthe clone of migrant founders to a new, already-existing ecological niche. It was established that monohostal specialization of the plague microbe was made possible due to heterothermia (5-37 degrees C) of marmots in the hibernation period. The factors of the speciation process--isolation, the struggle for existence, and natural selection--were analyzed.