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pestis fulminans [keywords]
- A bivalent typhoid live vector vaccine expressing both chromosomal and plasmid-encoded Y. pestis antigens fully protects against murine lethal pulmonary plague infection. [JOURNAL ARTICLE]
- Infect Immun 2014 Oct 20.
Live attenuated bacteria hold great promise as multivalent mucosal vaccines against a variety of pathogens. A major challenge of this approach has been the successful delivery of sufficient amounts of vaccine antigens to adequately prime the immune system without over-attenuating the live vaccine. Here we have used a live attenuated Salmonella enterica serovar Typhi strain to create a bivalent mucosal plague vaccine that produces both the protective F1 capsular antigen of Yersinia pestis as well as the LcrV protein required for secretion of virulence effector proteins. To reduce metabolic burden associated with the co-expression of F1 and LcrV within the live vector, we balanced expression of both antigens by combining plasmid-based expression of F1 with chromosomal expression of LcrV from three independent loci. The immunogenicity and protective efficacy of this novel vaccine were assessed in mice using a heterologous prime-boost immunization strategy, and compared to a conventional strain in which F1 and LcrV were expressed from a single low copy number plasmid. The serum antibody responses to LPS induced by the optimized bivalent vaccine were indistinguishable from those elicited by the parent strain, suggesting adequate immunogenic capacity maintained through preservation of bacterial fitness; by contrast, LPS titers were 10-fold lower in mice immunized with the conventional vaccine strain. Importantly, mice receiving the optimized bivalent vaccine were fully protected against lethal pulmonary challenge. These results demonstrate the feasibility of distributing foreign antigen expression across both chromosomal and plasmid locations within a single vaccine organism for induction of protective immunity.
- Draft Genome Sequences of Yersinia pestis Strains from the 1994 Plague Epidemic of Surat and 2002 Shimla Outbreak in India. [Journal Article]
- Indian J Microbiol 2014 Dec; 54(4):480-2.
We report the first draft genome sequences of the strains of plague-causing bacteria, Yersinia pestis, from India. These include two strains from the Surat epidemic (1994), one strain from the Shimla outbreak (2002) and one strain from the plague surveillance activity in the Deccan plateau region (1998). Genome size for all four strains is ~4.49 million bp with 139-147 contigs. Average sequencing depth for all four genomes was 21x.
- Older Siblings' Contributions to Young Child's Cognitive Skills. [JOURNAL ARTICLE]
- Econ Model 2013 Sep.:235-248.
This work finds that older siblings as well as early parenting influence young children's cognitive skills directly or indirectly, for example, Mathematics, and English. Our findings challenge a pervasive view in the economical literatures that early parenting play a dominant role in explaining child development. In economics, early environmental conditions are important to demonstrate the evolution of adolescent and adult cognitive skills (Knudsen, Heckman, Cameron, and Shonkoff, 2006; Cunha and Heckman, 2007), and it establishes causal impacts of early parental inputs and other environmental factors on cognitive and non-cognitive skills (Heckman, Stixrud, and Urzua, 2006; Borghans, Duckworth, Heckman, and Weel, 2006; Cunha, Heckman, and Schennach, 2010). Early parenting as well as older siblings should explain a diverse array of academic and social outcomes, for example, Mathematics, English, maritage and pregnancy. In fact, older siblings' characteristics are as important, if not more important, than parenting for child development. Our analysis addresses the problems of measurement error, imperfect proxies, and reverse causality that plague conventional approach in psychology. We find that older brother contributes much more than older sister to child's mathematical achievement, while older sister contributes much more to child's english achievement. Our evidence is consistent with psychology literature, for example, Hetherington (1988), Jenkins (1992), Zukow-Goldring (1995), Marshall, Garcia-Coll, Marx, McCartney, Keffe, and Rub (1997), Maynard (2002), and Brody Ge, Kim, Murry, Simons, Gibbons, Gerrard, and Conger (2003) for siblings' direct contributions to child development, Bronfenbrenner (1997), East (1998), Whiteman and Buchanan (2002), and Brody, Ge, Kim, Murry, Simons, Gibbons, Gerrard, and Conger (2003) for siblings's indirect contributions, and Reiss, Neiderhiser, Hetherington, and Plomin (2000), Feinberg and Hetherington (2001), Kowal, Kramer, Krull, and Crick (2002) for parental differential treatment.
- Detection of Rickettsia felis, Rickettsia typhi, Bartonella Species and Yersinia pestis in Fleas (Siphonaptera) from Africa. [Journal Article]
- PLoS Negl Trop Dis 2014 Oct; 8(10):e3152.
Little is known about the presence/absence and prevalence of Rickettsia spp, Bartonella spp. and Yersinia pestis in domestic and urban flea populations in tropical and subtropical African countries.Fleas collected in Benin, the United Republic of Tanzania and the Democratic Republic of the Congo were investigated for the presence and identity of Rickettsia spp., Bartonella spp. and Yersinia pestis using two qPCR systems or qPCR and standard PCR. In Xenopsylla cheopis fleas collected from Cotonou (Benin), Rickettsia typhi was detected in 1% (2/199), and an uncultured Bartonella sp. was detected in 34.7% (69/199). In the Lushoto district (United Republic of Tanzania), R. typhi DNA was detected in 10% (2/20) of Xenopsylla brasiliensis, and Rickettsia felis was detected in 65% (13/20) of Ctenocephalides felis strongylus, 71.4% (5/7) of Ctenocephalides canis and 25% (5/20) of Ctenophthalmus calceatus calceatus. In the Democratic Republic of the Congo, R. felis was detected in 56.5% (13/23) of Ct. f. felis from Kinshasa, in 26.3% (10/38) of Ct. f. felis and 9% (1/11) of Leptopsylla aethiopica aethiopica from Ituri district and in 19.2% (5/26) of Ct. f. strongylus and 4.7% (1/21) of Echidnophaga gallinacea. Bartonella sp. was also detected in 36.3% (4/11) of L. a. aethiopica. Finally, in Ituri, Y. pestis DNA was detected in 3.8% (1/26) of Ct. f. strongylus and 10% (3/30) of Pulex irritans from the villages of Wanyale and Zaa.Most flea-borne infections are neglected diseases which should be monitored systematically in domestic rural and urban human populations to assess their epidemiological and clinical relevance. Finally, the presence of Y. pestis DNA in fleas captured in households was unexpected and raises a series of questions regarding the role of free fleas in the transmission of plague in rural Africa, especially in remote areas where the flea density in houses is high.
- A Non-Stationary Relationship between Global Climate Phenomena and Human Plague Incidence in Madagascar. [Journal Article]
- PLoS Negl Trop Dis 2014 Oct; 8(10):e3155.
Plague, a zoonosis caused by Yersinia pestis, is found in Asia and the Americas, but predominantly in Africa, with the island of Madagascar reporting almost one third of human cases worldwide. Plague's occurrence is affected by local climate factors which in turn are influenced by large-scale climate phenomena such as the El Niño Southern Oscillation (ENSO). The effects of ENSO on regional climate are often enhanced or reduced by a second large-scale climate phenomenon, the Indian Ocean Dipole (IOD). It is known that ENSO and the IOD interact as drivers of disease. Yet the impacts of these phenomena in driving plague dynamics via their effect on regional climate, and specifically contributing to the foci of transmission on Madagascar, are unknown. Here we present the first analysis of the effects of ENSO and IOD on plague in Madagascar.We use a forty-eight year monthly time-series of reported human plague cases from 1960 to 2008. Using wavelet analysis, we show that over the last fifty years there have been complex non-stationary associations between ENSO/IOD and the dynamics of plague in Madagascar. We demonstrate that ENSO and IOD influence temperature in Madagascar and that temperature and plague cycles are associated. The effects on plague appear to be mediated more by temperature, but precipitation also undoubtedly influences plague in Madagascar. Our results confirm a relationship between plague anomalies and an increase in the intensity of ENSO events and precipitation.This work widens the understanding of how climate factors acting over different temporal scales can combine to drive local disease dynamics. Given the association of increasing ENSO strength and plague anomalies in Madagascar it may in future be possible to forecast plague outbreaks in Madagascar. The study gives insight into the complex and changing relationship between climate factors and plague in Madagascar.
- Evaluation of the effect of host immune status on short-term Yersinia pestis infection in fleas with implications for the enzootic host model for maintenance of Y. pestis during interepizootic periods. [Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.]
- J Med Entomol 2014 Sep; 51(5):1079-86.
Plague, a primarily flea-borne disease caused by Yersinia pestis, is characterized by rapidly spreading epizootics separated by periods of quiescence. Little is known about how and where Y. pestis persists between epizootics. It is commonly proposed, however, that Y pestis is maintained during interepizootic periods in enzootic cycles involving flea vectors and relatively resistant host populations. According to this model, while susceptible individuals serve as infectious sources for feeding fleas and subsequently die of infection, resistant hosts survive infection, develop antibodies to the plague bacterium, and continue to provide bloodmeals to infected fleas. For Y. pestis to persist under this scenario, fleas must remain infected after feeding on hosts carrying antibodies to Y. pestis. Studies of other vector-borne pathogens suggest that host immunity may negatively impact pathogen survival in the vector. Here, we report infection rates and bacterial loads for fleas (both Xenopsylla cheopis (Rothschild) and Oropsylla montana (Baker)) that consumed an infectious bloodmeal and subsequently fed on an immunized or age-matched naive mouse. We demonstrate that neither the proportion of infected fleas nor the bacterial loads in infected fleas were significantly lower within 3 d of feeding on immunized versus naive mice. Our findings thus provide support for one assumption underlying the enzootic host model of interepizootic maintenance of Y. pestis.
- [Development and testing of an enzyme immunoassay-based monoclonal test system for the detection of the Yersinia pestis V antigen]. [English Abstract, Journal Article]
- Prikl Biokhim Mikrobiol 2014 Mar-Apr; 50(2):211-8.
An enzyme immunoassay-based test system for Y. pestis V antigen detection was developed. The specificity and sensitivity of this system met the requirements for medical immunobiological preparations for the identification of causative agents of highly fatal diseases. The sensitivity of the test system was assessed, and its high specificity was also demonstrated: the test system did not detect bacterial cells of closely related (four Y. pseudotuberculosis strains) and heterologous microorganism strains. The test system developed was able to detect the V antigen at concentrations as low as 2.0 ng/mL in cells of nine experimental Y. pestis cultures. The obtained preparation can be recommended for use in laboratory diagnostics of plaque.
- Dynamics of CRISPR Loci in Microevolutionary Process of Yersinia pestis Strains. [Journal Article]
- PLoS One 2014; 9(9):e108353.
The potential use of CRISPR loci genotyping to elucidate population dynamics and microevolution of 146 Yersinia pestis strains from different biovars and locations was investigated in this work. The majority of strains from the Orientalis biovar presented specific spacer arrays, allowing for the establishment of a CRISPR signature for their respective isolates. Twenty-one new spacers were found in the Y. pestis strains from plague foci in Brazil. Ninety-three (64%) strains were grouped in the G1 genotype, whereas the others were distributed in 35 genotypes. This study allowed observing a microevolutionary process in a group of Y. pestis isolated from Brazil. We also identified specific genotypes of Y. pestis that were important for the establishment of the bacteria in plague foci in Brazil. The data have provided supporting evidence for the diversity and dynamics of CRISPR loci present in the genome of Y. pestis strains from plague foci in Brazil.
- Evaluation of the Murine Immune Response to Xenopsylla cheopis Flea Saliva and Its Effect on Transmission of Yersinia pestis. [JOURNAL ARTICLE]
- PLoS Negl Trop Dis 2014 Sep; 8(9):e3196.
Arthropod-borne pathogens are transmitted into a unique intradermal microenvironment that includes the saliva of their vectors. Immunomodulatory factors in the saliva can enhance infectivity; however, in some cases the immune response that develops to saliva from prior uninfected bites can inhibit infectivity. Most rodent reservoirs of Yersinia pestis experience fleabites regularly, but the effect this has on the dynamics of flea-borne transmission of plague has never been investigated. We examined the innate and acquired immune response of mice to bites of Xenopsylla cheopis and its effects on Y. pestis transmission and disease progression in both naïve mice and mice chronically exposed to flea bites.The immune response of C57BL/6 mice to uninfected flea bites was characterized by flow cytometry, histology, and antibody detection methods. In naïve mice, flea bites induced mild inflammation with limited recruitment of neutrophils and macrophages to the bite site. Infectivity and host response in naïve mice exposed to flea bites followed immediately by intradermal injection of Y. pestis did not differ from that of mice infected with Y. pestis without prior flea feeding. With prolonged exposure, an IgG1 antibody response primarily directed to the predominant component of flea saliva, a family of 36-45 kDa phosphatase-like proteins, occurred in both laboratory mice and wild rats naturally exposed to X. cheopis, but a hypersensitivity response never developed. The incidence and progression of terminal plague following challenge by infective blocked fleas were equivalent in naïve mice and mice sensitized to flea saliva by repeated exposure to flea bites over a 10-week period.Unlike what is observed with many other blood-feeding arthropods, the murine immune response to X. cheopis saliva is mild and continued exposure to flea bites leads more to tolerance than to hypersensitivity. The immune response to flea saliva had no detectable effect on Y. pestis transmission or plague pathogenesis in mice.
- Yersinia pestis and the three plague pandemics-Authors' reply. [Letter]
- Lancet Infect Dis 2014 Oct; 14(10):919.