The Role of Early-Phase Transmission in the Spread of Yersinia pestis.

Early-phase transmission (EPT) of Yersinia pestis by unblocked fleas is a well-documented, replicable phenomenon with poorly defined mechanisms. We review evidence demonstrating EPT and current knowledge on its biological and biomechanical processes. We discuss the importance of EPT in the epizootic spread of Y. pestis and its role in the maintenance of plague bacteria in nature. We further address the role of EPT in the epidemiology of plague.

The genetic match between vaccine strains and circulating seasonal influenza A viruses in Vietnam, 2001-2009.

BACKGROUND: Vietnam is currently developing domestic capability to manufacture influenza vaccines but information on the genetic and antigenic characteristics of locally circulating seasonal influenza viruses is limited. To assess the relevance of WHO recommended vaccine strains to the situation in Vietnam, we analyzed the genetic relatedness of the hemagglutinin (HA) gene of seasonal influenza A viruses circulating in Vietnam from 2001 to 2009 to WHO recommended vaccine strains over the same period. METHODS AND PRINCIPAL FINDINGS: We sequenced the HA gene of 32 H1N1 and 44 H3N2 seasonal influenza A isolates from laboratory-based sentinel surveillance sites in Hanoi from 2001 to 2005 and from a national influenza surveillance system from 2005 to 2009. H1 and H3 HA phylogenetic trees rooted to vaccine strains A/Beijing/295/1995 (H1N1) and A/Moscow/10/1999 (H3N2), respectively, were constructed with contemporary HA sequences of isolates from neighboring countries. We found some genetic differences between seasonal influenza H3N2 viruses and three WHO influenza vaccine strains recommended for use in the Northern and Southern Hemispheres for the 2001-2004 and 2007-2008 seasons and close genetic identity of circulating H3N2 strains with the recommended WHO Southern Hemisphere vaccine strains for 2004 and 2009 seasons. The genetic similarity of circulating H1N1 strains with the WHO recommended vaccine strains are described for the study period 2001-2009. CONCLUSIONS: The HA gene of seasonal influenza virus strains in Vietnam (especially influenza A/H3N2) showed varying degrees of genetic identity compared with those of the Northern or Southern Hemisphere vaccine strains recommended by WHO. The close relatedness of the HA of Vietnamese strains and contemporary strains from nearby countries indicate a good genetic match of circulating strains during study period. Greater representation of virus isolates from South East Asia in the vaccine strain selection process is desirable of influenza vaccine development in Vietnam.

National influenza surveillance in Vietnam, 2006-2007.

In 2006, national influenza surveillance was implemented in Vietnam. Epidemiologic and demographic data and a throat swab for influenza testing were collected from a subset of outpatients with influenza-like illness (ILI). During January 1, 2006 through December 31, 2007, of 184,521 ILI cases identified at surveillance sites, 11,082 were tested and 2112 (19%) were positive for influenza by reverse transcription polymerase chain reaction. Influenza viruses were detected year-round, and similar peaks in influenza activity were observed in all surveillance regions, coinciding with cooler and rainy periods. Studies are needed to ascertain the disease burden and impact of influenza in Vietnam.

Molecular tailoring of farnesylation for plant drought tolerance and yield protection.

Protecting crop yield under drought stress is a major challenge for modern agriculture. One biotechnological target for improving plant drought tolerance is the genetic manipulation of the stress response to the hormone abscisic acid (ABA). Previous genetic studies have implicated the involvement of the beta-subunit of Arabidopsis farnesyltransferase (ERA1) in the regulation of ABA sensing and drought tolerance. Here we show that molecular manipulation of protein farnesylation in Arabidopsis, through downregulation of either the alpha- or beta-subunit of farnesyltransferase enhances the plant's response to ABA and drought tolerance. To test the effectiveness of tailoring farnesylation in a crop plant, transgenic Brassica napus carrying an ERA1 antisense construct driven by a drought-inducible rd29A promoter was examined. In comparison with the non-transgenic control, transgenic canola showed enhanced ABA sensitivity, as well as significant reduction in stomatal conductance and water transpiration under drought stress conditions. The antisense downregulation of canola farnesyltransferase for drought tolerance is a conditional and reversible process, which depends on the amount of available water in the soil. Furthermore, transgenic plants were more resistant to water deficit-induced seed abortion during flowering. Results from three consecutive years of field trial studies suggest that with adequate water, transgenic canola plants produced the same amount of seed as the parental control. However, under moderate drought stress conditions at flowering, the seed yields of transgenic canola were significantly higher than the control. Using protein farnesyltransferase as an effective target, these results represent a successful demonstration of engineered drought tolerance and yield protection in a crop plant under laboratory and field conditions.

Evidence that the hexose-to-sucrose ratio does not control the switch to storage product accumulation in oilseeds: analysis of tobacco seed development and effects of overexpressing apoplastic invertase.

Wild-type tobacco (Nicotiana tabacum L.) seed development was characterized with respect to architecture and carbohydrate metabolism. Tobacco seeds accumulate oil and protein in the embryo, cellular endosperm and inner layer of the seed coat. They have high cell wall invertase (INV) and hexoses in early development which is typical of seeds. INV and the ratio of hexose to sucrose decline during development, switching from high hex to high suc, but not until most oil and all protein accumulation has occurred. The oil synthesis which coincides with the switch is mostly within the embryo. INV activity is greater than sucrose synthase activity throughout development, and both activities exceed the demand for carbohydrate for dry matter accumulation. To investigate the role of INV-mediated suc metabolism in oilseeds, genes for yeast INV and/or hexokinase (HK) were expressed under a seed-specific napin promoter, targeting activity to the apoplast and cytosol, respectively. Manipulating the INV pathway in an oilseed could either increase oil accumulation and sink strength, or disrupt carbohydrate metabolism, possibly through sugar-sensing, and decrease the storage function. Neither effect was found: transgenics with INV and/or HK increased 30-fold and 10-fold above wild-type levels had normal seed size and composition. This contrasted with dramatic effects on sugar contents in the INV lines.

Characterization of NADP-dependent malic enzyme from developing castor oil seed endosperm.

Metabolic pathways sequestered within the leucoplast of developing oilseeds ensure a balanced supply of substrates and cofactors for fatty acid biosynthesis. NADP-dependent malic enzyme (NADP-ME) may be important in supplying both carbon and NADPH for fatty acid biosynthesis in the developing endosperm of the oilseed Ricinus communis. NADP-ME was purified 5160-fold to a specific activity of 18.2 U/mg protein. NADP-ME is a homotetramer with a native mass of 254 kDa and a subunit size of approximately 63 kDa. Effectors of castor NADP-ME are typical of the NADP-malic enzymes, with the exception of acetyl-CoA and its derivatives, which were found to act as activators. This is consistent with a regulatory role for these molecules during fatty acid biosynthesis in vivo. NADP-ME was found to have maximal activity at stage 7 of endosperm development, coincident with maximal lipid accumulation.

Coccidioidomycosis among workers at an archeological site, northeastern Utah.

In 2001, an outbreak of acute respiratory disease occurred among persons working at a Native American archeological site at Dinosaur National Monument in northeastern Utah. Epidemiologic and environmental investigations were undertaken to determine the cause of the outbreak. A clinical case was defined by the presence of at least two of the following symptoms: self-reported fever, shortness of breath, or cough. Ten workers met the clinical case definition; 9 had serologic confirmation of coccidioidomycosis, and 8 were hospitalized. All 10 were present during sifting of dirt through screens on June 19; symptoms began 9-12 days later (median 10). Coccidioidomycosis also developed in a worker at the site in September 2001. A serosurvey among 40 other Dinosaur National Monument workers did not find serologic evidence of recent infection. This outbreak documents a new endemic focus of coccidioidomycosis, which extends northward its known geographic distribution in Utah by approximately 200 miles.

First reported prairie dog-to-human tularemia transmission, Texas, 2002.

A tularemia outbreak, caused by Francisella tularensis type B, occurred among wild-caught, commercially traded prairie dogs. F. tularensis microagglutination titers in one exposed person indicated recent infection. These findings represent the first evidence for prairie-dog-to-human tularemia transmission and demonstrate potential human health risks of the exotic pet trade.

Gentamicin and tetracyclines for the treatment of human plague: review of 75 cases in new Mexico, 1985-1999.

Streptomycin, an antimicrobial with limited availability, is the treatment of choice for plague, a fulminating and potentially epidemic disease that poses a bioterrorism concern. We evaluated the efficacy of gentamicin and tetracyclines for treating human plague. A medical record review was conducted on all 75 patients with plague who were reported in New Mexico during 1985-1999. Fifty patients were included in an analysis that compared streptomycin-treated patients (n=14) with those treated with gentamicin and/or a tetracycline (n=36). The mean numbers of fever days, hospital days, and complications and the number of deaths did not differ between patients treated with streptomycin and those treated with gentamicin. One patient who received tetracycline alone experienced a serious complication. Gentamicin alone or in combination with a tetracycline was as efficacious as streptomycin for treating human plague. The efficacy of a tetracycline alone could not be determined from the study.

Tularemia outbreak investigation in Kosovo: case control and environmental studies.

A large outbreak of tularemia occurred in Kosovo in the early postwar period, 1999-2000. Epidemiologic and environmental investigations were conducted to identify sources of infection, modes of transmission, and household risk factors. Case and control status was verified by enzyme-linked immunosorbent assay, Western blot, and microagglutination assay. A total of 327 serologically confirmed cases of tularemia pharyngitis and cervical lymphadenitis were identified in 21 of 29 Kosovo municipalities. Matched analysis of 46 case households and 76 control households suggested that infection was transmitted through contaminated food or water and that the source of infection was rodents. Environmental circumstances in war-torn Kosovo led to epizootic rodent tularemia and its spread to resettled rural populations living under circumstances of substandard housing, hygiene, and sanitation.

Plague manual: epidemiology, distribution, surveillance and control.

It presents information on diagnosis and treatment of plague and a review of the control of rodent reservoirs and flea vectors, with epidemiology and distribution, diagnosis and clinical manifestations, treatment, control of transmission, surveillance, and prevention. Document in pdf format.