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  <title type="text">PLoS ONE Alerts: Infectuous Diseases</title>
  <link rel="self" href="http://www.plosone.org/" title="PLoS ONE" />
  <author>
    <name>PLoS</name>
    <uri>http://www.plosone.org/</uri>
    <email>webmaster@plos.org</email>
  </author>
  <subtitle>Publishing science</subtitle>
  <id>info:doi/10.1371/feed.pone?category=Infectious Diseases</id>
  <rights>This work is licensed under a Creative Commons Attribution-Share Alike 3.0 License</rights>
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  <updated>2009-11-22T06:13:07Z</updated>
  <atom10:link xmlns:atom10="http://www.w3.org/2005/Atom" rel="hub" href="http://pubsubhubbub.appspot.com" /><entry>
    <title>Heterosexual and Homosexual Partners Practising Unprotected Sex May Develop Allogeneic Immunity and to a Lesser Extent Tolerance</title>
    <link rel="alternate" href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007938" title="Heterosexual and Homosexual Partners Practising Unprotected Sex May Develop Allogeneic Immunity and to a Lesser Extent Tolerance" />
    <link rel="related" type="text/xml" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007938&amp;representation=XML" title="(XML) Heterosexual and Homosexual Partners Practising Unprotected Sex May Develop Allogeneic Immunity and to a Lesser Extent Tolerance" />
    <link rel="related" type="application/pdf" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007938&amp;representation=PDF" title="(PDF) Heterosexual and Homosexual Partners Practising Unprotected Sex May Develop Allogeneic Immunity and to a Lesser Extent Tolerance" />
    <author>
      <name>Cherry Kingsley et al.</name>
    </author>
    <id>info:doi/10.1371/journal.pone.0007938</id>
    <updated>2009-11-23T08:00:00Z</updated>
    <published>2009-11-23T08:00:00Z</published>
    <content type="html">Background

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Epidemiological studies suggest that allogeneic immunity may inhibit HIV-1 transmission from mother to baby and is less frequent in multiparous than uniparous women. Alloimmune responses may also be elicited during unprotected heterosexual intercourse, which is associated &lt;i&gt;ex vivo&lt;/i&gt; with resistance to HIV infection.&lt;/p&gt;

Methodology/Principal Findings

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;The investigation was carried out in well-defined heterosexual and homosexual monogamous partners, practising unprotected sex and a heterosexual cohort practising protected sex. Allogeneic CD4&lt;sup&gt;+&lt;/sup&gt; and CD8&lt;sup&gt;+&lt;/sup&gt; T cell proliferative responses were elicited by stimulating PBMC with the partners' irradiated monocytes and compared with 3&lt;sup&gt;rd&lt;/sup&gt; party unrelated monocytes, using the CFSE method. Significant increase in allogeneic proliferative responses was found in the CD4&lt;sup&gt;+&lt;/sup&gt; and CD8&lt;sup&gt;+&lt;/sup&gt; T cells to the partners' irradiated monocytes, as compared with 3&lt;sup&gt;rd&lt;/sup&gt; party unrelated monocytes (p≤0.001). However, a significant decrease in proliferative responses, especially of CD8&lt;sup&gt;+&lt;/sup&gt; T cells to the partners' compared with 3&lt;sup&gt;rd&lt;/sup&gt; party monocytes was consistent with tolerization, in both the heterosexual and homosexual partners (p&amp;lt;0.01). Examination of CD4&lt;sup&gt;+&lt;/sup&gt;CD25&lt;sup&gt;+&lt;/sup&gt;FoxP3&lt;sup&gt;+&lt;/sup&gt; regulatory T cells by flow cytometry revealed a significantly greater proportion of these cells in the homosexual than heterosexual partners practising unprotected sex (p&amp;lt;0.05). &lt;i&gt;Ex vivo&lt;/i&gt; studies of infectivity of PBMC with HIV-1 showed significantly greater inhibition of infectivity of PBMC from heterosexual subjects practising unprotected compared with those practising protected sex (p = 0.02).&lt;/p&gt;

Conclusions/Significance

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Both heterosexual and homosexual monogamous partners practising unprotected sex develop allogeneic CD4&lt;sup&gt;+&lt;/sup&gt; and CD8&lt;sup&gt;+&lt;/sup&gt; T cell proliferative responses to the partners' unmatched cells and a minority may be tolerized. However, a greater proportion of homosexual rather than heterosexual partners developed CD4&lt;sup&gt;+&lt;/sup&gt;CD25FoxP3&lt;sup&gt;+&lt;/sup&gt; regulatory T cells. These results, in addition to finding greater inhibition of HIV-1 infectivity in PBMC &lt;i&gt;ex vivo&lt;/i&gt; in heterosexual partners practising unprotected, compared with those practising protected sex, suggest that allogeneic immunity may play a significant role in the immuno-pathogenesis of HIV-1 infection.&lt;/p&gt;</content>
  </entry>
  <entry>
    <title>Anthrax Toxin Uptake by Primary Immune Cells as Determined with a Lethal Factor-β-Lactamase Fusion Protein</title>
    <link rel="alternate" href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007946" title="Anthrax Toxin Uptake by Primary Immune Cells as Determined with a Lethal Factor-β-Lactamase Fusion Protein" />
    <link rel="related" type="text/xml" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007946&amp;representation=XML" title="(XML) Anthrax Toxin Uptake by Primary Immune Cells as Determined with a Lethal Factor-β-Lactamase Fusion Protein" />
    <link rel="related" type="application/pdf" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007946&amp;representation=PDF" title="(PDF) Anthrax Toxin Uptake by Primary Immune Cells as Determined with a Lethal Factor-β-Lactamase Fusion Protein" />
    <author>
      <name>Haijing Hu et al.</name>
    </author>
    <id>info:doi/10.1371/journal.pone.0007946</id>
    <updated>2009-11-23T08:00:00Z</updated>
    <published>2009-11-23T08:00:00Z</published>
    <content type="html">Background

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;To initiate infection, &lt;i&gt;Bacillus anthracis&lt;/i&gt; needs to overcome the host innate immune system. Anthrax toxin, a major virulence factor of &lt;i&gt;B. anthracis&lt;/i&gt;, impairs both the innate and adaptive immune systems and is important in the establishment of anthrax infections.&lt;/p&gt;

Methodology/Principal Findings

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;To measure the ability of anthrax toxin to target immune cells, studies were performed using a fusion of the anthrax toxin lethal factor (LF) N-terminal domain (LFn, aa 1–254) with β-lactamase (LFnBLA). This protein reports on the ability of the anthrax toxin protective antigen (PA) to mediate LF delivery into cells. Primary immune cells prepared from mouse spleens were used in conjunction with flow cytometry to assess cleavage and resulting FRET disruption of a fluorescent β-lactamase substrate, CCF2/AM. In spleen cell suspensions, the macrophages, dendritic cells, and B cells showed about 75% FRET disruption of CCF2/AM due to cleavage by the PA–delivered LFnBLA. LFnBLA delivery into CD4+ and CD8+ T cells was lower, with 40% FRET disruption. When the analyses were done on purified samples of individual cell types, similar results were obtained, with T cells again having lower LFnBLA delivery than macrophages, dendritic cells, and B cells. Relative expression levels of the toxin receptors CMG2 and TEM8 on these cells were determined by real-time PCR. Expression of CMG2 was about 1.5-fold higher in CD8+ cells than in CD4+ and B cells, and 2.5-fold higher than in macrophages.&lt;/p&gt;

Conclusions/Significance

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Anthrax toxin entry and activity differs among immune cells. Macrophages, dendritic cells, and B cells displayed higher LFnBLA activity than CD4+ and CD8+ T cells in both spleen cell suspension and the purified samples of individual cell types. Expression of anthrax toxin receptor CMG2 is higher in CD4+ and CD8+ T cells, which is not correlated to the intracellular LFnBLA activity.&lt;/p&gt;</content>
  </entry>
  <entry>
    <title>Prevalence of Antibodies against Avian Influenza A (H5N1) Virus among Cullers and Poultry Workers in Ho Chi Minh City, 2005</title>
    <link rel="alternate" href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007948" title="Prevalence of Antibodies against Avian Influenza A (H5N1) Virus among Cullers and Poultry Workers in Ho Chi Minh City, 2005" />
    <link rel="related" type="application/pdf" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007948&amp;representation=PDF" title="(PDF) Prevalence of Antibodies against Avian Influenza A (H5N1) Virus among Cullers and Poultry Workers in Ho Chi Minh City, 2005" />
    <link rel="related" type="text/xml" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007948&amp;representation=XML" title="(XML) Prevalence of Antibodies against Avian Influenza A (H5N1) Virus among Cullers and Poultry Workers in Ho Chi Minh City, 2005" />
    <author>
      <name>Constance Schultsz et al.</name>
    </author>
    <id>info:doi/10.1371/journal.pone.0007948</id>
    <updated>2009-11-23T08:00:00Z</updated>
    <published>2009-11-23T08:00:00Z</published>
    <content type="html">Background

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Between 2003 and 2005, highly pathogenic avian influenza A (H5N1) viruses caused large scale outbreaks in poultry in the Ho Chi Minh City area in Vietnam. We studied the prevalence of antibodies against H5N1 in poultry workers and cullers who were active in the program in Ho Chi Minh City in 2004 and 2005.&lt;/p&gt;

Methodology/Principal Findings

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Single sera from 500 poultry workers and poultry cullers exposed to infected birds were tested for antibodies to avian influenza H5N1, using microneutralization assays and hemagglutination inhibition assay with horse blood. All sera tested negative using microneutralization tests. Three samples showed a 1∶80 titer in the hemagglutination inhibition assay.&lt;/p&gt;

Conclusions/Significance

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;This study provides additional support for the low transmissibility of clade 1 H5N1 to humans, but limited transmission to highly exposed persons cannot be excluded given the presence of low antibody titers in some individuals.&lt;/p&gt;</content>
  </entry>
  <entry>
    <title>Outcomes after Chemotherapy with WHO Category II Regimen in a Population with High Prevalence of Drug Resistant Tuberculosis</title>
    <link rel="alternate" href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007954" title="Outcomes after Chemotherapy with WHO Category II Regimen in a Population with High Prevalence of Drug Resistant Tuberculosis" />
    <link rel="related" type="application/pdf" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007954&amp;representation=PDF" title="(PDF) Outcomes after Chemotherapy with WHO Category II Regimen in a Population with High Prevalence of Drug Resistant Tuberculosis" />
    <link rel="related" type="text/xml" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007954&amp;representation=XML" title="(XML) Outcomes after Chemotherapy with WHO Category II Regimen in a Population with High Prevalence of Drug Resistant Tuberculosis" />
    <author>
      <name>Francine Matthys et al.</name>
    </author>
    <id>info:doi/10.1371/journal.pone.0007954</id>
    <updated>2009-11-23T08:00:00Z</updated>
    <published>2009-11-23T08:00:00Z</published>
    <content type="html">&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Standard short course chemotherapy is recommended by the World Health Organization to control tuberculosis worldwide. However, in settings with high drug resistance, first line standard regimens are linked with high treatment failure. We evaluated treatment outcomes after standardized chemotherapy with the WHO recommended category II retreatment regimen in a prison with a high prevalence of drug resistant tuberculosis (TB). A cohort of 233 culture positive TB patients was followed through smear microscopy, culture, drug susceptibility testing and DNA fingerprinting at baseline, after 3 months and at the end of treatment. Overall 172 patients (74%) became culture negative, while 43 (18%) remained positive at the end of treatment. Among those 43 cases, 58% of failures were determined to be due to treatment with an inadequate drug regimen and 42% to either an initial mixed infection or re-infection while under treatment. Overall, drug resistance amplification during treatment occurred in 3.4% of the patient cohort. This study demonstrates that treatment failure is linked to initial drug resistance, that amplification of drug resistance occurs, and that mixed infection and re-infection during standard treatment contribute to treatment failure in confined settings with high prevalence of drug resistance.&lt;/p&gt;</content>
  </entry>
  <entry>
    <title>Taipei's Use of a Multi-Channel Mass Risk Communication Program to Rapidly Reverse an Epidemic of Highly Communicable Disease</title>
    <link rel="alternate" href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007962" title="Taipei's Use of a Multi-Channel Mass Risk Communication Program to Rapidly Reverse an Epidemic of Highly Communicable Disease" />
    <link rel="related" type="application/pdf" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007962&amp;representation=PDF" title="(PDF) Taipei's Use of a Multi-Channel Mass Risk Communication Program to Rapidly Reverse an Epidemic of Highly Communicable Disease" />
    <link rel="related" type="text/xml" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007962&amp;representation=XML" title="(XML) Taipei's Use of a Multi-Channel Mass Risk Communication Program to Rapidly Reverse an Epidemic of Highly Communicable Disease" />
    <author>
      <name>Muh-Yong Yen et al.</name>
    </author>
    <id>info:doi/10.1371/journal.pone.0007962</id>
    <updated>2009-11-23T08:00:00Z</updated>
    <published>2009-11-23T08:00:00Z</published>
    <content type="html">Background

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;In September 2007, an outbreak of acute hemorrhagic conjunctivitis (AHC) occurred in Keelung City and spread to Taipei City. In response to the epidemic, a new crisis management program was implemented and tested in Taipei.&lt;/p&gt;

Methodology and Principal Findings

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Having noticed that transmission surged on weekends during the Keelung epidemic, Taipei City launched a multi-channel mass risk communications program that included short message service (SMS) messages sent directly to approximately 2.2 million Taipei residents on Friday, October 12th, 2007. The public was told to keep symptomatic students from schools and was provided guidelines for preventing the spread of the disease at home. Epidemiological characteristics of Taipei's outbreak were analyzed from 461 sampled AHC cases. Median time from exposure to onset of the disease was 1 day. This was significantly shorter for cases occurring in family clusters than in class clusters (mean±SD: 2.6±3.2 &lt;i&gt;vs.&lt;/i&gt; 4.39±4.82 days, p = 0.03), as well as for cases occurring in larger family clusters as opposed to smaller ones (1.2±1.7 days &lt;i&gt;vs.&lt;/i&gt; 3.9±4.0 days, p&amp;lt;0.01). Taipei's program had a significant impact on patient compliance. Home confinement of symptomatic children increased from 10% to 60% (p&amp;lt;0.05) and helped curb the spread of AHC. Taipei experienced a rapid decrease in AHC cases between the Friday of the SMS announcement and the following Monday, October 15, (0.70% vs. 0.36%). By October 26, AHC cases reduced to 0.01%. The success of this risk communication program in Taipei (as compared to Keelung) is further reflected through rapid improvements in three epidemic indicators: (1) significantly lower crude attack rates (1.95% &lt;i&gt;vs.&lt;/i&gt; 14.92%, p&amp;lt;0.001), (2) a short epidemic period of AHC (13 &lt;i&gt;vs.&lt;/i&gt; 34 days), and (3) a quick drop in risk level (1~2 weeks) in Taipei districts that border Keelung (the original domestic epicenter).&lt;/p&gt;

Conclusions and Significance

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;The timely launch of this systematic, communication-based intervention proved effective at preventing a dangerous spike in AHC and was able to bring this high-risk disease under control. We recommend that public health officials incorporate similar methods into existing guidelines for preventing pandemic influenza and other emerging infectious diseases.&lt;/p&gt;</content>
  </entry>
  <entry>
    <title>TLR–Dependent Control of &lt;italic&gt;Francisella tularensis&lt;/italic&gt; Infection and Host Inflammatory Responses</title>
    <link rel="alternate" href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007920" title="TLR–Dependent Control of &lt;italic&gt;Francisella tularensis&lt;/italic&gt; Infection and Host Inflammatory Responses" />
    <link rel="related" type="application/pdf" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007920&amp;representation=PDF" title="(PDF) TLR–Dependent Control of &lt;italic&gt;Francisella tularensis&lt;/italic&gt; Infection and Host Inflammatory Responses" />
    <link rel="related" type="text/xml" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007920&amp;representation=XML" title="(XML) TLR–Dependent Control of &lt;italic&gt;Francisella tularensis&lt;/italic&gt; Infection and Host Inflammatory Responses" />
    <author>
      <name>Allison L. Abplanalp et al.</name>
    </author>
    <id>info:doi/10.1371/journal.pone.0007920</id>
    <updated>2009-11-20T08:00:00Z</updated>
    <published>2009-11-20T08:00:00Z</published>
    <content type="html">Background

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;&lt;i&gt;Francisella tularensis&lt;/i&gt; is the causative agent of tularemia and is classified as a Category A select agent. Recent studies have implicated TLR2 as a critical element in the host protective response to &lt;i&gt;F. tularensis&lt;/i&gt; infection, but questions remain about whether TLR2 signaling dominates the response in all circumstances and with all species of &lt;i&gt;Francisella&lt;/i&gt; and whether &lt;i&gt;F. tularensis&lt;/i&gt; PAMPs are predominantly recognized by TLR2/TLR1 or TLR2/TLR6. To address these questions, we have explored the role of Toll-like receptors (TLRs) in the host response to infections with &lt;i&gt;F. tularensis&lt;/i&gt; Live Vaccine Strain (LVS) and &lt;i&gt;F. tularensis&lt;/i&gt; subspecies (subsp.) &lt;i&gt;novicida in vivo&lt;/i&gt;.&lt;/p&gt;

Methodology/Principal Findings

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;C57BL/6 (B6) control mice and TLR– or MyD88-deficient mice were infected intranasally (i.n.) or intradermally (i.d.) with &lt;i&gt;F. tularensis&lt;/i&gt; LVS or with &lt;i&gt;F. tularensis&lt;/i&gt; subsp. &lt;i&gt;novicida&lt;/i&gt;. B6 mice survived &amp;gt;21 days following infection with LVS by both routes and survival of TLR1&lt;sup&gt;−/−&lt;/sup&gt;, TLR4&lt;sup&gt;−/−&lt;/sup&gt;, and TLR6&lt;sup&gt;−/−&lt;/sup&gt; mice infected i.n. with LVS was equivalent to controls. Survival of TLR2&lt;sup&gt;−/−&lt;/sup&gt; and MyD88&lt;sup&gt;−/−&lt;/sup&gt; mice, however, was significantly reduced compared to B6 mice, regardless of the route of infection or the subspecies of &lt;i&gt;F. tularensis&lt;/i&gt;. TLR2&lt;sup&gt;−/−&lt;/sup&gt; and MyD88&lt;sup&gt;−/−&lt;/sup&gt; mice also showed increased bacterial burdens in lungs, liver, and spleen compared to controls following i.n. infection. Primary macrophages from MyD88&lt;sup&gt;−/−&lt;/sup&gt; and TLR2&lt;sup&gt;−/−&lt;/sup&gt; mice were significantly impaired in the ability to secrete TNF and other pro-inflammatory cytokines upon &lt;i&gt;ex vivo&lt;/i&gt; infection with LVS. TNF expression was also impaired &lt;i&gt;in vivo&lt;/i&gt; as demonstrated by analysis of bronchoalveolar lavage fluid and by &lt;i&gt;in situ&lt;/i&gt; immunofluorescent staining.&lt;/p&gt;

Conclusions/Significance

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;We conclude from these studies that TLR2 and MyD88, but not TLR4, play critical roles in the innate immune response to &lt;i&gt;F. tularensis&lt;/i&gt; infection regardless of the route of infection or the subspecies. Moreover, signaling through TLR2 does not depend exclusively on TLR1 or TLR6 during &lt;i&gt;F. tularensis&lt;/i&gt; LVS infection.&lt;/p&gt;</content>
  </entry>
  <entry>
    <title>Gene Expression Profiling during Early Acute Febrile Stage of Dengue Infection Can Predict the Disease Outcome</title>
    <link rel="alternate" href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007892" title="Gene Expression Profiling during Early Acute Febrile Stage of Dengue Infection Can Predict the Disease Outcome" />
    <link rel="related" type="application/pdf" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007892&amp;representation=PDF" title="(PDF) Gene Expression Profiling during Early Acute Febrile Stage of Dengue Infection Can Predict the Disease Outcome" />
    <link rel="related" type="text/xml" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007892&amp;representation=XML" title="(XML) Gene Expression Profiling during Early Acute Febrile Stage of Dengue Infection Can Predict the Disease Outcome" />
    <author>
      <name>Eduardo J. M. Nascimento et al.</name>
    </author>
    <id>info:doi/10.1371/journal.pone.0007892</id>
    <updated>2009-11-19T08:00:00Z</updated>
    <published>2009-11-19T08:00:00Z</published>
    <content type="html">Background

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;We report the detailed development of biomarkers to predict the clinical outcome under dengue infection. Transcriptional signatures from purified peripheral blood mononuclear cells were derived from whole-genome gene-expression microarray data, validated by quantitative PCR and tested in independent samples.&lt;/p&gt;

Methodology/Principal Findings

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;The study was performed on patients of a well-characterized dengue cohort from Recife, Brazil. The samples analyzed were collected prospectively from acute febrile dengue patients who evolved with different degrees of disease severity: classic dengue fever or dengue hemorrhagic fever (DHF) samples were compared with similar samples from other non-dengue febrile illnesses. The DHF samples were collected 2–3 days before the presentation of the plasma leakage symptoms. Differentially-expressed genes were selected by univariate statistical tests as well as multivariate classification techniques. The results showed that at early stages of dengue infection, the genes involved in effector mechanisms of innate immune response presented a weaker activation on patients who later developed hemorrhagic fever, whereas the genes involved in apoptosis were expressed in higher levels.&lt;/p&gt;

Conclusions/Significance

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Some of the gene expression signatures displayed estimated accuracy rates of more than 95%, indicating that expression profiling with these signatures may provide a useful means of DHF prognosis at early stages of infection.&lt;/p&gt;</content>
  </entry>
  <entry>
    <title>Synergy between Repellents and Organophosphates on Bed Nets: Efficacy and Behavioural Response of Natural Free-Flying &lt;italic&gt;An. gambiae&lt;/italic&gt; Mosquitoes</title>
    <link rel="alternate" href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007896" title="Synergy between Repellents and Organophosphates on Bed Nets: Efficacy and Behavioural Response of Natural Free-Flying &lt;italic&gt;An. gambiae&lt;/italic&gt; Mosquitoes" />
    <link rel="related" type="application/pdf" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007896&amp;representation=PDF" title="(PDF) Synergy between Repellents and Organophosphates on Bed Nets: Efficacy and Behavioural Response of Natural Free-Flying &lt;italic&gt;An. gambiae&lt;/italic&gt; Mosquitoes" />
    <link rel="related" type="text/xml" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007896&amp;representation=XML" title="(XML) Synergy between Repellents and Organophosphates on Bed Nets: Efficacy and Behavioural Response of Natural Free-Flying &lt;italic&gt;An. gambiae&lt;/italic&gt; Mosquitoes" />
    <author>
      <name>Cédric Pennetier et al.</name>
    </author>
    <id>info:doi/10.1371/journal.pone.0007896</id>
    <updated>2009-11-19T08:00:00Z</updated>
    <published>2009-11-19T08:00:00Z</published>
    <content type="html">Background

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Chemicals are used on bed nets in order to prevent infected bites and to kill aggressive malaria vectors. Because pyrethroid resistance has become widespread in the main malaria vectors, research for alternative active ingredients becomes urgent. Mixing a repellent and a non-pyrethroid insecticide seemed to be a promising tool as mixtures in the laboratory showed the same features as pyrethroids.&lt;/p&gt;

Methodology/Principal Findings

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;We present here the results of two trials run against free-flying &lt;i&gt;Anopheles gambiae&lt;/i&gt; populations comparing the effects of two insect repellents (either DEET or KBR 3023, also known as icaridin) and an organophosphate insecticide at low-doses (pirimiphos-methyl, PM) used alone and in combination on bed nets. We showed that mixtures of PM and the repellents induced higher exophily, blood feeding inhibition and mortality among wild susceptible and resistant malaria vectors than compounds used alone. Nevertheless the synergistic interactions are only involved in the high mortality induced by the two mixtures.&lt;/p&gt;

Conclusion

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;These field trials argue in favour of the strategy of mixing repellent and organophosphate on bed nets to better control resistant malaria vectors.&lt;/p&gt;</content>
  </entry>
  <entry>
    <title>Socioeconomic Predictors of Cognition in Ugandan Children: Implications for Community Interventions</title>
    <link rel="alternate" href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007898" title="Socioeconomic Predictors of Cognition in Ugandan Children: Implications for Community Interventions" />
    <link rel="related" type="application/pdf" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007898&amp;representation=PDF" title="(PDF) Socioeconomic Predictors of Cognition in Ugandan Children: Implications for Community Interventions" />
    <link rel="related" type="text/xml" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007898&amp;representation=XML" title="(XML) Socioeconomic Predictors of Cognition in Ugandan Children: Implications for Community Interventions" />
    <author>
      <name>Paul Bangirana et al.</name>
    </author>
    <id>info:doi/10.1371/journal.pone.0007898</id>
    <updated>2009-11-19T08:00:00Z</updated>
    <published>2009-11-19T08:00:00Z</published>
    <content type="html">Background

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Several interventions to improve cognition in at risk children have been suggested. Identification of key variables predicting cognition is necessary to guide these interventions. This study was conducted to identify these variables in Ugandan children and guide such interventions.&lt;/p&gt;

Methods

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;A cohort of 89 healthy children (45 females) aged 5 to 12 years old were followed over 24 months and had cognitive tests measuring visual spatial processing, memory, attention and spatial learning administered at baseline, 6 months and 24 months. Nutritional status, child's educational level, maternal education, socioeconomic status and quality of the home environment were also measured at baseline. A multivariate, longitudinal model was then used to identify predictors of cognition over the 24 months.&lt;/p&gt;

Results

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;A higher child's education level was associated with better memory (&lt;i&gt;p&lt;/i&gt; = 0.03), attention (&lt;i&gt;p&lt;/i&gt; = 0.005) and spatial learning scores over the 24 months (&lt;i&gt;p&lt;/i&gt; = 0.05); higher nutrition scores predicted better visual spatial processing (&lt;i&gt;p&lt;/i&gt; = 0.002) and spatial learning scores (&lt;i&gt;p&lt;/i&gt; = 0.008); and a higher home environment score predicted a better memory score (&lt;i&gt;p&lt;/i&gt; = 0.03).&lt;/p&gt;

Conclusion

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Cognition in Ugandan children is predicted by child's education, nutritional status and the home environment. Community interventions to improve cognition may be effective if they target multiple socioeconomic variables.&lt;/p&gt;</content>
  </entry>
  <entry>
    <title>Feasibility of Provider-Initiated HIV Testing and Counselling of Tuberculosis Patients Under the TB Control Programme in Two Districts of South India</title>
    <link rel="alternate" href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007899" title="Feasibility of Provider-Initiated HIV Testing and Counselling of Tuberculosis Patients Under the TB Control Programme in Two Districts of South India" />
    <link rel="related" type="application/pdf" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007899&amp;representation=PDF" title="(PDF) Feasibility of Provider-Initiated HIV Testing and Counselling of Tuberculosis Patients Under the TB Control Programme in Two Districts of South India" />
    <link rel="related" type="text/xml" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007899&amp;representation=XML" title="(XML) Feasibility of Provider-Initiated HIV Testing and Counselling of Tuberculosis Patients Under the TB Control Programme in Two Districts of South India" />
    <author>
      <name>Sophia Vijay et al.</name>
    </author>
    <id>info:doi/10.1371/journal.pone.0007899</id>
    <updated>2009-11-19T08:00:00Z</updated>
    <published>2009-11-19T08:00:00Z</published>
    <content type="html">Background

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Provider-initiated HIV testing and counselling (PITC) is internationally recommended for tuberculosis (TB) patients, but the feasibility, effectiveness, and impact of this policy on the TB programme in India are unknown. We evaluated PITC of TB patients across two districts in India considered to have generalized HIV epidemics, Tiruchirappalli (population 2.5 million) and Mysore (population 2.8 million).&lt;/p&gt;

Methodology/Principal Findings

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Starting June 2007, healthcare providers in both districts were instructed to ascertain HIV status for all TB patients, and refer those with unknown HIV status to the nearest Integrated Counselling and Testing Centre (ICTC)—often in the same facility—for counselling and voluntary HIV testing. All TB patients registered from June 2007 to March 2008 were followed prospectively. Field investigators assessed PITC practices and abstracted data from routine TB programme records and HIV counselling registers to determine the proportion of TB patients appropriately evaluated for HIV infection. Patient records were traced to determine the efficiency of referral links to HIV care and antiretroviral treatment (ART). Between July 2007 and March 2008, 5299 TB patients were registered in both study districts. Of the 4701 with unknown HIV status at the time of TB treatment initiation, 3368 (72%) were referred to an ICTC, and 3111 (66%) were newly tested for HIV. PITC implementation resulted in the ascertainment of HIV status for 3709/5299 (70%) of TB patients, and detected 200 cases with previously undiagnosed HIV infection. Overall, 468 (8.8%) of all registered TB patients were HIV-infected; 177 (37%) were documented to have also received any ART.&lt;/p&gt;

Conclusions

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;With implementation of PITC in India, HIV status was successfully ascertained for 70% of TB patients. Previously undiagnosed HIV-infection was detected in 6.4% of those TB patients newly tested, enabling referral for life-saving anti-retroviral treatment. ART uptake, however, was poor, suggesting that PITC implementation should include measures to strengthen and support ART referral, evaluation, and initiation.&lt;/p&gt;</content>
  </entry>
  <entry>
    <title>Performance of an Influenza Rapid Test in Children in a Primary Healthcare Setting in Nicaragua</title>
    <link rel="alternate" href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007907" title="Performance of an Influenza Rapid Test in Children in a Primary Healthcare Setting in Nicaragua" />
    <link rel="related" type="application/pdf" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007907&amp;representation=PDF" title="(PDF) Performance of an Influenza Rapid Test in Children in a Primary Healthcare Setting in Nicaragua" />
    <link rel="related" type="text/xml" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007907&amp;representation=XML" title="(XML) Performance of an Influenza Rapid Test in Children in a Primary Healthcare Setting in Nicaragua" />
    <author>
      <name>Aubree Gordon et al.</name>
    </author>
    <id>info:doi/10.1371/journal.pone.0007907</id>
    <updated>2009-11-19T08:00:00Z</updated>
    <published>2009-11-19T08:00:00Z</published>
    <content type="html">Background

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Influenza is major public health threat worldwide, yet the diagnostic accuracy of rapid tests in developing country settings is not well described.&lt;/p&gt;

Methodology/Principal Findings

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;To investigate the diagnostic accuracy of the QuickVue Influenza A+B test in a primary care setting in a developing country, we performed a prospective study of diagnostic accuracy of the QuickVue Influenza A+B test in comparison to reverse transcriptase-polymerase chain reaction (RT-PCR) in a primary healthcare setting in children aged 2 to 12 years in Managua, Nicaragua. The sensitivity and specificity of the QuickVue test compared to RT-PCR were 68.5% (95% CI 63.4, 73.3) and 98.1% (95% CI 96.9, 98.9), respectively, for children with a fever or history of a fever and cough and/or sore throat. Test performance was found to be lower on the first day that symptoms developed in comparison to test performance on days two or three of illness.&lt;/p&gt;

Conclusions/Significance

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Our study found that the QuickVue Influenza A+B test performed as well in a developing country primary healthcare facility setting as in developed country settings.&lt;/p&gt;</content>
  </entry>
  <entry>
    <title>Comparative Analysis of the Global Transcriptome of &lt;italic&gt;Anopheles funestus&lt;/italic&gt; from Mali, West Africa</title>
    <link rel="alternate" href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007976" title="Comparative Analysis of the Global Transcriptome of &lt;italic&gt;Anopheles funestus&lt;/italic&gt; from Mali, West Africa" />
    <link rel="related" type="text/xml" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007976&amp;representation=XML" title="(XML) Comparative Analysis of the Global Transcriptome of &lt;italic&gt;Anopheles funestus&lt;/italic&gt; from Mali, West Africa" />
    <link rel="related" type="application/pdf" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007976&amp;representation=PDF" title="(PDF) Comparative Analysis of the Global Transcriptome of &lt;italic&gt;Anopheles funestus&lt;/italic&gt; from Mali, West Africa" />
    <author>
      <name>Andrew C. Serazin et al.</name>
    </author>
    <id>info:doi/10.1371/journal.pone.0007976</id>
    <updated>2009-11-19T08:00:00Z</updated>
    <published>2009-11-19T08:00:00Z</published>
    <content type="html">Background

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;&lt;i&gt;Anopheles funestus&lt;/i&gt; is a principal vector of malaria across much of tropical Africa and is considered one of the most efficient of its kind, yet studies of this species have lagged behind those of its broadly sympatric congener, &lt;i&gt;An. gambiae&lt;/i&gt;. In aid of future genomic sequencing of &lt;i&gt;An. funestus&lt;/i&gt;, we explored the whole body transcriptome, derived from mixed stage progeny of wild-caught females from Mali, West Africa.&lt;/p&gt;

Principal Findings

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Here we report the functional annotation and comparative genomics of 2,005 expressed sequence tags (ESTs) from &lt;i&gt;An. funestus&lt;/i&gt;, which were assembled with a previous EST set from adult female salivary glands from the same mosquito. The assembled ESTs provided for a nonredundant catalog of 1,035 transcripts excluding mitochondrial sequences.&lt;/p&gt;

Conclusions/Significance

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Comparison of the &lt;i&gt;An. funestus&lt;/i&gt; and &lt;i&gt;An. gambiae&lt;/i&gt; transcriptomes using computational and macroarray approaches revealed a high degree of sequence identity despite an estimated 20–80 MY divergence time between lineages. A phylogenetically broader comparative genomic analysis indicated that the most rapidly evolving proteins– those involved in immunity, hematophagy, formation of extracellular structures, and hypothetical conserved proteins– are those that probably play important roles in how mosquitoes adapt to their nutritional and external environments, and therefore could be of greatest interest in disease control.&lt;/p&gt;</content>
  </entry>
  <entry>
    <title>Mutations in H5N1 Influenza Virus Hemagglutinin that Confer Binding to Human Tracheal Airway Epithelium</title>
    <link rel="alternate" href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007836" title="Mutations in H5N1 Influenza Virus Hemagglutinin that Confer Binding to Human Tracheal Airway Epithelium" />
    <link rel="related" type="application/pdf" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007836&amp;representation=PDF" title="(PDF) Mutations in H5N1 Influenza Virus Hemagglutinin that Confer Binding to Human Tracheal Airway Epithelium" />
    <link rel="related" type="text/xml" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007836&amp;representation=XML" title="(XML) Mutations in H5N1 Influenza Virus Hemagglutinin that Confer Binding to Human Tracheal Airway Epithelium" />
    <author>
      <name>Guadalupe Ayora-Talavera et al.</name>
    </author>
    <id>info:doi/10.1371/journal.pone.0007836</id>
    <updated>2009-11-18T08:00:00Z</updated>
    <published>2009-11-18T08:00:00Z</published>
    <content type="html">&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;The emergence in 2009 of a swine-origin H1N1 influenza virus as the first pandemic of the 21st Century is a timely reminder of the international public health impact of influenza viruses, even those associated with mild disease. The widespread distribution of highly pathogenic H5N1 influenza virus in the avian population has spawned concern that it may give rise to a human influenza pandemic. The mortality rate associated with occasional human infection by H5N1 virus approximates 60%, suggesting that an H5N1 pandemic would be devastating to global health and economy. To date, the H5N1 virus has not acquired the propensity to transmit efficiently between humans. The reasons behind this are unclear, especially given the high mutation rate associated with influenza virus replication. Here we used a panel of recombinant H5 hemagglutinin (HA) variants to demonstrate the potential for H5 HA to bind human airway epithelium, the predominant target tissue for influenza virus infection and spread. While parental H5 HA exhibited limited binding to human tracheal epithelium, introduction of selected mutations converted the binding profile to that of a current human influenza strain HA. Strikingly, these amino-acid changes required multiple simultaneous mutations in the genomes of naturally occurring H5 isolates. Moreover, H5 HAs bearing intermediate sequences failed to bind airway tissues and likely represent mutations that are an evolutionary “dead end.” We conclude that, although genetic changes that adapt H5 to human airways can be demonstrated, they may not readily arise during natural virus replication. This genetic barrier limits the likelihood that current H5 viruses will originate a human pandemic.&lt;/p&gt;</content>
  </entry>
  <entry>
    <title>Visualisation and Quantitative Analysis of the Rodent Malaria Liver Stage by Real Time Imaging</title>
    <link rel="alternate" href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007881" title="Visualisation and Quantitative Analysis of the Rodent Malaria Liver Stage by Real Time Imaging" />
    <link rel="related" type="text/xml" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007881&amp;representation=XML" title="(XML) Visualisation and Quantitative Analysis of the Rodent Malaria Liver Stage by Real Time Imaging" />
    <link rel="related" type="application/pdf" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007881&amp;representation=PDF" title="(PDF) Visualisation and Quantitative Analysis of the Rodent Malaria Liver Stage by Real Time Imaging" />
    <author>
      <name>Ivo H. J. Ploemen et al.</name>
    </author>
    <id>info:doi/10.1371/journal.pone.0007881</id>
    <updated>2009-11-18T08:00:00Z</updated>
    <published>2009-11-18T08:00:00Z</published>
    <content type="html">&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;The quantitative analysis of &lt;i&gt;Plasmodium&lt;/i&gt; development in the liver in laboratory animals in cultured cells is hampered by low parasite infection rates and the complicated methods required to monitor intracellular development. As a consequence, this important phase of the parasite's life cycle has been poorly studied compared to blood stages, for example in screening anti-malarial drugs. Here we report the use of a transgenic &lt;i&gt;P. berghei&lt;/i&gt; parasite, &lt;i&gt;Pb&lt;/i&gt;GFP-Luc&lt;sub&gt;con&lt;/sub&gt;, expressing the bioluminescent reporter protein luciferase to visualize and quantify parasite development in liver cells both in culture and in live mice using real-time luminescence imaging. The reporter-parasite based quantification in cultured hepatocytes by real-time imaging or using a microplate reader correlates very well with established quantitative RT-PCR methods. For the first time the liver stage of &lt;i&gt;Plasmodium&lt;/i&gt; is visualized in whole bodies of live mice and we were able to discriminate as few as 1–5 infected hepatocytes per liver in mice using 2D-imaging and to identify individual infected hepatocytes by 3D-imaging. The analysis of liver infections by whole body imaging shows a good correlation with quantitative RT-PCR analysis of extracted livers. The luminescence-based analysis of the effects of various drugs on &lt;i&gt;in vitro&lt;/i&gt; hepatocyte infection shows that this method can effectively be used for &lt;i&gt;in vitro&lt;/i&gt; screening of compounds targeting &lt;i&gt;Plasmodium&lt;/i&gt; liver stages. Furthermore, by analysing the effect of primaquine and tafenoquine &lt;i&gt;in vivo&lt;/i&gt; we demonstrate the applicability of real time imaging to assess parasite drug sensitivity in the liver. The simplicity and speed of quantitative analysis of liver-stage development by real-time imaging compared to the PCR methodologies, as well as the possibility to analyse liver development in live mice without surgery, opens up new possibilities for research on &lt;i&gt;Plasmodium&lt;/i&gt; liver infections and for validating the effect of drugs and vaccines on the liver stage of &lt;i&gt;Plasmodium&lt;/i&gt;.&lt;/p&gt;</content>
  </entry>
  <entry>
    <title>Impact of RTS,S/AS02&lt;sub&gt;A&lt;/sub&gt; and RTS,S/AS01&lt;sub&gt;B&lt;/sub&gt; on Genotypes of &lt;italic&gt;P. falciparum&lt;/italic&gt; in Adults Participating in a Malaria Vaccine Clinical Trial</title>
    <link rel="alternate" href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007849" title="Impact of RTS,S/AS02&lt;sub&gt;A&lt;/sub&gt; and RTS,S/AS01&lt;sub&gt;B&lt;/sub&gt; on Genotypes of &lt;italic&gt;P. falciparum&lt;/italic&gt; in Adults Participating in a Malaria Vaccine Clinical Trial" />
    <link rel="related" type="text/xml" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007849&amp;representation=XML" title="(XML) Impact of RTS,S/AS02&lt;sub&gt;A&lt;/sub&gt; and RTS,S/AS01&lt;sub&gt;B&lt;/sub&gt; on Genotypes of &lt;italic&gt;P. falciparum&lt;/italic&gt; in Adults Participating in a Malaria Vaccine Clinical Trial" />
    <link rel="related" type="application/pdf" href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.pone.0007849&amp;representation=PDF" title="(PDF) Impact of RTS,S/AS02&lt;sub&gt;A&lt;/sub&gt; and RTS,S/AS01&lt;sub&gt;B&lt;/sub&gt; on Genotypes of &lt;italic&gt;P. falciparum&lt;/italic&gt; in Adults Participating in a Malaria Vaccine Clinical Trial" />
    <author>
      <name>John N. Waitumbi et al.</name>
    </author>
    <id>info:doi/10.1371/journal.pone.0007849</id>
    <updated>2009-11-17T08:00:00Z</updated>
    <published>2009-11-17T08:00:00Z</published>
    <content type="html">Objective

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;RTS,S, a candidate vaccine for malaria, is a recombinant protein expressed in yeast containing part of the circumsporozoite protein (&lt;b&gt;CSP&lt;/b&gt;) sequence of 3D7 strain of &lt;i&gt;Plasmodium falciparum&lt;/i&gt; linked to the hepatitis B surface antigen in a hybrid protein. The RTS,S antigen is formulated with GSK Biologicals' proprietary Adjuvant Systems AS02&lt;sub&gt;A&lt;/sub&gt; or AS01&lt;sub&gt;B&lt;/sub&gt;. A recent trial of the RTS,S/AS02&lt;sub&gt;A&lt;/sub&gt; and RTS,S/AS01&lt;sub&gt;B&lt;/sub&gt; vaccines evaluated safety, immunogenicity and impact on the development of parasitemia of the two formulations. Parasite isolates from this study were used to determine the molecular impact of RTS,S/AS02&lt;sub&gt;A&lt;/sub&gt; and RTS,S/AS01&lt;sub&gt;B&lt;/sub&gt; on the multiplicity of infection (MOI) and the &lt;i&gt;csp&lt;/i&gt; allelic characteristics of subsequent parasitemias.&lt;/p&gt;

Design

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;The distribution of &lt;i&gt;csp&lt;/i&gt; sequences and the MOI of the infecting strains were examined at baseline and in break-through infections from vaccinated individuals and from those receiving a non-malarial vaccine.&lt;/p&gt;

Setting

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;The study was conducted in Kombewa District, western Kenya.&lt;/p&gt;

Participants

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Semi-immune adults from the three study arms provided isolates at baseline and during break-through infections.&lt;/p&gt;

Outcome

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Parasite isolates used for determining MOI and divergence of &lt;i&gt;csp&lt;/i&gt; T cell–epitopes were 191 at baseline and 87 from break-through infections.&lt;/p&gt;

Results

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Grouping recipients of RTS,S/AS01&lt;sub&gt;A&lt;/sub&gt; and RTS,S/AS02&lt;sub&gt;B&lt;/sub&gt; together, vaccine recipients identified as parasite-positive by microscopy contained significantly fewer parasite genotypes than recipients of the rabies vaccine comparator (median in pooled RTS,S groups: 3 versus 4 in controls, &lt;i&gt;P = 0.0313&lt;/i&gt;). When analyzed separately, parasitaemic individuals in the RTS,S/AS01&lt;sub&gt;B&lt;/sub&gt; group, but not the RTS,S/AS02&lt;sub&gt;A&lt;/sub&gt; group, were found to have significantly fewer genotypes than the comparator group. Two individual amino acids found in the vaccine construct (Q339 in Th2R and D371 in Th3R) were observed to differ in incidence between vaccine and comparator groups but in different directions; parasites harboring Q339 were less common among pooled RTS,S/AS vaccine recipients than among recipients of rabies vaccine, whereas parasites with D371 were more common among the RTS,S/AS groups.&lt;/p&gt;

Conclusions

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;It is concluded that both RTS,S/AS vaccines reduce multiplicity of infection. Our results do not support the hypothesis that RTS,S/AS vaccines elicit preferential effects against &lt;i&gt;pfcsp&lt;/i&gt; alleles with sequence similarity to the 3D7 &lt;i&gt;pfcsp&lt;/i&gt; sequence employed in the vaccine construct.&lt;/p&gt;</content>
  </entry>
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