Archive for January 22, 2013

Risk of Fetal Death after Pandemic Influenza Virus Infection or Vaccination

N Engl J of Med Jan.16, 2013 

Siri E. Håberg, M.D., Ph.D., Lill Trogstad, M.D., Ph.D., Nina Gunnes, Ph.D., Allen J. Wilcox, M.D., Ph.D., Håkon K. Gjessing, Ph.D., Sven Ove Samuelsen, Ph.D., Anders Skrondal, Ph.D., Inger Cappelen, Ph.D., Anders Engeland, Ph.D., Preben Aavitsland, M.D., Steinar Madsen, M.D., Ingebjørg Buajordet, Ph.D., Kari Furu, Ph.D., Per Nafstad, M.D., Ph.D., Stein Emil Vollset, M.D., Dr.P.H., Berit Feiring, M.Sc.Pharm., Hanne Nøkleby, M.D., Per Magnus, M.D., Ph.D., and Camilla Stoltenberg, M.D., Ph.D.


During the 2009 influenza A (H1N1) pandemic, pregnant women were at risk for severe influenza illness. This concern was complicated by questions about vaccine safety in pregnant women that were raised by anecdotal reports of fetal deaths after vaccination.


We explored the safety of influenza vaccination of pregnant women by linking Norwegian national registries and medical consultation data to determine influenza diagnosis, vaccination status, birth outcomes, and background information for pregnant women before, during, and after the pandemic. We used Cox regression models to estimate hazard ratios for fetal death, with the gestational day as the time metric and vaccination and pandemic exposure as time-dependent exposure variables.


There were 117,347 eligible pregnancies in Norway from 2009 through 2010. Fetal mortality was 4.9 deaths per 1000 births. During the pandemic, 54% of pregnant women in their second or third trimester were vaccinated. Vaccination during pregnancy substantially reduced the risk of an influenza diagnosis (adjusted hazard ratio, 0.30; 95% confidence interval [CI], 0.25 to 0.34). Among pregnant women with a clinical diagnosis of influenza, the risk of fetal death was increased (adjusted hazard ratio, 1.91; 95% CI, 1.07 to 3.41). The risk of fetal death was reduced with vaccination during pregnancy, although this reduction was not significant (adjusted hazard ratio, 0.88; 95% CI, 0.66 to 1.17).


Pandemic influenza virus infection in pregnancy was associated with an increased risk of fetal death. Vaccination during pregnancy reduced the risk of an influenza diagnosis. Vaccination itself was not associated with increased fetal mortality and may have reduced the risk of influenza-related fetal death during the pandemic. (Funded by the Norwegian Institute of Public Health.)



January 22, 2013 at 9:11 am

Yersinia pestis – New Evidence for an Old Infection.

PLoS One. 2012;7(11):e49803.

Bos KI, Stevens P, Nieselt K, Poinar HN, Dewitte SN, Krause J.


Institute for Archeological Sciences, University of Tübingen, Tübingen, Germany ; Laboratoire de Paléoanthropologie, École Pratique des Hautes Études, Université de Bordeaux, Bordeaux, France.


The successful reconstruction of an ancient bacterial genome from archaeological material presents an important methodological advancement for infectious disease research. The reliability of evolutionary histories inferred by the incorporation of ancient data, however, are highly contingent upon the level of genetic diversity represented in modern genomic sequences that are publicly accessible, and the paucity of available complete genomes restricts the level of phylogenetic resolution that can be obtained. Here we add to our original analysis of the Yersinia pestis strain implicated in the Black Death by consolidating our dataset for 18 modern genomes with single nucleotide polymorphism (SNP) data for an additional 289 strains at over 600 positions. The inclusion of this additional data reveals a cluster of Y. pestis strains that diverge at a time significantly in advance of the Black Death, with divergence dates roughly coincident with the Plague of Justinian (6(th) to 8(th) century AD). In addition, the analysis reveals further clues regarding potential radiation events that occurred immediately preceding the Black Death, and the legacy it may have left in modern Y. pestis populations. This work reiterates the need for more publicly available complete genomes, both modern and ancient, to achieve an accurate understanding of the history of this bacterium.




January 22, 2013 at 9:09 am

Efficacy of ciprofloxacin-gentamicin combination therapy in murine bubonic plague.

PLoS One. 2012;7(12):e52503..

Lemaître N, Ricard I, Pradel E, Foligné B, Courcol R, Simonet M, Sebbane F.


Laboratoire de Bactériologie-Hygiène, Centre Hospitalier Universitaire, Lille, France ; Université Lille Nord de France, Lille, France ; Université Lille 2, Lille, France ; INSERM U1019, Lille, France ; Centre National de la Recherche Scientifique UMR8204, Lille, France ; Institut Pasteur, Lille, France.


Potential benefits of combination antibiotic therapy for the treatment of plague have never been evaluated. We compared the efficacy of a ciprofloxacin (CIN) and gentamicin (GEN) combination therapy with that of each antibiotic administered alone (i) against Yersinia pestis in vitro and (ii) in a mouse model of bubonic plague in which animals were intravenously injected with antibiotics for five days, starting at two different times after infection (44 h and 56 h). In vitro, the CIN+GEN combination was synergistic at 0.5x the individual drugs’ MICs and indifferent at 1x- or 2x MIC. In vivo, the survival rate for mice treated with CIN+GEN was similar to that observed with CIN alone and slightly higher than that observed for GEN alone 100, 100 and 85%, respectively when treatment was started 44 h post challenge. 100% of survivors were recorded in the CIN+GEN group vs 86 and 83% in the CIN and GEN groups, respectively when treatment was delayed to 56 h post-challenge. However, these differences were not statistically significant. Five days after the end of treatment, Y. pestis were observed in lymph nodes draining the inoculation site (but not in the spleen) in surviving mice in each of the three groups. The median lymph node log(10) CFU recovered from persistently infected lymph nodes was significantly higher with GEN than with CIN (5.8 vs. 3.2, p=0.04) or CIN+GEN (5.8 vs. 2.8, p=0.01). Taken as the whole, our data show that CIN+GEN combination is as effective as CIN alone but, regimens containing CIN are more effective to eradicate Y. pestis from the draining lymph node than the recommended GEN monotherapy. Moreover, draining lymph nodes may serve as a reservoir for the continued release of Y. pestis into the blood – even after five days of intravenous antibiotic treatment.


January 22, 2013 at 9:08 am


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