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Tips from the Journals of the American Society for Microbiology

American Society for Microbiology

New NA Inhibitor Offers Long-Lasting Protection Against Influenza Virus

A recent study suggests that a derivative of a new potent neuraminidase (NA) inhibitor offers long-lasting protection against various strains of influenza viruses A and B, including the avian influenza subtype N1 and current drug-resistant strains. The researchers from Daiichi Sankyo Co. Ltd., Tokyo, Japan report their findings in the January 2009 issue of the journal Antimicrobial Agents and Chemotherapy.

Influenza is a serious respiratory illness caused by influenza A and B viruses and is highly contagious among humans. Approximately 3.5 million cases of severe illness and between 300,000 and 500,000 deaths are attributed to influenza outbreaks each year. Current antiviral drugs available include two NA inhibitors zanamivir and oseltamivir, both of which require twice-daily administration. In addition, oseltamivir (the predominant choice for treatment) has reached such high levels of circulation that drug-resistant mutations are emerging emphasizing the need for a new potent and lasting treatment option.

NA inhibitors bind to the NA surface protein of new virus particles and prevent their release from the host cell. In the study the newly identified NA inhibitor R-125489 inhibited the NA activities of various influenza type A and B viruses, including subtypes N1 to N9 and oseltamivir-resistant strains. When administered intranasally to mice, the survival rate of R-125489 was similar to that of zanamivir. Further, when compared to R-125489 and zanamivir in the same mouse model, a concentrated form of R-125489, now identified as CS-8958 resulted in a prolonged survival rate after a single dose even when administered 7 days before infection.

"It is suggested that intranasally administered CS-8958 works as a long-acting NA inhibitor and shows in vitro efficacy as a result of a single intranasal administration," say the researchers.

(M. Yamashita, T. Tomozawa, M. Kakuta, A. Tokumitsu, H. Nasu, S. Kubo. 2009. CS-8958, a prodrug of the new neuraminidase inhibitor R-125489, shows long-acting anti-influenza virus activity.
Antimicrobial Agents and Chemotherapy, 53. 1: 186-192.)

Human Metapneumovirus Infection Predisposes Mice to Severe Pneumococcal Pneumonia

A new study suggests that prior infection with human metapneumovirus or influenza A virus predisposes mice to a severe secondary bacterial infection with pneumococcal pneumonia. The researchers from the Universitaire de Quebec and Laval University, Quebec, Canada and Virion Systems, Inc., Rockville, Maryland, report their findings in the February 2009 issue of the Journal of Virology.

A newly discovered member of the Paramyxoviridae family, human metapneumovirus (hMPV) has been associated with upper and lower respiratory tract symptoms such as common colds, bronchitis, and pneumonia. Previous studies suggest that hMPV infects virtually all individuals worldwide by the age of 5 resulting in a significant number of hospitalizations of young children. Research on co-infecting pathogens in hMPV-infected individuals has focused more exclusively on other viruses, however some instances of bacterial coinfections in hMPV infected individuals have been reported.

In the study researchers compared the response of mice initially infected with hMPV or influenza A virus followed by superinfection with Streptococcus pneumoniae 5 days later to mice infected with hMPV, influenza virus, or pneumococcus alone. Results showed that superinfected mice suffered significant weight loss and greater levels of airway obstruction than those mice only infected with hMPV, influenza, or pneumococcus. Bacterial counts increased in superinfected mice and higher rates of interstitial and alveolar inflammation were also observed.

"Prior infection with either hMPV or influenza A virus predisposes mice to severe pneumococcus infection," say the researchers. "Our results stress the importance of the conjugate pneumococcal vaccine in reducing the severity of hMPV and influenza virus infections by preventing pneumococcal superinfections."

(I. Kukavica-Ibrulj, M.E. Hamelin, G.A. Prince, C. Gagnon, Y. Bergeron, M.G. Bergeron, G. Boivin. 2009. Infection with human metapneumovirus predisposes mice to severe pneumococcal pneumonia.
Journal of Virology, 83. 3: 1341-1349.)

Previously Unidentified Bacteria May Cause Preterm Birth

A new study suggests that that previously unidentified bacteria may play a key role in intra-amniotic inflammation and ultimately preterm births. The researchers report their findings in the January 2009 issue of the Journal of Clinical Microbiology.

Intra-amniotic infection and inflammation have long been associated with preterm births, however, intra-amniotic inflammation is often detected despite the absence of infection.

Researchers attribute this partly to the inability of the current microbial culture method used in hospitals (considered the "gold standard" for identifying intra-amniotic infection) to recognize uncultivated species. In a prior study new culture-independent techniques recognized a previously unidentified oral species implicated in a case of extremely early preterm birth.

In the study amniotic fluid specimens were collected from women who experienced pregnancies complicated by preterm births as well as asymptomatic women and examined using both the "gold standard" culture method and 16S rRNA-based culture independent methods. No bacterial DNA in the amniotic fluid from the asymptomatic women was detected, however, bacterial DNA was found in all of the culture-positive samples as well as 17% of the culture-negative samples in the amniotic fluid from preterm birth mothers. Additional species were detected in more than half of the culture-positive group and approximately two-thirds of the species identified by the culture-independent methods were not isolated by the "gold standard" culture.

"Previously unrecognized, uncultivated, or difficult-to-cultivate species may play a key role in the initiation of preterm birth," say the researchers.

(Y.W. Han, T. Shen, P. Chung, I.A. Buhimschi, C.S. Buhimschi. 2009. Uncultivated bacteria as etiologic agents of intra-amniotic inflammation leading to preterm birth.
Journal of Clinical Microbiology, 47. 1: 38-47.)


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