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Emerging Infectious Diseases (1)
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McGrane, James (2)
Azhar, Muhammad (1)
Barrett, Susan (1)
Chaves, Sandra (1)
Kim, Mia (1)
McKimm-Breschkin, Jennifer L. (1)
Mohr, Peter G. (1)
Morales, Gustavo J. (1)
Selleck, Paul (1)
Widdowson, Marc-Alain (1)
Wong, Frank Y. K. (1)
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I222 Neuraminidase Mutations Further Reduce Oseltamivir Susceptibility of Indonesian Clade 2.1 Highly Pathogenic Avian Influenza A(H5N1) Viruses
McKimm-Breschkin, Jennifer L.
Wong, Frank Y. K.
Mohr, Peter G.
We have tested the susceptibility to neuraminidase inhibitors of 155 clade 2.1 H5N1 viruses from Indonesia, isolated between 2006–2008 as well as 12 clade 1 isolates from Thailand and Cambodia from 2004–2007 using a fluorometric MUNANA-based enzyme inhibition assay. The Thailand and Cambodian clade 1 isolates tested here were all susceptible to oseltamivir and zanamivir, and sequence comparison indicated that reduced oseltamivir susceptibility we observed previously with clade 1 Cambodian isolates correlated with an S246G neuraminidase mutation. Eight Indonesian viruses (5%), all bearing I222 neuraminidase mutations, were identified as mild to extreme outliers for oseltamivir based on statistical analysis by box plots. IC50s were from 50 to 500-fold higher than the reference clade 1 virus from Viet Nam, ranging from 43–75 nM for I222T/V mutants and from 268–349 nM for I222M mutants. All eight viruses were from different geographic locales; all I222M variants were from central Sumatra. None of the H5N1 isolates tested demonstrated reduced susceptibility to zanamivir (IC50s all <5 nM). All I222 mutants showed loss of slow binding specifically for oseltamivir in an IC50 kinetics assay. We identified four other Indonesian isolates with higher IC50s which also demonstrated loss of slow binding, including one virus with an I117V mutation. There was a minimal effect on the binding of zanamivir and peramivir for all isolates tested. As H5N1 remains a potential pandemic threat, the incidence of mutations conferring reduced oseltamivir susceptibility is concerning and emphasizes the need for greater surveillance of drug susceptibility.
Epidemiology of Urban Canine Rabies, Santa Cruz, Bolivia, 1972–1997
Morales, Gustavo J.
Emerging Infectious Diseases
We analyzed laboratory data from 1972 to 1997 from Santa Cruz, Bolivia, to determine risk factors for laboratory canine samples’ testing positive for Rabies virus (RABV). Of 9,803 samples, 50.7% tested positive for RABV; the number of cases and the percentage positive has dropped significantly since 1978. A 5- to 6-year cycle in rabies incidence was clearly apparent, though no seasonality was noted. Male dogs had significantly increased odds of testing positive for RABV (odds ratio [OR]=1.14), as did 1- to 2-year-old dogs (OR=1.73); younger and older dogs were at lower risk. Samples submitted from the poorer suburbs of the city were more likely to test positive for RABV (OR=1.71). We estimated the distribution of endemic canine rabies in an urban environment to facilitate control measures in a resource-poor environment.
Epidemiology; rabies; Bolivia; urban health; risk factors; canine
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