RESUMO
BACKGROUND: Oseltamivir resistance in A(H1N1)pdm09 influenza is rare, particularly in untreated community cases. Sustained community transmission has not previously been reported. METHODS: Influenza specimens from the Asia-Pacific region were collected through sentinel surveillance, hospital, and general practitioner networks. Clinical and epidemiological information was collected on patients infected with oseltamivir-resistant viruses. RESULTS: Twenty-nine (15%) of 191 A(H1N1)pdm09 viruses collected between May and September 2011 from Hunter New England (HNE), Australia, contained the H275Y neuraminidase substitution responsible for oseltamivir resistance. Only 1 patient had received oseltamivir before specimen collection. The resistant strains were genetically very closely related, suggesting the spread of a single variant. Ninety percent of cases lived within 50 kilometers. Three genetically similar oseltamivir-resistant variants were detected outside of HNE, including 1 strain from Perth, approximately 4000 kilometers away. Computational analysis predicted that neuraminidase substitutions V241I, N369K, and N386S in these viruses may offset the destabilizing effect of the H275Y substitution. CONCLUSIONS: This cluster represents the first widespread community transmission of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza. These cases and data on potential permissive mutations suggest that currently circulating A(H1N1)pdm09 viruses retain viral fitness in the presence of the H275Y mutation and that widespread emergence of oseltamivir-resistant strains may now be more likely.
Assuntos
Antivirais/farmacologia , Surtos de Doenças , Farmacorresistência Viral , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Influenza Humana/virologia , Oseltamivir/farmacologia , Adolescente , Adulto , Austrália/epidemiologia , Sequência de Bases , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas , DNA Viral/química , Feminino , Humanos , Lactente , Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/epidemiologia , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação , Neuraminidase/genética , Filogenia , Alinhamento de Sequência , Adulto JovemRESUMO
A novel influenza A(H1N1)2009 variant with mildly reduced oseltamivir and zanamivir sensitivity has been detected in more than 10% of community specimens in Singapore and more than 30% of samples from northern Australia during the early months of 2011. The variant, which has also been detected in other regions of the Asia-Pacific, contains a S247N neuraminidase mutation. When combined with the H275Y mutation, as detected in an oseltamivir-treated patient, the dual S247N+H275Y mutant had extremely high oseltamivir resistance.
Assuntos
Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/epidemiologia , Influenza Humana/genética , Neuraminidase/genética , Oseltamivir/uso terapêutico , Polimorfismo de Nucleotídeo Único/genética , Zanamivir/uso terapêutico , Antivirais/uso terapêutico , Austrália/epidemiologia , Resistência a Medicamentos/genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Variação Genética/genética , Humanos , Incidência , Influenza Humana/tratamento farmacológico , Neuraminidase/antagonistas & inibidores , Vigilância da População/métodos , Medição de Risco , Fatores de Risco , Singapura/epidemiologiaRESUMO
Thirty-eight human immunodeficiency virus-1 (HIV-1)-infected pregnant women were administered tenofovir disoproxil fumarate (TDF; 300 mg)-emtricitabine (FTC; 200 mg) tablets: two at labor initiation and one daily for 7 days postpartum. Maternal, umbilical, and neonatal plasma tenofovir concentrations were measured by high-performance liquid chromatography and analyzed using a population approach. Data were described using a two-compartment model for the mother, an effect compartment linked to maternal circulation for cord, and a neonatal compartment disconnected after delivery. Absorption was greater for women delivering by caesarian section than for those delivering vaginally. The maternal 600 mg TDF administration before delivery produces the same concentrations as 300 mg administration in other adults. If the time elapsed between maternal administration and delivery is >or=12 h, two tablets of TDF-FTC should be readministered. Tenofovir showed good placental transfer (60%). Administering 13 mg/kg of TDF as soon as possible after birth should produce neonatal concentrations comparable with those observed in adults.
