RESUMO
Pyomyositis is a severe bacterial infection of skeletal muscle, commonly affecting children in tropical regions, predominantly caused by Staphylococcus aureus. To understand the contribution of bacterial genomic factors to pyomyositis, we conducted a genome-wide association study of S. aureus cultured from 101 children with pyomyositis and 417 children with asymptomatic nasal carriage attending the Angkor Hospital for Children, Cambodia. We found a strong relationship between bacterial genetic variation and pyomyositis, with estimated heritability 63.8% (95% CI 49.2-78.4%). The presence of the Panton-Valentine leucocidin (PVL) locus increased the odds of pyomyositis 130-fold (p=10-17.9). The signal of association mapped both to the PVL-coding sequence and to the sequence immediately upstream. Together these regions explained over 99.9% of heritability (95% CI 93.5-100%). Our results establish staphylococcal pyomyositis, like tetanus and diphtheria, as critically dependent on a single toxin and demonstrate the potential for association studies to identify specific bacterial genes promoting severe human disease.
Assuntos
Toxinas Bacterianas/metabolismo , Exotoxinas/metabolismo , Leucocidinas/metabolismo , Piomiosite/fisiopatologia , Infecções Estafilocócicas/fisiopatologia , Staphylococcus aureus/metabolismo , Fatores de Virulência/metabolismo , Toxinas Bacterianas/genética , Camboja , Exotoxinas/genética , Estudo de Associação Genômica Ampla , Humanos , Leucocidinas/genética , Staphylococcus aureus/genética , Fatores de Virulência/genéticaRESUMO
There are limited data on osteoarticular infections from resource-limited settings in Asia. A retrospective study of patients presenting to the Angkor Hospital for Children, Cambodia, January 2007-July 2011, identified 81 cases (28% monoarticular septic arthritis, 51% single-limb osteomyelitis and 15% multisite infections). The incidence was 13.8/100 000 hospital attendances. The median age was 7.3 years, with a male/female ratio of 1.9:1; 35% presented within 5 days of symptom onset (median 7 days). Staphylococcus aureus was cultured in 29 (36%) cases (52% of culture-positive cases); one isolate was methicillin-resistant (MRSA). Median duration of antimicrobial treatment was 29 days (interquartile range 21-43); rates of surgical intervention were 96%, and 46% of children had sequelae, with one fatality. In this setting osteoarticular infections are relatively common with high rates of surgical intervention and sequelae. Staphylococcus aureus is the commonest culturable cause, but methicillin-resistant S. aureus is not a major problem, unlike in other Asian centers.
Assuntos
Artrite Infecciosa/epidemiologia , Osteomielite/epidemiologia , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/isolamento & purificação , Adolescente , Antibacterianos/uso terapêutico , Artrite Infecciosa/diagnóstico , Artrite Infecciosa/microbiologia , Artrite Infecciosa/terapia , Camboja/epidemiologia , Criança , Pré-Escolar , Feminino , Hospitais Pediátricos , Humanos , Incidência , Modelos Logísticos , Masculino , Análise Multivariada , Osteomielite/diagnóstico , Osteomielite/microbiologia , Osteomielite/terapia , Pediatria , Estudos Retrospectivos , Fatores de Risco , Distribuição por Sexo , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Procedimentos Cirúrgicos Operatórios , Resultado do TratamentoRESUMO
The causes of suppurative parotitis in Cambodian children are not known. We describe 39 cases at the Angkor Hospital for Children, Siem Reap, between January 2007 and July 2011 (0.07/1000 hospital attendances). The median age was 5.7 years with no neonates affected. Burkholderia pseudomallei was cultured in 29 (74%) cases. No deaths occurred; 1 child developed facial nerve palsy.
