Cutaneous S. aureus infection does not reliably provoke durable, protective immune responses. This study provides the first link between protection from disease recurrence and the humoral response to Hla, a virulence factor already implicated in disease pathogenesis. These observations can be utilized to refine ongoing vaccine and immunotherapy efforts and inform the design of clinical trials.
Background
Congenital pancytopenia is a rare and often lethal condition. Current knowledge of lymphoid and hematopoietic development in mice, as well as understanding regulators of human hematopoiesis, have led to the recent discovery of genetic causes of bone marrow failure disorders. However, in the absence of mutations of specific genes or a distinct clinical phenotype, many cases of aplastic anemia are labeled as idiopathic, while congenital immune deficiencies are described as combined immune deficiency.
Procedure
We describe the case of a 33-week gestation age male with severe polyhydramnios, hydrops, and ascites who was noted to be pancytopenic at birth. Bone marrow examination revealed a hypocellular marrow with absent myelopoiesis. An immune workup demonstrated profound B lymphopenia, near absent NK cells, and normal T cell number. Due to the similarity of the patient's phenotype with the IKAROS knockout mouse, studies were performed on bone marrow and peripheral blood to assess a potential pathogenic role of Ikaros.
Results
DNA studies revealed a point mutation in one allele of the IKAROS gene, resulting in an amino acid substitution in the DNA-binding zinc finger domain. Functional studies demonstrated that the observed mutation decreased Ikaros DNA-binding affinity, and immunofluorescence microscopy revealed aberrant Ikaros pericentromeric localization.
Conclusions
Our report describes a novel case of congenital pancytopenia associated with mutation of the IKAROS gene. Furthermore, these data suggest a critical role of IKAROS in human hematopoiesis and immune development.
Synopsis
Staphylococcus aureus infections pose a significant health burden. The emergence of community-associated methicillin-resistant S. aureus has resulted in an epidemic of skin and soft tissue infections (SSTI), and many patients experience recurrent SSTI. As S. aureus colonization is associated with subsequent infection, decolonization is recommended for patients with recurrent SSTI or in settings of ongoing transmission. S. aureus infections often cluster within households and asymptomatic carriers serve as reservoirs for transmission; therefore, a household approach to decolonization is more effective than measures performed by individuals alone. Other factors, such as environmental surface contamination, may also be considered. Novel strategies for the prevention of recurrent SSTI are needed.
IMPORTANCE
Household environmental surfaces may serve as vectors for acquisition and spread of methicillin-resistant Staphylococcus aureus (MRSA) among household members, though few studies have evaluated which objects are important MRSA reservoirs.
OBJECTIVES
Determine the prevalence of environmental MRSA contamination in households of children with MRSA infection; define the molecular epidemiology of environmental, pet, and human MRSA strains within households; and identify factors associated with household MRSA contamination.
DESIGN, SETTING, AND PARTICIPANTS
Fifty households of children with active or recent culture-positive community-associated MRSA infection were enrolled from 2012–13 at St. Louis Children’s Hospital and community pediatric practices affiliated with the Washington University Pediatric and Adolescent Ambulatory Research Consortium.
MAIN OUTCOMES AND MEASURES
Participants’ nares, axillae, and inguinal folds were cultured to detect S. aureus colonization. Twenty-one environmental surfaces and pet dogs and cats were cultured. Molecular typing of S. aureus strains was performed by repetitive-sequence polymerase chain reaction to determine strain relatedness within households.
RESULTS
MRSA was recovered from environmental surfaces in 23 (46%) households, most frequently from the participant’s bed linens (18%), television remote control (16%), and bathroom hand towel (15%). MRSA colonized 12% of dogs and 7% of cats. At least 1 surface was contaminated with a strain type matching the participant’s isolate in 20 (40%) households. Participants colonized with S. aureus had a higher proportion of MRSA-contaminated surfaces (0.15 ± 0.17) than non-colonized participants [0.03± 0.06; mean difference 0.12 (95% CI 0.05, 0.20)]. A greater number of individuals per 1000 ft2 was also associated with a higher proportion of MRSA-contaminated surfaces (β=0.34, p=0.03). The frequency of cleaning household surfaces was not associated with S. aureus environmental contamination.
CONCLUSIONS AND RELEVANCE
MRSA strains concordant with infecting and colonizing strains are present on commonly handled household surfaces, a factor that likely perpetuates MRSA transmission and recurrent disease. Future studies are needed to determine methods to eradicate environmental contamination and prevent MRSA transmission in households.
This expert guidance document was developed as a resource to provide healthcare epidemiologists working in acute-care hospitals with a high-level overview of incident management for infectious diseases outbreaks and to prepare them to work within an emergency response framework. It addresses how the epidemiologist's skills and expertise apply to scenarios that require enhanced preparedness and response efforts, eg, when pathogens associated with outbreaks are poorly characterized or when outbreaks require additional interventions including, but not limited to, healthcare personnel education, enhanced infection prevention and control measures, added staffing, supplies, and resources, adjustments to clinical and support activities, and external communications. Its recommendations are not pathogen-specific and are meant to apply to a range of potential infectious diseases outbreaks. To provide high-level guidance and context for incident management, the authors specify recommendations for the healthcare epidemiologist, as well as involvement and responsibilities of the facility and other healthcare personnel (HCP). 2017, vol. 38, no. 12 The SHEA/CDC ORTP Expert Guidance Writing Panel (ie, the authors) were selected based on additional expertise in guidance and guideline-writing, and are the primary authors of this document. Advisory Panel members, the overseeing body for the entire ORTP, contributed to this guidance by conducting a needs assessment to determine knowledge gaps and identify effective strategies for outbreak response and incident management, and by reviewing, analyzing, and summarizing resources identified by the CDC for the Expert Guidance Panel to consider for inclusion in the expert guidance document, and by reviewing and providing comments on drafts and the final version of the expert guidance document (see the Methods section).background
We assessed the relatedness by repetitive-sequence polymerase chain reaction of isolates obtained from children with recurrent methicillin-resistant Staphylococcus aureus cutaneous infections over 6 years. Ninety percent of the cases could be attributed to recurrence of the same strain type, suggesting that optimized decolonization methods in children might effectively prevent recurrent infection.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.