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1.
Sex Reprod Healthc ; 41: 100997, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38901061

ABSTRACT

Literature surrounding miscarriage is broad in scope, yet narrative constructions following miscarriage are significantly under-researched. Few studies have sought to understand sense-making processes following miscarriage, including how and why people story their experience. Consequently, the complexities and nuances of these processes have not been adequately explored. This review aimed to gain insight into what is already known about how people story their experience of miscarriage, as well as research gaps and limitations. A systematic literature review of qualitative literature was conducted across four databases to identify relevant research related to miscarriage narratives and sense-making. Eligibility criteria was applied to a staged screening process to identify the highest quality, peer-reviewed research. Ten studies were included in the review and presented as a narrative synthesis. The literature was divided into five collective themes: women's perspectives, male partner's perspectives, couples' perspectives, healthcare professional's perspectives, and cultural perspectives. The literature review summarises existing knowledge about narrative processes in relation to miscarriage, as well as highlighting research gaps, clinical implications, and directions for future research. When working with those who have experienced involuntary child loss and infertility, there is a need for professionals to have appropriate training to support the provision of compassionate, individualised care and decision-making. The role of language requires consideration as there is a need to address over-medicalised systems of knowledge, and it is important that there is understanding regarding the need for expression, and the various ways that individuals might express their feelings and loss.

2.
Complement Ther Clin Pract ; 47: 101564, 2022 May.
Article in English | MEDLINE | ID: mdl-35247689

ABSTRACT

The therapeutic benefits of Animal Assisted Therapy (AAT) are well-documented and AAT research often involves dogs. Despite growing research into the therapeutic value of therapy dogs' visitation within health and psychiatric contexts, research specifically into the integration of dogs into psychological therapies is limited. Current Dog Assisted Psychological Therapy (DAPT) research is novel and limited. DAPT research predominantly focuses on therapist perspectives and use quantitative or case study methodologies. Research into adults' experience of DAPT is limited. Therefore, this research explored the experiences of adults receiving DAPT, who self-identified as experiencing mental health difficulties. Specific aims were to gain a broad insight into the experienced opportunities, challenges and factors impacting participants' experience of therapy, to help inform the clinical implications of DAPT. Qualitative methodology was used by conducting semi-structured interviews with six participants sharing their experiences of DAPT. Interpretative Phenomenological Analysis (IPA) enabled exploration of important issues regarding participants' experiences. Five themes emerged: 1) Relationship with dog(s); 2) Providing a safe therapeutic atmosphere; 3) Distraction; 4) Facilitating personal insights; and 5) Concern for the dog's wellbeing. Relationships between the themes are illustrated, and the theoretical relevance to psychological models and clinical applications are discussed. This research demonstrated that, where clinically and ethically appropriate, DAPT can provide therapeutic opportunities to facilitate psychological therapies. The therapist's skills in managing interactions and potential distraction, the client's prior experiences of dogs and the dog's wellbeing are all important considerations to manage some of the identified challenges within DAPT. Further research is needed to inform practice guidelines, specifically in terms of which psychological models and patient groups DAPT might be best suited to, and further exploration of DAPT practice within different clinical and cultural populations.


Subject(s)
Animal Assisted Therapy , Animals , Dogs , Humans , Mental Health , Platelet Aggregation Inhibitors , Qualitative Research
3.
Vaccine ; 38(45): 6979-6984, 2020 10 21.
Article in English | MEDLINE | ID: mdl-32981779

ABSTRACT

Incidence of measles is increasing in the US, largely due to transmission among growing unvaccinated communities. To elucidate predictors of parental decision to obtain measles, mumps, and rubella (MMR) vaccine for unvaccinated children during a measles outbreak, we surveyed families among a vaccine-hesitant Somali community in Minnesota. The survey assessed attitudes and beliefs about MMR vaccine, motivators for vaccinating, and intention to vaccinate future children on time. Among 300 families surveyed, 95% vaccinated their child with MMR due to fear of measles. The predominating parental concern about MMR vaccine (71%) was a fallacious presumed connection between vaccination and autism. Only 41% of parents intended to vaccinate future children on time with MMR; parents who received recommendations for MMR vaccination from multiple sources were more likely than other parents to intend to do so. These findings support the importance of diverse outreach efforts to increase vaccine coverage among undervaccinated communities.


Subject(s)
Measles , Mumps , Rubella , Attitude , Child , Disease Outbreaks , Humans , Measles/epidemiology , Measles/prevention & control , Measles-Mumps-Rubella Vaccine , Minnesota/epidemiology , Parents , Somalia , Vaccination
5.
Wellcome Open Res ; 4: 74, 2019.
Article in English | MEDLINE | ID: mdl-31231691

ABSTRACT

Background: Salmonella Typhimurium ST313 exhibits signatures of adaptation to invasive human infection, including higher resistance to humoral immune responses than gastrointestinal isolates. Full resistance to antibody-mediated complement killing (serum resistance) among nontyphoidal Salmonellae is uncommon, but selection of highly resistant strains could compromise vaccine-induced antibody immunity. Here, we address the hypothesis that serum resistance is due to a distinct genotype or transcriptome response in S. Typhimurium ST313. Methods: Six S. Typhimurium ST313 bloodstream isolates, three of which were antibody resistant, were studied. Genomic content (single nucleotide polymorphisms and larger chromosomal modifications) of the strains was determined by Illumina and PACBIO sequencing, and functionally characterized using RNA-seq, transposon directed insertion site sequencing (TraDIS), targeted gene deletion and transfer of selected point mutations in an attempt to identify features associated with serum resistance.   Results: Sequence polymorphisms in genes from strains with atypical serum susceptibility when transferred from strains that were highly resistant or susceptible to a strain that exhibited intermediate susceptibility did not significantly alter serum killing phenotype. No large chromosomal modifications typified serum resistance or susceptibility. Genes required for resistance to serum identified by TraDIS and RNA-seq included those involved in exopolysaccharide synthesis, iron scavenging and metabolism. Most of the down-regulated genes were associated with membrane proteins. Resistant and susceptible strains had distinct transcriptional responses to serum, particularly related to genes responsible for polysaccharide biosynthesis. There was higher upregulation of wca locus genes, involved in the biosynthesis of colanic acid exopolysaccharide, in susceptible strains and increased expression of fepE, a regulator of very long-chain lipopolysaccharide in resistant strains. Conclusion: Clinical isolates of S. Typhimurium ST313 exhibit distinct antibody susceptibility phenotypes that may be associated with changes in gene expression on exposure to serum.

6.
Patient Educ Couns ; 102(9): 1730-1735, 2019 09.
Article in English | MEDLINE | ID: mdl-30962077

ABSTRACT

BACKGROUND: Children's burn injuries can have a significant psychosocial impact on parents. However, the stress involved in caring for a child following a burn can often go unrecognized and does not necessarily prompt help seeking by parents. OBJECTIVE: It is common for adults to seek health-related support and information via the Internet. Many benefit from immediate and easy access to online psychological interventions. A prototype burn-specific, parent-focused, peer-informed, supportive website, designed to provide easy access to information and psychoeducation, was created and tested for acceptability. PATIENT INVOLVEMENT: Using a partnership-based method of website development, parents and professionals (clinical, academic and support organizations) were recruited and their particular expertise was acknowledged and valued. A participatory action approach was adopted to determine the acceptability of the website for parents/carers. METHODS: 31 participants (9 parents, 22 professionals) tested a prototype version of the website. Data was collected using the eHealth Impact Questionnaire and the concurrent think-aloud protocol. RESULTS: Parents and professionals had favorable opinions of the website. Parents' ratings tended to be more favorable than professionals', which was significant for the information and presentation. Participants' thoughts were categorized into seven topics: need, structure/navigation, trust/relevance, language/comprehension, therapeutic content, mode of delivery, and suggested improvements. DISCUSSION: Many practical and psychological barriers can prevent parents of burn-injured children accessing psychosocial support and contribute to a feeling of isolation. Participants felt that the website would be a valuable addition to UK pediatric burn care. The existence of an accessible resource could help to normalize parents' experience of their child's injury and reduce their perceived isolation, although peer interaction is not provided by the website. PRACTICAL VALUE: This online resource, hosting information and peers' personal experiences, offers promising and exciting opportunities to empower parents whilst providing accessible supportive advice to encourage self-care and formal/informal support seeking when necessary.


Subject(s)
Burns/nursing , Health Education/methods , Internet , Parents/psychology , Child , Female , Humans , Male , Peer Group , United Kingdom
7.
Sex Reprod Healthc ; 19: 42-49, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30928134

ABSTRACT

OBJECTIVES: To investigate: (1) whether women self-report an ability to choose their preferred termination of pregnancy (TOP) procedure, (2) what factors influence this choice, and (3) what effect this choice has on emotional responses and satisfaction with care. STUDY DESIGN: A mixed-method prospective comparative study in which women requesting a TOP between five and eighteen weeks gestation for social reasons (as opposed to medical indications), were invited to complete a semi-structured pre-TOP interview and questionnaire, and a post-TOP questionnaire four weeks after the procedure. MAIN OUTCOME MEASURES: Quantitative data was collected using the Patient Health Questionnaire, Generalised Anxiety Disorder Scale, Positive and Negative Affect Scale, Impact of Event Scale - Revised, and Client Satisfaction Questionnaire. RESULTS: Pre-TOP emotion-based factors did not differ between groups. Most women felt that they were able to choose their preferred method of TOP. Their decisions were based on factors categorised as procedure-related, lifestyle or social circumstance-related, emotional, or other factors. When no choice was perceived, common reasons reported were that: (1) gestation was too far along for there to be another option, or (2) an appointment was not available within the required timeframe. When women felt that the method of TOP performed was not their choice they found the procedure more stressful. All women reported high satisfaction with care. CONCLUSION: A better understanding of the patient experience can inform service development, enabling staff to ensure that the services provided meet women's needs. The perception that one is able to choose their preferred TOP procedure is important for reducing procedure-related stress and ensuring high satisfaction with care.


Subject(s)
Abortion, Legal/psychology , Emotions , Patient Preference , Abortion, Legal/methods , Adult , Choice Behavior , Female , Humans , Middle Aged , Pregnancy , Pregnancy Trimester, First , Pregnancy Trimester, Second , Prospective Studies , Surveys and Questionnaires , Young Adult
8.
Public Health Rep ; 134(3): 241-248, 2019.
Article in English | MEDLINE | ID: mdl-30912998

ABSTRACT

In Minneapolis-St Paul, Minnesota, factors such as cultural and linguistic diversity make it difficult for public health agencies to reach immigrant and racial/ethnic minority populations with health initiatives. Founded in 2006, the Minnesota Immunization Networking Initiative (MINI) is a community project that has provided more than 80 000 free influenza vaccinations to vulnerable populations, including immigrants and racial/ethnic minority groups. MINI administered 5910 vaccinations through 99 community-based vaccination clinics during the 2017-2018 influenza season and surveyed the clients in their own language about influenza vaccination knowledge and practices. Among those surveyed, 2545 (43.1%) were uninsured and 408 (6.9%) received a first-time influenza vaccination at the MINI clinic. A total of 2893 (49.0%) respondents heard about the clinic through their faith community. Lessons learned included the importance of building relationships with community leaders and involving them as full partners, holding clinics in community-based settings to bring vaccinations to clients, and reporting outcomes to partners.


Subject(s)
Community Health Services/organization & administration , Emigrants and Immigrants , Health Promotion/organization & administration , Immunization Programs/organization & administration , Minority Groups , Adolescent , Adult , Aged , Child , Child, Preschool , Communication , Community-Institutional Relations , Ethnicity , Female , Health Knowledge, Attitudes, Practice , Humans , Infant , Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Interinstitutional Relations , Male , Middle Aged , Minnesota , Program Evaluation , Racial Groups , Socioeconomic Factors , Young Adult
10.
Appl Nurs Res ; 43: 30-35, 2018 10.
Article in English | MEDLINE | ID: mdl-30220360

ABSTRACT

BACKGROUND: Often researchers use only one interview method within a single study. However, it is increasingly common for a variety of interview methods to be employed within a project. Providing choice to participants may facilitate recruitment, particularly when research focuses on a sensitive subject. AIM: This paper aims to explore participants' reasons for their choice of interview method in qualitative research focusing on a sensitive subject. METHODS: Qualitative data was collected from 12 participants regarding their choice of interview method (face-to-face, Skype, telephone or email) in a wider study investigating parents' experiences following their child's burn-injury. Interview data was transcribed verbatim and thematic analysis was used to analyse responses. RESULTS: Participants most frequently chose to take part in an interview by telephone (n = 5), followed by email (n = 4), then Skype (n = 2), and face-to-face (n = 1). Four themes emerged suggesting that participants' decisions to participate via a particular method were determined by personal convenience, their belief in their ability to be open with the researcher despite potential upset caused by the topic, their ability to get a "feel" for the researcher, and concern about giving adequate depth in responses. CONCLUSIONS: Flexibility regarding the ways in which participants can take part in qualitative research may improve participant access to research, recruitment, and response-rate. Although, the depth and quantity of data gathered using different methods can vary. It is important that researchers consider the procedures and appropriateness of using different methods of interviewing and what impact such methods might have upon themselves and their participants.


Subject(s)
Data Collection/methods , Patient Participation , Female , Humans , Male , Qualitative Research
12.
Scars Burn Heal ; 4: 2059513118763801, 2018.
Article in English | MEDLINE | ID: mdl-29873333

ABSTRACT

INTRODUCTION: Burn injuries can be traumatic and distressing for the affected child and family, with a prolonged period of recovery. This research explores parents' experiences of support following their child's injury and their thoughts on peer support specifically. METHODS: Thirteen semi-structured interviews were conducted with parents/caregivers, a mean of three years after their child's injury, either face-to-face or remotely. Responses were analysed using thematic analysis. RESULTS: Analysis produced four themes and 11 sub-themes. These described parents' experiences of loss, change, isolation and access to psychosocial support. This paper focuses on themes of isolation and parents' access to psychosocial support. DISCUSSION: Findings indicate that parents access psychosocial support following their child's injury and often find it helpful; however, there is a prevailing sense of isolation. Parents often seek information online and find that this is lacking. Many parents reported that peer support would be valuable to them, particularly the sharing of experiential knowledge. CONCLUSION: An online resource may be beneficial for parents, but further research is needed to confirm the exploratory data gained to date, ensuring that any resource developed would meet the identified needs of parents.

13.
J Immunol ; 199(12): 4103-4109, 2017 12 15.
Article in English | MEDLINE | ID: mdl-29127147

ABSTRACT

In mice, the IgG subclass induced after Ag encounter can reflect the nature of the Ag. Th2 Ags such as alum-precipitated proteins and helminths induce IgG1, whereas Th1 Ags, such as Salmonella Typhimurium, predominantly induce IgG2a. The contribution of different IgG isotypes to protection against bacteria such as S. Typhimurium is unclear, although as IgG2a is induced by natural infection, it is assumed this isotype is important. Previously, we have shown that purified S. Typhimurium porins including outer membrane protein OmpD, which induce both IgG1 and IgG2a in mice, provide protection to S. Typhimurium infection via Ab. In this study we report the unexpected finding that mice lacking IgG1, but not IgG2a, are substantially less protected after porin immunization than wild-type controls. IgG1-deficient mice produce more porin-specific IgG2a, resulting in total IgG levels that are similar to wild-type mice. The decreased protection in IgG1-deficient mice correlates with less efficient bacterial opsonization and uptake by macrophages, and this reflects the low binding of outer membrane protein OmpD-specific IgG2a to the bacterial surface. Thus, the Th2-associated isotype IgG1 can play a role in protection against Th1-associated organisms such as S. Typhimurium. Therefore, individual IgG subclasses to a single Ag can provide different levels of protection and the IgG isotype induced may need to be a consideration when designing vaccines and immunization strategies.


Subject(s)
Antibodies, Bacterial/immunology , Immunoglobulin G/immunology , Porins/immunology , Salmonella Vaccines/immunology , Salmonella typhimurium/immunology , Animals , Antigen-Antibody Reactions , Bacterial Adhesion/immunology , Bacterial Proteins/immunology , Cell Line , Female , IgG Deficiency/immunology , Immunization , Immunoglobulin Class Switching , Immunoglobulin Isotypes/immunology , Male , Mice, Inbred C57BL , Phagocytosis/immunology , Salmonella Infections, Animal/prevention & control
14.
MMWR Morb Mortal Wkly Rep ; 66(27): 713-717, 2017 Jul 14.
Article in English | MEDLINE | ID: mdl-28704350

ABSTRACT

On April 10, 2017, the Minnesota Department of Health (MDH) was notified about a suspected measles case. The patient was a hospitalized child aged 25 months who was evaluated for fever and rash, with onset on April 8. The child had no history of receipt of measles-mumps-rubella (MMR) vaccine and no travel history or known exposure to measles. On April 11, MDH received a report of a second hospitalized, unvaccinated child, aged 34 months, with an acute febrile rash illness with onset on April 10. The second patient's sibling, aged 19 months, who had also not received MMR vaccine, had similar symptoms, with rash onset on March 30. Real-time reverse transcription-polymerase chain reaction (rRT-PCR) testing of nasopharyngeal swab or throat specimens performed at MDH confirmed measles in the first two patients on April 11, and in the third patient on April 13; subsequent genotyping identified genotype B3 virus in all three patients, who attended the same child care center. MDH instituted outbreak investigation and response activities in collaboration with local health departments, health care facilities, child care facilities, and schools in affected settings. Because the outbreak occurred in a community with low MMR vaccination coverage, measles spread rapidly, resulting in thousands of exposures in child care centers, schools, and health care facilities. By May 31, 2017, a total of 65 confirmed measles cases had been reported to MDH (Figure 1); transmission is ongoing.


Subject(s)
Disease Outbreaks , Measles/epidemiology , Adolescent , Adult , Child , Child, Preschool , Humans , Infant , Measles/prevention & control , Measles virus/genetics , Measles virus/isolation & purification , Measles-Mumps-Rubella Vaccine/administration & dosage , Middle Aged , Minnesota/epidemiology , Vaccination/statistics & numerical data , Young Adult
15.
Infect Immun ; 85(9)2017 09.
Article in English | MEDLINE | ID: mdl-28674031

ABSTRACT

The ST313 pathovar of Salmonella enterica serovar Typhimurium contributes to a high burden of invasive disease among African infants and HIV-infected adults. It is characterized by genome degradation (loss of coding capacity) and has increased resistance to antibody-dependent complement-mediated killing compared with enterocolitis-causing strains of S Typhimurium. Vaccination is an attractive disease-prevention strategy, and leading candidates focus on the induction of bactericidal antibodies. Antibody-resistant strains arising through further gene deletion could compromise such a strategy. Exposing a saturating transposon insertion mutant library of S Typhimurium to immune serum identified a repertoire of S Typhimurium genes that, when interrupted, result in increased resistance to serum killing. These genes included several involved in bacterial envelope biogenesis, protein translocation, and metabolism. We generated defined mutant derivatives using S Typhimurium SL1344 as the host. Based on their initial levels of enhanced resistance to killing, yfgA and sapA mutants were selected for further characterization. The S Typhimurium yfgA mutant lost the characteristic Salmonella rod-shaped appearance, exhibited increased sensitivity to osmotic and detergent stress, lacked very long lipopolysaccharide, was unable to invade enterocytes, and demonstrated decreased ability to infect mice. In contrast, the S Typhimurium sapA mutants had similar sensitivity to osmotic and detergent stress and lipopolysaccharide profile and an increased ability to infect enterocytes compared with the wild type, but it had no increased ability to cause in vivo infection. These findings indicate that increased resistance to antibody-dependent complement-mediated killing secondary to genetic deletion is not necessarily accompanied by increased virulence and suggest the presence of different mechanisms of antibody resistance.


Subject(s)
ATP-Binding Cassette Transporters/metabolism , Antibodies, Bacterial/immunology , Bacterial Proteins/metabolism , Blood Bactericidal Activity , Complement System Proteins/immunology , Salmonella typhimurium/immunology , Salmonella typhimurium/pathogenicity , ATP-Binding Cassette Transporters/genetics , Animals , Bacterial Proteins/genetics , DNA Transposable Elements , Female , Gene Knockout Techniques , Mice, Inbred C57BL , Mutagenesis, Insertional , Salmonella typhimurium/physiology , Virulence , Virulence Factors/genetics , Virulence Factors/metabolism
16.
Qual Life Res ; 26(9): 2409-2419, 2017 09.
Article in English | MEDLINE | ID: mdl-28551835

ABSTRACT

PURPOSE: Chronic kidney disease (CKD) can place restrictions upon biopsychosocial development in children; consequently, assessment of self-reported quality of life (QoL) is important in patient evaluations. This research aimed to evaluate a generic and renal-specific self-report QoL scale, assess children's attitudes towards living with CKD and propose an appropriate tool for future individual clinical use or departmental audit. METHODS: Seventy-one children (41 male, 30 female; mean age = 13.60 years, range = 6.00-18.96) with CKD completed the Generic Children's QoL Measure (GCQ), PedsQL 3.0 End Stage Renal Disease Module (PedsQL) and Child Attitude Toward Illness Scale (CATIS). Descriptive and cross-sectional analyses were performed, along with an examination of associations between scores on each measure. RESULTS: The mean GCQ score for patients was comparable with normative data (p = 0.27). Generic QoL, disease-specific QoL and attitudes towards CKD did not vary by CKD stage, age, time since diagnosis or duration of current treatment. Gender was not associated with QoL, although males had more negative CATIS scores than females (p < 0.05). Pre-emptive transplant patients had more positive GCQ and PedsQL scores (p < 0.05 for each), but there was no relationship between treatment and CATIS scores. Scores on all scales were moderately correlated (r = 0.35-0.59), suggesting that clinicians may choose the most appropriate measure for assessment of psychological/psychosocial functioning based on clinical judgement. CONCLUSIONS: This study further confirmed that using child self-reported QoL measures is possible and may help psychosocial teams to individualise work. The GCQ is simple and convenient, and could be used as an annual screening tool to facilitate discussion of QoL with children and young people. Further work is necessary before such things as cut-off scores can be recommended.


Subject(s)
Quality of Life/psychology , Renal Insufficiency, Chronic/psychology , Adolescent , Adult , Aged , Attitude , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Renal Insufficiency, Chronic/pathology , Surveys and Questionnaires , Young Adult
17.
Nat Microbiol ; 1: 15023, 2016 Jan 25.
Article in English | MEDLINE | ID: mdl-27572160

ABSTRACT

Host adaptation is a key factor contributing to the emergence of new bacterial, viral and parasitic pathogens. Many pathogens are considered promiscuous because they cause disease across a range of host species, while others are host-adapted, infecting particular hosts(1). Host adaptation can potentially progress to host restriction, where the pathogen is strictly limited to a single host species and is frequently associated with more severe symptoms. Host-adapted and host-restricted bacterial clades evolve from within a broader host-promiscuous species and sometimes target different niches within their specialist hosts, such as adapting from a mucosal to a systemic lifestyle. Genome degradation, marked by gene inactivation and deletion, is a key feature of host adaptation, although the triggers initiating genome degradation are not well understood. Here, we show that a chronic systemic non-typhoidal Salmonella infection in an immunocompromised human patient resulted in genome degradation targeting genes that are expendable for a systemic lifestyle. We present a genome-based investigation of a recurrent blood-borne Salmonella enterica serotype Enteritidis (S. Enteritidis) infection covering 15 years in an interleukin-12 ß1 receptor-deficient individual that developed into an asymptomatic chronic infection. The infecting S. Enteritidis harboured a mutation in the mismatch repair gene mutS that accelerated the genomic mutation rate. Phylogenetic analysis and phenotyping of multiple patient isolates provides evidence for a remarkable level of within-host evolution that parallels genome changes present in successful host-restricted bacterial pathogens but never before observed on this timescale. Our analysis identifies common pathways of host adaptation and demonstrates the role that immunocompromised individuals can play in this process.


Subject(s)
Adaptation, Biological , Bacteremia/microbiology , Host-Pathogen Interactions , Immunocompromised Host , Salmonella Infections/microbiology , Salmonella enteritidis/genetics , Salmonella enteritidis/isolation & purification , Evolution, Molecular , Gene Deletion , Genetic Variation , Genome, Bacterial , Humans , MutS DNA Mismatch-Binding Protein/deficiency , Mutation Rate , Phylogeny , Salmonella enteritidis/classification , Time Factors
18.
Clin Vaccine Immunol ; 23(7): 601-9, 2016 07.
Article in English | MEDLINE | ID: mdl-27170644

ABSTRACT

Nontyphoidal Salmonella is a leading cause of sepsis in African children. Cytokine responses are central to the pathophysiology of sepsis and predict sepsis outcome in other settings. In this study, we investigated cytokine responses to invasive nontyphoidal Salmonella (iNTS) disease in Malawian children. We determined serum concentrations of 48 cytokines with multiplexed immunoassays in Malawian children during acute iNTS disease (n = 111) and in convalescence (n = 77). Principal component analysis and logistic regression were used to identify cytokine signatures of acute iNTS disease. We further investigated whether these responses are altered by HIV coinfection or severe malnutrition and whether cytokine responses predict inpatient mortality. Cytokine changes in acute iNTS disease were associated with two distinct cytokine signatures. The first is characterized by increased concentrations of mediators known to be associated with macrophage function, and the second is characterized by raised pro- and anti-inflammatory cytokines typical of responses reported in sepsis secondary to diverse pathogens. These cytokine responses were largely unaltered by either severe malnutrition or HIV coinfection. Children with fatal disease had a distinctive cytokine profile, characterized by raised mediators known to be associated with neutrophil function. In conclusion, cytokine responses to acute iNTS infection in Malawian children are reflective of both the cytokine storm typical of sepsis secondary to diverse pathogens and the intramacrophage replicative niche of NTS. The cytokine profile predictive of fatal disease supports a key role of neutrophils in the pathogenesis of NTS sepsis.


Subject(s)
Cytokines/blood , Salmonella Infections/mortality , Salmonella Infections/pathology , Sepsis/mortality , Sepsis/pathology , Adolescent , Child , Child, Preschool , Female , HIV Infections/complications , Humans , Infant , Infant, Newborn , Macrophages/immunology , Malawi , Male , Malnutrition/complications , Neutrophils/immunology , Survival Analysis
19.
Nat Microbiol ; 1(3)2016 03.
Article in English | MEDLINE | ID: mdl-27127642

ABSTRACT

Host adaptation is a key factor contributing to the emergence of new bacterial, viral and parasitic pathogens. Many pathogens are considered promiscuous because they cause disease across a range of host species, while others are host-adapted, infecting particular hosts1. Host adaptation can potentially progress to host restriction where the pathogen is strictly limited to a single host species and is frequently associated with more severe symptoms. Host-adapted and host-restricted bacterial clades evolve from within a broader host-promiscuous species and sometimes target different niches within their specialist hosts, such as adapting from a mucosal to a systemic lifestyle. Genome degradation, marked by gene inactivation and deletion, is a key feature of host adaptation, although the triggers initiating genome degradation are not well understood. Here, we show that a chronic systemic non-typhoidal Salmonella infection in an immunocompromised human patient resulted in genome degradation targeting genes that are expendable for a systemic lifestyle. We present a genome-based investigation of a recurrent blood-borne Salmonella enterica serotype Enteritidis (S. Enteritidis) infection covering 15 years in an interleukin (IL)-12 ß-1 receptor-deficient individual that developed into an asymptomatic chronic infection. The infecting S. Enteritidis harbored a mutation in the mismatch repair gene mutS that accelerated the genomic mutation rate. Phylogenetic analysis and phenotyping of multiple patient isolates provides evidence for a remarkable level of within-host evolution that parallels genome changes present in successful host-restricted bacterial pathogens but never before observed on this timescale. Our analysis identifies common pathways of host adaptation and demonstrates the role that immunocompromised individuals can play in this process.


Subject(s)
Adaptation, Physiological/genetics , Genome, Bacterial , Host-Pathogen Interactions , Immunocompromised Host , Immunologic Deficiency Syndromes/complications , Salmonella Infections/microbiology , Salmonella enteritidis/genetics , Adult , Bacteremia/microbiology , Chronic Disease , Evolution, Molecular , Host Specificity , Humans , Interleukin-12 Receptor beta 1 Subunit/deficiency , Interleukin-12 Receptor beta 1 Subunit/genetics , Mutation , Mutation Rate , Salmonella Infections/complications , Salmonella enteritidis/classification , Salmonella enteritidis/isolation & purification , Salmonella enteritidis/pathogenicity , Virulence
20.
Stud Health Technol Inform ; 216: 453-7, 2015.
Article in English | MEDLINE | ID: mdl-26262091

ABSTRACT

High speed physiological data represents one of the most untapped resources in healthcare today and is a form of Big Data. Physiological data is captured and displayed on a wide range of devices in healthcare environments. Frequently this data is transitory and lost once initially displayed. Researchers wish to store and analyze these datasets, however, there is little evidence of any engagement with citizens regarding their perceptions of physiological data capture for secondary use. This paper presents the findings of a self-administered household survey (n=165, response rate = 34%) that investigated Australian and Canadian citizens' perceptions of such physiological data capture and re-use. Results indicate general public support for the secondary use of physiological streaming data. Discussion considers the potential application of such data in neonatal intensive care contexts in relation to our Artemis research. Consideration of the perceptions of secondary use of the streaming data as early as possible will assist in building appropriate use models, with a focus on parents in the neonatal context.


Subject(s)
Attitude to Health , Biomedical Research/statistics & numerical data , Datasets as Topic/statistics & numerical data , Intensive Care, Neonatal/statistics & numerical data , Monitoring, Physiologic/statistics & numerical data , Public Opinion , Australia , Canada , Electronic Health Records/statistics & numerical data , Information Storage and Retrieval/methods , Information Storage and Retrieval/statistics & numerical data , Parents , Surveys and Questionnaires
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