Critical care nursing is a speciality that continues to evolve and transform. Critical care nurses of the 21st century routinely care for the complex, critically ill patient, integrating sophisticated technology with the accompanying psychosocial challenges and the ethical conflicts associated with critical illness – while, at the same time, addressing the needs and concerns of the family. Providing nursing care in such a dynamic and fast-track unit can pose various challenges for the critical care nurse. Professional nurses are the backbone of any health-care system. The quality of nursing directly affects the patients’ outcomes, and nursing care must therefore be rendered meticulously. Mechanical ventilator support is routinely needed for critically ill adults in these care units and is also a common therapy in sub-acute and long-term care settings. The care of the mechanically ventilated patient is the core of a professional nurse`s practice in the critical care unit. The mechanically ventilated patient presents many challenges for the professional nurse, while the critical care unit poses as a stressful environment for the professional nurse as well as the patient. The objectives of this study therefore were to explore and describe the lived experiences of professional nurses while caring for mechanically ventilated patients, and to develop recommendations to support professional nurses while caring for mechanically ventilated patients. A qualitative, explorative, descriptive and contextual research design was utilised. Data was collected by means of semi-structured interviews and analysed according to the framework provided by Tesch. Purposive sampling was used to select a sample of professional nurses working in a critical care environment. Guba’s model was utilised to verify data and to ensure trustworthiness of the study. Ethical principles were adhered to throughout this research study. With the analysed data, recommendations were to support professional nurses while caring for mechanically ventilated.

Respiratory viral testing in hospitalized patients is thought to improve quality of care by reducing the use of diagnostic tests, guiding infection control precautions, and rationalizing antimicrobial therapies. Few small published studies have tested these assumptions, and have demonstrated conflicting results. We conducted a retrospective cohort study of 24,567 hospitalizations using administrative data to determine the associations between viral testing, patient outcomes, and process of care. Viral testing was not associated with improved mortality or length of stay in hospital, and resulted in more resource utilization. The test result did not influence the duration of isolation precautions. This implies that health care providers may not use the results of testing in making management decisions, or in guiding the use of isolation precautions. This study provides the foundation for further scientific evaluation and reform of our current respiratory infection control policy.

A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfillment of the requirements for the degree of Master of Science in Medicine in the field of Clinical Microbiology and Infectious Diseases Johannesburg, 2018. / Background: Respiratory Syncytial Virus (RSV) is a common cause of upper and lower respiratory tract infections (LRTI), primarily in children having severe disease manifestation. In South Africa, RSV is identified in approximately 25-30% of children hospitalized for LRTI. There is a spectrum of RSV-associated LRTI severity. Understanding associations between immune mediators and RSV-LRTI severity could assist clinicians in the triaging for level of care. Several cytokines have been implicated in RSV-LRTI severity. Aim: Study the associations between cytokine levels from plasma and nasopharyngeal aspirate with RSV infection or RSV-associated LRTI severity in hospitalized infants ranging from 0-12 months of age. The correlation between plasma and nasopharyngeal aspirate cytokine concentrations was also evaluated. Methods: Paired plasma and nasopharyngeal aspirate (NPA) samples were collected from polymerase chain reaction confirmed RSV-infected infants without coinfection with other pathogens that we investigated for. Paired samples were also collected from RSV negative-control infants (n=31) who did not have any respiratory symptoms. Control-infants were scheduled for elective surgery; samples were collected before administration of medication and surgical procedure. RSV associated LRTI episodes were grouped into mild (n=89) and severe RSV-LRTI (n=113) using the Respiratory Index of Severity in Children (RISC) Score. Interferon gamma (IFN-γ), interleukins (IL) IL-1α, IL-1β, IL-4, IL5, IL-6, IL-8, IL-9, IL-10, IL-12(p70)IL-13, macrophage inducing protein (MIP-1α), monocyte chemo attractant protein (MCP-1), tumour necrosis alpha (TNF-α), Regulated on activation, normal T cell expressed and secreted (RANTES) and were measured with multiplex immunosorbent assay using Luminex® technology. Cytokine profiles were evaluated for association of RSV-LRTI severity and between RSV LRTI cases and controls. Results: Comparing hospitalized RSV-associated LRTI to control infants, RSV cases had elevated plasma TNF-α (0.7pg/ml vs. 0.5pg/ml; p=0.007), and IL-10 (1.0pg/ml vs. 0.6pg/ml; p=0.02) concentrations, and reduced plasma MIP-1α (12pg/ml vs. 28pg/ml; p=0.008) and IFN-γ (3pg/ml vs. 5pg/ml; p=0.02) levels. Nasopharyngeal aspirate TNF-α (8.0pg/ml vs. 1.0pg/ml; p=0.01), IL-8 (2682pg/ml vs. 184pg/ml; p=0.002), MCP-1 (287pg/ml vs. 66pg/ml; p<0.001), MIP-1α (27pg/ml vs. 6.7pg/ml; p=0.004) concentrations were elevated in RSV-LRTI cases compared to control infants. Infants hospitalized with severe RSV-associated LRTI (RISC score ≥2) were younger than mild cases (3.9 vs. 4.5 months; p=0.01). In RSV cases, severe RSV-LRTI was associated with increased plasma IFN-γ levels (4pg/ml vs. 3pg/ml) and NPA MIP-1α concentrations (88pg/ml vs. 50pg/ml, mean; all other values medians) compared to mild RSV-LRTI. In a multivariate analysis, NPA MIP-1α levels remained associated with RSV-LRTI (p=0.05), but could not predict RSV-LRTI severity. Conclusion: This study observed that during RSV-associated LRTI, immune response was directed at the respiratory tract. Reduced concentrations of plasma IFN-γ and elevated levels of cytokines in the NPA may suggest that the blood of RSV-LRTI cases had reduced number of IFN-γ producing cells. There was no evidence of distinct Th1 or Th2 type immune response and the cytokines associated with RSV-LRTI severity could not predict the outcome of severe RSV-associated LRTI. Key words: Respiratory Syncytial Virus, Lower respiratory tract infections, Severity, Plasma, Nasopharyngeal aspirate, IFN-γ, MIP-1α, Luminex® / LG2018

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The human respiratory syncytial virus (hRSV) infection is a global public health burden in children aged under 2 years and immunocompromised or elderly adults. The choice for prophylaxis and therapy of hRSV infection was constrained to Palivizumab and Ribavirin. Therefore, this study aimed to develop effective anti-hRSV infection agents, such as short interfering RNA (siRNA) and β-defensin-4 (β-D-4). Since there still is no compatible animal model to evaluate antiviral effect of anti-hRSV agents, we first attempted to establish suitable animal model. A clinical isolate of hRSV (KI-RSV-W) was adapted in BALB/c mice by serial passages. Old male mice (age > 8 months) were used for establishment of hRSV infection model, because the more efficient viral infection in lungs of the old male mice than that old female mice and young mice (age < 3 weeks). After the virus was propagated in old male mice for 20 passages, a virus variant KI-RSV-P70-4 exhibited more efficient infection/replication in the mice. Its viral load was about 100-fold higher than that of wild type strain KI-RSV-W. The infection of KI-RSV-P70-4 also caused more severe histopathological changes in lung tissues. Although KI-RSV-P70-4 could not result in death of the infected mice, both viral load and pathological change in lungs may be good indicators for evaluating antiviral effect. The mouse model and adapted hRSV strain solidly laid the foundation for evaluation of anti-hRSV agents. We then designed and evaluated anti-hRSV effect of siRNAs. A total of 25 siRNAs targeting 4 viral genes (M2-1, NS2, N and F) were designed and their anti-hRSV effect was assessed in vitro. The results showed that 6 siRNAs respectively targeting M2-1, N and F genes exhibited higher anti-hRSV effect than that of the positive control, whereas those targeting NS2 gene did not show significant antiviral effect. The 50% inhibitory concentrations (IC50) of three most potent siRNAs (M2-1-361, N889 and F-1143) were 0.51, 2.14 and 0.64 nM, respectively. Antiviral activity of β-D-4 against hRSV infection was evaluated in vitro and in vivo. In vitro experiments showed supreme antiviral effect with IC50 around 3.4 μg/ml when the virus was pretreated with β-D-4, but no significant inhibitory effect was observed when the cells were pretreated with β-D-4 or β-D-4 was maintained in the culture medium after viral infection. These results indicated that the inhibitory effect of β-D-4 was associated with direct interaction with the virus itself and blocked virus entry of the cells. Furthermore, a single dose (13.6 μg) of β-D-4 intratracheal (i.t.) administration in old male mice after the viral infection resulted in about 0.7 log reduce of viral load in lung tissues, while inoculation of premixed β-D-4 and the virus caused about 3 logs decrease of viral load in lungs. These results have demonstrated that β-D-4 may be an effective anti-hRSV agent. Taken together, old male BALB/c mice might be used to establish hRSV infection model. Three siRNAs and the β-D-4 were validated as the potent anti-hRSV agents, respectively. / published_or_final_version / Microbiology / Doctoral / Doctor of Philosophy

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