ETD Collection

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Molecular epidemiology and cellular immunology of respiratory syncytial virus in South Africa.
(2003-03-31) Venter., Maria.
Respiratory syncytial virus (RSV) is the major viral cause of severe lower respiratory tract infection in children and there is currently no commercial vaccine available. Research about RSV epidemiology and protective immunology is crucial for the development of effective vaccines and vaccination programs. No information exists about the molecular epidemiology and RSV-specific cytotoxic T-cell (CTL) response in South Africa, which is thought to be essential for the disease-free control of RSV.
The response to natural RSV infection in HIV-infected children compared to HIV-uninfected children
(2004-10-11) Sorour., Gillian. Ann.
Respiratory syncytial virus ( RSV ) is the most important virus causing acute respiratory tract infections in children and is an important cause of morbility and mortality. HIV- infected children are also at an increased risk of recurrent and more severe RSV infections. There are few studies looking at how HIV-Infected infants respond immunologically to natural RSV infection.
Role of molecular evolution in respiratory syncytial virus antigenic proteins during annual epidemics in South Africa
(2004-05-28) Agenbach., Elizabeth.
Respiratory syncytial virus (RSV) is a major cause of pneumonia in children worldwide and there is currently no vaccine available. Molecular analysis of annual RSV epidemics in Soweto (1997 to 2000), revealed co-circulation and displacement of dominant genotypes. However in 1999 to 2000, one genotype GA2, predominated. To further elucidate the molecular epidemiology of RSV in South Africa the 2001 RSV epidemic in Soweto was characterised. Phylogenetic analysis of the G-protein revealed subtype B dominance (89%). Sequences clustered in genotypes GA2, GA5, SAA1, GB3, SAB1 and SAB3. SAB3 dominanted (69%) followed by SAB1 (18%), thereby displacing GA2, which dominated the previous two seasons. Evidence of positive selection may account for the genetic variability observed and may contribute to the reestablishment of annual epidemics. To investigate if this influences evolution of other RSV antigenic proteins the F-protein of South African genotypes was characterised. Most amino acid differences identified within known neutralising and CTL epitopes were conserved within subtype A, and although this does not suggest immune selection these epitopes may not be recognised efficiently by antibodies or CTL specific to subtype B viruses
Association between cytokine profile and disease severity in children infected with respiratory syncytial virus causing lower respiratory tract infection
(2018) Montlha, Mahlodi Petunia
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®

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