3. Electronic Theses and Dissertations (ETDs) - All submissions
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Item Association between cytokine profile and disease severity in children infected with respiratory syncytial virus causing lower respiratory tract infection(2018) Montlha, Mahlodi PetuniaBackground: 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®Item The value of lateral chest X-rays for the diagnosis of lymphadenopathy in children with pulmonary tuberculosis(2018) Poyiadji, Thalia LetoINTRODUCTION: Tuberculosis (TB) is an important public health issue, but diagnosis in children can be challenging. The radiological hallmark of pulmonary TB (PTB) in children is mediastinal lymphadenopathy, however there is inter-observer variability in detecting this. The value of the lateral CXR in addition to the frontal view to detect lymphadenopathy has not been well studied. OBJECTIVES: To investigate the prevalence of lymphadenopathy in children with confirmed PTB detected on frontal compared to frontal-lateral CXRs. METHODS: This was a secondary analysis of a study from Red Cross Children’s Hospital in Cape Town. Children with definite TB and a control group (Lower respiratory tract infection other than TB) who had frontal and lateral CXRs were included in this study. Three radiologists independently read the CXRs in 2 separate sittings (frontal CXR and ‘combination frontallateral’ CXR). A 3 reader consensus reading was used during data analysis. Odds ratios and 95% confidence intervals were calculated to determine the presence of lymphadenopathy. Kappa statistics were calculated to determine inter reader agreement. RESULTS: Of 172 children (88 confirmed TB and 84 control children), with a median age of 29 months, lymphadenopathy was reported in 86 (50%) patients on the frontal CXR alone and in 143 (83%) on the frontal-lateral CXR combination, p= 0.00. Amongst confirmed PTB cases, 52 (60%) had lymphadenopathy on the frontal CXR alone while 72 (82%) had lymphadenopathy on the frontal-lateral CXR combination, p= 0.00. Amongst the control group, 34 (40%) had lymphadenopathy on the frontal CXR alone while 71 (85%) had lymphadenopathy on the frontal-lateral CXR combination, p= 0.00. The consensus reading using a frontal-lateral CXR combination resulted in a 5 fold increase (OR 4,9; 95% CI 2,9-8,4) in diagnosis of lymphadenopathy compared to a frontal CXR only. Overall inter reader agreement for all 3 readers was fair on both the frontal CXR (Kappa= 0,21) and the frontal-lateral CXR (Kappa= 0,23) combination. CONCLUSION: The addition of a lateral view to the frontal CXR increased detection of lymphadenopathy, however, the prevalence of lymphadenopathy was similar in children with PTB and those in the control group, with fair inter reader agreement.Item Risk factors associated with anaemia among children under five years of age in Uganda(2018) Ali, Muhammad MustanserBackground Anaemia remains a public health challenge, especially in developing countries because of its relationship to neurocognitive delays, especially among children under five. According to the World Health Organization (WHO) report for 1993-2005, 293.1 million children were affected by anaemia globally. Risk factors for anaemia that need to be examined in children include socio-demographic characteristics, infection with the Human Immunodeficiency virus (HIV), malnutrition and malaria. Objectives The objectives of the study were to estimate the prevalence of anaemia and identify the potential risk factors (including socio-demographic factors) among children under five years of age who participated in a cross-sectional survey in Uganda in 2011. Methods Data that were collected in a cross-sectional survey during 2011 in Uganda (N = 1 808) were analysed. Children were defined as being anaemic if their haemoglobin levels were below 11.0 g/dl, as per the WHO definition. Cross tabulations, and ordinary and ordinal logistic regression analysis were the primary methods used. Results The main finding was that the prevalence of anaemia in children under five years of age was high, at 50.3% (95% CI: 46% - 54%). Of those with anaemia 1.6% had severe anaemia, 26.2% had moderate anaemia, and 22.6% had mild anaemia. From the multiple ordinary and ordinal logistic regression analyses, age group of the child, region, breastfeeding status of the mother, v use of antenatal health care facilities, household wealth index, household age group, marital status of household head, and literacy level of the household head were associated with childhood anaemia. Children with anaemia were more likely to be younger than 24 months old, have had malaria, have poor nutritional status, and live in rural areas. The children were also more likely to be anaemic if their mothers had a high education, and were young , and if they lived with a household head aged 79-95 years. They were less likely to be anaemic if they had a household head in one of the relatively higher wealth indices, a household head with a literacy level of ‘medium’, and a household head who was divorced. Conclusion Anaemia was highly prevalent among children under five years of age in Uganda in 2011. Several child- maternal- and household head-related risk factors were identified. Modifiable risk factors should be targeted in Uganda to reduce anaemia in children. Malaria and nutrition programmes (including iron supplementation) should be stepped up, and pregnant women and mothers of new born children should be encouraged to attend health care centres, including antenatal care facilities. Children with un-modifiable risk factors, such as living in rural or low GDP areas should be closely monitored for risk factors that predispose them to anaemia.Item Prevalence of Disability in a Cohort of HIV-Infected children attending an urban paediatric HIV Clinic in Johannesburg, South Africa(2018) Brassell, Shane (Nee Hodges)Background: With the success of evolving antiretroviral therapy (ART), human immunodeficiency virus (HIV) has become a chronic condition, however, children infected with HIV have been shown to have developmental difficulties and disabilities. This study aimed to investigate the extent of disability among a cohort of HIV infected children in South Africa and whether they are being referred and accessing rehabilitative services. Methods: A cross-sectional study was conducted at an HIV clinic in Johannesburg. Caregivers/parents were interviewed about their child, using the Ten Question Screen for Disability Questionnaire (TQSD) along with a general additional questionnaire devised by the researchers on medical history, services referred to and accessed and socioeconomic status (SES). Clinical data, from the child’s clinic file were recorded. Results Of the 200 children whose caregivers/parents were interviewed, 50.5% experienced disabilities were 58.4% of those had more than one co-existing disability. Of the children who reported disability only 46% had been referred to one or more of the following support services; audiologist, physiotherapist (PT), psychologist, occupational therapist (OT) and/or speech and language therapist (SLT). Previous diagnosis of tuberculosis (TB), lower respiratory tract infections (LRTI) and low pre-combination ART (cART) CD4% were found to be associated factors in the presence of developmental disability and/or delay. Conclusion The prevalence of children with HIV and disability is high and these children are not being referred to and/or accessing the appropriate support services. Government policy and clinic practice need to shift their focus of management of children living with HIV, in order to integrate services that can assist children reach their developmental potential and improve their quality-of-life.