Doctoral Degrees (Paediatrics and Child Health)
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Browsing Doctoral Degrees (Paediatrics and Child Health) by browse.metadata.advisor "Gie, R. P."
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- ItemBronchoscopic assessment and management of children presenting with clinically significant airway obstruction due to tuberculosis(Stellenbosch : Stellenbosch University, 2015-04) Goussard, Pierre; Gie, R. P.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health.ENGLISH ABSTRACT: Tuberculosis (TB) in children is a common infectious disease in the world affecting approximately 550 000 children annually and contributing to approximately 10-15% of the TB caseload. The estimate is that 75% of the children who have TB live in the 22 countries that have the highest burden of TB disease. In these 22 countries, the technology required to make the diagnosis and manage complicated cases is limited. The epidemiological data required to estimate the proportion of children with severe disease requiring intervention at a global level are lacking. Airway involvement is commonly seen in children with primary TB, but only in a small group of children the compression is severe, needing intervention. The incidence of children with airway obstruction requiring intervention due to primary TB in the chemotherapeutic era is not known. The incidence of complicated lymph node disease in two recent reports varied from 8-38% in children younger than 15 years of age. Flexible bronchoscopy (FB) is an invasive procedure performed under general anesthetic is used to assess the airways of children. Few studies have been published on the use of FB in the diagnosis of paediatric TB and most have concentrated on the use of bronchoscopy as an intervention for obtaining samples to diagnose pulmonary TB (PTB). All previous studies only examined broncho-alveolar lavage (BAL) for Ziehl Neelsen (ZN) positive organisms and mycobacterial culture. All the published studies are from developed countries with a very low incidence of PTB in children. It has been postulated that HIV positive children with TB are more likely to have airway obstruction, but this hypothesis has not been studied. The same is true for children infected with drug-resistant strains of tuberculosis. Similarly, there have been few reports on the correlation between the findings at bronchoscopy and those found on chest computer tomography (CT). The aim of this research project was to systematically determine airways involvement in childhood pulmonary TB and assess the role paediatric bronchoscopy plays in the diagnosis, sample collection and the management of severe airway obstruction. The first part of the thesis describes the bronchoscopic assessment of airway obstruction due to pulmonary TB in children, specifically concentrating on the areas of the airway involved and the severity of the obstruction. We investigated which factors determine the severity of airway obstruction and this included age, sex, HIV status and drug sensitivities. We have shown that there was no difference in airway obstruction in HIV positive children and in children with drug resistance TB. More severe airway obstruction was seen in the younger child. The second question that was analysed is the value of flexible bronchoscopy in collecting samples for TB culture and drug sensitivity testing. It has previously been reported that BAL culture was inferior to gastric lavage in isolating the bacilli. We set out to evaluate which factors determine if a child will be culture-positive on BAL. Most childhood pulmonary TB is postulated to have a low yield of ZN positive cases. We found a higher yield from BAL as was previously reported, and the yield was increased if segmental or lobar pneumonia was present on the chest radiography. We developed novel interventions of finding the organism and increasing the yield from BAL. About 80% of children with PTB have enlarged subcarinal lymph nodes. We performed a trans-bronchial needle aspiration (TBNA) biopsy of these lymph nodes for culture. This technique enables us to differentiate the cause of enlarged mediastinal lymph nodes. This is especially important in children who are HIV positive, as they are prone to have other causes of enlarged lymph nodes. We successfully performed TBNA, even in very young infants, which resulted in a diagnostic yield of 55%. The use of Xpert has been described on other tissue, but not on BAL. We wanted to test if the use of Xpert on BAL is feasible in children, and determine if it will increase the diagnostic yield by using BAL samples. The third aspect of this research was to compare flexible bronchoscopy findings with those of chest CT scan finding. Firstly, the aim was to describe the CT scan findings of mediastinal glands and lungs in children with significant airway obstruction due to PTB. The second aim was to investigate how these two investigations of airway obstruction compared, with particular emphasis on their advantages and disadvantages. The areas of airway obstruction as well as the severity of the obstruction as determined by CT scan were very similar to the findings with bronchoscopy. The final part under this aspect of the study was to analyze airway shape using a computer model to asses if this could predict TB. This was done by extracting components of the airway surface mesh and branch radius and orientation features. This method showed the potential of computer-assisted detection of TB and other airway pathology by using airway shape deformation analysis. The fourth aspect investigated was to determine which children with severe airway obstruction would benefit from a surgical intervention. Surgical enucleation is done via a lateral thoracotomy in children with severe airway obstruction. We investigated which factors determine the need for surgical enucleation, the optimal timing of this intervention, and – if surgical enucleation was done as an emergency intervention – which factors would predict for this. The combination of trachea, left main bronchus and bronchus intermedius involvement was the best predictor for children requiring surgical enucleation. Involvement of the smaller airway divisions did not play a significant role. Children needing enucleation were younger and had more severe airway obstruction. The fifth aspect of this thesis was to measure the outcome following surgical enucleation. Measurements used included clinical measurements, radiological measurements and bronchoscopy. The response in children treated surgically were compared to those treated medically by estimating airway size with flexible bronchoscopy. Both groups showed significant improvement with the magnitude of improvement greater in those surgically treated. We have demonstrated in this thesis that the site and severity of severe airway obstruction can be assessed by either bronchoscopy or chest CT scan. Approximately one third of children with severe airway compression due to TB lymph nodes can be successfully treated surgically with a low morbidity and mortality.
- ItemChildhood intra-thoracic tuberculosis : addressing the diagnostic dilemma(Stellenbosch : University of Stellenbosch, 2006-04) Marais, Barend Jacobus; Beyers, Nulda; Gie, R. P.; University of Stellenbosch. Faculty of Health Sciences. Dept. of Paediatrics and Child Health.ENGLISH ABSTRACT: Children contribute little to disease transmission and the maintenance of the tuberculosis epidemic, but they constitute a significant proportion of the total tuberculosis (TB) caseload and experience considerable morbidity and mortality in endemic areas, despite the availability of cheap and effective treatment. The difficulty of diagnosing childhood tuberculosis is one of the major obstacles that hinder the provision of antituberculosis treatment to children in endemic areas. The diagnosis of childhood tuberculosis is complicated by the lack of a practical gold standard, as bacteriologic specimens are difficult to collect and the yield is low. In non-endemic countries the diagnosis of childhood tuberculosis is based on the triad of: 1) exposure to an adult index case, 2) a positive tuberculin skin test, and 3) suggestive radiographic signs. However, the triad has limited value in endemic areas where exposure to and/or infection with Mycobacterium tuberculosis is common, and chest radiography is rarely available. The objective of this dissertation was to address the diagnostic dilemma faced by health professionals in endemic areas with limited resources, where children currently have poor access to chemoprophylaxis and antituberculosis treatment. We first clarified basic disease concepts, through a critical review of the pre-chemotherapy literature that documented the natural history of childhood tuberculosis. Three central concepts were identified; 1) the importance of accurate case definition, 2) the relevance of risk stratification, and 3) the diverse spectrum of disease, which necessitates accurate disease classification. The importance of accurate case definition is illustrated by the fact that isolated hilar adenopathy, considered the principal radiographic sign of primary tuberculosis, becomes transiently visible in the majority of children following recent primary infection. Our analysis of the natural history of childhood tuberculosis allowed accurate quantification of the risk to progress to disease following primary infection with M.tuberculosis. This demonstrated that the risk depends mainly on the age and/or immune-status of the child, the time since primary infection occurred and the presence or absence of symptoms. After analysing these historic studies, we proceeded to document the burden of childhood tuberculosis in an endemic area. We first conducted a retrospective study to describe current diagnostic practices and demonstrated almost exclusive reliance on chest radiography. We then calculated the burden of childhood tuberculosis in a prospective descriptive study. The corrected tuberculosis incidence rate in children was 407/100 000/year and children with severe forms of disease, such as disseminated (miliary) tuberculosis and/or tuberculous meningitis, were rarely recorded in the TB treatment register used for routine community-based surveillance. An additional obstacle to progress in the field of childhood tuberculosis has been the lack of standard descriptive terminology. Following a careful review of the literature, we proposed a radiological classification of childhood intra-thoracic tuberculosis and explored the different pathologic mechanisms that underlie these diverse disease manifestations. We then conducted a prospective descriptive study to document the disease spectrum in children treated for tuberculosis in an endemic area. The disease patterns observed were consistent with those described in the pre-chemotherapy literature. In addition, we demonstrated that bacteriologic confirmation may be achieved in the majority of children with intra-thoracic tuberculosis, in highly endemic settings. Finally we developed a novel symptom-based approach to diagnose pulmonary tuberculosis in children from endemic areas with limited resources. We followed a step-wise approach by first conducting a community-based survey to document the prevalence of symptoms traditionally associated with tuberculosis in a random selection of children from an endemic area. The survey demonstrated that poorly defined symptoms offer poor diagnostic value. The second step was to evaluate the diagnostic value of well-defined (persistent, non-remitting) symptoms in a small prospective study. Well-defined symptoms demonstrated good diagnostic value, but these promising results required further validation. As a final step, we validated the diagnostic value of a novel symptom-based approach in a large prospective, community-based study. In this study, a simple symptom-based approach diagnosed childhood pulmonary tuberculosis with a remarkable degree of accuracy, particularly in HIV-uninfected children older than 3 years of age. This novel diagnostic approach offers the exciting prospect of extending antituberculosis treatment to children in endemic areas with limited resources, where current treatment access is poor.