Michelle Wong

Early treatment outcomes and HIV status of patients with extensively drug-resistant tuberculosis in South Africa: a retrospective cohort study

BACKGROUNDnData from Kwazulu Natal, South Africa, suggest that almost all patients with extensively drug-resistant (XDR) tuberculosis are HIV-positive, with a fatal outcome. Since, there are few data for the treatment-related outcomes of XDR tuberculosis in settings with a high HIV prevalence, we investigated the associations of these diseases in such settings to formulate recommendations for control programmes.nnnMETHODSnIn a retrospective cohort study, we analysed the case records of patients (>16 years old) with XDR tuberculosis (culture-proven at diagnosis) between August, 2002, and February, 2008, at four designated provincial treatment facilities in South Africa. We used Cox proportional hazards regression models to assess risk factors associated with the outcomes-mortality and culture conversion.nnnFINDINGSn195 of 227 patients were analysed. 21 died before initiation of any treatment, and 174 patients (82 with HIV infection) were treated. 62 (36%) of these patients died during follow-up. The number of deaths was not significantly different in patients with or without HIV infection: 34 (41%) of 82 versus 28 (30%) of 92 (p=0.13). Treatment with moxifloxacin (hazard ratio 0.11, 95% CI 0.01-0.82; p=0.03), previous culture-proven multidrug-resistant tuberculosis (5.21, 1.93-14.1; p=0.001), and number of drugs used in a regimen (0.59, 0.45-0.78, p<0.0001) were independent predictors of death. Fewer deaths occurred in patients with HIV infection given highly active antiretroviral therapy than in those who were not (0.38, 0.18-0.80; p=0.01). 33 (19%) of 174 patients showed culture conversion, of which 23 (70%) converted within 6 months of initiation of treatment.nnnINTERPRETATIONnIn South Africa, patients with XDR tuberculosis, a substantial proportion of whom are not infected with HIV, have poor management outcomes. Nevertheless, survival in patients with HIV infection is better than previously reported. The priorities for the country are still prevention of XDR tuberculosis, and early detection and management of multidrug-resistant and XDR tuberculosis through strengthened programmes and laboratory capacity.nnnFUNDINGnSouth African Medical Research Council, European Union Framework 7 program, and European Developing Countries Clinical Trials Partnership.

Missed opportunities in TB diagnosis: a TB Process-Based Performance Review tool to evaluate and improve clinical care

BackgroundTraditional tuberculosis (TB) treatment outcome measures, such as cure rate, do not provide insight into the underlying reasons for missing clinical targets. We evaluated a TB Process-Based Performance Review (TB-PBPR) tool, developed to identify missed opportunities for timely and accurate diagnosis of TB. The tool enables performance assessment at the level of process and quality of care.MethodsThe TB-PBPR tool is a single-page structured flow-sheet that identifies 14 clinical actions (grouped into elicited symptoms, clinical examination and investigations). Medical records from selected deceased patients were reviewed at two South African mine hospitals (A = 56 cases; B = 26 cases), a South African teaching hospital (C = 20 cases) and a UK teaching hospital (D = 13 cases).ResultsIn hospital A, where autopsy was routine, TB was missed in life in 52% (23/44) of cases and was wrongly attributed as the cause of death in 16% (18/110). Clinical omissions were identified at each hospital and at every stage of clinical management. For example, recording of chest symptoms was omitted in up to 39% of cases, sputum smear examination in up to 85% and chest radiograph in up to 38% of cases respectively.ConclusionsThis study introduces the TB-PBPR tool as a novel method to review and evaluate clinical performance in TB management. We found that simple clinical actions were omitted in many cases. The tool, in conjunction with a manual describing best practice, is adaptable to a range of settings, is educational and enables detailed feedback within a TB programme. The TB-PBPR tool and manual are both freely available for general use.

Prevalence of DHPS polymorphisms associated with sulfa resistance in South African Pneumocystis jirovecii strains.

IT is estimated that 5–6 million South Africans, including some of the growing number of AIDS orphans (over one million to date), are at risk for developing Pneumocystis pneumonia (PcP) at some point in their lives, especially as the availability of highly active antiretroviral therapy (HAART) is limited (UNAIDS/ UNICEF/USAID 2004). The prevalence of HIV among prenatal clinic attendees in South Africa has risen dramatically from 0.7% in 1990 to 30.2% in 2005 (Table 1; Department of Health 2006). Pneumocystis jirovecii was the most common pathogen isolated from HIV-infected children hospitalized for pneumonia during a study at Chris Hani Baragwanath Hospital (Madhi et al. 2003). This hospital is one of the largest in the world with 2,700 beds (maximum 3,200) in current use and serves an estimated population of four million people. Trimethoprim-sulfamethoxazole (TMP-SMX) is the drug of choice for treatment and prophylaxis of PcP. An increased rate of point mutations at amino acid residues 55 (M1) and 57 (M2) in the P. jirovecii dihydropteroate synthase (DHPS) gene have been linked to sulfa prophylaxis (Helweg-Larsen et al. 1999; Huang et al. 2000; Kazanjian et al. 2000; Ma, Borio, and Masur 1999; Nahimana et al. 2003; Zingale et al. 2003). Dihydropteroate synthase mutations have been shown to confer resistance to sulfa compounds in some bacteria and protozoan parasites (Brooks et al. 1994; Dallas et al. 1992). The general aims of this project are to (1) estimate the burden of P. jirovecii infections in South African adults and children, (2) increase awareness of PcP in Africa, and (3) assess the prevalence of DHPS mutations in a South African P. jirovecii population as part of this clinical study. An initial pilot study was conducted to determine the rate of DHPS mutations in P. jirovecii strains circulating in the population. The majority of specimens were from HIV-positive adults in the Gauteng province. Specimen types included sputum, bronchial washings, and bronchoalveolar lavage. Strains detected in routine diagnostic respiratory specimens were screened for the presence of M1 and M2 DHPS polymorphisms. In the current prospective clinical study we are investigating the prevalence of P. jirovecii DHPS mutations in patients with PcP and its correlation with sulfa prophylaxis and clinical outcome. MATERIALS AND METHODS

Recommendations for the management of idiopathic pulmonary fibrosis in South Africa: a position statement of the South African Thoracic Society

Idiopathic pulmonary fibrosis (IPF) is a very specific form of a chronic, progressive fibroproliferative interstitial pneumonia of unknown aetiology. The disease is generally associated with a poor prognosis. Several international evidence-based guidelines on the diagnosis and management of IPF and other interstitial lung diseases (ILDs) have been published and updated in the last decade, and while the body of evidence for the use of some treatment modalities has grown, others have been shown to be futile and even harmful to patients. In a patient who presents with the classic clinical features, restrictive ventilatory impairment with impaired diffusion and a high resolution computed tomography (HRCT) scan of the lungs showing a usual interstitial pneumonia (UIP) pattern, a definitive diagnosis of IPF can be made, provided all other causes of a radiological UIP pattern are excluded. Patients who present with atypical clinical features or an HRCT pattern classified as possible UIP, should be referred for a surgical lung biopsy. Once the diagnosis of IPF is confirmed, a patient-centred approached should be followed, as the stage of the disease, degree of impairment, rate of disease progression, comorbid illnesses and patient preferences all impact on long-term management. The South African Thoracic Society (SATS) suggests that anti-fibrotic treatment should be offered to appropriate candidates [confirmed IPF with a forced vital capacity (FVC) of 50-80%], but discontinued should there be evidence of disease progression (a decline in FVC of ≥10% within any 12-month period). The routine use of high dose oral steroids, immunosuppressive drugs and anticoagulants is not recommended whilst anti-acid therapy may be considered in patients without advanced disease.

Radial Endobronchial Ultrasound Greyscale Texture Analysis Using Whole-Lesion Analysis Can Characterise Benign and Malignant Lesions without Region-of-Interest Selection Bias

Background: Radial-probe endobronchial ultrasound (RP-EBUS) is predominantly used clinically for the localisation of peripheral pulmonary lesions prior to biopsy. However, the RP-EBUS image itself contains information that can characterise the aetiology of lesions. Objectives: The aim of this study was to show the utility of RP-EBUS image analysis using unconstrained regions of interest (ROIs) that utilise more image information and eliminate ROI selection bias. Methods: We developed custom software to analyse RP-EBUS images digitally captured during clinical procedures. Unconstrained ROIs were mapped onto lesions. We computed first-order greyscale image statistics of minimum, maximum, mean, standard deviation and range of pixel intensities, and entropy. We also computed second-order greyscale texture features of contrast, correlation, energy and homogeneity. The results of image analysis were compared to gold-standard tissue diagnosis. Features from expert- and non-expert-defined ROIs were also compared. Results: Eighty-five images were analysed (38 benign and 47 malignant). Five greyscale features were significantly different between benign and malignant lesions. Benign lesions had higher mean (p < 0.01) and maximal (p < 0.001) intensity, greater range (p < 0.001) of pixel intensities and greater entropy (p < 0.01). The highest positive predictive values were associated with maximal (87.8%) and range of pixel (83.8%) intensities. There were no significant differences between expert- and non-expert-defined ROIs. Conclusion: RP-EBUS image analysis using unconstrained ROIs eliminates ROI selection bias and can characterise benign and malignant lesions with an accuracy of up to 85%.

Accuracy of rapid on-site evaluation of endobronchial ultrasound guided transbronchial needle aspirates by respiratory registrars in training and medical scientists compared to specialist pathologists—an initial pilot study

BackgroundnRapid on-site evaluation (ROSE) of endobronchial ultrasound guided transbronchial needle aspirates (EBUS-TBNA) increases diagnostic accuracy but in many institutions requires a specialist pathologist. This study aimed to determine if medical scientists or respiratory registrars could adequately perform ROSE to determine sufficiency of EBUS samples.nnnMethodsnROSE was performed on the first two EBUS-TBNA passes per patient by a pathologist, a medical scientist and two respiratory registrars. The medical scientists involved had all previously performed ROSE on over 50 procedures. The two respiratory registrars received cytology education from a pathologist in four separate hour-long training sessions. Each ROSE reviewer recorded whether each sample was sufficient or insufficient. Pathologist interpretation was taken as gold standard. Specific diagnosis was not required. Final diagnosis and the total number of passes were also recorded. This study recruited 25 patients (50 passes) for statistical evaluation.nnnResultsnAssessment by specialist pathologists deemed 16/50 (32%) to be sufficient and 34/50 (68%) insufficient respectively. Medical scientists were 90% concordant with the pathologist (K =0.774; 95% CI, 0.587-0.961). The two respiratory registrars were 78% (K =0.568; 95% CI, 0.338-0.798) and 72% (K =0.448; 95% CI, 0.222-0.674) concordant, respectively. The mean number of passes per patient was 4.9 (range, 3-7). A diagnosis was established in 21/25 (82%) patients from the first EBUS-TBNA procedures with the remaining four patients requiring a further procedure or monitoring with serial CT scans to establish the diagnosis. Malignancy was found in 14/25 (56%) patients and a benign process in 11/25 (44%) patients.nnnConclusionsnMedical scientist review of ROSE samples is not significantly different to a specialist pathologist and is an acceptable alternative. Respiratory registrars are not a realistic alternative for ROSE without more intensive training, which may be difficult to facilitate in addition to existing respiratory training commitments.

Rheumatic disease mimicking an infiltrative mass of the mitral valve

A 32-year-old man previously was diagnosed with sarcoidosis on the basis of bilateral lung infiltrates, hypercalcaemia, multiple renal calculi and an elevated serum angiotensin-converting enzyme level, all of which improved on corticosteroids. Nine months later he developed symptomatic, sputum-positive pulmonary tuberculosis and tuberculous lymphadenitis, which were successfully treated.nnAt his initial presentation, …

Multiple bilateral intraparenchymal pulmonary artery aneurysms.

A 41-year-old male with cough and subtle chest radiograph opacities demonstrated bilateral intraparenchymal pulmonary artery aneurysms on computed tomography (Figs 1 and 2). Causes include congenital cardiac defects, pulmonary arterial hypertension and infection. The patient had been treated during childhood for Staphylococcal pneumonia prior to ventricular septal defect closure. He declined further investigation.