Bradykinin-evoked sensitization of airway sensory nerves: a mechanism for ACE-inhibitor cough.

Cough accompanied by an increased sensitivity of the cough reflex is the most common symptom of inflammatory airway disease. This symptom is also frequently reported in patients receiving angiotensin-converting enzyme (ACE) inhibitors as therapy for heart failure or hypertension, although the underlying mechanism is unknown. We have investigated the possibility that the inflammatory peptide bradykinin, normally degraded by ACE, causes sensitization of airway sensory nerves and an enhancement of the cough reflex in conscious guinea pigs. Treatment of guinea pigs for two weeks with captopril led to an increased cough response to inhaled citric acid, which was prevented by concomitant treatment with the bradykinin receptor antagonist icatibant. A similar icatibant-sensitive enhancement of citric acid-evoked cough was seen in untreated animals after prior inhalation of bradykinin, although cough evoked by hypertonic saline was unaffected. In electrophysiological studies performed in vitro, responses of single vagal C fibers to capsaicin, applied to receptive fields of single-fiber units in the trachea, were also markedly increased after perfusion with bradykinin, whereas A delta fiber responses to hypertonic saline were unaffected. These results indicate that bradykinin-evoked sensitization of airway sensory nerves may underlie the pathogenesis of ACE-inhibitor cough. Bradykinin receptor antagonists may be of benefit in treating chronic cough seen with this and other inflammatory conditions.

Guidelines for the management of asthma in adults and adolescents: Position statement of the South African Thoracic Society - 2021 update.

Asthma prevalence is increasing worldwide, and surveys indicate that most patients in developed and developing countries, including South Africa, do not receive optimal care and are therefore not well controlled. Standard management guidelines adapted to in-country realities are important to support optimal care. The South African Thoracic Society (SATS) first published a guideline for the management of chronic persistent asthma in 1992, which has subsequently been revised several times. The main aim of the present document was to revise and update SATS' statement on the suggested management of chronic asthma, based on the need to promote optimal care and control of asthma, together with the incorporation of new concepts and drug developments. This revised document reinforces optimal care and incorporates the following primary objectives to achieve the recent advances in asthma care: continued emphasis on the use of inhaled corticosteroids (ICS) as the foundation of asthma treatmentto reduce the reliance on short-acting beta-2 agonist (SABA) monotherapy for asthma symptomsto incorporate the evidence and strategy for the use of the combination of an ICS and formoterol for acute symptom relief (instead of a SABA)to incorporate the evidence and strategy for the use of as-needed ICS-long-acting beta agonists (LABA) for patients with infrequent symptoms or 'mild' asthmato incorporate the evidence and strategy for the use of a long-acting muscarinic antagonist (LAMA) in combination with ICS-LABA; andto incorporate the evidence and strategy for the use of and management with a biologic therapy in severe asthma.

A position statement and practical guide to the use of particulate filtering facepiece respirators (N95, FFP2, or equivalent) for South African health workers exposed to respiratory pathogens including Mycobacterium tuberculosis and SARS-CoV-2.

SUMMARY: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is transmitted mainly by aerosol in particles <10 µm that can remain suspended for hours before being inhaled. Because particulate filtering facepiece respirators ('respirators'; e.g. N95 masks) are more effective than surgical masks against bio-aerosols, many international organisations now recommend that health workers (HWs) wear a respirator when caring for individuals who may have COVID-19. In South Africa (SA), however, surgical masks are still recommended for the routine care of individuals with possible or confirmed COVID-19, with respirators reserved for so-called aerosol-generating procedures. In contrast, SA guidelines do recommend respirators for routine care of individuals with possible or confirmed tuberculosis (TB), which is also transmitted via aerosol. In health facilities in SA, distinguishing between TB and COVID-19 is challenging without examination and investigation, both of which may expose HWs to potentially infectious individuals. Symptom-based triage has limited utility in defining risk. Indeed, significant proportions of individuals with COVID-19 and/or pulmonary TB may not have symptoms and/or test negative. The prevalence of undiagnosed respiratory disease is therefore likely significant in many general clinical areas (e.g. waiting areas). Moreover, a proportion of HWs are HIV-positive and are at increased risk of severe COVID-19 and death. RECOMMENDATIONS: Sustained improvements in infection prevention and control (IPC) require reorganisation of systems to prioritise HW and patient safety. While this will take time, it is unacceptable to leave HWs exposed until such changes are made. We propose that the SA health system adopts a target of 'zero harm', aiming to eliminate transmission of respiratory pathogens to all individuals in every healthcare setting. Accordingly, we recommend: the use of respirators by all staff (clinical and non-clinical) during activities that involve contact or sharing air in indoor spaces with individuals who: (i) have not yet been clinically evaluated; or (ii) are thought or known to have TB and/or COVID-19 or other potentially harmful respiratory infections;the use of respirators that meet national and international manufacturing standards;evaluation of all respirators, at the least, by qualitative fit testing; andthe use of respirators as part of a 'package of care' in line with international IPC recommendations. We recognise that this will be challenging, not least due to global and national shortages of personal protective equipment (PPE). SA national policy around respiratory protective equipment enables a robust framework for manufacture and quality control and has been supported by local manufacturers and the Department of Trade, Industry and Competition. Respirator manufacturers should explore adaptations to improve comfort and reduce barriers to communication. Structural changes are needed urgently to improve the safety of health facilities: persistent advocacy and research around potential systems change remain essential.

A partially randomised trial of pretomanid, moxifloxacin and pyrazinamide for pulmonary TB.

BACKGROUND: Treatment for TB is lengthy and toxic, and new regimens are needed.METHODS: Participants with pulmonary drug-susceptible TB (DS-TB) were randomised to receive: 200 mg pretomanid (Pa, PMD) daily, 400 mg moxifloxacin (M) and 1500 mg pyrazinamide (Z) for 6 months (6Pa200MZ) or 4 months (4Pa200MZ); 100 mg pretomanid daily for 4 months in the same combination (4Pa100MZ); or standard DS-TB treatment for 6 months. The primary outcome was treatment failure or relapse at 12 months post-randomisation. The non-inferiority margin for between-group differences was 12.0%. Recruitment was paused following three deaths and not resumed.RESULTS: Respectively 4/47 (8.5%), 11/57 (19.3%), 14/52 (26.9%) and 1/53 (1.9%) DS-TB outcomes were unfavourable in patients on 6Pa200MZ, 4Pa200MZ, 4Pa100MZ and controls. There was a 6.6% (95% CI -2.2% to 15.4%) difference per protocol and 9.9% (95%CI -4.1% to 23.9%) modified intention-to-treat difference in unfavourable responses between the control and 6Pa200MZ arms. Grade 3+ adverse events affected 68/203 (33.5%) receiving experimental regimens, and 19/68 (27.9%) on control. Ten of 203 (4.9%) participants on experimental arms and 2/68 (2.9%) controls died.CONCLUSION: PaMZ regimens did not achieve non-inferiority in this under-powered trial. An ongoing evaluation of PMD remains a priority.

South African Thoracic Society statement on obstructive airways disease and COVID-19.

Asthmatics do not appear to have increased susceptibility to COVID-19.Uncontrolled severe asthma may be associated with worsened COVID-19 outcomes, especially in asthmatics managed with oral corticosteroids. Risk mitigation measures such as hand hygiene, social distancing and wearing of face masks must be observed at all times. Asthma should be managed as outlined in local and international guidelines.Ensure an adequate supply of medication, and inhaled corticosteroids should not be withdrawnChronic obstructive pulmonary disease (COPD) is associated with severe COVID-19 disease and poor outcomes. Maintenance of background medication is important to avoid exacerbations of COPD.Vaccination against influenza is strongly advised for all patients with asthma and COPDVaccination against pneumococcal infection is advisable for patients with COPD. Patients with obstructive airway disease on oral corticosteroids and/or with impaired lung function should take stringent safety precautions. This statement will be updated when more data become available Asthma and COPD occur commonly in South Africa. SARS-CoV-2 is a novel coronavirus, which can result in COVID-19-associated severe respiratory infection with respiratory failure and the need for mechanical ventilation. The South African Thoracic Society has prepared a guidance statement to assist clinicians and patients with asthma and COPD during the current epidemic.

TB presenting as community-acquired pneumonia in a setting of high TB incidence and high HIV prevalence.

SETTING: Sub-Saharan Africa has the highest prevalence of human immunodeficiency virus (HIV)/acquired immune-deficiency syndrome (AIDS) and a high incidence of tuberculosis (TB). OBJECTIVES: To determine the aetiology of and mortality due to community-acquired pneumonia (CAP) in HIV and non-HIV-infected adults. METHODS: Consecutive patients with CAP admitted to a teaching hospital in KwaZulu-Natal over a 17-month period were studied prospectively. Systematic investigation of samples of sputum and blood cultures was performed. A subset of patients had urine antigen tests and serum serology. RESULTS: A total of 430 patients with a mean age of 33 years (range 18-82) were enrolled. Of the 382 patients tested, 311 (81.4%) were HIV-infected. Pathogens were isolated in 222 patients (52%). The most common organisms were Mycobacterium tuberculosis (39.6%) and Streptococcus pneumoniae (34.5%). M. tuberculosis was the most common agent in both HIV and non-HIV-infected subjects (40% and 35%, respectively). In-hospital mortality was 17% overall, 15.9% in the HIV-infected, 25% in the non-HIV-infected and 38% in patients with polymicrobial infections. CONCLUSIONS: M. tuberculosis was the leading cause of CAP and reflects the worsening TB epidemic in the region. Aggressive intervention is required to address both the HIV and TB epidemics in sub-Saharan Africa.

Management of chronic asthma in adults in diverse regions of the world.

Asthma is a chronic inflammatory disease of the lungs associated with significant morbidity and mortality worldwide. Adoption of current treatment guidelines that propose inhaled corticosteroids (ICS) as the foundation for asthma treatment should control most patients with chronic asthma. Rapid-acting inhaled beta (beta) 2-agonists are best reserved for acute symptom relief. Long-acting beta-2-agonists in combination with ICS are the most effective asthma treatment currently available when asthma is not controlled on low-dose ICS alone; however, they are not universally available due to cost. Slow-release theophylline may be an alternative cost-effective add-on therapy to ICS in resource-poor areas, although its potential for toxicity has limited its use over the last decade. New targeted anti-inflammatory therapies lack the broad anti-inflammatory activity of ICS and are unaffordable in most settings. Implementation of guidelines for asthma care is an unresolved challenge, and major gaps in asthma care are consistent across the globe. Review of asthma management worldwide shows that control of the disease in relation to the Global Initiative for Asthma (GINA) goals of asthma treatment is not achieved in a large proportion of patients, despite the widespread availability of guidelines and even with access to effective treatment in resource-rich settings. Many resource-poor countries have the additional challenge of lack of access to basic asthma treatment such as ICS. The challenge is to provide global access to core asthma medications, particularly ICS, at affordable prices, to improve implementation of treatment guidelines and to encourage better health care provider and patient education.

Serum procalcitonin distinguishes CAP due to bacteria, Mycobacterium tuberculosis and PJP.

SETTING: Procalcitonin (PCT), a propeptide of the hormone calcitonin, is a novel marker of the inflammatory response to infection. It has been used to discriminate between infectious and non-infectious causes of inflammation, and as a marker of severe sepsis in the intensive care unit. OBJECTIVE: To evaluate the utility of PCT in distinguishing community-acquired pneumonia (CAP) due to common bacteria, Mycobacterium tuberculosis and Pneumocystis jirovecii in a high human immunodeficiency virus (HIV) prevalence setting. METHODS: Two hundred and sixty-six patients admitted with a diagnosis of CAP were investigated. Serum samples for PCT were collected on admission. PCT levels were measured using a commercial immunoluminometric assay. RESULTS: A microbiological diagnosis was obtained in 169/266 patients: 44 pulmonary tuberculosis (PTB), 31 P. jirovecii pneumonia (PJP), and 35 bacterial pneumonia. The PCT levels were PTB 4.16 ng/ml (SEM 1.197; 95% CI 1.749-6.579); PJP 1.138 ng/ml (SEM 0.2911; 95% CI 0.543-1.734); and bacterial pneumonia 19.48 ng/ml (SEM 5.64; 95% CI 8.021-30.938, P < 0.0004). Thirty-six had co-infections. CONCLUSION: PCT levels differ significantly in patients with CAP due to TB, PJP and bacteria. PCT may be important in distinguishing M. tuberculosis and PJP in a high HIV prevalence setting where atypical presentations often confound the empirical clinical diagnosis.

Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study.

BACKGROUND: The 2NN Study was a randomised comparison of the non-nucleoside reverse-transcriptase inhibitors (NNRTI) nevirapine and efavirenz. METHODS: In this multicentre, open-label, randomised trial, 1216 antiretroviral-therapy-naive patients were assigned nevirapine 400 mg once daily, nevirapine 200 mg twice daily, efavirenz 600 mg once daily, or nevirapine (400 mg) and efavirenz (800 mg) once daily, plus stavudine and lamivudine, for 48 weeks. The primary endpoint was the proportion of patients with treatment failure (less than 1 log(10) decline in plasma HIV-1 RNA in the first 12 weeks or two consecutive measurements of more than 50 copies per mL from week 24 onwards, disease progression [new Centers for Disease Control and Prevention grade C event or death], or change of allocated treatment). Analyses were by intention to treat. FINDINGS: Treatment failure occurred in 96 (43.6%) of 220 patients assigned nevirapine once daily, 169 (43.7%) of 387 assigned nevirapine twice daily, 151 (37.8%) of 400 assigned efavirenz, and 111 (53.1%) of 209 assigned nevirapine plus efavirenz. The difference between nevirapine twice daily and efavirenz was 5.9% (95% CI -0.9 to 12.8). There were no significant differences among the study groups in the proportions with plasma HIV-1 RNA concentrations below 50 copies per mL at week 48 (p=0.193) or the increases in CD4-positive cells (p=0.800). Nevirapine plus efavirenz was associated with the highest frequency of clinical adverse events, and nevirapine once daily with significantly more hepatobiliary laboratory toxicities than efavirenz. Of 25 observed deaths, two were attributed to nevirapine. INTERPRETATION: Antiretroviral therapy with nevirapine or efavirenz showed similar efficacy, so triple-drug regimens with either NNRTI are valid for first-line treatment. There are, however, differences in safety profiles. Combination of nevirapine and efavirenz did not improve efficacy but caused more adverse events.

Management of pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is a potentially lethal disease mainly affecting young females. Although the precise mechanism of PAH is unknown, the past decade has seen the advent of many new classes of drugs with improvement in the overall prognosis of the disease. Unfortunately the therapeutic options for PAH in South Africa are severely limited. The Working Group on PAH is a joint effort by the South African Heart Association and the South African Thoracic Society tasked with improving the recognition and management of patients with PAH. This article provides a brief summary of the disease and the recommendations of the first meeting of the Working Group.

Exhaled nitric oxide is elevated in patients with progressive systemic sclerosis without interstitial lung disease.

BACKGROUND: Progressive systemic sclerosis (PSS) is a multisystem disorder of unknown etiology. Interstitial lung disease (ILD) is a major cause of mortality in this condition, and a major challenge in this regard is to identify parameters that would predict the onset or progression of ILD in patients with PSS. Abnormal cellularity of BAL fluid (BALF) has been demonstrated in patients with PSS without ILD. STUDY OBJECTIVES: We investigated exhaled nitric oxide (NO) as a noninvasive marker of pulmonary inflammation in patients with PSS with and without clinical and radiologic evidence of ILD. This was compared with the cellularity of BALF. Our hypothesis was that exhaled NO was elevated in patients with PSS without ILD who had abnormal BALF cellularity. SETTING: Pulmonology and rheumatology units of a university-based, tertiary referral hospital in Durban, South AFRICA: STUDY METHODS: Exhaled NO was measured using a chemiluminescence analyzer in 12 patients with PSS and ILD and in 12 patients without clinical or radiologic evidence of ILD and in 30 healthy control subjects. BAL was performed in patients with PSS with and without the presence of ILD and in six healthy control subjects. RESULTS: Subclinical inflammation was confirmed by increased inflammatory cell counts in BALF from patients with PSS without ILD. Exhaled NO (mean [SEM]) was elevated in patients with PSS without ILD at 9.6 (0.7) parts per billion (ppb) compared to patients with PSS and ILD at 6.2 (0.6) ppb (p < 0.001) and healthy control subjects at 6.3 (0.2) ppb (p < 0.001). CONCLUSION: Exhaled NO may therefore be an important noninvasive surrogate marker of inflammation in patients with PSS without ILD.

Capsazepine inhibits cough induced by capsaicin and citric acid but not by hypertonic saline in guinea pigs.

Acidic solutions mimick many of the effects of capsaicin (Cap), including pain, bronchoconstriction, cough, and sensory neuropeptide release. Evidence from the use of the Cap antagonist capsazepine suggests that in some cases protons act at the Cap receptor. In the present study, we have investigated whether cough evoked by Cap and citric acid (CA) is mediated specifically via the Cap receptor on airway sensory nerves. We have examined the effects of capsazepine on Cap-, CA-, and hypertonic saline-induced cough and also on CA-induced nasal irritation in awake guinea pigs. Capsazepine was nebulized for 5 min before cough challenges with Cap for 5 min and CA for 10 min. Control animals were pretreated with vehicle alone. Capsazepine (100 microM) inhibited the cough response to 30 microM Cap from 0.77 +/- 0.14 coughs/min in control animals to 0.23 +/- 0.08 coughs/min (P < 0.05) and to 80 microM Cap from 1.4 +/- 0.23 to 0.3 +/- 0.11 coughs/min (P < 0.01). There was no effect, however, of lower concentrations of capsazepine (5 and 10 microM) against Cap-evoked cough. At a concentration of 100 microM, capsazepine also inhibited the coughing induced by 0.25 M CA from 1.8 +/- 0.26 to 0.93 +/- 0.31 coughs/min (P < 0.05) but not that induced by 0.5 M CA. Nasal irritation induced by 0.25 M CA, but not by 0.5 M CA, was also inhibited by capsazepine from 2.47 +/- 0.37 to 0.75 +/- 0.31 nose wipes/min (P < 0.05). This inhibitory effect of capsazepine did not appear to reflect a nonspecific suppression of the cough reflex, since cough evoked by exposure to hypertonic (7%) saline for 10 min was unaffected by pretreatment with capsazepine (100 microM). These data show that capsazepine is a specific inhibitor of Cap- and CA-induced cough in guinea pigs. Moreover, they suggest that low pH stimuli evoke cough and nasal irritation by an action at the Cap receptor, either directly or through the release of an intermediate agent.

Airway and cough responsiveness and exhaled nitric oxide in non-smoking patients with stable chronic heart failure.

OBJECTIVE: To investigate the airway and cough responsiveness in non-smoking patients with stable chronic heart failure. Cough and wheeze, features associated with hyper-responsive airways, are not uncommon especially in decompensated chronic heart failure. Bronchial hyperresponsiveness has previously been demonstrated in chronic heart failure but this may have been confounded by smoking and acute decompensation. DESIGN: Case-control study. SETTING: Tertiary specialist hospital. PATIENTS AND INTERVENTIONS: Airway responsiveness to methacholine (a direct stimulant of smooth muscle in the airways), sodium metabisulphite (a putative stimulant of airway sensory nerves), and exercise was examined in 10 non-smoking patients with stable chronic heart failure (age 56.5 (3.2) (SEM) years; 7 men; radionuclide left ventricular ejection fraction 20.8 (2.9)%; radiographic cardiothoracic ratio 0.56 (0.02)). Exhaled nitric oxide, a product of the action of proinflammatory cytokines, was also measured to assess the contribution of local inflammation to airway responsiveness. The cough responses to low-concentration chloride solutions and to capsaicin were studied. Because all patients were receiving angiotensin-converting enzyme inhibitors, which may influence airway responsiveness and cough, 8 asymptomatic non-smoking controls taking angiotensin-converting enzyme inhibitors for essential hypertension were also studied (age 54.3 (2.8) years; 6 men; radiographic cardiothoracic ratio 0.46 (0.01)). RESULTS: The mean provocative concentration that induced a 20% decrease in forced expiratory volume in 1 second (FEV1) was 67.6 v 79.8 mg/ml (P = 0.71) for methacholine and 276.7 v 290.4 mg/ml (P = 0.79) for sodium metabisulphite in chronic heart failure patients and controls respectively. The change in FEV1 after maximal cardiopulmonary exercise testing was +1.44% in patients and +2.53% in controls (P = 0.47), indicating that there was no exercise-induced bronchospasm in either group (peak oxygen consumption was 16.9 (1.3) v 26.5 (2.3) ml/kg/min respectively, P < 0.01). Exhaled nitric oxide concentration was not increased in chronic heart failure (12.3 (1.7) v 16.2 (3.3) ppb, P = 0.32). The median cough counts after nebulised 0 mM and 37.5 mM chloride solutions were 2.5 v 1.0 (P = 0.6) and 5.5 v 5.5 (P = 0.5) respectively and the capsaicin concentration causing two or more coughs was 13.5 v 6.5 microM (P = 0.5). CONCLUSION: Airway hyper-responsiveness is not a predominant feature in non-smoking patients with stable chronic heart failure treated with, and tolerant to, angiotensin-converting enzyme inhibitors. It is unlikely to contribute to the exertional dyspnoea seen in these patients.

Symbicort: controlling asthma in adults.

Inhaled corticosteroids reduce airway inflammation and bronchial hyper-responsiveness in asthma. Their regular use is associated with a reduction in morbidity and mortality from asthma. International guidelines recommend their use as first-line treatment in asthma and the dose should be increased stepwise in accordance with asthma severity. Short-acting beta2-agonists are recommended for use as reliever medication for the acute relief of symptoms. Long-acting beta2-agonists have a sustained bronchodilator action but are not recommended for use as monotherapy in asthma, particularly because they lack clinically relevant anti-inflammatory action. The seminal observation in a controlled trial that the addition of salmeterol to low-dose inhaled beclomethasone dipropionate was superior to doubling the dose ofthe beclomethasone dipropionate was followed by several well-controlled studies that confirmed this observation. These included multinational and multicentre trials in large numbers of patients and the use of different inhaled corticosteroids and the two long-acting beta2-agonists, formoterol and salmeterol. Therefore level A evidence (randomized controlled trials with a rich body of evidence) is available for this recommendation. Based on this, updated asthma guidelines recommend the addition of long-acting beta2-agonists for chronic asthma that is at least moderately severe or mild asthmathat is not well controlled with low-dose inhaled corticosteroids. Attention was therefore focused on developing combination inhalers that included inhaled corticosteroids and long-acting beta2-agonists in order to simplify asthma treatment and improve adherence to prescribed medication. Symbicort Turbuhaler (budesonide/formoterol in a single inhaler) is one such development. Studies to date in over 800 adult patients have confirmed that budesonide/formoterol is superior to double the dose of budesonide monotherapy and at least as effective and safe as budesonide and formoterol in separate inhalers, These studies also demonstrate that there are no physico-chemical interactions when the two medications are combined in a single inhaler. Symbicort in its easy to use formulation and inhaler device represents a valuable addition to the pharmacological management of asthma.

Experience with azathioprine in systemic sclerosis associated with interstitial lung disease.

The aim of this study was to evaluate the safety and efficacy of azathioprine in the treatment of interstitial lung disease (ILD) associated with systemic sclerosis (SSc). The records of patients with SSc with ILD who were treated with azathioprine were reviewed. Patients were treated with azathioprine and low-dose prednisone if they had progressive pulmonary symptoms (deterioration in the dyspnea score) or poor or deteriorating lung function. Response was classified as improved if the FVC increased more than 10% from baseline, and stable if it remained within 10% of baseline. Serial dyspnea scores were recorded. Eleven patients were treated with azathioprine, three of whom received treatment for 6 months or less owing to adverse effects (nausea, leukopenia and pulmonary tuberculosis in one patient each). The remaining eight patients received at least 12 months' treatment and the results suggested an improvement in the mean percent predicted FVC from a baseline value of 54.25+/-3.53 to 63.38+/-6.15 after 12 months ( p=0.101). Overall, five patients improved and three remained stable. The mean dyspnea score ( n=8) improved from a baseline of 1.55+/-0.19 to 0.50+/-0.19 at 12 months ( p=0.011). This is the first case series of patients with SSc-associated ILD treated with azathioprine. Our results suggest that azathioprine may have a role in stabilizing lung function and improving symptoms in SSc, although this needs confirmation by a randomized controlled trial.

A critical analysis of ICU/HC beds in South Africa: 2008-2009.

OBJECTIVE: To determine the national distribution of intensive care unit (ICU)/high care (HC) beds and the implications for ICU bed availability in the envisaged national health insurance (NHI) scheme. METHODS: A descriptive, non-interventional, observational study design was used. A desk-top audit of all public and private sector ICUs, including ICU/HC beds, in South Africa was undertaken for the period 2008 - 2009. For this study, both categories were analysed and referred to as ICU beds, as they reflect the critical care component of the health service in South Africa. RESULTS: In 2008 - 2009, there were 4 719 ICU beds in the private and public sectors in South Africa, with 75% (3 533) in the former and 25% (1 186) in the latter. The majority of ICU beds in the two sectors were located in three provinces: Gauteng (49%), KwaZulu-Natal (14%) and Western Cape (15%), representing 78% of ICU beds (3 703/4 719) and catering for 54% of the country's population. Eastern Cape had fewer than 300 beds, North West and Mpumalanga had fewer than 150 beds, and Limpopo and Northern Cape had 66 and 47 beds respectively. With the proposed NHI scheme, the number of ICU beds available would be 4 719, which would translate into a bed:population ratio of approximately 1:10 000. However, there are large variations across the provinces, which makes the availability of this level of care in some provinces non-existent. CONCLUSION: While increasing the number of ICU beds in the public sector will open critical care services to more users, the NHI scheme would not solve the huge discrepancies of access to ICUs, and availability of critical care staff, across the provinces.

Tuberculosis in medical doctors - a study of personal experiences and attitudes.

BACKGROUND: The concurrent TB and HIV epidemics in sub-Saharan Africa place all health care workers (HCWs) at increased risk of exposure to Mycobacterium tuberculosis. AIM: This study explores personal experiences, attitudes and perceptions of medical doctors following treatment for TB within the healthcare system. METHOD: Sixty-two medical doctors who were diagnosed and treated for TB during 2007 - 2009 agreed to participate and complete a semi-structured questionnaire. RESULTS: The response rate was 64.5% (N=40). Mean age ±SD of participants was 33.7±10.6 years. A correct diagnosis of TB was made within 7 days of clinical presentation in 20% of participants, and was delayed beyond 3 weeks in 52.5%. Non-routine special investigations and procedures were performed in 26 participants. Complications following invasive procedures were reported by 8 participants. Multi-drug resistant TB (MDR-TB) was diagnosed in 4 participants. Nineteen considered defaulting on their treatment because of drug side-effects. The majority (n=36) expressed concerns regarding lack of infection control at the workplace, delays in TB diagnosis and negative attitudes of senior medical colleagues and administrators. Ninety per cent of participants indicated that their personal illness experiences had positively changed their professional approach to patients in their current practice. CONCLUSION: The inappropriate delays in diagnosis in a large number of participants, coupled with a number of negative personal perceptions towards their treatment, are cause for concern. The results further amplify the need for improved educational and awareness programmes among all healthcare personnel (including hospital administrators), adherence to national health guidelines, effective infection control measures, pre- and post-employment screening in all HCWs, and changes in attitudes on the part of senior medical colleagues and administrators.

Screening for pulmonary tuberculosis in HIV-infected individuals: AIDS Clinical Trials Group Protocol A5253.

BACKGROUND: Improved tuberculosis (TB) screening is urgently needed for human immunodeficiency virus (HIV) infected patients. METHODS: An observational, multi-country, cross-sectional study of HIV-infected patients to compare a standardized diagnostic evaluation (SDE) for TB with standard of care (SOC). SOC evaluations included TB symptom review (current cough, fever, night sweats and/or weight loss), sputum Ziehl-Neelsen staining and chest radiography. SDE screening added extended clinical signs and symptoms and fluorescent microscopy (FM). All participants underwent all evaluations. Mycobacterium tuberculosis on sputum culture was the primary outcome. RESULTS: A total of 801 participants were enrolled from Botswana, Malawi, South Africa, Zimbabwe, India, Peru and Brazil. The median age was 33 years; 37% were male, and median CD4 count was 275 cells/mm(3). Thirty-one participants (4%) had a positive culture on Löwenstein-Jensen media and 54 (8%) on MGIT. All but one positive culture came from sub-Saharan Africa, where the prevalence of TB was 54/445 (12%). SOC screening had 54% sensitivity (95%CI 40-67) and 76% specificity (95%CI 72-80). Positive and negative predictive values were respectively 24% and 92%. No elements of the SDE improved the predictive values of SOC. CONCLUSIONS: Symptom-based screening with smear microscopy was insufficiently sensitive. More sensitive diagnostic testing is required for HIV-infected patients.

Guideline for the management of acute asthma in adults: 2013 update.

Acute asthma attacks (asthma exacerbations) are increasing episodes of shortness of breath, cough, wheezing or chest tightness associated with a decrease in airflow that can be quantified and monitored by measurement of lung function (peak expiratory flow (PEF) or forced expiratory volume in the 1st second) and requiring emergency room treatment or admission to hospital for acute asthma and/or systemic glucocorticosteroids for management. The goals of treatment are to relieve hypoxaemia and airflow obstruction as quickly as possible, restore lung function, and provide a suitable plan to avoid relapse. Severe exacerbations are potentially life-threatening and their treatment requires baseline assessment of severity, close monitoring, and frequent reassessment using objective measures of lung function (PEF) and oxygen saturation. Patients at high risk of asthma-related death require particular attention. First-line therapy consists of oxygen supplementation, repeated administration of inhaled short-acting bronchodilators (beta-2-agonists and ipratropium bromide), and early systemic glucocorticosteroids. Intravenous magnesium sulphate and aminophylline are second- and third-line treatment strategies, respectively, for poorly responding patients. Intensive care is indicated for severe asthma that is not responsive to first-line treatment. Antibiotics are only indicated when there are definite features of bacterial infection. Factors that precipitated the acute asthma episode should be identified and preventive measures implemented. Acute asthma is preventable with optimal control of chronic asthma.

Integrated, home-based treatment for MDR-TB and HIV in rural South Africa: an alternate model of care.

SETTING: Treatment outcomes for multidrug-resistant tuberculosis (MDR-TB) in South Africa have suffered as centralized, in-patient treatment programs struggle to cope with rising prevalence and human immunodeficiency virus (HIV) co-infection rates. A new treatment model is needed to expand treatment capacity and improve MDR-TB and HIV outcomes. OBJECTIVE: To describe the design and preliminary results of an integrated, home-based MDR-TB-HIV treatment program created in rural KwaZulu-Natal. METHOD: In 2008, a decentralized center was established to provide out-patient MDR-TB and HIV treatment. Nurses, community health workers and family supporters have been trained to administer injections, provide adherence support and monitor adverse reactions in patients' homes. Physicians assess clinical response, adherence and the severity of adverse reactions to MDR-TB and HIV treatment at monthly follow-up visits. Treatment outcomes are assessed by monthly cultures and CD4 and viral load every 6 months. RESULTS: Of 80 patients initiating MDR-TB treatment from February 2008 to April 2010, 66 were HIV-co-infected. Retention has been high (only 5% defaults, 93% of visits attended), and preliminary outcomes have been favorable (77% cured/still on treatment, 82% undetectable viral load). Few patients have required escalation of care (9%), had severe adverse events (8%) or died (6%). CONCLUSION: Integrated, home-based treatment for MDR-TB and HIV is a promising treatment model to expand capacity and achieve improved outcomes in rural, resource-poor and high HIV prevalent settings.