No previous sub-Saharan studies have compared patients with community-acquired pneumonia (CAP) and COVID-19 pneumonia, the focus of this study. Consecutive adult patients hospitalized with CAP (n = 59) or COVID-19 pneumonia (n = 74) were compared regarding multiple characteristics, including cardiac biomarkers. In multivariable logistic regression analysis, differences were noted among various clinical features. Troponin I concentrations (p = 0.00028) and the Troponin I/NT-pro BNP ratio (p = 0.00048) were significantly higher in COVID-19 compared with CAP. After adjustment for age, these differences remained significant (troponin I p = 0.0019; ratio p = 0.00054), while BNP concentrations were now higher in CAP (p = 0.009). PCA demonstrated that BNP and NT-pro BNP contributed most strongly to the dominant cardiac biomarker signature, suggesting shared cardiopulmonary stress across both diseases. Exploratory subgroup analyses suggested higher troponin I levels among people living with HIV and COVID-19, although interaction modelling did not demonstrate significant effect modification by HIV status. Both CAP and COVID-19 pneumonia were associated with evidence of cardiac stress; however, COVID-19 demonstrated a relatively stronger myocardial injury signature characterized by higher troponin I concentrations and an increased Troponin I/NT-pro BNP ratio while CAP had evidence of greater hemodynamic cardiac strain, as evidenced by the higher levels of BNP. The findings suggest that the mechanisms of cardiac involvement may differ between viral and bacterial respiratory infections.

Air pollution and climate change are intricately linked, each amplifying the other's effects. Both have an impact on respiratory conditions such as asthma, chronic obstructive pulmonary disease, and allergy, most commonly associated with exacerbations of these conditions. They also impact on the occurrence, etiology, and severity, including mortality, of respiratory infections, in particular pneumonia, especially among vulnerable populations. Commonly affected pathogens are many and include bacteria, viruses, and fungi. Ongoing research needs to determine fully the mechanisms and consequences of these environmental changes to understand how best to mitigate against these effects.

Compelling evidence has identified smoking and excessive alcohol consumption as eminently avoidable risks for both development and severity of CAP, while various comorbid disorders, including diabetes mellitus and the metabolic syndrome, also represent known risk factors, albeit of a more intransigent nature. Acquired immune suppression is the common thread underpinning these diverse, often co-existent, risk factors for development of severe CAP even in the face of seemingly appropriate antimicrobial chemotherapy. Importantly, in addition to a keen awareness of these risks on the part of infectious disease clinicians, the acquisition of innovative host-targeted immunotherapies represents a promising adjunctive approach to improving the outcome of persons at high-risk for development of severe CAP.

Glucocorticoid sensitivity varies between individuals, influencing stress and inflammatory responses, however its relationship with the synthetic ACTH [1–24] stimulation test, is not well evaluated. To evaluate glucocorticoid sensitivity and plasma total cortisol (TC) and plasma free cortisol (PFC) responses to stimulation with 250 μg of synthetic ACTH [1–24]) in healthy adults. Prospective, single-centre observational study. Forty-eight healthy adults (24 females, 24 males) underwent basal and stimulated TC and PFC level measurements using liquid chromatography-tandem mass spectrometry. Peak cortisol values were defined as the highest TC or PFC at either 30- or 60-min. Glucocorticoid sensitivity was measured using the dexamethasone suppression of cytokine production (DSCP) assay, based on interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) production from lipopolysaccharide-stimulated (LPS) monocytes. A whole blood sample was incubated with buffer, LPS, or LPS with dexamethasone (Dex). TNF-α and IL-6 concentrations were measured in the supernatants (ng/L). The ratio of cytokine levels between LPS + Dex and LPS indicated glucocorticoid sensitivity. Data from 45 participants were analysed. Peak TC levels ranged from 391 to 1570 nmol/L (median: 618 nmol/L, IQR: 555–729), while PFC levels ranged from 27 to 133 nmol/L (median: 62 nmol/L, IQR: 53–73). No significant associations were found between baseline or peak TC and PFC levels and glucocorticoid sensitivity ratios. Synthetic ACTH (1–24) test results did not predict glucocorticoid sensitivity. Males exhibited higher BMI (median: 26 vs. 22; p = 0.031), however no significant differences were observed in age, baseline PFC and TC levels between sexes. In this exploratory study, ACTH [1–24]—stimulated cortisol responses did not correlate with glucocorticoid sensitivity measured by the DSCP assay. Findings should be interpreted as preliminary and hypothesis-generating given current assay limitations.

Respiratory syncytial virus (RSV) infection was originally considered to be simply a disease of childhood. However, it has increasingly been recognized that the virus may also cause infection in adults. Furthermore, great strides have been made in understanding the clinical manifestations, as well as aspects of its management and prevention, requiring the need for greater awareness of the various aspects of this infection in adults. There are several potential reasons that RSV may have been overlooked in adults. Firstly, it was due to a lack of knowledge that this infection could occur in this age group. Secondly, there was infrequent testing for RSV infection in adults, both for this reason and because RSV antigen testing in adults is less sensitive than in children. Thirdly, RSV diagnosis, therefore, required the performance of polymerase chain reaction (PCR) testing, which is both expensive and underutilized. Finally, there was also the belief at that time that if the infection was due to RSV, there was little one could do to about it in terms of treatment and/or prevention. More recently, however, enormous advances have been made particularly in the management and prevention of this infection. This manuscript, which is an extensive literature review, describes the modern understanding of the burden of infection, the clinical presentation, risk factors, immunopathogenesis, management, and prevention of RSV infections in adults. RSV virus is a common cause of respiratory tract infections in adults and advances in recent research have not only enhanced our knowledge of this infection but have led to the development of effective treatment and prevention of the infection.

Background:There are few studies of long coronavirus disease (COVID) in low- and middle-income countries. Objectives:This study investigated long-term pulmonary manifestations of long COVID among adults in Johannesburg, South Africa. Method:This was a respiratory sub-study of a larger long COVID investigation. Cases with self-reported long COVID symptoms were recruited into four cohorts: prior asymptomatic infection, mild to moderate infection, hospitalised for severe infection and vaccinated prior to infection. Cases with respiratory comorbidity and/or well-characterised exposure to certain conditions (e.g. cigarette smoking) were excluded. Demographics, clinical features, spirometry, six-minute walk test (6MWT) and high-resolution computerised tomographic (HRCT) scan of the chest were recorded. Results:Of the 171 patients interviewed from the initial study, 36 with appropriate inclusion criteria were recruited a median of 2.1 years following their acute COVID-19 illness. Accordingly, the incidence of long COVID was 21.1% (36/171 patients) for the group as a whole and 5.9% (3/51), 25.0% (14/56), 37.8% (17/45) and 10.5% (2/19) for cohorts 1-4, respectively (p = 0.001). The major symptoms were tiredness and/or fatigue, shortness of breath and cough. Overall, 33 patients had abnormal 6MWT results, and 10 had abnormalities on spirometry; obstructive pattern in five, restrictive in three and mixed in two. Seven patients (six of whom were previously hospitalised) had probable/possible abnormalities compatible with long COVID on HRCT scan (p = 0.045). Conclusion:This study documented respiratory abnormalities in patients as long as 2 years after prior SARS-CoV-2 infection, especially among those with severe prior infection. Contribution:This was among the first studies comprehensively documenting pulmonary abnormalities in patients with long COVID in South Africa.

Background/Objectives: Pseudomonas aeruginosa (Psa) can circumvent antimicrobial chemotherapy, an ability enhanced by cigarette smoking (CS). This study probed potential benefits of combinations of anti-pseudomonal agents, and potential augmentation by a macrolide, in the absence or presence of cigarette smoke condensate (CSC). Methods: Two susceptible (WT: wild-type and DS: drug-sensitive) and one multidrug-resistant (MDR) strains of Psa were treated with amikacin, cefepime, and ciprofloxacin, individually and in combination, and with and without clarithromycin, followed by the measurement of planktonic growth and biofilm formation by spectrophotometry. Antibiotic interactions were determined using the fractional inhibitory concentration index (FICI) method. Effects on preformed biofilm density were measured following the addition of antibiotics: all procedures were performed in the absence and presence of CSC. Results: The minimal inhibitory concentrations (MICs) of the three agents ranged from 0.125 mg/L to 1 mg/L (WT and DS strains) and 16 mg/L to 64 mg/L (MDR strain), with all resistant to clarithromycin (125 mg/L). MIC values closely correlated with the antibiotic concentrations required to inhibit biofilm formation. FICI revealed synergism between most combinations, with augmentation by clarithromycin. Amikacin had the greatest effect on biofilm density, which was potentiated by combination with the other antibiotics, particularly clarithromycin. Exposure to CSC had variable, albeit modest, effects on bacterial growth and biofilm formation, but low concentrations increased biofilm mass and attenuated synergistic antimicrobial interactions and effects on biofilm density. Conclusions: Amikacin, cefepime, and ciprofloxacin, especially with clarithromycin, exhibit synergistic anti-pseudomonal activity and decrease preformed biofilm density. CSC attenuated these effects, illustrating the pro-infective potential of CS.

One of the earliest studies documenting the occurrence of cardiac changes in patients with community-acquired pneumonia, was an investigation of the electrocardiographic, echocardiographic, and cardiac biomarker changes in patients between the ages of 15 and 50 years, without evidence of any pre-existing or underlying cardiorespiratory illness, admitted to hospital for community-acquired pneumonia of all-cause aetiology [1]. A variety of electrocardiographic changes were documented to occur in 31% (32/102) of the patients, varying from clockwise rotation through to cardiac arrythmias. These electrocardiographic changes, especially those compatible with acute cor pulmonale and accompanied by a cardiac enzyme leak (creatinine kinase, and cardiac fraction of creatinine kinase [CK-MB] leak), correlated with severity of illness but not mortality and most of these abnormalities returned to normal in survivors within 2 days. In 2007, Musher and colleagues documented the association between acute cardiac changes and pneumococcal pneumonia [2]. These investigators documented the occurrence of myocardial infarction, serious arrythmia or new or worsening congestive heart failure in these patients, with 33 of 170 patients (19.4%) having one or more of these events, and in the study these events were significantly associated with mortality. Thereafter, others continued to document cardiac complications in patients with community-acquired pneumonia, which were noted to be associated with increased short-term mortality (30-days) [3, 4]. In the former study, older age, residents of nursing homes, those with underlying cardiovascular conditions and pneumonia severity were important risk factors. Additional studies documented that these intrahospital cardiac complications, occurring early during the course of pneumonia were also associated with cardiovascular events and death even in long-term follow up after hospital discharge [5, 6]. Among the risk factors for both early and late events following community-acquired pneumonia were age, smoking, severity of pneumonia, infection with S. pneumoniae, as well as hypertension and diabetes mellitus, factors that were also associated with increased risk of mortality [5, 6]. The latter authors also noted that measurement of some of the newer cardiac biomarkers and systemic inflammatory markers (especially interleukin-6) were able to predict those patients at risk for both early and for long-term cardiac events and indicated that these biomarkers may be helpful for use in planning personalised treatment of cases with community-acquired pneumonia [7]. Studies have also evaluated whether people living with HIV were at increased risk of cardiovascular events, or mortality, following hospitalisation for community-acquired pneumonia [8]. In one study, the risk of cardiovascular events was similar in people living with HIV compared to HIV-negative cases; however, after adjusting for known cardiovascular disease risk and severity of CAP, HIV was noted on multivariable analysis to be an independent predictor of mortality at 30-days. Perhaps not surprisingly, cardiovascular complications were noted to occur in 18% of patients hospitalised with severe acute respiratory syndrome (SARS)-CoV-2 pneumonia [9]. Prior comorbidities, older age, male sex, severity of illness and presence of hypoxaemia were associated with the occurrence of cardiovascular complications, and once these occurred the risk of death was extremely high. Much recent research has studied potential mechanisms for these cardiovascular events occurring in association with community-acquired pneumonia, some of which has been reviewed elsewhere [10]. Most interestingly, one group of researchers noted the occurrence of microlesions in the myocardium in association with invasive pneumococcal disease in a variety of animal species, including subsequently, in non-human primates, and even in humans, which housed extracellular S. pneumoniae [11]. The thiol-activated pore forming toxin of the pneumococcus, pneumolysin, was required for the formation of these microlesions and among other factors, platelet activating factor receptor was required for translocation of the microorganisms into the ventricular lesions. Interestingly, administration of antibiotics was associated with a robust immune response to these lesions with subsequent deposition of collagen tissue, associated with long-term scarring in the myocardium, compatible with the long-term cardiovascular events following community-acquired pneumonia. Other researchers have documented additional potential mechanisms of cardiovascular events concentrating their research onto the prothrombotic/proinflammatory mechanisms of pneumococcal mediated myocardial damage [10]. These investigators, in a series of in vitro investigations, noted that pneumococcal virulence factors, particularly pneumolysin, initiate a chain of events leading to platelet activation, with homotypic platelet aggregation, formation of heterotypic neutrophil: platelet aggregates, as well as the formation of neutrophil extracellular traps all of which may pose the risk of intravascular coagulation leading to further myocardial injury. Figure 1 shows the proposed mechanisms involved in the pathogenesis of pneumolysin-mediated cardiac injury in patients with invasive pneumococcal disease. The latter authors further reviewed the concept of persistent antigenaemia and inflammation that may underpin the long-term cardiovascular consequences of community-acquired pneumonia. While it has been known that low-grade endotoxaemia may occur in community-acquired pneumonia, its possible role in these cardiovascular events had until more recently not been elucidated. Cangemi and colleagues studied the occurrence of cardiovascular events in patients with community-acquired pneumonia and noted that there was a progressive increased in these events from the lowest to the highest tertile of lipopolysaccharide [12]. Logistic regression analysis confirmed that the higher tertile of lipopolysaccharide was independently associated with cardiovascular events. These authors recommended further studies to determine the effects of lowering lipopolysaccharide using non-absorbable antibiotics. Clearly, while the occurrence of a cardiovascular event in a patient with community-acquired pneumonia needs to be recognised early, and appropriately managed, the ongoing challenge is how to prevent them from occurring in the first place. In this regard, there have been studies investigating possible options. For example, one study noted that use of aspirin was associated with a reduction in the short-term occurrence of ischaemic stroke and myocardial infarction in participants in primary care who developed pneumonia [13], while a retrospective study documented that patient's hospitalised with community-acquired pneumonia, who were on corticosteroids, has a lower incidence of myocardial infarction [14]. There is also the important consideration that vaccination can prevent many of these infections in the first place, which has several potential benefits both to the individual and to society. The author declares no conflicts of interest.

Introduction There are no studies from sub-Saharan Africa comparing patients with community-acquired pneumonia (CAP) and those with COVID-19 pneumonia, which is what was undertaken in this study. Methods Consecutive adult patients hospitalized with CAP (n=59), or COVID-19 pneumonia (n=74) were compared with regard to co-morbidities, HIV status, routine laboratory parameters, and levels of systemic inflammatory and cardiac biomarkers. Results There were an equal number of males and females, but CAP patients were younger. Human immunodeficiency virus infection was more common in CAP patients, whereas other comorbidities were more prevalent in COVID-19 pneumonia. CAP patients had more cough, fever, greater tachycardia, and lower blood pressure, while dyspnoea, tachypnoea, and respiratory alkalosis were more prevalent in COVID-19. Several routine laboratory parameters differed. Cardiovascular biomarkers were mostly elevated in both groups compared to controls. However, levels of creatinine kinase-MB (CK-MB) and cardiac troponin I were significantly elevated in COVID-19 versus CAP patients. When compared by HIV status no difference in the cardiac biomarker levels was seen in CAP patients with and without HIV, but significantly higher levels were noted in the HIV-positive COVID-19 group. Conclusion Cardiac biomarker analysis suggests that HIV-infected patients with COVID-19 pneumonia may be at greatest risk of cardiovascular events.

Purpose: There is a paucity of data from sub-Saharan Africa describing Severe Community Acquired Pneumonia (SCAP), a condition with significant morbidity and mortality. Materials and methods: This was a retrospective, single-centre, observational study of consecutive patients with SCAP admitted to the ICU at Charlotte Maxeke Johannesburg Academic Hospital, in South Africa between 1 July 2007 and 31 May 2019. Pneumonia was categorised as community-acquired if there had been no hospitalization in the preceding 2 weeks. Results: We identified 931 patients, (median age 37 [IQR 30-48] years), with the predominant co-morbidity being HIV co-infection (77.1 %). The median CURB-65 and APACHE II scores were 3 (IQR 2-3) and 18 (IQR 14-23) respectively, and most patients had multilobar consolidation on chest X-ray. Mycobacterium tuberculosis was the most common aetiology, followed by Streptococcus pneumoniae. The latter, and Pneumocystis jirovecii were more common amongst survivors and non-survivors, respectively. ICU mortality was 50.1 % and 85 % of patients required ventilation, mostly invasive mechanical ventilation. Ventilated patients and those requiring inotropic support and/or dialysis were more likely to die. Conclusion: We have described a cohort of patients with SCAP, with a comprehensive overview of all putative microbiological causes, which to our knowledge, is the largest reported in the literature.

Background/Objectives: In sub-Saharan Africa, there is paucity of data regarding non-tuberculous mycobacterial (NTM) infections, leading to underappreciation of disease burden. Consequently, fewer resources are allocated, leading to potential adverse outcomes. This study examines long-term mortality and risk factors of South African patients with positive NTM samples. Methods: We conducted a retrospective analysis of clinical isolates of NTMs between 1 January 2010 and 30 June 2017. We retrieved and thoroughly reviewed the corresponding medical records of patients treated at Charlotte Maxeke Johannesburg Academic Hospital. Outcomes were compared between patients who underwent different therapy regimens, including macrolide-based regimens and ‘watchful waiting’. Results: A total of 123 patients were followed for a median of 1 year (interquartile range [IQR], 0.5–4.5). The median age was 39 years (IQR, 31–51) with male predominance, 58%. The common comorbid conditions were HIV (encountered in 78%) and previous TB (58%). Pulmonary disease due to Mycobacterium avium complex (MAC-PD) was found in 74% of patients, M. fortiutum in 5%, and M. gordonae in 4%. The mortality relative risk for patients on initial macrolide-containing therapy was 0.54 (95% confidence interval [CI], 0.22–1.36), p = 0.194, while that for macrolide-free antimicrobials was 1.38 (95% CI, 0.57–3.34), p = 0.471. The adjusted hazard rate for mortality with low CD4 counts < 50 cells/mm3 was 2.79 (95%, 1.20–6.50), while that for unknown CD4 counts was 4.01 (95% CI, 1.17–13.77), compared to CD4 counts > 50 cells/mm3. Conclusions: Among HIV patients, NTM-PD predominated, and not disseminated disease. MAC-PD was the most common infection. Low CD4 counts was a significant risk factor for early death, while sex, NTM species, macrolide therapy, and previous TB were not.

It has been noted by the World Health Organisation that cases of tuberculosis in 2022 globally numbered 10.6 million, resulting in 1.3 million deaths, such that TB is one of the infectious diseases causing the greatest morbidity and mortality worldwide. Since as early as 1918, there has been an ongoing debate as to the relationship between cigarette smoking and TB. However, numerous epidemiological studies, as well as meta-analyses, have indicated that both active and passive smoking are independent risk factors for TB infection, development of reactivation TB, progression of primary TB, increased severity of cavitary disease, and death from TB, among several other considerations. With this considerable body of evidence confirming the association between smoking and TB, it is not surprising that TB control programmes represent a key potential preventative intervention. In addition to coverage of the epidemiology of TB and its compelling causative link with smoking, the current review is also focused on evidence derived from clinical- and laboratory-based studies of disease pathogenesis, most prominently the protective anti-mycobacterial mechanisms of the alveolar macrophage, the primary intracellular refuge of M. tuberculosis. This section of the review is followed by an overview of the major strategies utilised by the pathogen to subvert these antimicrobial mechanisms in the airway, which are intensified by the suppressive effects of smoke inhalation on alveolar macrophage function. Finally, consideration is given to a somewhat under-explored, pro-infective activity of cigarette smoking, namely augmentation of antibiotic resistance due to direct effects of smoke per se on the pathogen. These include biofilm formation, induction of cellular efflux pumps, which eliminate both smoke-derived toxicants and antibiotics, as well as gene modifications that underpin antibiotic resistance.

Continued improvements in the treatment of pulmonary infections have paradoxically resulted in a growing challenge of individuals with postinfectious pulmonary complications (PIPCs). PIPCs have been long recognized after tuberculosis, but recent experiences such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have underscored the importance of PIPCs following other lower respiratory tract infections. Independent of the causative pathogen, most available studies of pulmonary infections focus on short-term outcomes rather than long-term morbidity among survivors. In this document, we establish a conceptual scope for PIPCs with discussion of globally significant pulmonary pathogens and an examination of how these pathogens can damage different components of the lung, resulting in a spectrum of PIPCs. We also review potential mechanisms for the transition from acute infection to PIPC, including the interplay between pathogen- mediated injury and aberrant host responses, which together result in PIPCs. Finally, we identify cross-cutting research priorities for the field to facilitate future studies to establish the incidence of PIPCs, define common mechanisms, identify therapeutic strategies, and ultimately reduce the burden of morbidity in survivors of pulmonary infections.

People living with HIV comprise a substantial number of the patients admitted to intensive care. This number varies according to geography, but all areas of the world are affected. In lower-income and middle-income countries, the majority of intensive care unit (ICU) admissions relate to infections, whereas in high-income countries, they often involve HIV-associated non-communicable diseases diagnoses. Management of infections potentially resulting in admission to the ICU in people living with HIV include sepsis, respiratory infections, COVID-19, cytomegalovirus infection, and CNS infections, both opportunistic and non-opportunistic. It is crucial to know which antiretroviral therapy (ART) is appropriate, when is the correct time to administer it, and to be aware of any safety concerns and potential drug interactions with ART. Although ART is necessary for controlling HIV infections, it can also cause difficulties relevant to the ICU such as immune reconstitution inflammatory syndrome, and issues associated with ART administration in patients with gastrointestinal dysfunction on mechanical ventilation. Managing infection in people with HIV in the ICU is complex, requiring collaboration from a multidisciplinary team knowledgeable in both the management of the specific infection and the use of ART. This team should include intensivists, infectious disease specialists, pharmacists, and microbiologists to ensure optimal outcomes for patients.

PurposeLimitations of life sustaining therapies (LLST) are frequent in intensive care units (ICUs), but no previous studies have examined end-of-life (EOL) care and LLST in South Africa (SA).Materials and methodsThis study evaluated LLST in SA from the data of a prospective, international, multicentre, observational study (Ethicus-2) and compared practices with countries in the rest of the world.ResultsLLST was relatively common in SA, and withholding was more frequent than withdrawing therapy. However, withdrawing and withholding therapy were less common, while failed CPR was more common, than in many other countries. No patients had an advance directive. Primary reasons for LLST in SA were poor quality of life, multisystem organ failure and patients' unresponsiveness to maximal therapy. Primary considerations for EOL decision-making were good medical practice and patients' best-interest, with the need for an ICU bed only rarely considered.ConclusionsWithholding was more common than withdrawing treatment both in SA and worldwide, although both were significantly less frequent in SA compared with the world average.

Antimicrobial resistance (AMR), in which microbes adapt to and resist current therapies, is a well-recognised global problem that threatens to reverse gains made by modern medicine in the last decades. AMR is a complex issue; however, at its core, it is driven by the overuse and inappropriate use of antimicrobials. Socioeconomic factors have been identified as significant contributors to the emergence and exacerbation of AMR, especially in populations facing inadequate access to healthcare, poor sanitation services and high morbidity and mortality rates. Weak healthcare systems and water, sanitation and hygiene have been highlighted as fundamental risk factors for AMR emergence and transmission. Behavioural factors, such as purchasing antibiotics without a prescription from a registered healthcare professional, not completing the prescribed course or overly prolonged courses of antibiotics, using antibiotics to treat viral infections, lack of access to quality antibiotics, and the proliferation of substandard or falsified (SF) drugs, have also been identified as significant contributors to AMR. Low- and middle-income countries have a higher incidence of antibiotics being dispensed without a prescription than higher-income countries.

The recent global resurgence of severe infections caused by the Group A streptococcus (GAS) pathogen, Streptococcus pyogenes, has focused attention on this microbial pathogen, which produces an array of virulence factors, such as the pore-forming toxin, streptolysin O (SOT). Importantly, the interactions of SOT with human neutrophils (PMN), are not well understood. The current study was designed to investigate the effects of pretreatment of isolated human PMN with purified SOT on several pro-inflammatory activities, including generation of reactive oxygen species (ROS), degranulation (elastase release), influx of extracellular calcium (Ca2+) and release of extracellular DNA (NETosis), using chemiluminescence, spectrophotometric and fluorimetric procedures, respectively. Exposure of PMN to SOT alone caused modest production of ROS and elastase release, while pretreatment with the toxin caused significant augmentation of chemoattractant (fMLP)-activated ROS generation and release of elastase by activated PMN. These effects of treatment of PMN with SOT were associated with both a marked and sustained elevation of cytosolic Ca2+(2+)concentrations and significant increases in the concentrations of extracellular DNA, indicative of NETosis. The current study has identified a potential role for SOT in augmenting the Ca2+-dependent pro-inflammatory interactions of PMN, which, if operative in a clinical setting, may contribute to hyper-activation of PMN and GAS-mediated tissue injury.

Background:Bronchiectasis is a chronic lung disorder that affects the lives of many South Africans. Post-tuberculosis (TB) bronchiectasis is an important complication of previous pulmonary TB and a common cause of bronchiectasis in South Africa (SA). No previous statements on the management of bronchiectasis in SA have been published.Objectives:To provide a position statement that will act as a template for the management of adult patients with bronchiectasis in SA.Methods:The South African Thoracic Society appointed an editorial committee to compile a position statement on the management of adult non-cystic fibrosis (CF) bronchiectasis in SA.Results:A position statement addressing the management of non-CF bronchiectasis in adults in SA was compiled. This position statement covers the epidemiology, aetiology, diagnosis, investigations and various aspects of management of adult patients with non-CF bronchiectasis in SA.Conclusion:Bronchiectasis has largely been a neglected lung condition, but new research has improved the outlook for patients. Collaboration between interprofessional team members in patient management is important. In SA, more research into the epidemiology of bronchiectasis, especially post-TB bronchiectasis and HIV-associated bronchiectasis, is required.Abstract:The South African Thoracic Society mandated a multidisciplinary team of healthcare providers to compile a position statement on the management of non-cystic fibrosis bronchiectasis in South Africa (SA). International guidelines on the management of bronchiectasis were reviewed and used as a basis from which the current position statement was compiled. This is the first position statement on the management of adult non-cystic fibrosis bronchiectasis in SA. A description of the epidemiology and aetiology of bronchiectasis is provided, as well as guidance on its diagnosis and management. The position statement provides guidance on the management of bronchiectasis to healthcare providers, policymakers and regulatory authorities.