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RationalePulmonary tuberculosis (PTB) can cause post-TB lung disease (PTLD) associated with respiratory symptoms, spirometric and radiological abnormalities. Understanding of the predictors and natural history of PTLD is limited.ObjectivesTo describe the symptoms and lung function of Malawian adults up to 3 years following PTB-treatment completion, and to determine the evolution of PTLD over this period.MethodsAdults successfully completing PTB treatment in Blantyre, Malawi were followed up for 3 years and assessed using questionnaires, post-bronchodilator spirometry, 6 min walk tests, chest X-ray and high-resolution CT. Predictors of lung function at 3 years were identified by mixed effects regression modelling.Measurement and main resultsWe recruited 405 participants of whom 301 completed 3 years follow-up (mean (SD) age 35 years (10.2); 66.6% males; 60.4% HIV-positive). At 3 years, 59/301 (19.6%) reported respiratory symptoms and 76/272 (27.9%) had abnormal spirometry. The proportions with low FVC fell from 57/285 (20.0%) at TB treatment completion to 33/272 (12.1%), while obstruction increased from and 41/285 (14.4%) to 43/272 (15.8%) at 3 years. Absolute FEV1 and FVC increased by mean 0.03 L and 0.1 L over this period, but FEV1 decline of more than 0.1 L was seen in 73/246 (29.7%). Higher spirometry values at 3 years were associated with higher body mass index and HIV coinfection at TB-treatment completion.ConclusionSpirometric measures improved over the 3 years following treatment, mostly in the first year. However, a third of PTB survivors experienced ongoing respiratory symptoms and abnormal spirometry (with accelerated FEV1 decline). Effective interventions are needed to improve the care of this group of patients.

Objective To refine and validate a neutrophil function assay with clinical relevance for patients with community-acquired pneumonia (CAP). Design Two phase cross-sectional study to standardise and refine the assay in blood from healthy volunteers and test neutrophil phagocytic function in hospital patients with CAP. Participants Phase one: Healthy adult volunteers (n = 30). Phase two: Critical care patients with severe CAP (n = 16), ward-level patients with moderate CAP (n = 15) and respiratory outpatients (no acute disease, n = 15). Results Our full standard operating procedure for the assay is provided. Patients with severe CAP had significantly decreased neutrophil function compared to moderate severity disease (median phagocytic index 2.8 vs. 18.0, p = 0.014). Moderate severity pneumonia neutrophil function was significantly higher than control samples (median 18.0 vs. 1.6, p = 0.015). There was no significant difference between critical care and control neutrophil function (median 2.8 vs. 1.6, p = 0.752). Conclusions Our whole blood neutrophil assay is simple, reproducible and clinically relevant. Changes in neutrophil function measured in this pneumonia cohort is in agreement with previous studies. The assay has potential to be used to identify individuals for clinical trials of immunomodulatory therapies, to risk-stratify patients with pneumonia, and to refine our understanding of ‘normal’ neutrophil function in infection.

Abstract Rationale Noncommunicable respiratory diseases and exposure to air pollution are thought to be important contributors to morbidity and mortality in sub-Saharan African adults. Objectives We set out to explore the prevalence and determinants of noncommunicable respiratory disease among adults living in Chikhwawa District, Malawi. Methods We performed a cross-sectional study among adults in communities participating in a randomized controlled trial of a cleaner-burning biomass-fueled cookstove intervention (CAPS [Cooking and Pneumonia Study]) in rural Malawi. We assessed chronic respiratory symptoms, spirometric abnormalities, and personal exposure to air pollution (particulate matter <2.5 μm in aerodynamic diameter [PM2.5] and carbon monoxide [CO]). Weighted prevalence estimates were calculated; multivariable and intention-to-treat analyses were done. Measurements and Main Results One thousand four hundred eighty-one participants (mean [SD] age, 43.8 [17.8] yr; 57% female) were recruited. The prevalence of chronic respiratory symptoms, spirometric obstruction, and restriction were 13.6% (95% confidence interval [CI], 11.9–15.4), 8.7% (95% CI, 7.0–10.7), and 34.8% (95% CI, 31.7–38.0), respectively. Median 48-hour personal PM2.5 and CO exposures were 71.0 μg/m3 (interquartile range [IQR], 44.6–119.2) and 1.23 ppm (IQR, 0.79–1.93), respectively. Chronic respiratory symptoms were associated with current/ex-smoking (odds ratio [OR], 1.59; 95% CI, 1.05–2.39), previous tuberculosis (OR, 2.50; 95% CI, 1.04–15.58), and CO exposure (OR, 1.46; 95% CI, 1.04–2.05). Exposure to PM2.5 was not associated with any demographic, clinical, or spirometric characteristics. There was no effect of the CAPS intervention on any of the secondary trial outcomes. Conclusions The burden of chronic respiratory symptoms, abnormal spirometry, and air pollution exposures in adults in rural Malawi is of considerable potential public health importance. We found little evidence that air pollution exposures were associated with chronic respiratory symptoms or spirometric abnormalities and no evidence that the CAPS intervention had effects on the secondary trial outcomes. More effective prevention and control strategies for noncommunicable respiratory disease in sub-Saharan Africa are needed. Clinical trial registered with www.isrctn.com (ISRCTN 59448623).

Chronic obstructive pulmonary disease (COPD) continues to pose a global public health challenge. However, literature is scarce on the burden of COPD in Malawi. We assessed the prevalence and risk factors for COPD among adults in Neno, Malawi. We conducted a population-based analytical cross-sectional study in Neno District between December 2021 and November 2022. Using a multi-stage sampling technique, we included 525 adults aged≥40 years. All participants underwent spirometry according to the American Thoracic Society (ATS) guidelines and were interviewed using the IMPALA questionnaire. For this study, we utilized the definition of COPD as a post-bronchodilator FEV1/FVC <0.70. We collected data using Kobo collect, exported to Microsoft Excel, and analysed using R software. We used descriptive statistics and logistic regression analysis; a p-value of <0.05 was considered statistically significant. Out of 525 participants, 510 participants were included in the final analysis. Fifty-eight percent of the participants were females (n=296), and 62.2% (n=317) were between 40 and 49 years with a median (IQR) age of 46 (40-86). For patient characteristics, 15.1% (n=77) were current smokers, and 4.1% (n=21) had a history of pulmonary tuberculosis (PTB). Cough was the most commonly reported respiratory symptom (n=249, 48.8%). The prevalence of COPD was 10.0% (n=51) and higher (15.0%) among males compared to females (6.4%). Factors significantly associated with COPD were age 60 years and above (adjusted odds ratio [aOR] = 3.27, 95% CI: 1.48-7.34, p<0.004), ever smoked (aOR = 6.17, 95% CI:1.89-18.7, p<0.002), current smoker (aOR = 17.6, 95% CI: 8.47-38.4, p<0.001), and previous PTB (aOR = 4.42, 95% CI: 1.16-15.5, p<0.023). The cross-sectional prevalence of COPD in rural Malawi is high, especially among males. Factors significantly associated were older age (60 years and above), cigarette smoking, and previous PTB. Longitudinal studies are needed to better understand disease etiology and progression in this setting.

A scheme for visualizing and quantifying the complexity of multidimensional energy landscapes and multiple pathways is presented employing principal component-based disconnectivity graphs and the Shannon entropy of relative \"sizes\" of superbasins. The principal component-based disconnectivity graphs incorporate a metric relationship between the stationary points of the system, which enable us to capture not only the actual assignment of the superbasins but also the size of each superbasin in the multidimensional configuration space. The landscape complexity measure quantifies the degree of topographical complexity of a multidimensional energy landscape and tells us at which energy regime branching of the main path becomes significant, making the system more likely to be kinetically trapped in local minima. The path complexity measure quantifies the difficulty encountered by the system to reach a connected local minimum by the path in question, implying that the more significant the branching points along the path the more difficult it is to end up in the desired local minimum. As an illustrative example, we apply this analysis to two kinds of small model protein systems exhibiting a highly frustrated and an ideal funnel-like energy landscape.

Haules Robbins Zaniku,1,2 Emilia Connolly,3–5 Moses Banda Aron,6,7 Beatrice Matanje,8 Myness Kasanda Ndambo,9 George Talama,10 Fabien Munyaneza,11 Todd Ruderman,8 Jamie Rylance,12,13 Luckson Dullie,14 Rejani Lalitha,15 Ndaziona Peter Kwanjo Banda,16,* Adamson S Muula17,*1Department of Physiotherapy, Ministry of Health, Neno District Health Office, Lilongwe, Malawi; 2Department of Epidemiology and Biostatistics, School of Global and Public Health, Kamuzu University of Health Sciences, Lilongwe, Malawi; 3Department of Partnerships and Policy, Partners in Health/Abwenzi Pa za Umoyo (PIH/APZU), Lilongwe, Malawi; 4Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA; 5Division of Hospital Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 45529, USA; 6Monitoring and Evaluation Department, Partners in Health/Abwenzi Pa za Umoyo (PIH/APZU), Lilongwe, Malawi; 7Snakebite Envenoming Department, Research Group Snakebite Envenoming, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany; 8Clinical Department, Partners in Health/Abwenzi Pa za Umoyo (PIH/APZU), Lilongwe, Malawi; 9Department of Health Systems and Policy, Training and Research Unit of Excellence (TRUE), Kamuzu University of Health Sciences, Blantyre, Malawi; 10Programs Directorate, Partners in Hope, Lilongwe, Malawi; 11Research Department, Partners in Health/Abwenzi Pa za Umoyo (PIH/APZU), Lilongwe, Malawi; 12Malawi–Liverpool–Wellcome Trust Clinical Research Programme, Blantyre, Malawi; 13Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK; 14Global Leadership Ecosystem, Partners in Health/Abwenzi Pa za Umoyo (PIH/APZU), Lilongwe, Malawi; 15Pulmonary Division, Department of Medicine, School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; 16Department of Medicine, School of Medicine and Oral Health, Kamuzu University of Health Sciences, Lilongwe, Malawi; 17Community and Environmental Health Department, School of Global and Public Health, Kamuzu University of Health Sciences, Lilongwe, Malawi*These authors contributed equally to this workCorrespondence: Haules Robbins Zaniku, Neno District Health Office, P.O. Box 52, Neno, Malawi, Tel +265-994-922-140, Email [email protected]View the original paper by Mr Zaniku and colleaguesThis is in response to the Letter to the Editor