Questionnaires for Lung Health in Africa across the Life Course.

Respiratory infections remain a leading cause of morbidity and mortality in many low and middle-income countries but non-communicable disease rates are rising fast. Prevalence studies have been primarily symptom-focused, with tools developed in countries in the Global North such as the United States and the United Kingdom. Systematic study in sub-Saharan African populations is necessary to accurately reflect disease risk factors present in these populations. We present tools for such studies, developed as part of the International Multidisciplinary Programme to Address Lung Health and TB in Africa ('IMPALA'), which includes lay representatives. At a preliminary meeting, the adequacy and suitability of existing tools was discussed and a new questionnaire set proposed. Individual questionnaires were developed, and an expert panel considered content and criterion validity. Questionnaires underwent a cross-cultural adaptation process, incorporating translation and contextual 'sense-checking', through the use of pre-established lay focus groups in Malawi, before consensus-approval by project collaborators. The complete set of research questionnaires, providing information on lung health symptoms and a relevant range of potential risk factors for lung disease, is now available online. In developing the tools, cultural and contextual insights were important, as were translational considerations. The process benefitted from a foundation in expert knowledge, starting with validated tools and internationally respected research groups, and from a coordinated collaborative approach. We present and discuss a newly devised, contextually appropriate set of questionnaires for non-communicable lung disease research in Africa that are now available in open access for all to use

Community-Acquired Pneumonia in Sub-Saharan Africa

Community-acquired pneumonia (CAP) in sub-Saharan Africa is a common cause of adult hospitalization and is associated with significant mortality. Human immunodeficiency virus (HIV) prevalence in the region leads to differences in CAP epidemiology compared with most high-income settings: patients are younger, and coinfection with tuberculosis and opportunistic infections is common and difficult to diagnose. Resource limitations affect the availability of medical expertise as well as radiological and laboratory diagnostic services. These factors impact on key aspects of health care, including pathways of investigation, severity assessment, and the selection of empirical antimicrobial therapy. This review summarizes recent data from sub-Saharan Africa describing the burden, etiology, risk factors, and outcome of CAP. We describe the rational and context-appropriate approach to CAP diagnosis and management, including supportive therapy. Priorities for future research to inform strategies for CAP prevention and initial management are suggested

Inability to Walk Predicts Death among Adult Patients in Hospitals in Malawi

Objective. Vital signs are often used in triage, but some may be difficult to assess in low-resource settings. A patient’s ability to walk is a simple and rapid sign that requires no equipment or expertise. This study aimed to determine the predictive performance for death of an inability to walk among hospitalized Malawian adults and to compare its predictive value with the vital signs-based National Early Warning Score (NEWS). Methods. It is a prospective cohort study of adult in-patients on selected days in two hospitals in Malawi. Patients were asked to walk five steps with close observation and their vital signs were assessed. Sensitivities, specificities, and predictive values for in-patient death of an inability to walk were calculated and an inability to walk was compared with NEWS. Results. Four-hundred and forty-three of the 1094 participants (40.5%) were unable to walk independently. In this group, 70 (15.8 %) died in-hospital compared to 16 (2.5%) among those who could walk: OR 7.4 (95% CI 4.3-13.0 p6 had sensitivity 70.9%, specificity 70.6%, PPV 17.1%, and NPV 96.6%. An inability to walk had a fair concordance with NEWS>6 (kappa 0.21). Conclusion. Inability to walk predicted mortality as well as NEWS among hospitalized adults in Malawi. Patients who were able to walk had a low risk of death. Walking ability could be considered an additional vital sign and may be useful for triage

Unexpectedly High Prevalence of Cytomegalovirus DNAemia in Older Children and Adolescents With Perinatally Acquired Human Immunodeficiency Virus Infection

Background Older children and adolescents with perinatally acquired human immunodeficiency virus (PHIV) infection in Africa experience multiple comorbidities that are not typical of HIV-associated opportunistic infections, including growth impairment and chronic lung disease. We examined associations between plasma cytomegalovirus (CMV) DNA and lung function and growth. Methods Plasma CMV DNA loads were measured children aged 6–16 years with PHIV (n = 402) and HIV-uninfected controls (n = 224). The HIV-infected children were either newly diagnosed or known HIV infected and stable on antiretroviral therapy (ART) for >6 months. CMV DNA loads were measured using quantitative polymerase chain reaction. CMV DNAemia was modeled as a time-varying outcome using longitudinal mixed-effects logistic regression. Results At enrollment, CMV DNAemia ≥1000 copies/mL (defined as “clinically significant”) was detected in 5.8% of uninfected children, 14.7% of HIV-infected participants stable on ART, and 22.6% of HIV-infected ART-naive children (χ2 = 23.8, P < .001). The prevalence of CMV DNAemia ≥1000 copies/mL was associated with CD4 counts <350 cells/µL. Among HIV-infected ART-naive children, the presence of CMV DNAemia of ≥1000 copies/mL was independently associated with reduced lung function (adjusted odds ratio [aOR] = 3.23; 95% confidence interval [CI], 1.23–8.46; P = .017). Among ART-treated children, stunting was associated with CMV DNAemia of ≥1000 copies/mL (aOR = 2.79; 95% CI, 0.97–8.02; P = .057). Conclusions Clinically significant levels of CMV DNAemia were common in older children with PHIV, even those on ART, suggesting a role for inadequately controlled CMV infection in the pathogenesis of PHIV comorbidities in Afric

The role of redox balance in pulmonary innate immunity

Introduction: Household air pollution (HAP) affects one half of the world population, comprises 90% of global particulate exposure, and is associated with mortality from respiratory infections. Particulates are known to alter cellular redox balance, including that of the alveolar macrophage (AM). We investigate redox balance as a mechanism to explain the link between particulate exposure and failure of innate immune function. Methods: Bronchoalveolar lavage was performed on healthy human volunteers in the UK (low HAP) and Malawi (high HAP). Antioxidant capacity was determined (concentrations of oxidised and reduced glutathione, and antioxidant capacities of glutathione peroxidase and superoxide dismutase). AM function was assessed by capacity to phagocytose, and to produce oxidative burst and proteolysis activity within the phagosome using reporter-fluorophore coated silica beads. AM cytokine responses to lipopolysaccharide and to respirable size wood smoke particles were measured before and after ex vivo treatment to reduce glutathione content. Personal exposure to particulates was estimated by the cytoplasmic content of black carbon within AM. Results: AM glutathione was similar in UK and Malawi non-smokers (of which 4.3% was in oxidised form). One quarter of Malawians exhibited a high oxidised glutathione phenotype (8.6% of total). Malawians exhibited higher levels of extracellular glutathione, and intracellular malondialdehyde and particulate content than UK volunteers. Nrf2 levels in Malawian AM were proportional to levels of particulate matter. We demonstrated no association between particulate matter content and AM cytokine responses to lipopolysaccharide or wood. Glutathione depletion did not consistently alter AM cytokine production. In vivo particulate exposure correlates with reduced AM phagosomal oxidative capacity, and increased cellular Nrf-2 concentration, but phagocytosis and phagosomal proteolysis are unaffected. Conclusion: Malawians have high levels of AM particulate exposure, as expected from HAP surveys. This is associated with evidence of oxidative stress (lipid peroxidation), antioxidant upregulation (raised extracellular glutathione, intracellular Nrf2) and a specific defect in AM function (reduced oxidative burst). Antibacterial function of the AM is key to preventing pulmonary infection: in a population subjected to high levels of household air pollution, particulate related defects in AM function could explain the high prevalence of infective respiratory illness

Aetiology and outcomes of sepsis in adults in sub-Saharan Africa: a systematic review and meta-analysis

Background Aetiology and outcomes of sepsis in sub-Saharan Africa (sSA) are poorly described; we performed a systematic review and meta-analysis to summarise the available data. Methods Systematic searches of PubMed and Scopus were undertaken to identify prospective studies recruiting adults (> 13 years) with community-acquired sepsis in sSA post-2000. Random effects meta-analysis of in-hospital and 30-day mortality was undertaken and available aetiology data also summarised by random effects meta-analysis. Results Fifteen studies of 2800 participants were identified. Inclusion criteria were heterogeneous. The majority of patients were HIV-infected, and Mycobacterium tuberculosis was the most common cause of blood stream infection where sought. Pooled in-hospital mortality for Sepsis-2-defined sepsis and severe sepsis was 19% (95% CI 12–29%) and 39% (95% CI 30–47%) respectively, and sepsis mortality was associated with the proportion of HIV-infected participants. Mortality and morbidity data beyond 30 days were absent. Conclusions Sepsis in sSA is dominated by HIV and tuberculosis, with poor outcomes. Optimal antimicrobial strategies, including the role of tuberculosis treatment, are unclear. Long-term outcome data are lacking. Standardised sepsis diagnostic criteria that are easily applied in low-resource settings are needed to establish an evidence base for sepsis management in sSA

Comparison of methods for the analysis of airway macrophage particulate load from induced sputum, a potential biomarker of air pollution exposure.

BACKGROUND Air pollution is associated with a high burden or morbidity and mortality, but exposure cannot be quantified rapidly or cheaply. The particulate burden of macrophages from induced sputum may provide a biomarker. We compare the feasibility of two methods for digital quantification of airway macrophage particulate load. METHODS Induced sputum samples were processed and analysed using ImageJ and Image SXM software packages. We compare each package by resources and time required. RESULTS 13 adequate samples were obtained from 21 patients. Median particulate load was 0.38 μm(2) (ImageJ) and 4.0 % of the total cellular area of macrophages (Image SXM), with no correlation between results obtained using the two methods (correlation coefficient = -0.42, p = 0.256). Image SXM took longer than ImageJ (median 26 vs 54 mins per participant, p = 0.008) and was less accurate based on visual assessment of the output images. ImageJ's method is subjective and requires well-trained staff. CONCLUSION Induced sputum has limited application as a screening tool due to the resources required. Limitations of both methods compared here were found: the heterogeneity of induced sputum appearances makes automated image analysis challenging. Further work should refine methodologies and assess inter- and intra-observer reliability, if these methods are to be developed for investigating the relationship of particulate and inflammatory response in the macrophage

Non-communicable respiratory disease in Malawi: a systematic review and meta-analysis

Background Non-communicable respiratory diseases are important contributors to morbidity and mortality in sub-Saharan African countries such as Malawi. Aim To conduct a systematic review of the available literature relating to chronic respiratory disease in Malawi. Methods We conducted a systematic protocol-driven literature search of key scientific databases including Scopus and Medline. Papers were independently assessed for eligibility by two authors and included if they reported objective measures (including self-reported standard symptoms) of chronic respiratory disease and were conducted in Malawi. A meta-analysis of available estimates was then conducted. We re-analysed data from three of these studies in a secondary data analysis to allow for between-study comparisons. Results Our search identified 393 papers of which 17 (5 involving children and 12 involving adults) met the inclusion criteria. Wheeze was the symptom most frequently reported in children in the community (12.1%), hospital (11.2%) and HIV clinic (8.1%) settings. Cough was the symptom most frequently reported by adults in the community (3–18%). Spirometric abnormalities varied substantially between studies. For example, in adults, airflow obstruction varied between 2.3% and 20% and low forced vital capacity (varied between 2.7% and 52.8%. Conclusion We identified a high burden of chronic respiratory symptoms and abnormal spirometry (particularly low FVC) within paediatric and adult populations in Malawi. The estimates for country-wide burden related to this disease were limited by the heterogeneity of the methods used to assess symptoms and spirometry. There is an urgent need to develop a better understanding of the determinants and natural history of non-communicable respiratory disease across the life-course in Malawi

Early warning scores generated in developed healthcare settings are not sufficient at predicting early mortality in Blantyre, Malawi : a prospective cohort study

Early warning scores (EWS) are widely used in well-resourced healthcare settings to identify patients at risk of mortality. The Modified Early Warning Score (MEWS) is a well-known EWS used comprehensively in the United Kingdom. The HOTEL score (Hypotension, Oxygen saturation, Temperature, ECG abnormality, Loss of independence) was developed and tested in a European cohort; however, its validity is unknown in resource limited settings. This study compared the performance of both scores and suggested modifications to enhance accuracy