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Cook J.,Kaleidoscope Center for Children | Jefferis O.,Queen Elizabeth Central Hospital | Matchere P.,Queen Elizabeth Central Hospital | Mbale E.,Queen Elizabeth Central Hospital | Rylance J.,Malawi Liverpool Wellcome Clinical Research Programme
International Journal of Tuberculosis and Lung Disease | Year: 2013

BACKGROUND: A proportion of children with sicklecell disease (SCD) demonstrate clinical findings consistent with the diagnosis of asthma. These children are at increased risk of complications, including acute chest syndrome. OBJECTIVE: To assess lung function and symptoms of asthma in children with SCD in Blantyre, Malawi. DESIGN: Twenty-five children aged 7-16 years with electrophoretically confirmed SCD were recruited to u ndergo spirometry and questionnaire screening of asthma symptoms. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio were compared with local and international reference ranges. Symptoms were assessed using the International Study of Asthma and Allergies in Childhood questionnaire. RESULTS: Mean spirometric indices, represented as Zscores derived from international reference ranges, were low: FEV1 -1.64 (95%CI -2.04 to -1.23), FVC -1.49 (95%CI -1.90 to -1.09), FEV1/FVC -0.39 (95%CI -0.76 to -0.03). Comparison with local reference ranges, represented as percentage of predicted value, revealed similar impairments: FEV1 86.9 (95%CI 81.1 to 92.7), FVC 89.0 (95%CI 83.5 to 94.4), FEV1/FVC ratio 97.7 (95%CI 95.4 to 99.9). The prevalence of wheeze was 16.7%. CONCLUSION: We present spirometric abnormalities suggestive of restrictive lung disease with no evidence of obstructive defects or increased prevalence of wheeze. © 2013 The Union. Source

Waitt C.J.,Malawi Liverpool Wellcome Clinical Research Programme | Waitt C.J.,University of Liverpool
International Journal of Tuberculosis and Lung Disease | Year: 2011

BACKGROUND: Despite effective anti-tuberculosis chemotherapy, case-fatality rates of up to 25% are described in both industrialised and resource-poor settings. An understanding of the factors predisposing to poor outcome may allow the development of adjunctive treatment strategies or closer clinical monitoring in high-risk individuals. OBJECTIVES: To describe the definitions and timing of deaths due to tuberculosis (TB), and the reported range of risk factors for death. METHODS: All electronically available studies investigating risk factors for death in TB patients from 1966 to 2010 were analysed. Included were peer-reviewed reports of cohort, case control or cross-sectional studies with the primary objective of determination of quantitative effect estimates of the relationship between risk factors and death in adults treated for TB. Many studies were limited by their retrospective design, reliance on data from registries and charts, and risk of reporting bias. RESULTS: Most studies reported risk factors for all-cause mortality throughout anti-tuberculosis treatment. In the context of high TB incidence and human immunodeficiency virus (HIV) prevalence, risk factors for death are HIV positivity, advancing immunosuppression, smear-negative disease and malnutrition. In regions of low TB incidence and HIV prevalence, risk factors include non-infective comorbidities, sputum smear-positive disease and alcohol and substance misuse. CONCLUSIONS: There remains a need for prospective clinical studies, particularly with a focus on deaths occurring during the first months of anti-tuberculosis treatment. Qualitative research should be used to further explore the relationship between sex and health-seeking behaviour, and to optimise delivery of health care to socially marginalised groups. © 2011 The Union. Source

Gay C.L.,University of North Carolina at Chapel Hill | Mwapasa V.,Malawi Liverpool Wellcome Clinical Research Programme | Murdoch D.M.,Duke University | Kwiek J.J.,University of North Carolina at Chapel Hill | And 4 more authors.
Diagnostic Microbiology and Infectious Disease | Year: 2010

There are limited data on acute HIV infection (AHI) prevalence during pregnancy. Malawian pregnant women admitted in the third trimester and meeting eligibility criteria underwent dual HIV rapid antibody testing. AHI prevalence was retrospectively detected through HIV RNA pooling of seronegative plasma. Among 3,825 pregnant women screened, dual HIV rapid testing indicated that 30.2% were HIV positive, 69.7% were HIV negative, and 0.1% were indeterminate. Sensitivity and specificity of dual rapid testing was 99.0% and 98.7%, respectively. Of 2,666 seronegative specimens, 2,327 had samples available for HIV RNA pooling; 5 women (0.21%) (95% confidence interval, 0.03-0.40%) had AHI with a median peripartum viral load of 1,324,766 copies/mL. Pregnant women are at risk for AHI, warranting counseling of all women and their sexual partners about incident HIV during pregnancy. Dual HIV rapid tests have high sensitivity and specificity. HIV testing should be repeated in the third trimester and/or at delivery. © 2010 Elsevier Inc. All rights reserved. Source

Rylance J.,University of Liverpool | Rylance J.,Malawi Liverpool Wellcome Clinical Research Programme | Chimpini C.,Malawi Liverpool Wellcome Clinical Research Programme | Semple S.,University of Aberdeen | And 5 more authors.
PLoS ONE | Year: 2015

Background. Household air pollution in low income countries is an important cause of mortality from respiratory infection. We hypothesised that chronic smoke exposure is detrimental to alveolar macrophage function, causing failure of innate immunity. We report the relationship between macrophage function and prior smoke exposure in healthy Malawians. Methods. Healthy subjects exposed daily to cooking smoke at home volunteered for bronchoalveolar lavage. Alveolar macrophage particulate content was measured as a known correlate of smoke exposure. Phagocytosis and intraphagosomal function (oxidative burst and proteolysis) were measured by a flow cytometric assay. Cytokine responses in macrophages were compared following re-exposure in vitro to wood smoke, before and after glutathione depletion. Results. Volunteers had a range of alveolar macrophage particulate loading. The macrophage capacity for phagosomal oxidative burst was negatively associated with alveolar macrophage particulate content (n = 29, r2 = 0.16, p = 0.033), but phagocytosis per se and proteolytic function were unaffected. High particulate content was associated with lower baseline CXCL8 release (ratio 0.51, CI 0.29-0.89) and lower final concentrations on re-exposure to smoke in vitro (ratio 0.58, CI 0.34-0.97). Glutathione depletion augmented CXCL8 responses by 1.49× (CI 1.02-2.17) compared with wood smoke alone. This response was specific to smoke as macrophages response to LPS were not modulated by glutathione. Conclusion. Chronic smoke exposure is associated with reduced human macrophage oxidative burst, and dampened inflammatory cytokine responses. These are critical processes in lung defence against infection and likely to underpin the relationship between air pollution and pneumonia. © 2015 Rylance et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Source

Moxon C.A.,Malawi Liverpool Wellcome Clinical Research Programme | Moxon C.A.,University of Liverpool | Chisala N.V.,Malawi Liverpool Wellcome Clinical Research Programme | Wassmer S.C.,New York University | And 9 more authors.
Journal of Infectious Diseases | Year: 2014

Endothelial dysregulation is central to the pathogenesis of acute Plasmodium falciparum infection. It has been assumed that this dysregulation resolves rapidly after treatment, but this return to normality has been neither demonstrated nor quantified. We therefore measured a panel of plasma endothelial markers acutely and in convalescence in Malawian children with uncomplicated or cerebral malaria. Evidence of persistent endothelial activation and inflammation, indicated by increased plasma levels of soluble intracellular adhesion molecule 1, angiopoetin 2, and C-reactive protein, were observed at 1 month follow-up visits. These vascular changes may represent a previously unrecognized contributor to ongoing malaria-associated morbidity and mortality. © 2013 The Author. Source

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