Browsing by Author "Corbett, Elizabeth L"

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    Azithromycin versus placebo for the treatment of HIV-associated chronic lung disease in children and adolescents (BREATHE trial): study protocol for a randomised controlled trial
    (BioMed Central, 2017-12-28) Gonzalez-Martinez, Carmen; Kranzer, Katharina; McHugh, Grace; Corbett, Elizabeth L; Mujuru, Hilda; Nicol, Mark P; Rowland-Jones, Sarah; Rehman, Andrea M; Gutteberg, Tore J; Flaegstad, Trond; Odland, Jon O; Ferrand, Rashida A
    Background: Human immunodeficiency virus (HIV)-related chronic lung disease (CLD) among children is associated with substantial morbidity, despite antiretroviral therapy. This may be a consequence of repeated respiratory tract infections and/or dysregulated immune activation that accompanies HIV infection. Macrolides have anti-inflammatory and antimicrobial properties, and we hypothesised that azithromycin would reduce decline in lung function and morbidity through preventing respiratory tract infections and controlling systemic inflammation. Methods/design: We are conducting a multicentre (Malawi and Zimbabwe), double-blind, randomised controlled trial of a 12-month course of weekly azithromycin versus placebo. The primary outcome is the mean change in forced expiratory volume in 1 second (FEV1) z-score at 12 months. Participants are followed up to 18 months to explore the durability of effect. Secondary outcomes are FEV1 z-score at 18 months, time to death, time to first acute respiratory exacerbation, number of exacerbations, number of hospitalisations, weight for age z-score at 12 and 18 months, number of adverse events, number of malaria episodes, number of bloodstream Salmonella typhi infections and number of gastroenteritis episodes. Participants will be followed up 3-monthly, and lung function will be assessed every 6 months. Laboratory substudies will be done to investigate the impact of azithromycin on systemic inflammation and on development of antimicrobial resistance as well as impact on the nasopharyngeal, lung and gut microbiome. Discussion: The results of this trial will be of clinical relevance because there are no established guidelines on the treatment and management of HIV-associated CLD in children in sub-Saharan Africa, where 80% of the world’s HIVinfected children live and where HIV-associated CLD is highly prevalent. Trial registration: ClinicalTrials.gov, NCT02426112. Registered on 21 April 2015.
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    Development of a standardized screening rule for tuberculosis in people living with HIV in resource-constrained settings: individual participant data meta-analysis of observational studies
    (Public Library of Science, 2011) Getahun, Haileyesus; Kittikraisak, Wanitchaya; Heilig, Charles M; Corbett, Elizabeth L; Ayles, Helen; Cain, Kevin P; Grant, Alison D; Churchyard, Gavin J; Kimerling, Michael; Shah, Sarita
    Haileyesus Getahun and colleagues report the development of a simple, standardized tuberculosis (TB) screening rule for resource-constrained settings, to identify people living with HIV who need further investigation for TB disease.
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    Predicting the long-term impact of antiretroviral therapy scale-up on population incidence of tuberculosis
    (Public Library of Science, 2013) Dodd, Peter J; Knight, Gwenan M; Lawn, Stephen D; Corbett, Elizabeth L; White, Richard G
    Objective To investigate the impact of antiretroviral therapy (ART) on long-term population-level tuberculosis disease (TB) incidence in sub-Saharan Africa. METHODS: We used a mathematical model to consider the effect of different assumptions about life expectancy and TB risk during long-term ART under alternative scenarios for trends in population HIV incidence and ART coverage. RESULTS: All the scenarios we explored predicted that the widespread introduction of ART would initially reduce population-level TB incidence. However, many modelled scenarios projected a rebound in population-level TB incidence after around 20 years. This rebound was predicted to exceed the TB incidence present before ART scale-up if decreases in HIV incidence during the same period were not sufficiently rapid or if the protective effect of ART on TB was not sustained. Nevertheless, most scenarios predicted a reduction in the cumulative TB incidence when accompanied by a relative decline in HIV incidence of more than 10% each year. CONCLUSIONS: Despite short-term benefits of ART scale-up on population TB incidence in sub-Saharan Africa, longer-term projections raise the possibility of a rebound in TB incidence. This highlights the importance of sustaining good adherence and immunologic response to ART and, crucially, the need for effective HIV preventive interventions, including early widespread implementation of ART.
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    Treatment-seeking for tuberculosis-suggestive symptoms: a reflection on the role of human agency in the context of universal health coverage in Malawi
    (Public Library of Science, 2016) Kumwenda, Moses; Desmond, Nicola; Hart, Graham; Choko, Augustine; Chipungu, Geoffrey A; Nyirenda, Deborah; Shand, Tim; Corbett, Elizabeth L; Chikovore, Jeremiah
    Tuberculosis (TB) is highly infectious and one of the leading killers globally. Several studies from sub-Saharan Africa highlight health systems challenges that affect ability to cope with existing disease burden, including TB, although most of these employ survey-type approaches. Consequently, few address community or patient perspectives and experiences. At the same time, understanding of the mechanisms by which the health systems challenges translate into seeking or avoidance of formal health care remains limited. This paper applies the notion of human agency to examine the ways people who have symptoms suggestive of TB respond to and deal with the symptoms vis-à-vis major challenges inherent within health delivery systems. Empirical data were drawn from a qualitative study exploring the ways in which notions of masculinity affect engagement with care, including men's well-documented tendency to delay in seeking care for TB symptoms. The study was carried out in three high-density locales of urban Blantyre, Malawi. Data were collected in March 2011 -March 2012 using focus group discussions, of which eight (mixed sex = two; female only = three; male only = three) were with 74 ordinary community members, and two (both mixed sex) were with 20 health workers; and in-depth interviews with 20 TB patients (female = 14) and 20 un-investigated chronic coughers (female = eight). The research process employed a modified version of grounded theory. Data were coded using a coding scheme that was initially generated from the study aims and subsequently progressively amended to incorporate concepts emerging during the analysis. Coded data were retrieved, re-read, and broken down and reconnected iteratively to generate themes. A myriad of problems were described for health systems at the primary health care level, centring largely on shortages of resources (human, equipment, and drugs) and unprofessional conduct by health care providers. Participants consistently pointed out how the problems could drive patients from promptly reporting symptoms at primary healthcare centres. The accounts suggest that in responding to illness symptoms including those suggestive of TB, patients navigate their options taking into cognisance past and current experiences with formal health systems. Understanding and factoring in the mediating role of such 'agency' is critical when implementing efforts to promote timely response to TB-suggestive symptoms.