Browsing by Author "Mujuru, Hilda"
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- ItemOpen AccessAzithromycin 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 ABackground: 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.
- ItemOpen AccessPrevalence and antimicrobial resistance profiles of respiratory microbial flora in African children with HIV-associated chronic lung disease(2021-02-25) Abotsi, Regina E; Nicol, Mark P; McHugh, Grace; Simms, Victoria; Rehman, Andrea M; Barthus, Charmaine; Mbhele, Slindile; Moyo, Brewster W; Ngwira, Lucky G; Mujuru, Hilda; Makamure, Beauty; Mayini, Justin; Odland, Jon Ø; Ferrand, Rashida A; Dube, Felix SBackground HIV-associated chronic lung disease (CLD) is common among children living with HIV (CLWH) in sub-Saharan Africa, including those on antiretroviral therapy (ART). However, the pathogenesis of CLD and its possible association with microbial determinants remain poorly understood. We investigated the prevalence, and antibiotic susceptibility of Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI), and Moraxella catarrhalis (MC) among CLWH (established on ART) who had CLD (CLD+), or not (CLD-) in Zimbabwe and Malawi. Methods Nasopharyngeal swabs (NP) and sputa were collected from CLD+ CLWH (defined as forced-expiratory volume per second z-score < − 1 without reversibility post-bronchodilation with salbutamol), at enrolment as part of a randomised, placebo-controlled trial of azithromycin (BREATHE trial - NCT02426112 ), and from age- and sex-matched CLD- CLWH. Samples were cultured, and antibiotic susceptibility testing was conducted using disk diffusion. Risk factors for bacterial carriage were identified using questionnaires and analysed using multivariate logistic regression. Results A total of 410 participants (336 CLD+, 74 CLD-) were enrolled (median age, 15 years [IQR = 13–18]). SP and MC carriage in NP were higher in CLD+ than in CLD- children: 46% (154/336) vs. 26% (19/74), p = 0.008; and 14% (49/336) vs. 3% (2/74), p = 0.012, respectively. SP isolates from the NP of CLD+ children were more likely to be non-susceptible to penicillin than those from CLD- children (36% [53/144] vs 11% [2/18], p = 0.036). Methicillin-resistant SA was uncommon [4% (7/195)]. In multivariate analysis, key factors associated with NP bacterial carriage included having CLD (SP: adjusted odds ratio (aOR) 2 [95% CI 1.1–3.9]), younger age (SP: aOR 3.2 [1.8–5.8]), viral load suppression (SP: aOR 0.6 [0.4–1.0], SA: 0.5 [0.3–0.9]), stunting (SP: aOR 1.6 [1.1–2.6]) and male sex (SA: aOR 1.7 [1.0–2.9]). Sputum bacterial carriage was similar in both groups (50%) and was associated with Zimbabwean site (SP: aOR 3.1 [1.4–7.3], SA: 2.1 [1.1–4.2]), being on ART for a longer period (SP: aOR 0.3 [0.1–0.8]), and hot compared to rainy season (SP: aOR 2.3 [1.2–4.4]). Conclusions CLD+ CLWH were more likely to be colonised by MC and SP, including penicillin-non-susceptible SP strains, than CLD- CLWH. The role of these bacteria in CLD pathogenesis, including the risk of acute exacerbations, should be further studied.