Regina E Abotsi1,2, Mark P Nicol3, Grace McHugh4, Victoria Simms5, Andrea M Rehman5, Charmaine Barthus6, Slindile Mbhele6, Brewster W Moyo7, Lucky G Ngwira7,8, Hilda Mujuru9, Beauty Makamure4, Justin Mayini4, Jon Ø Odland10,11,12, Rashida A Ferrand4,13, Felix S Dube14. 1. Department of Molecular and Cell Biology & Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa. abtreg001@myuct.ac.za. 2. Department of Pharmaceutical Microbiology, School of Pharmacy, University of Health and Allied Sciences, Ho, Ghana. abtreg001@myuct.ac.za. 3. Division of Infection and Immunity, School of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Australia. 4. Biomedical Research and Training Institute, Harare, Zimbabwe. 5. MRC International Statistics & Epidemiology Group, London School of Hygiene and Tropical Medicine, London, UK. 6. Division of Medical Microbiology, University of Cape Town, Cape Town, South Africa. 7. Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi. 8. Liverpool School of Tropical Medicine, Liverpool, UK. 9. Department of Paediatrics, University of Zimbabwe, Harare, Zimbabwe. 10. Department of Community Medicine, University of Tromsø, Tromsø, Norway. 11. International Research Laboratory for Reproductive Ecotoxicology, The National Research University Higher School of Economics, Moscow, Russia. 12. School of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa. 13. Clinical Research Department, London School of Hygiene and Tropical Medicine, London, UK. 14. Department of Molecular and Cell Biology & Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Abstract
BACKGROUND: 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.
RCT Entities:
BACKGROUND: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.
Authors: Lisa M McNally; Prakash M Jeena; Kavitha Gajee; A Willem Sturm; Andrew M Tomkins; Hoosen M Coovadia; David Goldblatt Journal: J Infect Dis Date: 2006-06-30 Impact factor: 5.226
Authors: Janneke A Cox; Robert L Lukande; Sebastian Lucas; Ann M Nelson; Eric Van Marck; Robert Colebunders Journal: AIDS Rev Date: 2010 Oct-Dec Impact factor: 2.500
Authors: Osman Abdullahi; Angela Karani; Caroline C Tigoi; Daisy Mugo; Stella Kungu; Eva Wanjiru; Jane Jomo; Robert Musyimi; Marc Lipsitch; J Anthony G Scott Journal: PLoS One Date: 2012-02-20 Impact factor: 3.240
Authors: Eszter Kovács; Judit Sahin-Tóth; Adrienn Tóthpál; Mark van der Linden; Tamás Tirczka; Orsolya Dobay Journal: PLoS One Date: 2020-02-07 Impact factor: 3.240
Authors: Amy Price; Grace McHugh; Victoria Simms; Robina Semphere; Lucky G Ngwira; Tsitsi Bandason; Hilda Mujuru; Jon O Odland; Rashida A Ferrand; Andrea M Rehman Journal: EClinicalMedicine Date: 2021-11-13
Authors: Regina E Abotsi; Mark P Nicol; Grace McHugh; Victoria Simms; Andrea M Rehman; Charmaine Barthus; Lucky G Ngwira; Brenda Kwambana-Adams; Robert S Heyderman; Jon Ø Odland; Rashida A Ferrand; Felix S Dube Journal: ERJ Open Res Date: 2021-02-07