Albert, R. K. et al. Azithromycin for prevention of exacerbations of COPD. New Engl. J. Med. 365(8), 689–698 (2011).
Saiman, L. et al. Azithromycin in patients with cystic fibrosis chronically infected with pseudomonas aeruginosaA randomized controlled trial. JAMA 290(13), 1749–1756 (2003).
Wong, C. et al. Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): A randomised, double-blind, placebo-controlled trial. Lancet 380(9842), 660–667 (2012).
Brusselle, G. G. & Joos, G. Is there a role for macrolides in severe asthma?. Curr. Opin. Pulm. Med. 20(1), 95–102 (2014).
Altenburg, J. et al. Effect of azithromycin maintenance treatment on infectious exacerbations among patients with non-cystic fibrosis bronchiectasis: The BAT randomized controlled trial. Jama 309(12), 1251–1259 (2013).
Wolter, J. et al. Effect of long term treatment with azithromycin on disease parameters in cystic fibrosis: A randomised trial. Thorax 57(3), 212–216 (2002).
Gottlieb, J. et al. Long-term azithromycin for bronchiolitis obliterans syndrome after lung transplantation. Transplantation 85(1), 36–41 (2008).
Donath, E., Chaudhry, A., Hernandez-Aya, L. F. & Lit, L. A meta-analysis on the prophylactic use of macrolide antibiotics for the prevention of disease exacerbations in patients with chronic obstructive pulmonary disease. Respir. Med. 107(9), 1385–1392 (2013).
Reiter, J. et al. Macrolides for the long-term management of asthma – a meta-analysis of randomized clinical trials. Allergy 68(8), 1040–1049 (2013).
Kim, L., McGee, L., Tomczyk, S. & Beall, B. Biological and epidemiological features of antibiotic-resistant streptococcus pneumoniae in pre- and post-conjugate vaccine eras: A United States perspective. Clin. Microbiol. Rev. 29(3), 525–552 (2016).
Kanoh, S. & Rubin, B. K. Mechanisms of action and clinical application of macrolides as immunomodulatory medications. Clin. Microbiol. Rev. 23(3), 590–615 (2010).
Bosch, A. A., Biesbroek, G., Trzcinski, K., Sanders, E. A. & Bogaert, D. Viral and bacterial interactions in the upper respiratory tract. PLoS Pathog. 9(1), e1003057 (2013).
Wurzel, D. F. et al. Prospective characterization of protracted bacterial bronchitis in children. Chest 145(6), 1271–1278 (2014).
Baillie, V. L. et al. Epidemiology of the rhinovirus (RV) in African and Southeast asian children: A case-control pneumonia etiology study. Viruses 13(7), 1249 (2021).
Garcha, D. S. et al. Changes in prevalence and load of airway bacteria using quantitative PCR in stable and exacerbated COPD. Thorax 67(12), 1075–1080 (2012).
Ferrand, R. A. et al. Chronic lung disease in adolescents with delayed diagnosis of vertically acquired HIV infection. Clin. Infect Dis. 55(1), 145–152 (2012).
Mwalukomo, T. et al. Clinical characteristics and lung function in older children vertically infected with human immunodeficiency virus in malawi. J. Pediatr. Infect. Dis. Soc. 5(2), 161–169 (2015).
Githinji, L. N., Gray, D. M., Hlengwa, S., Myer, L. & Zar, H. J. Lung function in south african adolescents infected perinatally with HIV and treated long term with antiretroviral therapy. Annal. Am. Thorac. Soc. 14(72R), 729 (2017).
Ferrand, R. A. et al. Effect of once-weekly azithromycin vs placebo in children with HIV-associated chronic lung disease: The BREATHE randomized clinical trial. JAMA Netw. Open 3(12), e2028484 (2020).
Abotsi, R. E. et al. The impact of long-term azithromycin on antibiotic resistance in HIV-associated chronic lung disease. ERJ Open Res. 8, 00491–02021 (2021).
Techasaensiri, B., Techasaensiri, C., Mejías, A., McCracken, G. H. Jr. & Ramilo, O. Viral coinfections in children with invasive pneumococcal disease. Pediatr. Infect. Dis. J 29(6), 519–523 (2010).
DeMuri, G. P., Gern, J. E., Eickhoff, J. C., Lynch, S. V. & Wald, E. R. Dynamics of bacterial colonization with streptococcus pneumoniae, haemophilus influenzae, and moraxella catarrhalis during symptomatic and asymptomatic viral upper respiratory tract infection. Clin. Infect. Dis. 66(7), 1045–1053 (2017).
Song, J.-H., Dagan, R., Klugman, K. P. & Fritzell, B. The relationship between pneumococcal serotypes and antibiotic resistance. Vaccine 30(17), 2728–2737 (2012).
Heinsbroek, E. et al. Pneumococcal carriage in households in Karonga District, Malawi, before and after introduction of 13-valent pneumococcal conjugate vaccination. Vaccine 36(48), 7369–7376 (2018).
Dondo, V. et al. pneumococcal conjugate vaccine impact on meningitis and pneumonia among children aged Clin. Infect. Dis. 69(Suppl 2), S72-s80 (2019).
Rodgers, G. L. & Klugman, K. P. The future of pneumococcal disease prevention. Vaccine 29, C43–C48 (2011).
Kamng’ona, A. W. et al. High multiple carriage and emergence of Streptococcus pneumoniae vaccine serotype variants in Malawian children. BMC Infect. Dis. 15(1), 234 (2015).
Massora, S. et al. Invasive disease potential of Streptococcus pneumoniae serotypes before and after 10-valent pneumococcal conjugate vaccine introduction in a rural area, southern Mozambique. Vaccine https://doi.org/10.1016/j.vaccine.2019.09.079 (2019).
Makenga, G. et al. Immunogenicity and efficacy of pneumococcal conjugate vaccine (Prevenar13®) in Preventing Acquisition Of Carriage Of Pneumococcal vaccine serotypes in Tanzanian children with HIV/AIDS. Front. Immunol. 12, 673392 (2021).
Müller, A. et al. Streptococcus pneumoniae serotypes associated with death, South Africa, 2012–2018. Emerg. Infect. Dis. 28(1), 166–179 (2022).
Langtry, H. D. & Balfour, J. A. Azithromycin. A review of its use in paediatric infectious diseases. Drugs 56(2), 273–297 (1998).
Haworth, C. S., Bilton, D. & Elborn, J. S. Long-term macrolide maintenance therapy in non-CF bronchiectasis: Evidence and questions. Respir. Med. 108(10), 1397–1408 (2014).
Hare, K. M. et al. Nasopharyngeal carriage and macrolide resistance in Indigenous children with bronchiectasis randomized to long-term azithromycin or placebo. Eur. J. Clin. Microbiol. Infect. Dis. 34(11), 2275–2285 (2015).
Smith, D. et al. British thoracic society guideline for the use of long-term macrolides in adults with respiratory disease. Thorax 75(5), 370–404 (2020).
Bogaert, D., de Groot, R. & Hermans, P. W. M. Streptococcus pneumoniae colonisation: The key to pneumococcal disease. Lancet Infect. Dis. 4(3), 144–154 (2004).
Lewnard, J. A. et al. Density, serotype diversity, and fitness of streptococcus pneumoniae in upper respiratory tract cocolonization with nontypeable haemophilus influenzae. J. Infect. Dis. 214(9), 1411–1420 (2016).
Hathaway, L. J. et al. Capsule type of streptococcus pneumoniae determines growth phenotype. PLoS Pathog. 8(3), e1002574 (2012).
Kadioglu, A., Weiser, J. N., Paton, J. C. & Andrew, P. W. The role of Streptococcus pneumoniae virulence factors in host respiratory colonization and disease. Nat. Rev. Microbiol. 6(4), 288–301 (2008).
Brueggemann, A. B., Pai, R., Crook, D. W. & Beall, B. Vaccine escape recombinants emerge after pneumococcal vaccination in the United States. PLoS Pathog. 3(11), e168 (2007).
Ladhani, S. N. et al. Invasive pneumococcal disease, comorbidities, and polysaccharide vaccine use in children aged 5–15 years in England and Wales. Clin. Infect. Dis. 58(4), 517–525 (2013).
Lekhuleni, C. et al. Impact of pneumococcal conjugate vaccines on invasive pneumococcal disease-causing lineages among South African children. Nat. Commun. 15(1), 8401 (2024).
Zimbabwe: WHO and UNICEF estimates of immunization coverage: 2022 revision [https://cdn.who.int/media/docs/default-source/country-profiles/immunization/2023-country-profiles/immunization_zwe_2023.pdf] (2022).
Malawi: WHOand UNICEF estimates of national immunization coverage: 2021 revision [https://cdn.who.int/media/docs/default-source/country-profiles/immunization/2022-country-profiles/immunization_mwi_2022.pdf] (2021).
Keenan, J. D. et al. Nasopharyngeal pneumococcal serotypes before and after mass azithromycin distributions for trachoma. J. Pediatr. Infect. Dis. Soc. 5(2), 222–226 (2016).
Burr, S. E. et al. Mass administration of azithromycin and Streptococcus pneumoniae carriage: Cross-sectional surveys in the Gambia. Bull. World Health Organ. 92, 490–498 (2014).
Johnson, C. N., Wilde, S., Tuomanen, E. & Rosch, J. W. Convergent impact of vaccination and antibiotic pressures on pneumococcal populations. Cell Chem. Biol. 31(2), 195–206 (2024).
Barcus, V. A., Ghanekar, K., Yeo, M., Coffey, T. J. & Dowson, C. G. Genetics of high level penicillin resistance in clinical isolates of Streptococcus pneumoniae. FEMS microbial. lett. 126(3), 299–303 (1995).
Iroh Tam, P.-Y., Madoff, L. C., Coombes, B. & Pelton, S. I. Invasive pneumococcal disease after implementation of 13-valent conjugate vaccine. Pediatrics 134(2), 210–217 (2014).
Roca, A. et al. Effect on nasopharyngeal pneumococcal carriage of replacing PCV7 with PCV13 in the Expanded Programme of Immunization in the Gambia. Vaccine 33(51), 7144–7151 (2015).
Hema-Ouangraoua, S. et al. Serotype profile of nasopharyngeal isolates of streptococcus pneumoniae obtained from children in burkina faso before and after mass administration of Azithromycin. Am. J. Trop. Med. Hyg. 103(2), 679–683 (2020).
Bojang, A. et al. Seasonality of pneumococcal nasopharyngeal carriage in rural gambia determined within the context of a cluster randomized pneumococcal vaccine trial. PLOS ONE 10(7), e0129649 (2015).
Mack, I. et al. Antimicrobial resistance following azithromycin mass drug administration: Potential surveillance strategies to assess public health impact. Clin. Infect. Dis. 70(7), 1501–1508 (2020).
Kawaguchiya, M. et al. High prevalence of antimicrobial resistance in non-vaccine serotypes of non-invasive/colonization isolates of Streptococcus pneumoniae: A cross-sectional study eight years after the licensure of conjugate vaccine in Japan. J. Infect. Pub. Health 13(8), 1094–1100 (2020).
Roberts Marilyn, C. et al. Nomenclature for macrolide and macrolide-lincosamide-streptogramin B resistance determinants. Antimicrob. Agent. Chemother. 43(12), 2823–2830 (1999).
Adetifa, I. M. et al. Pre-vaccination nasopharyngeal pneumococcal carriage in a Nigerian population: Epidemiology and population biology. PLoS One 7(1), e30548 (2012).
Abdullahi, O. et al. The Prevalence and risk factors for pneumococcal colonization of the nasopharynx among children in kilifi district, kenya. PLOS ONE 7(2), e30787 (2012).
Siegel, S. J. & Weiser, J. N. Mechanisms of bacterial colonization of the respiratory tract. Ann. Rev. Microbiol. 69(1), 425–444 (2015).
Hare, K. M. et al. Longitudinal nasopharyngeal carriage and antibiotic resistance of respiratory bacteria in indigenous Australian and Alaska native children with bronchiectasis. PloS one 8(8), e70478–e70478 (2013).
Turner, P. et al. A longitudinal study of streptococcus pneumoniae carriage in a cohort of infants and their mothers on the Thailand-Myanmar border. PloS one 7, e38271 (2012).
Pingault, N. M., Bowman, J. M., Lehmann, D. & Riley, T. V. Antimicrobial susceptibility of Moraxella catarrhalis isolated from children in Kalgoorlie-Boulder Western Australia. Pathology 42(3), 273–279 (2010).
Wildenbeest, J. G. et al. Prevalence of rhinoviruses in young children of an unselected birth cohort from the Netherlands. Clin. Microbiol. Infect. 22(8), 736.e739-736.e715 (2016).
Cohen, C. et al. Epidemiology of viral-associated acute lower respiratory tract infection among children Pediat. Infect. Dis. J. 34(1), 66–72 (2015).
Nunes, M. C. et al. Clinical epidemiology of bocavirus, rhinovirus, two polyomaviruses and four coronaviruses in HIV-infected and HIV-uninfected South African children. PLOS ONE 9(2), e86448 (2014).
van den Bergh, M. R. et al. Associations between Pathogens in the upper respiratory tract of young children: Interplay between viruses and bacteria. PLOS ONE 7(10), e47711 (2012).
Moore, H. C. et al. The interaction between respiratory viruses and pathogenic bacteria in the upper respiratory tract of asymptomatic Aboriginal and non-Aboriginal children. Pediatr. Infect. Dis. J. 29(6), 540–545 (2010).
Bénet, T. et al. Microorganisms associated with pneumonia in children Clin. Infect. Dis. 65(4), 604–612 (2017).
Gielen, V., Johnston, S. L. & Edwards, M. R. Azithromycin induces anti-viral responses in bronchial epithelial cells. European Respir. J. 36(3), 646–654 (2010).
Schögler, A. et al. Novel antiviral properties of azithromycin in cystic fibrosis airway epithelial cells. European Respire. J. 45(2), 428–439 (2015).
Oliver, M. E. & Hinks, T. S. C. Azithromycin in viral infections. Rev. Med. Virol. 31(2), e2163 (2021).
Gonzalez-Martinez, C. et al. 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. Trials 18(1), 622 (2017).
McHugh, G. et al. Chronic lung disease in children and adolescents with HIV: A case–control study. Trop. Med. Intern. Health 25(5), 590–599 (2020).
Rehman, A. M. et al. Exclusion of enrolled participants in randomised controlled trials: What to do with ineligible participants?. BMJ Open 10(12), e039546 (2020).
Mushunje, P. K. et al. Characterization of bacterial and viral pathogens in the respiratory tract of children with HIV-associated chronic lung disease: A case-control study. BMC Infect. Dis. 24(1), 637 (2024).
Downs, S. L., Madhi, S. A., van der Merwe, L., Nunes, M. C. & Olwagen, C. P. Optimization of a high-throughput nanofluidic real-time PCR to detect and quantify of 15 bacterial species and 92 Streptococcus pneumoniae serotypes. Sci. Rep. 13(1), 4588 (2023).
Olwagen, C. P., Adrian, P. V. & Madhi, S. A. Performance of the Biomark HD real-time qPCR System (Fluidigm) for the detection of nasopharyngeal bacterial pathogens and Streptococcus pneumoniae typing. Sci. Rep. 9(1), 1–11 (2019).
Cole, T. J. Growth monitoring with the British 1990 growth reference. Arch. Dis. Child 76(1), 47–49 (1997).
Twisk, J., de Boer, M., de Vente, W. & Heymans, M. Multiple imputation of missing values was not necessary before performing a longitudinal mixed-model analysis. J. Clin. Epidemiol. 66(9), 1022–1028 (2013).
