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Secondary Effects from Mass Azithromycin Administration: A Systematic Review and Meta-analysis

Jinhui LiDepartment of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China;

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Tao XiongDepartment of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China;

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Yan YueDepartment of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China;

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Imti ChoonaraAcademic Division of Child Health, University of Nottingham, Derbyshire Children’s Hospital, Derby, United Kingdom;

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Shamim QaziWorld Health Organization, Department of Maternal Newborn Child and Adolescent Health, Geneva, Switzerland;

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Jun TangDepartment of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China;

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Jing ShiDepartment of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China;

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Hua WangDepartment of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China;

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Yi QuDepartment of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China;

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Dezhi MuDepartment of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China;
Department of Pharmacy, Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education, Chengdu, Sichuan, China

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ABSTRACT.

The effects of azithromycin mass drug administration (MDA) on trachoma and yaws have been addressed. However, the secondary effects of azithromycin MDA remain unclear. This study aimed to explore the secondary effects of azithromycin MDA. PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched from conception to January 5, 2022. Studies on secondary effects of azithromycin MDA were included. A total of 34 studies were included. Six of them reported on child mortality, 10 on malaria, and 20 on general morbidity and condition. Azithromycin MDA reduced child mortality, and quarterly MDA may be most beneficial for reducing child mortality. The effect of azithromycin MDA on malaria was weak. No association was observed between azithromycin MDA and malaria parasitemia (rate ratio: 0.71, 95% confidence interval: 0.43–1.15). Azithromycin MDA was associated with a lower risk of respiratory tract infections and diarrhea. Additionally, it was associated with a lower risk of fever, vomiting, and headache. The carriage of pathogenic organisms such as Streptococcus pneumoniae and gut Campylobacter species was reduced. However, these secondary effects of azithromycin MDA appeared to last only a few weeks. Moreover, no association was observed between azithromycin MDA and nutritional improvement in children. In conclusion, azithromycin MDA had favorable secondary effects on child mortality and morbidity. However, the effects were short term.

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Author Notes

Address correspondence to Dezhi Mu or Yan Yue, No. 20, Section 3, South Renmin Road, Chengdu, Sichuan Province. E-mails: mudz@scu.edu.cn or yueyan_1994@163.com

Financial support: This work was supported by the National Science Foundation of China (Nos. 81971433, 81971428, 82171710); the grants from the WHO (WHO Registration 2018/859223-0); the National Key R&D Program of China (2021YFC2701704, 2017YFA0104200); and the grants from the Science and Technology Bureau of Sichuan Province (2021YJ0017, 2020YFS0041), the Fundamental Research Funds for the Central University (SCU2021D009), and National Key Project of Neonatal Children (1311200003303).

Authors’ addresses: Jinhui Li, Tao Xiong, Tao Xiong, Jun Tang, Jing Shi, Hua Wang, Yi Qu, and Dezhi Mu, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China, E-mails: yoyolee824@163.com, tao_xiong@126.com, yueyan_1994@163.com, tj1234753@sina.com, shijing4556@sina.com, duanwanghua@sina.com, quyi712002@163.com, and mudz@scu.edu.cn. Imti Choonara, University of Nottingham, Derbyshire Children’s Hospital, Derby, United Kingdom, E-mail: imti.choonara@nottingham.ac.uk. Shamim Qazi, Department of Maternal Newborn Child and Adolescent Health, World Health Organization, Geneva, Switzerland, E-mail: qazis550@gmail.com.

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