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2001 - 2015年莫桑比克南部低龄婴儿侵袭性细菌疾病趋势及B族链球菌分离株特征

Invasive bacterial disease trends and characterization of group B streptococcal isolates among young infants in southern Mozambique, 2001-2015.

作者信息

Sigaúque Betuel, Kobayashi Miwako, Vubil Delfino, Nhacolo Ariel, Chaúque Alberto, Moaine Benild, Massora Sérgio, Mandomando Inácio, Nhampossa Tacilta, Bassat Quique, Pimenta Fabiana, Menéndez Clara, Carvalho Maria da Gloria, Macete Eusebio, Schrag Stephanie J

机构信息

Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique.

John Snow Inc. (JSI) on the Maternal and Child Survival Program-MCSP (USAID Grantee), Maputo, Mozambique.

出版信息

PLoS One. 2018 Jan 19;13(1):e0191193. doi: 10.1371/journal.pone.0191193. eCollection 2018.

Abstract

BACKGROUND

Maternal group B streptococcal (GBS) vaccines under development hold promise to prevent GBS disease in young infants. Sub-Saharan Africa has the highest estimated disease burden, although data on incidence and circulating strains are limited. We described invasive bacterial disease (IBD) trends among infants <90 days in rural Mozambique during 2001-2015, with a focus on GBS epidemiology and strain characteristics.

METHODS

Community-level birth and mortality data were obtained from Manhiça's demographic surveillance system. IBD cases were captured through ongoing surveillance at Manhiça district hospital. Stored GBS isolates from cases underwent serotyping by multiplex PCR, antimicrobial susceptibility testing, and whole genome sequencing.

RESULTS

There were 437 IBD cases, including 57 GBS cases. Significant declines in overall IBD, neonatal mortality, and stillbirth rates were observed (P<0.0001), but not for GBS (P = 0.17). In 2015, GBS was the leading cause of young infant IBD (2.7 per 1,000 live births). Among 35 GBS isolates available for testing, 31 (88.6%) were highly related serotype III isolates within multilocus sequence types (STs) 17 (68.6%) or 109 (20.0%). All seven ST109 isolates (21.9%) had elevated minimum inhibitory concentration (MIC) to penicillin (≥0.12 μg/mL) associated with penicillin-binding protein (PBP) 2x substitution G398A. Epidemiologic and molecular data suggest this is a well-established clone.

CONCLUSION

A notable young infant GBS disease burden persisted despite improvements in overall maternal and neonatal health. We report an established strain with pbp2x point mutation, a first-step mutation associated with reduced penicillin susceptibility within a well-known virulent lineage in rural Mozambique. Our findings further underscores the need for non-antibiotic GBS prevention strategies.

摘要

背景

正在研发的B族链球菌(GBS)疫苗有望预防幼儿的GBS疾病。撒哈拉以南非洲的疾病负担估计最高,不过关于发病率和流行菌株的数据有限。我们描述了2001年至2015年莫桑比克农村地区90日龄以下婴儿侵袭性细菌疾病(IBD)的趋势,重点关注GBS的流行病学和菌株特征。

方法

社区层面的出生和死亡数据来自曼希卡人口监测系统。IBD病例通过曼希卡区医院的持续监测获取。对病例中储存的GBS分离株进行多重PCR血清分型、药敏试验和全基因组测序。

结果

共有437例IBD病例,其中57例为GBS病例。总体IBD、新生儿死亡率和死产率均显著下降(P<0.0001),但GBS病例数未下降(P = 0.17)。2015年,GBS是幼儿IBD的主要病因(每1000例活产中有2.7例)。在35株可供检测的GBS分离株中,31株(88.6%)是多位点序列类型(STs)17(68.6%)或109(20.0%)内高度相关的血清型III分离株。所有7株ST109分离株(21.9%)对青霉素的最低抑菌浓度(MIC)升高(≥0.12μg/mL),与青霉素结合蛋白(PBP)2x替代G398A有关。流行病学和分子数据表明这是一个已确立的克隆株。

结论

尽管孕产妇和新生儿的总体健康状况有所改善,但幼儿GBS疾病负担仍然显著。我们报告了一株具有pbp2x点突变的已确立菌株,这是莫桑比克农村地区一个著名的致病谱系中与青霉素敏感性降低相关的第一步突变。我们的研究结果进一步强调了非抗生素GBS预防策略的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91b3/5774717/5a16356afb1a/pone.0191193.g001.jpg

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