Abstract：
Approximately 2.9 million people worldwide suffer from cholera each year, many of whom are destitute. However, understanding of immunity against cholera is still limited. Several studies have reported the duration of antibodies following cholera; however, systematic reviews including a quantitative synthesis are lacking.
To meta-analyze cohort studies that have evaluated vibriocidal, cholera toxin B subunit (CTB), and lipopolysaccharide (LPS) antibody levels following a clinical cholera case.
Design: Systematic review and meta-analysis. We searched PubMed and Web of science for studies assessing antibodies against Vibrio cholerae in cohorts of patients with clinical cholera. Two authors independently extracted data and assessed the quality of included studies. Random effects models were used to pool antibody titers in adults and older children (aged ≥ 6 years). In sensitivity analysis, studies reporting data on young children (2-5 years) were included.
Nine studies met our inclusion criteria for systematic review and seven for meta-analysis. The pooled mean of vibriocidal antibody titers in adults and older children (aged ≥ 6 years) was 123 on day 2 post-symptom onset, which sharply increased on day 7 (pooled mean = 6956) and gradually waned to 2247 on day 30, 578 on day 90, and 177 on day 360. Anti-CTB IgA antibodies also peaked on day 7 (pooled mean = 49), followed by a rapid decrease on day 30 (pooled mean = 21), and further declined on day 90 (pooled mean = 10), after which it plateaued from day 180 (pooled mean = 8) to 360 (pooled mean = 6). Similarly, anti-CTB IgG antibodies peaked in early convalescence between days 7 (pooled mean = 65) and 30 (pooled mean = 69), then gradually waned on days 90 (pooled mean = 42) and 180 (pooled mean = 30) and returned to baseline on day 360 (pooled mean = 24). Anti-LPS IgA antibodies peaked on day 7 (pooled mean = 124), gradually declined on day 30 (pooled mean = 44), which persisted until day 360 (pooled mean = 10). Anti LPS IgG antibodies peaked on day 7 (pooled mean = 94). Thereafter, they decreased on day 30 (pooled mean = 85), and dropped further on days 90 (pooled mean = 51) and 180 (pooled mean = 47), and returned to baseline on day 360 (pooled mean = 32). Sensitivity analysis including data from young children (aged 2-5 years) showed very similar findings as in the primary analysis.
This study confirms that serological antibody (vibriocidal, CTB, and LPS) titers return to baseline levels within 1 year following clinical cholera, i.e., before the protective immunity against subsequent cholera wanes. However, this decay should not be interpreted as waning immunity because immunity conferred by cholera against subsequent disease lasts 3-10 years. Our study provides evidence for surveillance strategies and future research on vaccines and also demonstrates the need for further studies to improve our understanding of immunity against cholera.
To meta-analyze cohort studies that have evaluated vibriocidal, cholera toxin B subunit (CTB), and lipopolysaccharide (LPS) antibody levels following a clinical cholera case.
Design: Systematic review and meta-analysis. We searched PubMed and Web of science for studies assessing antibodies against Vibrio cholerae in cohorts of patients with clinical cholera. Two authors independently extracted data and assessed the quality of included studies. Random effects models were used to pool antibody titers in adults and older children (aged ≥ 6 years). In sensitivity analysis, studies reporting data on young children (2-5 years) were included.
Nine studies met our inclusion criteria for systematic review and seven for meta-analysis. The pooled mean of vibriocidal antibody titers in adults and older children (aged ≥ 6 years) was 123 on day 2 post-symptom onset, which sharply increased on day 7 (pooled mean = 6956) and gradually waned to 2247 on day 30, 578 on day 90, and 177 on day 360. Anti-CTB IgA antibodies also peaked on day 7 (pooled mean = 49), followed by a rapid decrease on day 30 (pooled mean = 21), and further declined on day 90 (pooled mean = 10), after which it plateaued from day 180 (pooled mean = 8) to 360 (pooled mean = 6). Similarly, anti-CTB IgG antibodies peaked in early convalescence between days 7 (pooled mean = 65) and 30 (pooled mean = 69), then gradually waned on days 90 (pooled mean = 42) and 180 (pooled mean = 30) and returned to baseline on day 360 (pooled mean = 24). Anti-LPS IgA antibodies peaked on day 7 (pooled mean = 124), gradually declined on day 30 (pooled mean = 44), which persisted until day 360 (pooled mean = 10). Anti LPS IgG antibodies peaked on day 7 (pooled mean = 94). Thereafter, they decreased on day 30 (pooled mean = 85), and dropped further on days 90 (pooled mean = 51) and 180 (pooled mean = 47), and returned to baseline on day 360 (pooled mean = 32). Sensitivity analysis including data from young children (aged 2-5 years) showed very similar findings as in the primary analysis.
This study confirms that serological antibody (vibriocidal, CTB, and LPS) titers return to baseline levels within 1 year following clinical cholera, i.e., before the protective immunity against subsequent cholera wanes. However, this decay should not be interpreted as waning immunity because immunity conferred by cholera against subsequent disease lasts 3-10 years. Our study provides evidence for surveillance strategies and future research on vaccines and also demonstrates the need for further studies to improve our understanding of immunity against cholera.
摘要：
全世界每年约有290万人患有霍乱。他们中的许多人是贫困的。然而,对霍乱免疫力的了解仍然有限。一些研究报道了霍乱后抗体的持续时间；然而，缺乏包括定量综合在内的系统评价。
对评估了杀弧菌的队列研究进行荟萃分析，霍乱毒素B亚基（CTB），和临床霍乱病例后的脂多糖（LPS）抗体水平。
设计：系统评价和荟萃分析。我们搜索了PubMed和Webofscience，以评估临床霍乱患者队列中抗霍乱弧菌抗体的研究。两位作者独立提取数据并评估纳入研究的质量。随机效应模型用于汇集成人和年龄较大的儿童(年龄≥6岁)的抗体滴度。在敏感性分析中，纳入了报告幼儿(2~5岁)数据的研究.
9项研究符合我们系统评价的纳入标准，7项研究符合荟萃分析的纳入标准。在症状发作后第2天，成人和年龄较大的儿童（年龄≥6岁）的抗弧菌抗体滴度的合并平均值为123，在第7天急剧增加（合并平均值=6956），并在第30天逐渐减弱至2247，在第90天逐渐减弱至578，在第360天逐渐减弱至177。抗CTBIgA抗体也在第7天达到峰值（合并平均值=49），随后在第30天迅速下降(合并平均值=21)，在第90天进一步下降(合并平均值=10)，此后从第180天(合并平均值=8)稳定到360天(合并平均值=6)。同样，抗CTBIgG抗体在第7天（合并平均值=65）和第30天（合并平均值=69）之间的早期康复中达到峰值，然后在第90天(合并平均值=42)和第180天(合并平均值=30)逐渐减弱,并在第360天(合并平均值=24)恢复至基线.抗LPSIgA抗体在第7天达到峰值（合并平均值=124），在第30天逐渐下降(合并平均值=44)，一直持续到第360天(合并平均值=10)。抗LPSIgG抗体在第7天达到峰值(合并平均值=94)。此后,它们在第30天下降(合并平均值=85)，在第90天（合并平均值=51）和第180天（合并平均值=47）进一步下降，并在第360天返回基线（合并平均值=32）。包括来自幼儿（2-5岁）的数据在内的敏感性分析显示出与主要分析非常相似的发现。
这项研究证实了血清学抗体(杀弧菌，CTB,和LPS）滴度在临床霍乱后1年内恢复到基线水平，即，在针对随后的霍乱的保护性免疫力减弱之前。然而,这种衰变不应被解释为免疫力下降，因为霍乱对随后疾病的免疫力持续3-10年。我们的研究为疫苗的监测策略和未来研究提供了证据，也表明需要进一步研究以提高我们对霍乱免疫的理解。
对评估了杀弧菌的队列研究进行荟萃分析，霍乱毒素B亚基（CTB），和临床霍乱病例后的脂多糖（LPS）抗体水平。
设计：系统评价和荟萃分析。我们搜索了PubMed和Webofscience，以评估临床霍乱患者队列中抗霍乱弧菌抗体的研究。两位作者独立提取数据并评估纳入研究的质量。随机效应模型用于汇集成人和年龄较大的儿童(年龄≥6岁)的抗体滴度。在敏感性分析中，纳入了报告幼儿(2~5岁)数据的研究.
9项研究符合我们系统评价的纳入标准，7项研究符合荟萃分析的纳入标准。在症状发作后第2天，成人和年龄较大的儿童（年龄≥6岁）的抗弧菌抗体滴度的合并平均值为123，在第7天急剧增加（合并平均值=6956），并在第30天逐渐减弱至2247，在第90天逐渐减弱至578，在第360天逐渐减弱至177。抗CTBIgA抗体也在第7天达到峰值（合并平均值=49），随后在第30天迅速下降(合并平均值=21)，在第90天进一步下降(合并平均值=10)，此后从第180天(合并平均值=8)稳定到360天(合并平均值=6)。同样，抗CTBIgG抗体在第7天（合并平均值=65）和第30天（合并平均值=69）之间的早期康复中达到峰值，然后在第90天(合并平均值=42)和第180天(合并平均值=30)逐渐减弱,并在第360天(合并平均值=24)恢复至基线.抗LPSIgA抗体在第7天达到峰值（合并平均值=124），在第30天逐渐下降(合并平均值=44)，一直持续到第360天(合并平均值=10)。抗LPSIgG抗体在第7天达到峰值(合并平均值=94)。此后,它们在第30天下降(合并平均值=85)，在第90天（合并平均值=51）和第180天（合并平均值=47）进一步下降，并在第360天返回基线（合并平均值=32）。包括来自幼儿（2-5岁）的数据在内的敏感性分析显示出与主要分析非常相似的发现。
这项研究证实了血清学抗体(杀弧菌，CTB,和LPS）滴度在临床霍乱后1年内恢复到基线水平，即，在针对随后的霍乱的保护性免疫力减弱之前。然而,这种衰变不应被解释为免疫力下降，因为霍乱对随后疾病的免疫力持续3-10年。我们的研究为疫苗的监测策略和未来研究提供了证据，也表明需要进一步研究以提高我们对霍乱免疫的理解。
