University of Texas Health Science Center, School of Public Health, Department of Epidemiology, Human Genetics, and Environmental Sciences, Center for Infectious Diseases, Houston, TX, USA.
University of Nairobi, School of Medicine, College of Health Sciences, Nairobi, Kenya.
Int J Infect Dis. 2019 Apr;81:66-72. doi: 10.1016/j.ijid.2019.01.024. Epub 2019 Jan 17.
Diarrhea causes significant morbidity and mortality among children worldwide. Regions most affected by diarrhea include Sub-Saharan Africa and Southeast Asia, where antibiotics are in common use and can make children more vulnerable to Clostridium difficile and pathogens that are not affected by these drugs. Indeed, C. difficile is a major diarrhea-associated pathogen and poses a significant threat to vulnerable and immunocompromised populations. Yet, little is known about the role and epidemiology of C. difficile in diarrhea-associated illness among young children. As a result, C. difficile is often neglected in regions such as Sub-Saharan Africa that are most impacted by childhood diarrhea. The purpose of this study was to establish the frequency of C. difficile in young children (<5 years) with diarrhea.
Children presenting with diarrhea at a national hospital in Kenya from 2015 to 2018 were enrolled consecutively. Following informed consent by a parent or legal guardian, stool samples were obtained from the children and demographic data were collected. The stools were examined for the presence of four common pathogens known to cause diarrhea: C. difficile, rotavirus, Cryptosporidium parvum, and Giardia lamblia. C. difficile was verified by toxigenic culture and PCR. The presence of C. parvum and/or G. lamblia was determined using the ImmunoCard STAT! Crypto/Giardia Rapid assay. Rotavirus was detected by ELISA.
The study population comprised 157 children; 62.4% were male and 37.6% were female and their average age was 12.4 months. Of the 157 stool specimens investigated, 37.6% were positive for C. difficile, 33.8% for rotavirus, 5.1% for Cryptosporidium, and 5.1% for Giardia. PCR analysis identified at least one of the C. difficile-specific - genes (tcdA, tcdB, or tcdC). Further, 57.6% of the stools had C. difficile colonies bearing a frame-shift deletion in the tcdC gene, a mutation associated with increased toxin production. The frequency of C. difficile was 32.6% in children ≤12 months old and increased to 46.6% in children 12-24 months old.
In Kenyan children presenting with diarrhea, C. difficile is more prevalent than rotavirus or Cryptosporidium, two leading causes of childhood diarrhea. These findings underscore the need to better understand the role of C. difficile in children with diarrhea, especially in areas with antibiotic overuse. Understanding C. difficile epidemiology and its relationship to co-infecting pathogens among African children with diarrhea will help in devising ways of reducing diarrhea-associated illness.
腹泻在全球范围内导致儿童发病率和死亡率居高不下。受腹泻影响最严重的地区包括撒哈拉以南非洲和东南亚，这些地区抗生素的使用非常普遍，这使得儿童更容易感染艰难梭菌和不受这些药物影响的病原体。事实上，艰难梭菌是一种主要的腹泻相关病原体，对脆弱和免疫功能低下的人群构成重大威胁。然而，人们对艰难梭菌在幼儿腹泻相关疾病中的作用和流行病学知之甚少。因此，艰难梭菌在受儿童腹泻影响最大的撒哈拉以南非洲等地区往往被忽视。本研究的目的是确定艰难梭菌在腹泻幼儿（<5 岁）中的频率。
2015 年至 2018 年，肯尼亚一家国家医院连续纳入出现腹泻的儿童。在父母或法定监护人同意后，从儿童中获得粪便样本并收集人口统计学数据。检查粪便中是否存在四种常见的已知引起腹泻的病原体：艰难梭菌、轮状病毒、微小隐孢子虫和蓝氏贾第鞭毛虫。艰难梭菌通过产毒培养和 PCR 进行验证。使用 ImmunoCard STAT！Crypto/Giardia Rapid 检测试剂盒确定微小隐孢子虫和/或蓝氏贾第鞭毛虫的存在。轮状病毒通过 ELISA 检测。
研究人群包括 157 名儿童；62.4%为男性，37.6%为女性，平均年龄为 12.4 个月。在 157 份粪便标本中，37.6%为艰难梭菌阳性，33.8%为轮状病毒阳性，5.1%为微小隐孢子虫阳性，5.1%为蓝氏贾第鞭毛虫阳性。PCR 分析鉴定出至少一种艰难梭菌特异性 - 基因（tcdA、tcdB 或 tcdC）。此外，57.6%的粪便中存在 tcdC 基因框移缺失的艰难梭菌菌落，这是一种与毒素产生增加相关的突变。12 个月以下儿童的艰难梭菌发生率为 32.6%，12-24 个月儿童的发生率增加至 46.6%。
在肯尼亚出现腹泻的儿童中，艰难梭菌比轮状病毒或微小隐孢子虫更为常见，这两种病原体是儿童腹泻的主要病因。这些发现强调了需要更好地了解艰难梭菌在腹泻儿童中的作用，特别是在抗生素过度使用的地区。了解艰难梭菌在非洲腹泻儿童中的流行病学及其与合并感染病原体的关系，有助于制定减少腹泻相关疾病的方法。
