A multicentre study of Shigella diarrhoea in six Asian countries: disease burden, clinical manifestations, and microbiology.
A multicentre study of Shigella diarrhoea in six Asian countries: disease burden, clinical manifestations, and microbiology.
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DOI：
10.1371/journal.pmed.0030353
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发表时间：
2006-09
期刊：
影响因子：
15.8
通讯作者：
Clemens J
中科院分区：
文献类型：
--
作者：
von Seidlein L;Kim DR;Ali M;Lee H;Wang X;Thiem VD;Canh DG;Chaicumpa W;Agtini MD;Hossain A;Bhutta ZA;Mason C;Sethabutr O;Talukder K;Nair GB;Deen JL;Kotloff K;Clemens J
志贺氏菌病的负担在资源贫乏的国家最为严重。虽然这种腹泻疾病被认为造成了相当大的发病率和死亡率，全球每年有超过100万人死亡，但最近很少有数据可用于指导亚洲的干预策略。我们在6个亚洲国家进行了一项基于人群的前瞻性研究，以更好地了解目前亚洲志贺氏菌病的疾病负担、临床表现和微生物学。居住在孟加拉国、中国、巴基斯坦、印度尼西亚、越南和泰国的所有年龄段的60多万人被纳入了监测范围。在2000年至2004年期间发现的56,958例腹泻病例中，从2,927例（5%）分离出志贺氏菌。接受治疗的志贺氏菌病总发病率为每1000名居民每年2.1例，60个月以下儿童每年13.2例。40岁以后志贺氏菌病发病率增加。除泰国外，所有站点分离最多的志贺氏梭菌为福氏梭菌（1976 / 2927[68%]），泰国sonnei梭菌最常见（124/146[85%]）。弗氏单胞菌血清型在不同地点、甚至不同年份的分布上具有高度的异质性。PCR在33%的培养阴性粪便标本中检测到编码入侵质粒抗原H的基因ipaH。各地点大多数弗氏球菌分离株均对阿莫西林和复方新诺明耐药。在中国（18/305[6%]）、巴基斯坦（8/242[3%]）和越南（5/282[2%]）鉴定出耐环丙沙星的弗氏沙门氏菌分离株。志贺氏菌在亚洲贫困人口中似乎比以前认为的更为普遍，并且出现了不同种类和血清型的耐抗生素菌株。把重点放在预防志贺氏菌病上，可以立即产生效益，首先可以大幅减少该地区的总体腹泻负担，其次可以防止具有全耐药性的志贺氏菌菌株的传播。志贺氏菌种类和血清型的异质分布表明，亚洲需要多价或交叉保护性志贺氏菌疫苗来预防志贺氏菌病。在6个亚洲国家进行的一项基于人群的前瞻性研究表明，志贺氏菌在亚洲贫困人口中似乎比以前认为的更为普遍，并且出现了耐抗生素菌株。在发展中国家和其他资源匮乏的地方，引起腹泻的感染是一个主要的公共卫生问题，特别是在幼儿中。虽然近几十年来腹泻死亡人数大幅减少，但腹泻病每年仍造成约250万人死亡。志贺氏菌是一组杆状细菌，与通常生活在人类肠道中的细菌密切相关，已知在发达国家和发展中国家都会引起严重腹泻，但志贺氏菌感染（志贺氏菌病）的全球影响尚未得到很好的描述。志贺氏菌存在于40多种不同的品种中，越来越多的病例被发现对现有抗生素具有耐药性，而且除了一种口服疫苗外，中国没有批准任何疫苗。关于志贺氏菌病影响的现有最佳信息是基于历史估计，这些估计可能不准确。最近的研究表明，较早的报告可能低估了志贺氏菌病的影响。这项研究的作者希望获得对发展中国家志贺氏菌病影响的更准确的当前估计。此外，对一种志贺氏菌的免疫并不一定提供对其他类型的保护。因此，为了开发一种有效的疫苗，研究人员需要知道哪些类型的志贺氏菌在世界受影响地区引起疾病。因此，本研究的作者还想调查痢疾病例中涉及的志贺氏菌的特定类型（称为“血清型”，因为它们可以通过免疫个体的血清来区分）。研究人员在亚洲6个发展中国家建立了腹泻监测项目：3个农村或半农村地区（中国、越南和泰国）和3个城市贫民窟地区（孟加拉国、巴基斯坦和印度尼西亚）。他们在每个地区开展了宣传活动，鼓励居民在他们或他们的孩子出现腹泻的情况下到参与的诊所就诊。出现腹泻的患者被纳入研究，他们的医学发现被记录在标准化的报告表格上。获得粪便或直肠拭子标本（经患者同意）并送往实验室检测志贺氏菌。发现志贺氏菌后，对该细菌进行了血清分型并进行了抗生素耐药性检测。由于标准培养方法并不总是在志贺氏菌存在时检测到它，作为一种双重检查，研究人员还测试了一些标本中的一种DNA（称为ipaH基因），这种DNA可以作为志贺氏菌的分子“足迹”。患者按照国家指导方针接受治疗。这项研究在1-3年的时间里涉及了大约60万名参与者，发现了大约6万例腹泻病例。在5%的腹泻发作中发现志贺氏菌，这意味着每年每1000人（所有年龄段）发生2例志贺氏菌病新发病例。儿童和40岁以上人群的发病率更高。在5岁以下儿童中，每年每1 000名儿童中有13例新病例。孟加拉国站点的志贺氏菌病发病率高于中国、巴基斯坦和印度尼西亚站点，而这些站点的发病率又高于越南和泰国站点。与以前的研究相反，在志贺氏菌病发作后未发现死亡，不到三分之一的志贺氏菌病病例伴有血性腹泻（痢疾）。发现血清型的分布在不同的地点和同一地点随时间不同而不同。在所有地点检测到的志贺氏菌对两种或两种以上抗生素具有耐药性的比例很高。ipaH基因检测能够在半数常规粪便培养未发现志贺氏菌的血性腹泻患者中识别出志贺氏菌。这项研究发现，志贺氏菌病在这些亚洲地区的发病率大约是工业化国家的100倍。志贺氏菌病经常发生在没有血便的情况下，这一发现意味着政府将痢疾作为病例定义一部分的数据收集可能会遗漏大多数志贺氏菌病病例。此外，40岁以上的志贺氏菌病发病率增加表明，老年人在很大程度上分担了志贺氏菌病的负担（并最有可能传播）。志贺氏菌相关腹泻的临床病程通常是良性的，这让人们对全球疫苗开发工作中应优先考虑这种疾病提出了质疑，特别是考虑到血清型分布复杂多变所带来的技术挑战。尽管如此，耐多药菌株的出现显然仍然是一种威胁，并提出了一个长期的问题，即改善卫生设施，而不是开发新的抗生素，作为解决水传播疾病过多的长期解决办法，这些疾病对发展中国家的影响不成比例。请通过本摘要的在线版本http://dx.doi.org/10.1371/journal.pmed.0030353访问这些网站。世界卫生组织腹泻主题页面疾病控制和预防中心：志贺氏菌病维基百科志贺氏菌条目（注：维基百科是一个免费的互联网百科全书，任何人都可以编辑）
The burden of shigellosis is greatest in resource-poor countries. Although this diarrheal disease has been thought to cause considerable morbidity and mortality in excess of 1,000,000 deaths globally per year, little recent data are available to guide intervention strategies in Asia. We conducted a prospective, population-based study in six Asian countries to gain a better understanding of the current disease burden, clinical manifestations, and microbiology of shigellosis in Asia. Over 600,000 persons of all ages residing in Bangladesh, China, Pakistan, Indonesia, Vietnam, and Thailand were included in the surveillance. Shigella was isolated from 2,927 (5%) of 56,958 diarrhoea episodes detected between 2000 and 2004. The overall incidence of treated shigellosis was 2.1 episodes per 1,000 residents per year in all ages and 13.2/1,000/y in children under 60 months old. Shigellosis incidence increased after age 40 years. S. flexneri was the most frequently isolated Shigella species (1,976/2,927 [68%]) in all sites except in Thailand, where S. sonnei was most frequently detected (124/146 [85%]). S. flexneri serotypes were highly heterogeneous in their distribution from site to site, and even from year to year. PCR detected ipaH, the gene encoding invasion plasmid antigen H in 33% of a sample of culture-negative stool specimens. The majority of S. flexneri isolates in each site were resistant to amoxicillin and cotrimoxazole. Ciprofloxacin-resistant S. flexneri isolates were identified in China (18/305 [6%]), Pakistan (8/242 [3%]), and Vietnam (5/282 [2%]). Shigella appears to be more ubiquitous in Asian impoverished populations than previously thought, and antibiotic-resistant strains of different species and serotypes have emerged. Focusing on prevention of shigellosis could exert an immediate benefit first by substantially reducing the overall diarrhoea burden in the region and second by preventing the spread of panresistant Shigella strains. The heterogeneous distribution of Shigella species and serotypes suggest that multivalent or cross-protective Shigella vaccines will be needed to prevent shigellosis in Asia. A prospective, population-based study in six Asian countries showed thatShigella appears to be more ubiquitous in Asian impoverished populations than previously thought, and antibiotic-resistant strains have emerged. Infections that cause diarrhea are a major public health problem in developing countries and other places where resources are scarce, particularly in young children. Although deaths from diarrhea have decreased considerably in recent decades, diarrheal illnesses continue to cause some 2.5 million deaths each year. Shigella, a group of rod-shaped bacteria closely related to those that normally live in the human intestine, is known to cause severe diarrhea in both developed and developing countries, but the global impact of Shigella infection (shigellosis) has not been well characterized. Shigella exists in more than 40 different varieties, an increasing number of cases have been found to be resistant to available antibiotics, and no vaccine is licensed except one oral vaccine in China. The best information available on the impact of shigellosis has been based on historical estimates, which are subject to inaccuracy. More recent studies suggest that the older reports may have underestimated the impact of shigellosis. The authors of this study wanted to obtain more accurate, current estimates of the impact of shigellosis in developing countries. In addition, immunity to one type of Shigella does not necessarily provide protection against other types. Therefore, in order to develop an effective vaccine, researchers would need to know which types of Shigella are causing illness in affected parts of the world. Accordingly, the authors of this study also wanted to investigate the specific types of Shigella (called “serotypes” because they can be distinguished using serum from immune individuals) involved in cases of diarrhea. The researchers set up surveillance projects for diarrhea in six developing countries throughout Asia: at three rural or semirural sites (in China, Vietnam, and Thailand) and three urban slum sites (in Bangladesh, Pakistan, and Indonesia). They conducted information campaigns in each area to encourage residents to visit a participating clinic if they or their children developed diarrhea. Patients presenting with diarrhea were enrolled in the study and their medical findings were documented on standardized report forms. Stool or rectal swab specimens were obtained (with patient consent) and sent to laboratories to test for Shigella. When Shigella was identified, the bacteria was serotyped and tested for resistance to antibiotics. Because standard culture methods do not always detect Shigella when it is present, as a double-check, the researchers also tested some of the specimens for a type of DNA (called the ipaH gene) that serves as a molecular “footprint” of Shigella. Patients received treatment according to national guidelines. The study involved approximately 600,000 participants over 1–3 years, and detected approximately 60,000 cases of diarrhea. Shigella was found in 5% of diarrhea episodes, meaning that two new cases of shigellosis occurred per 1,000 people (of all ages) per year. Rates were higher in children and in people over age 40. Among children less than 5 years old, there were 13 new cases per 1,000 children per year. Rates of shigellosis were higher in the Bangladesh site than in the China, Pakistan, and Indonesia sites, which in turn had higher rates than the Vietnam and Thailand sites. In contrast to prior studies, no deaths were detected following episodes of shigellosis, and less than one-third of cases of shigellosis were associated with bloody diarrhea (dysentery). The distribution of serotypes was found to differ from one site to another and within a given site over time. A high percentage of Shigella detected at all sites were resistant to two or more antibiotics. Testing for the ipaH gene was able to identify Shigella in half of patients with bloody diarrhea whose routine stool cultures did not reveal Shigella. This study found that shigellosis occurs in these Asian sites at a rate approximately 100 times higher than in industrialized countries. The finding that shigellosis frequently occurs in the absence of bloody stool means that government data collections using dysentery as part of the case definition can be expected to miss the majority of shigellosis cases. Also, the increased rate of shigellosis above age 40 shows that older people share significantly in the burden (and most likely the transmission) of shigellosis. The generally benign clinical course of Shigella-associated diarrhea calls into question the priority that this disease should receive in global vaccine development efforts, especially given the technological challenges posed by the complex and variable distribution of serotypes. Nonetheless, the emergence of multidrug-resistant strains clearly remains a threat, and raises the perennial issue of improved sanitation, rather than new antibiotics, as a long-term solution to the plethora of water-borne illnesses that disproportionately affect developing countries. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030353. World Health Organization topic page on diarrhea Centers for Disease Control and Prevention: Shigellosis Wikipedia entry on Shigella (note: Wikipedia is a free Internet encyclopedia that anyone can edit)
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影响因子：
11.8
作者：
Gupta, A;Polyak, CS;Mintz, ED
通讯作者：
Mintz, ED
影响因子：
4.9
作者：
Pazhani, GP;Sarkar, B;Niyogi, SK
通讯作者：
Niyogi, SK
影响因子：
5
作者：
FERRECCIO, C;PRADO, V;LEVINE, MM
通讯作者：
LEVINE, MM
影响因子：
3.1
作者：
Kotloff, KL;Noriega, FR;Levine, MM
通讯作者：
Levine, MM
影响因子：
5.5
作者：
KOTLOFF, KL;NATARO, JP;LEVINE, MM
通讯作者：
LEVINE, MM