THE EPIDEMIOLOGY OF SCRUB TYPHUS AND RICKETTISIAL INFECTIONS IN A HIGHLY ENDEMIC RURAL SETTING IN SOUTH INDIA: POPULATION-BASED COHORT STUDY

印度南部高度流行的农村地区恙虫病和立克次体感染的流行病学：基于人群的队列研究

• 批准号: MR/S023275/1
• 负责人: Wolf-Peter Schmidt
• 金额: $ 97.85万
• 依托单位: London School of Hygiene & Tropical Medicine
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS023275%2F1
• 关键词: EPIDEMIOLOGY; SCRUB; TYPHUS; RICKETTISIAL; INFECTIONS

Scrub typhus is a bacterial infection causing febrile illness in many tropical and subtropical countries in East, South East and South Asia. Countries where scrub typhus occurs include India, China, Bangladesh, Pakistan, Indonesia, Vietnam, Thailand, Japan and Australia. The bacterium (Orienta tsutsugamushi) is transmitted by the larvae of mites during blood-feeding. Scrub typhus can lead to severe complications including lung failure, kidney failure and brain infection. Scrub typhus appears to be very common in affected regions, accounting for up to a third of all fever cases in some settings. Nevertheless, little is known with respect to the transmission of scrub typhus. Scrub typhus is one of the most neglected tropical infections in terms of research, clinical management and prevention. We do not know how many cases develop fever after infection and how many cases with fever develop complications. We further do not know how scrub typhus infection is transmitted in the community and what role rodents play in attracting mite larvae. This study is the first large scale cohort study specifically designed to gain a fundamental understanding of scrub typhus epidemiology in a region that is highly affected by the disease. While the main emphasis of this study is on scrub typhus as the most important infection, we will study two less common infections caused by very similar bacteria called Rickettsia: flea-borne murine typhus and tick-borne spotted fever. The study will be conducted in South India (Tamil Nadu) and follows up 40,000 people living in affected villages. Participants will be followed up at 2 monthly intervals to ask for the occurrence of fever in the past 2 months. We will take blood samples of all identified fever cases and test for the three infections (scrub typhus, murine typhus and spotted fever). They will be asked to proactively come to study clinics in the case of any fever or subfebrile temperature. In these ongoing fever cases we will do additional blood tests including polymerase chain reaction to understand the genetic variety of Orienta tsutsugamushi. Participants will be asked questionnaires regarding living conditions, socio-economic data and occupational factors. We will use satellite images and GPS data to study the geographical risk factors for scrub typhus and Rickettsia infections. We will catch rodents (the main carriers of infected mite larvae) at different locations in the study area and explore whether there is a relationship between the number of infected mite larvae on rodents and the occurrence of human cases in the neighbourhood. The data collected in this study will be used to estimate the incidence of scrub typhus and severe scrub typhus in the community. We will calculate household and spatial risk factors for scrub typhus and the economic impact of scrub typhus in the community. While expected case numbers for murine typhus and spotted fever may be lower, we aim at estimating most of these same parameters for these two infections as well alongside scrub typhus.The data from this study will help doctors to decide on treatment approaches and public health services to decide on intervention efforts. The immunological data will help vaccine developers to understand better how scrub typhus infection confers immunity. Data on rodents and mites will help inform disease control policies. Data on murine typhus and spotted fever will provide a basic understanding of the epidemiology of these rarely studied infections.

恙虫病是一种细菌感染，在东亚、东南亚和南亚的许多热带和亚热带国家引起发热性疾病。发生恙虫病的国家包括印度、中国、孟加拉国、巴基斯坦、印度尼西亚、越南、泰国、日本和澳大利亚。恙虫病东方体（Orienta tsugamushi）是由螨类的幼虫在吸血过程中传播的。恙虫病可导致严重的并发症，包括肺衰竭、肾衰竭和脑感染。恙虫病似乎在受影响地区非常常见，在某些情况下占所有发热病例的三分之一。然而，关于恙虫病的传播知之甚少。恙虫病是在研究、临床管理和预防方面最被忽视的热带传染病之一。我们不知道有多少人在感染后发烧，又有多少人发烧后出现并发症。我们也不知道恙虫病感染是如何在社区传播的，啮齿动物在吸引螨幼虫方面起着什么作用。这项研究是第一个大规模的队列研究，专门设计来获得一个基本的了解，在一个地区，是高度受疾病的恙虫病流行病学。虽然本研究的主要重点是将恙虫病作为最重要的感染，但我们将研究两种由非常相似的称为立克次体的细菌引起的不太常见的感染：蚤传播的鼠斑疹伤寒和蜱传播的斑点热。这项研究将在印度南部（泰米尔纳德邦）进行，并对生活在受影响村庄的4万人进行跟踪调查。受试者将每隔2个月接受一次随访，询问过去2个月内是否发生发热。我们会抽取所有确诊发烧个案的血液样本，测试三种感染（恙虫病、鼠斑疹伤寒及斑疹热）。如果患者出现任何发热或亚热体温，将要求他们主动前往研究诊所。在这些持续发热的病例中，我们将做额外的血液检测，包括聚合酶链反应，以了解恙虫病东方体的遗传多样性。参加者将收到关于生活条件、社会经济数据和职业因素的问卷。我们将利用卫星图像和全球定位系统数据研究恙虫病和立克次体感染的地理风险因素。我们会在研究区内不同地点捕捉啮齿动物（受感染螨幼虫的主要带菌者），并探讨啮齿动物身上受感染螨幼虫的数目与邻近地区出现人类感染个案是否有关系。本研究收集的数据将用于估计社区中恙虫病和重症恙虫病的发病率。我们将计算家庭和空间的风险因素，恙虫病和恙虫病在社区的经济影响。虽然鼠斑疹伤寒和斑点热的预期病例数可能较低，但我们的目标是估计这两种感染以及恙虫病的大多数相同参数，这项研究的数据将有助于医生决定治疗方法和公共卫生服务决定干预措施。免疫学数据将帮助疫苗开发人员更好地了解恙虫病感染如何赋予免疫力。关于啮齿动物和螨类的数据将有助于为疾病控制政策提供信息。关于鼠斑疹伤寒和斑点热的数据将提供对这些很少研究的感染的流行病学的基本了解。

项目成果

High initial IgG antibody levels against Orientia tsutsugamushi are associated with an increased risk of severe scrub typhus infection.

• DOI: 10.1371/journal.pntd.0009283
• 发表时间: 2021-03
• 期刊: PLoS neglected tropical diseases
• 影响因子: 3.8
• 作者: Devamani CS;Prakash JAJ;Alexander N;Stone W;Gunasekaran K;Rose W;Schmidt WP
• 通讯作者: Schmidt WP

The incidence of Orientia tsutsugamushi infection in rural South India.

• DOI: 10.1017/s0950268822001170
• 发表时间: 2022-06-29
• 期刊: EPIDEMIOLOGY AND INFECTION
• 影响因子: 4.2
• 作者: Devamani, Carol S.;Prakash, John A. J.;Alexander, Neal;Stenos, John;Schmidt, Wolf-Peter
• 通讯作者: Schmidt, Wolf-Peter