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

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。发生丛林斑疹伤寒的国家包括印度、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。恙虫病病菌（东方恙虫病）是由螨类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、肾衰竭和脑部感染。恙虫病在受影响地区似乎非常常见，在某些情况下占所有发热病例的三分之一。然而，对恙虫病的传播知之甚少。在研究、临床管理和预防方面，恙虫病是最被忽视的热带感染之一。我们不知道有多少病例在感染后出现发热，也不知道有多少发热病例出现并发症。此外，我们还不清楚恙虫病是如何在社区传播的，以及啮齿动物在吸引螨幼虫方面起什么作用。本研究是第一个大规模队列研究，专门用于在受恙虫病严重影响的地区获得对恙虫病流行病学的基本了解。虽然本研究的重点是将恙虫病作为最重要的感染，但我们将研究由非常相似的立克次体细菌引起的两种不太常见的感染：跳蚤传播的鼠斑疹伤寒和蜱传播的斑疹热。这项研究将在印度南部（泰米尔纳德邦）进行，并跟踪调查生活在受影响村庄的4万人。每2个月随访一次，询问近2个月发热情况。我们将对所有已查明的发热病例采集血样，并检测三种感染（恙虫病、鼠斑疹伤寒和斑疹热）。他们将被要求在任何发烧或低体温的情况下主动来研究诊所。在这些持续发热病例中，我们将进行额外的血液检测，包括聚合酶链反应，以了解东方恙虫病的遗传多样性。参与者将被问及有关生活条件、社会经济数据和职业因素的问卷。我们将利用卫星图像和GPS数据研究丛林斑疹伤寒和立克次体感染的地理危险因素。我们将在研究区域的不同地点捕获啮齿动物（感染螨幼虫的主要载体），探讨啮齿动物身上感染螨幼虫的数量与附近人类病例的发生是否存在关系。本研究收集的数据将用于估计社区中恙虫病和重度恙虫病的发病率。我们将计算灌木林斑疹伤寒的家庭和空间风险因素以及灌木林斑疹伤寒对社区的经济影响。虽然鼠斑疹伤寒和斑疹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丛林斑疹伤寒的大多数相同参数。本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力度。免疫学数据将帮助疫苗开发人员更好地了解恙虫病感染是如何产生免疫力的。有关啮齿动物和螨虫的数据将有助于制定疾病控制政策。关于鼠斑疹伤寒和斑疹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。

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.