Acquisition and loss of Neisseria meningitidis carriage in households in Mali

描述（由申请人提供）：在非洲脑膜炎带（从塞内加尔延伸到埃塞俄比亚的地区），由脑膜炎奈瑟菌引起的脑膜炎球菌性脑膜炎暴发是造成大量发病率和死亡率的原因。与侵袭性疾病相比，无症状的脑膜炎奈索菌咽部定植（称为携带）相对常见，携带者是主要传播源。已经开发出一种负担得起的脑膜炎球菌结合血清A组疫苗，以减轻脑膜炎球菌疾病的负担，但尚未在该区域推广。为了阻断传播和预防流行性脑膜炎，新开发的疫苗将需要预防或减少携带。在引入这种疫苗之前，需要进行研究，以进一步确定这种情况下的流行病学和基本的自然历史。本研究与脑膜炎传播联盟（一项旨在确定脑膜炎奈菌传播流行病学特征的国际合作努力）和马里巴马科疫苗开发中心（CVD-Mali）合作，主要目的是调查家庭内感染和失传率，估计感染的平均持续时间，并评估感染的潜在风险因素。此外，其目的是在将这一研究设计引入脑膜炎带的七个国家之前，对发展中国家家庭进行纵向随访的实地和实验室试验方案进行试点。为了达到这些目的，我们建议进行一项以家庭为基础的脑膜炎奈瑟菌携带纵向研究，随访12个月。将对家庭进行随机抽样，以确定至少有一个携带者的家庭。最终，每月将有20个拥有运营商的家庭注册并访问。在每次访问时，将从所有家庭成员中收集口咽拭子以确定带菌者状态，并进行问卷调查以评估潜在的风险因素。将在实验室使用细菌学和分子方法分析拭子，以确定所携带菌株的特定血清群以及家庭成员所携带菌株之间的相关性。这些数据将使调查人员能够评估携带者状态随时间的变化，并确定马里一般人群中脑膜炎奈瑟菌携带者的基本流行病学。这项研究是了解脑膜炎奈瑟菌持续和传播动力学的重要一步。该项目将对研究领域产生实质性的、强有力的影响，为将在七个国家进行的类似纵向研究奠定基础。这项拟议的研究还将为评估非洲新型脑膜炎球菌血清A组疫苗的直接和间接影响提供基线数据。迫切需要试点试验场和实验室方案，以确定在这种情况下对脑膜炎奈瑟菌携带者进行纵向随访的可行性和可接受性。

DESCRIPTION (provided by applicant): Meningococcal meningitis outbreaks caused by Neisseria meningitidis are responsible for significant morbidity and mortality in the African meningitis belt, a region stretching from Senegal to Ethiopia. Asymptomatic pharyngeal colonization with N. meningitidis, known as carriage, is relatively common compared to invasive disease, and carriers are the primary source of transmission. An affordable conjugate meningococcal serogroup A vaccine has been developed to reduce the burden of meningococcal disease, but it has not yet been introduced into the region. To interrupt transmission and prevent epidemic meningitis, the newly developed vaccine will need to prevent or reduce carriage. Prior to the introduction of this vaccine, studies are needed to further define the epidemiology and basic natural history of carriage in this context. In partnership with the Meningitis Carriage Consortium, an international collaborative effort to characterize the epidemiology of N. meningitidis carriage, and the Centre pour le Diveloppement des Vaccins (CVD-Mali) in Bamako, Mali, the main objective of this study is to investigate rates of acquisition and loss of carriage within households over time, to estimate the average duration of carriage, and to evaluate potential risk factors for carriage. In addition, the aim is to pilot test field and lab protocols for longitudinal follow-up of households in a developing country setting prior to introducing this study design in seven countries of the meningitis belt. To meet these Aims, we propose a household-based longitudinal study of N. meningitidis carriage with 12 months of follow-up. Households will be randomly sampled to identify those households with at least one carrier. Ultimately, 20 households with carriers will be enrolled in and visited monthly. At each visit, an oropharyngeal swab will be collected from all members of the household to determine carrier status and a questionnaire administered to assess potential risk factors. Swabs will be analyzed in the lab using bacteriological and molecular methods to determine the specific serogroup of the strain being carried and the relatedness between strains carried by household members. These data will allow investigators to assess changes in carrier status over time and to define the basic epidemiology of N. meningitidis carriage in the general population in Mali. This study is an important step towards understanding the dynamics of persistence and spread of N. meningitidis. This project will exert a substantive, powerful influence on the research field by laying the foundation for similar longitudinal studies to be carried out in seven countries. This proposed study will also provide baseline data for evaluating the direct and indirect effects of the new meningococcal serogroup A vaccine in Africa. There is a significant need to pilot test field and lab protocols to determine the feasibility and acceptability of longitudinal follow-up of carriers of N. meningitidis in this setting. PUBLIC HEALTH RELEVANCE: This proposed study is relevant to public health because it will further our understanding of the epidemiology and natural history of N. meningitidis carriage, which is one of the primary targets for reducing transmission and preventing outbreaks of invasive meningococcal disease in the African meningitis belt. Our aim is to provide necessary baseline longitudinal data about the average duration of carriage, rates of acquisition and loss, and potential risk factors for carriage within households. Knowledge about these characteristics and the ability to pilot test this design will contribute to the implementation of the same design in seven African countries, which will ultimately assist in the evaluation a new conjugate meningococcal serogroup A vaccine.