Acquisition and loss of Neisseria meningitidis carriage in households in Mali

描述(申请人提供)：由脑膜炎奈瑟氏菌引起的脑膜炎双球菌脑膜炎暴发是非洲脑膜炎带严重发病率和死亡率的原因，该地区从塞内加尔延伸到埃塞俄比亚。与侵袭性疾病相比，无症状的脑膜炎奈瑟氏菌咽部定植(称为携带者)相对常见，携带者是主要的传播来源。已开发出一种负担得起的A群脑膜炎双球菌结合疫苗，以减轻脑膜炎双球菌疾病的负担，但尚未在该地区推广。为了阻断传播和预防流行性脑膜炎，新开发的疫苗将需要防止或减少携带。在引入这种疫苗之前，需要进行研究，以进一步确定在这方面的流行病学和基本的自然携带史。这项研究的主要目的是与脑膜炎携带者联合会和马里巴马科疫苗接种发展中心(CVD-马里)合作，调查家庭内随时间的携带率和携带率，估计携带者的平均持续时间，并评估携带者的潜在风险因素。此外，目的是在脑膜炎带的七个国家引入这项研究设计之前，在发展中国家对家庭进行纵向跟踪的试验场和实验室方案。为了达到这些目标，我们提出了一项以家庭为基础的脑膜炎奈瑟氏菌携带者的纵向研究，并进行了12个月的随访。家庭将被随机抽样，以确定那些至少有一种携带者的家庭。最终，每月将有20个拥有运营商的家庭注册和访问。在每次访问时，将从所有家庭成员那里收集口咽拭子以确定携带者状况，并发出问卷以评估潜在的风险因素。实验室将使用细菌学和分子方法对拭子进行分析，以确定携带的菌株的特定血清组以及家庭成员携带的菌株之间的亲缘关系。这些数据将使调查人员能够评估随着时间的推移携带者状况的变化，并确定马里普通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氏菌持续和传播的动力学的重要一步。该项目将对研究领域产生实质性的、强有力的影响，为在七个国家开展类似的纵向研究奠定基础。这项拟议的研究还将为评估新的A群脑膜炎双球菌疫苗在非洲的直接和间接影响提供基线数据。在这种情况下，有必要对试验场和实验室方案进行试点，以确定脑膜炎奈瑟菌携带者纵向随访的可行性和可接受性。 公共卫生相关性：这项拟议的研究与公共卫生相关，因为它将加深我们对携带脑膜炎奈瑟菌的流行病学和自然历史的了解，这是减少传播和预防侵袭性脑膜炎球菌病在非洲脑膜炎带暴发的主要目标之一。我们的目标是提供必要的基准纵向数据，关于家庭内运输的平均持续时间、获得率和损失率以及潜在的风险因素。了解这些特征和对这一设计进行试点测试的能力将有助于在七个非洲国家实施相同的设计，这最终将有助于评估一种新的A群脑膜炎双球菌结合血清疫苗。

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.