I. Adetifa, KEMRI-Wellcome Trust Research Programme, Kenya, Seroepidemiology for monitoring vaccination and informing vaccine policy in Africa

尽管疫苗对于预防许多严重且往往是致命的疾病是必不可少的，但它们只有在接种时才是有益的，因此它们的影响在很大程度上取决于实现高疫苗接种率。因此，疫苗接种覆盖率指数被广泛用于监测疫苗接种方案。疫苗接种覆盖率通常根据12-23个月大的儿童在12个月大时接种第三剂含白喉-百日咳-破伤风(DPT3)疫苗的比例进行评估。DPT3的覆盖范围通常来自行政记录(疫苗诊所的登记和疫苗消费总剂量的记录)。它也可以通过对疫苗卡/记录的家庭调查或通过要求照顾者通过回忆确认接种疫苗来获得。从行政记录获得的复盖率估计经常高估低收入和中等收入国家的复盖率，原因是跟踪疫苗剂量消费的错误和对目标人口的错误估计。虽然调查方法提供了更准确的估计，但它们扰乱了常规卫生服务，而且成本高昂。其他弱点包括对目标人口的描述不完整、报告不足以及缺少和(或)不完整的信息。重要的是，疫苗接种覆盖率的估计必须尽可能准确，特别是在接种疫苗时，即接种疫苗并不总是导致免疫接种，免疫接种被定义为疫苗诱导的针对目标疾病的保护。例如，在接种麻疹疫苗后，9个月大的儿童产生保护性抗体水平的比例约为85%，12个月大的儿童比例约为95%。传统的测量覆盖率的方法并没有告诉我们有多大比例的人口对感兴趣的疾病具有免疫力。在高收入国家，开展国家血清学调查以获取血液样本，以衡量接种疫苗保护的人口比例。对这些血样进行检测，看是否有针对疫苗产生的抗体。因此，这些国家在引入疫苗之前使用这些抗体调查来估计疾病负担和评估疫苗接种方案在减少疾病负担方面的绩效方面有较长的经验，例如乙肝。这些抗体调查还用于确定需要特别疫苗接种计划的高危群体，例如大规模运动，并评估疫苗诱导的保护持续时间。Serosurveys需要可靠的疫苗接种记录，这通常是在发达国家可以获得的。在非洲发展中国家，我发现用血清学调查监测疫苗接种和指导修订疫苗接种战略的使用非常有限，就像在高收入国家看到的那样。然而，我发现破伤风疫苗诱导的抗体检测对此可能是有用的，因为它克服了血清学调查的一个关键限制，即区分自然感染的抗体和接种疫苗产生的抗体。我将研究使用抗体检测来监测疫苗接种的可能性，并将其与基里菲的疫苗记录进行比较，将这一经验推广到全国调查的样本。该项目将受益于Kilifi 2009-2017年血清学调查期间收集的血清样本和Kilifi疫苗登记处提供的可靠疫苗记录所提供的绝佳机会。我将把统计学方法应用于抗体检测结果，以确定一个可靠的数学模型，当与疫苗记录相比较时，该模型可以可靠地预测疫苗接种覆盖率。在确定这一模式后，我将在全国范围内进行血清学调查，将在Kilifi验证的方法应用于抗体测试结果，以估计全国疫苗接种覆盖率，确定存在免疫力差距的高危人群，并为保护这些人群的干预措施提出建议。

Although vaccines are essential for preventing many severe and often fatal diseases, they are only beneficial when received so their impact is greatly dependent achieving high vaccination coverage. Consequently, vaccination coverage indices are widely used to monitor vaccination programmes. Vaccination coverage is commonly assessed as the proportion of children aged 12-23 months who received the 3rd dose of a diphtheria-pertussis-tetanus (DPT3)-containing vaccine at age 12 months. DPT3 coverage is typically obtained from administrative records (registers in vaccine clinics and records of total doses of vaccines consumed). It can be also obtained from household surveys of vaccine cards/records or by asking caregivers to confirm vaccination by memory recall. Coverage estimates obtained from administrative records frequently overestimate coverage in low and middle-income countries because of errors in tracking consumption of vaccine doses and wrongly estimated target population. While survey methods provide more accurate estimates, they are disruptive to routine health services and expensive. Other weaknesses are incomplete representation of the target population, underreporting, and missing and/or incomplete information. It is important to for estimates of vaccination coverage to be as accurate as possible especially as receiving a vaccine i.e. vaccination does not always result in immunisation which is defined as vaccine-induced protection against the targeted disease. For example, following measles vaccination, the proportions of children who develop protective antibody levels are approximately 85% at 9 months of age and 95% at 12 months of age. Conventional methods for measuring coverage do not tell us what proportion of the population has immunity against the disease of interest. In high income countries, national serological surveys are conducted to obtain blood samples to measure the proportion of the population that is protected by vaccination. These blood samples are tested for antibodies produced in response to vaccines. As a result, these countries have a longer experience of using these antibody surveys to estimate the burden of diseases before introducing vaccines and assessing the performance of vaccination programmes in reducing disease burden e.g. for hepatitis B. These antibody surveys are also used to identify at-risk groups requiring special vaccination programmes e.g.mass campaigns, and to assess the duration of vaccine induced protection. Serosurveys require reliable vaccination records which are typically available in developed countries. In the developing countries of Africa, I found very limited use of serological surveys to monitor vaccination and to guide revisions of vaccination strategies as seen in high income countries. However, I found that testing for antibodies induced by tetanus vaccine may be useful for this purpose because it overcomes one key limitation of serological surveys i.e. distinguishing between antibodies from natural infection and those resulting from vaccination. I will investigate the possibility of using antibody testing to monitor vaccination and to compare this to vaccine records in Kilifi, extend this experience to samples from a nationwide survey. This project will benefit from the excellent opportunities provided by the availability of serum samples collected during serological surveys in Kilifi from 2009-2017 and reliable vaccine records from the Kilifi vaccine registry. I will apply statistical methods to antibody test results to identify a reliable mathematic model that reliably predicts vaccination coverage when compared to vaccine records. On identifying this model, I will then carry out a nationwide serological survey, apply the methods validated in Kilifi to the antibody test results to estimate national vaccination coverage, identify at-risk populations with gaps in their immunity and make recommendations for interventions to protect these populations.