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

虽然疫苗对于预防许多严重且往往致命的疾病至关重要，但它们只有在接受时才有益，因此其影响在很大程度上取决于实现高疫苗接种覆盖率。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被评估为12-23个月的儿童在12个月时接受第三剂含白喉-百日咳-破伤风（三联疫苗）的疫苗的比例。三联疫苗接种率通常从行政记录（疫苗诊所的登记册和所用疫苗总剂量的记录）中获得。也可以通过对疫苗卡/记录的家庭调查或要求护理人员通过记忆回忆确认疫苗接种来获得。从行政记录中获得的覆盖率估计数往往高估了低收入和中等收入国家的覆盖率，原因是在追踪疫苗剂量消费方面存在错误，而且对目标人群的估计也有误。虽然调查方法提供了更准确的估计数，但它们会破坏常规卫生服务，而且费用昂贵。其他不足之处包括目标人口的代表性不完整、报告不足以及信息缺失和/或不完整。尽可能准确地估计疫苗接种覆盖率是很重要的，特别是在接种疫苗时，即疫苗接种并不总是导致免疫，免疫被定义为疫苗诱导的针对目标疾病的保护。例如，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个月大的儿童为95%。衡量覆盖率的传统方法并不能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，进行全国血清学调查以获取血液样本，以衡量受疫苗接种保护的人口比例。这些血液样本用于检测疫苗产生的抗体。因此，这些国家在采用疫苗和评估疫苗接种方案在减少疾病负担（如B型肝炎）方面的绩效之前，有较长的使用这些抗体调查来估计疾病负担的经验。这些抗体调查还用于确定需要特别疫苗接种计划（如大规模接种）的高危人群，并评估疫苗诱导保护的持续时间。血清调查需要可靠的疫苗接种记录，发达国家通常都有这种记录。在非洲的发展中国家，我发现血清学调查在监测疫苗接种和指导疫苗接种策略修订方面的应用非常有限，这与高收入国家的情况相同。然而，我发现检测破伤风疫苗诱导的抗体可能有助于这一目的，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。我将调查使用抗体检测来监测疫苗接种的可能性，并将其与基利菲的疫苗记录进行比较，将这一经验扩展到全国范围内的调查样本。该项目将受益于2009-2017年在Kilifi进行血清学调查期间收集的血清样本的可用性以及Kilifi疫苗登记处的可靠疫苗记录所提供的绝佳机会。我将对抗体检测结果应用统计方法，以确定一个可靠的数学模型，该模型与疫苗记录相比，可以可靠地预测疫苗接种覆盖率。在确定这一模式后，我将开展全国性的血清学调查，将在基利菲验证的方法应用于抗体检测结果，以估计全国疫苗接种覆盖率，确定免疫力存在差距的高危人群，并提出保护这些人群的干预措施建议。

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.