Use of serological surveys to generate key insights into the changing global landscape of infectious disease.

A central conundrum in the study of infectious disease dynamics is to defi ne the landscape of population immunity. The proportion of individuals protected against a specifi c pathogen determines the timing and scale of outbreaks, and the pace of evolution for infections that can evade prevailing humoral immunity. Serological surveys provide the most direct measurement to defi ne the immunity landscape for many infectious diseases, yet this methodology remains underexploited. To address this gap, we propose a World Serology Bank and associated major methodological developments in serological testing, study design, and quantitative analysis, which could drive a step change in our understanding and optimum control of infectious diseases. Epidemic dynamics result from an interaction between the contagious spread of infection, the resulting depletion of population susceptibility, and its replenishment via births, immigration, or waning immunity. Understanding this interaction is key to assess the eff ect of vaccination, which artifi cially reduces the number of people susceptible to infection. Researchers mainly observe infection dynamics and the eff ect of population (or herd) immunity in limiting spread via surveillance of clinically apparent cases of infection or deaths. This method has led to some powerful insights; however, even in the simplest instances in which subclinical infection is uncommon, cases only provide information about the dynamics of infection. Susceptibility and immunity are hidden variables. For infections that people can be completely immunised against, such as measles, susceptible reconstruction can be used to estimate immune profi les, but infection prevalence and vaccination coverage records are frequently inadequate to capture key social and geographical heterogeneities. Additionally, inference is weakened if the risk of infection is low. Serological surveys (usually used to quantify the proportion of people positive for a specifi c antibody or, better yet, the titre or concentrations of an antibody) are potentially the most direct and informative technique available to infer the dynamics of a population’s susceptibility and level of immunity. However, the use of current serological tests varies greatly depending on type of pathogens and there are major methodological gaps in some areas for some pathogens and tests. In terms of use of current serological methods, infections can be classifi ed into four broad groups (appendix). The fi rst group contains acute immunising, antigenically stable pathogens (eg, measles, rubella, and smallpox) for which serology provides a strong signal of lifetime protection and a clear marker of past infection (or vaccination). The second group contains immunising, but antigenically variable pathogens (eg, infl uenza, invasive bacterial diseases, and dengue). Despite complexities (appendix), serology in some cases can provide powerful evidence, both for vaccine formulation and pandemic planning. A serum bank would have been extremely useful in interpretation of the unusual profi le of susceptibility associated with age in the 2009 infl uenza pandemic. For these fi rst two groups, if suitable serum banks existed, the deployment of current serological tests could have helped to clarify the association between serological profi les and protective immunity. The third group includes infections for which infectioninduced antibodies are not thought to be protective, such as tuberculosis in which the targets of the immune response vary with stage of infection; malaria, whereby infected erythrocytes generate several antibodies whose individual importance has not been fully elucidated (and might indicate exposure rather than protection); and HIV. Although antibodies might not be representative of immunity against a pathogen, they do show current or previous infection. Finally, the last broad grouping consists of infections that do not lead to reliably sustained, measurable antibody responses or for which presence of specifi c antibodies do not correlate with protection from future infection. These include many enteric infections and the human papillomavirus. In these cases, serological data can nonetheless be valuable to assess a population’s coverage of vaccine programmes if vaccination leads to long-lasting antibody responses. In the context of public health, for immunisation against group one infections, vaccination programmes aim to protect vaccinated individuals and indirectly protect unvaccinated individuals by maintaining high population immunity. If a valid correlate of immunity is measurable in sera, serological surveys could be used to identify population subgroups in which immunity is low, or even to identify individuals in whom immunity has waned, and directly inform targeted vaccination strategies (appendix). Household surveys are a major source of data for vaccination coverage in low-income countries. The recent extension of eff orts to measure biomarkers for infections such as HIV (eg, the Demographic Health Surveys) could provide infrastructure for sera collection for an expanded range of infections, thus leveraging an existing platform. For many infections, however, to Lancet 2016; 388: 728–30