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Seroepidemiology: an underused tool for designing and monitoring vaccination programmes in low- and middle-income countries

Friday, 9th of September 2016

Seroepidemiology: an underused tool for designing and monitoring vaccination programmes in low- and middle-income countries

Authors

Felicity T. Cutts,

Matt Hanson

Excerpt below; full text is at http://onlinelibrary.wiley.com/doi/10.1111/tmi.12737/full

 

Introduction

Seroepidemiology, the collection and use of data on the prevalence of antibodies (or less frequently, antigens) in serum or related fluids to study the distribution and determinants of infection, is a potentially powerful tool to help design and monitor vaccination programmes [1, 2]. Its application to individual vaccine-preventable diseases (VPDs) depends on whether there is a serological marker of past infection or vaccination, whether vaccine-induced antibody can be distinguished from that following infection, the extent and duration of protection conferred by antibody, and whether the antibody level that correlates with protection is known [3]. To date, seroepidemiology has contributed most to the control and elimination of poliomyelitis, measles and rubella – acute viral VPDs where long-lasting immunity follows infection or their respective replicating vaccines – but it has also contributed to adapting vaccination strategies for non-replicating vaccines, including diphtheria,Haemophilus influenzae type B (Hib) and pertussis in high-income countries.

Challenges around specimen collection from representative populations, standardised high-quality conduct of laboratory assays and appropriate statistical analysis have limited the use of seroepidemiology in low- and middle-income countries. The need for accurate data on population immunity is increasing, however, as programmes move towards eradication of poliomyelitis and elimination of measles and rubella, and also need to adapt to maintain long-term control of other VPDs.

In this paper, we provide an overview of the use of seroepidemiology to design, monitor and adapt strategies for VPDs, briefly review the requirements to obtain high-quality data and draw appropriate programmatic conclusions and discuss how to increase its use in low- and middle-income countries. The use of serological endpoints in clinical trials of different vaccines, schedules or routes of administration, another important application of serology to vaccine programme design, is beyond the scope of this paper.

Uses of seroepidemiological data for vaccination programme design and monitoring

Uses of seroepidemiology before vaccination is introduced

For acute, antigenically stable infections, data on antibody prevalence by age are used in mathematical models to estimate the age-specific force of infection, the burden of disease (BOD) and theoretical immunity thresholds for elimination of infection.

Seroprevalence data (Table 1) have been most important for infections such as hepatitis B and rubella that are frequently subclinical yet have a measurable serological marker of infection. In the case of hepatitis B virus (HBV), the viral surface antigen (HBsAg) is measured whereas for other infections, specific antibody is used. The outcomes of HBV infection are age-dependant and include asymptomatic infection, acute hepatitis B illness or chronic HBV infection, which predisposes to cirrhosis and hepatocellular carcinoma [4]. Because data from developing countries on chronic liver disease and cancer are scarce, seroepidemiological data were critical to estimate global disease burden and vaccination impact. WHO classified countries into high (≥8%); medium (2–7%) or low (<2%) levels of endemicity according to the prevalence of HBsAg, an indicator of chronic HBV infection. In 1992, WHO recommended that HBV vaccine be introduced in highly endemic countries by 1995 and in all countries by 1997 [5]. Using data on the seroprevalence of hepatitis B in a large number of countries, mathematical modelling predicted that approximately 1.4 million HBV-related deaths would occur in the 2000 global birth cohort in the absence of vaccination, and 90% of these could be avoided through routine HBV vaccination starting at birth with 90% coverage [6].