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Multiplex Serosurveillance

What is multiplex serosurveillance?

Multiplex bead assay serosurveillance builds on serosurveillance for one pathogen at a time by allowing for multiple testing simultaneously. Bead-based technology allows detection of multiple analytes in one well.

This could allow testing against multiple antigens for the same pathogen, which increases the sensitivity and specificity of tests. Or you can do testing for antigens for different pathogens all at the same time.  From a single survey you can get surveillance patterns across multiple diseases. This allows for cross-cutting collaborations across public health programs, depending on what is included on the multiplex.

Why use multiplex serosurveillance?

Serosurveys provide valuable information but can be expensive to conduct. Using multiplex technologies like multiplex bead immunoassays (MBIAs) allow for the detection and quantification of antibodies to dozens of antigens from one or more pathogens in a single assay, therefore increasing the value of information.

MBIAs have been developed for detecting antibodies against a range of pathogens including vaccine preventable diseases such as measles, mumps, rubella, and varicella viruses;  respiratory pathogens, including SARS-CoV-2; neglected tropical diseases including trachoma, strongyloidiasis, schistosomiasis, and onchocerciasis; malaria; sexually transmitted infections like HIV, syphilis, and herpes simplex virus; arboviruses; and emerging infectious diseases, such as Ebola.

Use Cases for Serosurveillance and Example Pathogens

Use case

Estimating the burden and distribution of infections to complement or fill gaps in existing surveillance systems

Example pathogens

  • Neglected tropical diseases
    • Trypanosoma cruzi (Chagas disease), Chikungunya Virus, Taenia solium (cysticercosis), Strongyloides spp., Treponema pallidum subspecies pertenue (yaws)
  • Enteric pathogens
    • Campylobacter spp., Vibrio choleraeCryptosporidiumGiardia
  • Malaria
    • Plasmodium Species
  • HIV
  • Respiratory viruses
    • Respiratory Syncytial Virus (RSV), Influenza Virus

Example paper

Salje H, Paul KK, Paul R, Rodriguez-Barraquer I, Rahman Z, Alam MS, Rahman M, Al-Amin HM, Heffelfinger J, Gurley E, 2019. Nationally-representative serostudy of dengue in Bangladesh allows generalizable disease burden estimates. eLife 8: e42869 

Use case

Identifying emerging and reemerging infections

Example pathogens

  • Filoviruses
    • Ebolaviruses, Marburg Virus
  • Other viruses
    • Lassa Virus, mpox virus SARS-CoV-2, Zika Virus

Example paper

Basto-Abreu A, et al., 2022. Nationally representative SARSCoV-2 antibody prevalence estimates after the first epidemic wave in Mexico. Nat Commun 13: 589. 

Use case

Identifying vaccine program reach or gaps and geographic or demographic gaps

Example pathogens

  • Childhood diseases
    • Measles Virus, Polioviruses, Rubella Virus, Diphtheria, Tetanus, Pertussis
  • Other viruses
    • SARS-CoV-2, Yellow Fever Virus

Example paper

Murhekar MV, et al., 2022. Evaluating the effect of measles and rubella mass vaccination campaigns on seroprevalence in India: A before-and-after cross-sectional household serosurvey in four districts, 2018–2020. Lancet Glob Health 10: e1655–e1664.

Use case

Assessing changes in pathogen exposure due to behavioral, environmental, or (non-) pharmaceutical interventions or environmental changes

Example pathogens

  • Neglected tropical diseases
    • Chikungunya Virus, Dengue Virus, Lymphatic
  • Bacteria
    • Streptococcus pneumoniae spp., Salmonella serotype Typhi (Typhoid)
  • Malaria
    • Plasmodium Species

Example paper

Plucinski MM, et al., 2018. Multiplex serology for impact evaluation of bed net distribution on burden of lymphatic filariasis and four species of human malaria in northern Mozambique. PLoS Negl Trop Dis 12: e0006278. 

Use case

Monitoring peri- and post-elimination settings for diseases with elimination goals

Example pathogens

  • Neglected tropical diseases
    • Chlamydia trachomatis (trachoma), Dracunculus medinensis (Guinea worm), Leishmania spp. (visceral leishmaniasis), Nematodes (lymphatic filariasis), Onchocerca volvulus (onchocerciasis), Treponema pallidum subspecies pertenue (yaws), Trypanosoma brucei (human African trypanosomiasis)
  • Vaccine-preventable diseases
    • Polioviruses
  • Malaria
  • Plasmodium spp. (sub-national levels)

Example paper

Oguttu D, et al., 2014. Serosurveillance to monitor onchocerciasis elimination: The Ugandan experience. Am J Trop Med Hyg 90: 339–345. 

What’s the competitive advantage of multiplex serosurveillance?

  • Simultaneous estimation of prevalence of antibodies against multiple pathogens
  • Lower marginal cost as several antigens can be analysed at once
  • Can include pathogens not routinely surveilled or that may not have funding to conduct their own surveys (e.g. neglected tropical diseases)
  • Maximizes the information from one drop of blood, therefore conserving specimens

Use Cases for Multiplex Serosurveillance

Simultaneous Use

Enables multiple single-pathogen use cases simultaneously (e.g. efficiently identify gaps in immunity against multiple VPDs)

 

 

Identify High-Risk Areas

Identify high-risk geographical areas with overlapping exposures to target intervention delivery against multiple diseases (e.g. WASH interventions)

 

 

Identify Vulnerable Subpopulations

Identify vulnerable subpopulations of interest (e.g. people living with HIV more vulnerable to other pathogens)

 

 

Better Accuracy

More accurately monitor intervention effectiveness by measuring serological responses to multiple antigens from the same pathogen