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Analytical approaches for multi-disease antibody responses for integrated disease surveillance - NU/LSHTM project

Supervisory team

LSHTM


Nagasaki University

Project

Many infectious and tropical diseases, which cause high mortality and morbidity globally, are geographically co-endemic due to socio-economic, environmental and other factors. The epidemiology and the control and potential elimination of these diseases benefit from effective and continued surveillance and monitoring, particularly in identifying acute/recent infections and past exposure at the population level. Considerable efforts are aimed toward integrating control platforms across these co-endemic diseases due to recognised resource efficiency for targeted interventions. Serology has been shown to offer robust estimates of disease-specific exposure levels and transmission intensity in populations, which can provide surveillance operations with means to target disease control efforts [1-3]. Measurements of antibody levels against disease-specific and species-specific antigens enable sensitive and high throughput monitoring that is further improved with recent advancements in multiplex immunoassays, allowing simultaneous measurement of antibody levels against numerous pathogens, supporting integrated disease surveillance.  

The project builds and continues on our previous work on dengue and malaria infections, and applying the methodologies for neglected tropical diseases. For dengue, primary dengue infections are at risk of developing more severe secondary disease, thus could be targeted for disease prevention. Serology has been used to develop a framework to determine population-based primary and post-primary dengue cases [4-5], enabling analysis of immune-epidemiological patterns of transmission. In malaria elimination areas, assessing and differentiating areas with residual transmission becomes increasingly challenging. Serology has been demonstrated to be capable of detecting both historical and recent malaria infections, which can potentially be utilised to confirm the present or absence of transmission in these areas [1-3].  

This PhD project aims to assess various analytical approaches for interpreting multi-disease antibody data, and determine their utility in the public health surveillance for malaria, dengue and neglected tropical diseases in various settings. Antibody levels are normally analysed individually using seropositivity cut-offs to produce binary outcomes, or through estimations of seroconversion rates from reverse catalytic models fitted using maximum likelihood methods. For this project, methodologies will be extended to more dynamic application of multi-disease antibody data using machine and ensemble learning for improved predictions of disease-specific exposure levels and transmission intensity in populations.  

Data sources will be from cross-sectional surveys, which include serological responses to multiple antigenic targets and associated epidemiological data from The Philippines, Malaysia and East Timor. Analysis will initially focus on assessing optimal approaches to described spatial and demographic risk for exposure to individual diseases using both binary and continuous variables. Subsequent analysis will include developing approaches to analyses exposure to multiple pathogens using approaches analogous to systems immunology.  

References: 

  1. Wu L, Hall T, Ssewanyana I, Oulton T, Patterson C, Vasileva H, Singh S, Affara M, Mwesigwa J, Correa S, Bah M, D'Alessandro U, Sepúlveda N, Drakeley C, Tetteh KKA. Optimisation and standardisation of a multiplex immunoassay of diverse Plasmodium falciparum antigens to assess changes in malaria transmission using sero-epidemiology. Wellcome Open Res. 2020 Apr 23;4:26. doi: 10.12688/wellcomeopenres.14950.2. PMID: 32518839; PMCID: PMC7255915.
  2. Chan Y, Martin D, Mace KE, Jean SE, Stresman G, Drakeley C, Chang MA, Lemoine JF, Udhayakumar V, Lammie PJ, Priest JW, Rogier EW. Multiplex Serology for Measurement of IgG Antibodies Against Eleven Infectious Diseases in a National Serosurvey: Haiti 2014-2015. Front Public Health. 2022 Jun 9;10:897013. doi: 10.3389/fpubh.2022.897013. PMID: 35757611; PMCID: PMC9218545.
  3. Macalinao MLM, Fornace KM, Reyes RA, Hall T, Bareng APN, Adams JH, Huon C, Chitnis CE, Luchavez JS, Tetteh KKA, Yui K, Hafalla JCR, Espino FEJ, Drakeley CJ. Analytical approaches for antimalarial antibody responses to confirm historical and recent malaria transmission: an example from the Philippines. Lancet Reg Health West Pac. 2023 May 20;37:100792. doi: 10.1016/j.lanwpc.2023.100792. PMID: 37693871; PMCID: PMC10485684.
  4. Biggs JR, Sy AK, Brady OJ, Kucharski AJ, Funk S, Reyes MAJ, Quinones MA, Jones-Warner W, Tu YH, Avelino FL, Sucaldito NL, Mai HK, Lien LT, Do Thai H, Nguyen HAT, Anh DD, Iwasaki C, Kitamura N, Yoshida LM, Tandoc AO, la Paz EC, Capeding MRZ, Padilla CD, Hafalla JCR, Hibberd ML. A serological framework to investigate acute primary and post-primary dengue cases reporting across the Philippines. BMC Med. 2020 Nov 27;18(1):364. doi: 10.1186/s12916-020-01833-1. PMID: 33243267; PMCID: PMC7694902.
  5. Biggs JR, Sy AK, Brady OJ, Kucharski AJ, Funk S, Tu YH, Reyes MAJ, Quinones MA, Jones-Warner W, Ashall J, Avelino FL, Sucaldito NL, Tandoc AO, Cutiongco-de la Paz E, Capeding MRZ, Padilla CD, Hibberd ML, Hafalla JCR. Serological Evidence of Widespread Zika Transmission across the Philippines. Viruses. 2021 Jul 23;13(8):1441. doi: 10.3390/v13081441. PMID: 34452307; PMCID: PMC8402696.
     

The role of LSHTM and NU in this collaborative project

Chris Drakeley, Julius Hafalla and Kenji Hirayama have ongoing projects on malaria and neglected tropical diseases in the Philippines, whilst Chris Drakeley have ongoing projects on both topics across the world. Martin Hibberd and Julius Hafalla have ongoing projects on dengue in the Philippines, Vietnam and Indonesia. Chris Smith has on-going projects on dengue and other infections in the Philippines. The successful applicant will be primarily based in London, with substantial amount of time spent with the teams at NU, as well as with collaborators. Regular joint teleconferences will ensure a highly collaborative nature of the PhD. 

Particular prior educational requirements for a student undertaking this project

  • Background and/or interest in infectious diseases and interdisciplinary research; Masters degree in a related field
  • Quantitative, analytical and programming skills
  • Basic knowledge of data analysis
  • Evidence of collaborative work 

Skills we expect a student to develop/acquire whilst pursuing this project

  • Infectious disease epidemiology: malaria, dengue and neglected tropical diseases
  • Immunology, as applied to epidemiology
  • Applied statistics, data analysis, programmatic skills
  • Collaborative ethos