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Algorithms and multiplex assays for integrated serological surveillance of malaria and neglected tropical diseases

Periodic Reporting for period 2 - MultiSeroSurv (Algorithms and multiplex assays for integrated serological surveillance of malaria and neglected tropical diseases)

Periodo di rendicontazione: 2021-08-01 al 2023-01-31

Malaria and neglected tropical diseases (NTDs) such as lymphatic filariasis, onchocerciasis, trachoma and schistosomiasis affect almost 2 billion people every year. Coordinated targeting of these diseases will aid future control and elimination campaigns, but this will require integrated surveillance strategies. Malaria surveillance is routinely implemented through cross-sectional surveys where blood samples are tested for parasites. A major barrier to routine NTD surveillance is the range of samples required for parasite diagnosis: stool, urine, blood, eye swabs and skin snips. Instead of direct detection of parasites, there is an opportunity to implement serological surveillance by measuring antibodies to multiple pathogens in blood samples collected for malaria surveillance.

This proposal has four aims: (i) Characterise the sero-epidemiology of malaria and NTDs in longitudinal cohort studies in Senegal, Ethiopia, Cambodia and Papua New Guinea; (ii) Measure antibodies to 34 antigens from 12 pathogens from single blood samples; (iii) Model antibody kinetics and validate the use of serology for detecting infections; and (iv) Demonstrate how a population’s concurrent and past exposure to multiple parasites can be estimated by analysing multiplex data from cross-sectional surveys.

These aims will be achieved through innovative epidemiological studies, new technologies, and especially developed analytic methods, including: (1) utilisation of multiplex bead-based Luminex assays; (2) mixed-effects models in a Bayesian framework with data augmentation to identify serologically suspected infections, with validation against confirmed infections; and (3) statistical algorithms for reconstructing long-term and recent transmission trends.

This interdisciplinary project will undertake fundamental research in analytic methods for processing complex multiplex data and converting it to the actionable information needed for integrated serological surveillance of malaria and NTDs.
The main results achieved so far are:

(1) Development of high-throughput serological multi-pathogen assays using multiplex Luminex technology (Objective 2)
(2) Development of non-linear mixed-effects models of antibody kinetics (Objective 3)
The progress in the first half of the progress has used state-of-the-art research methods in serological assays and mathematical models. Progress at the half-way point of the progress would not be considered beyond state-of-the-art. It is anticipated that completion of the sero-epidemiological cohorts in Objective 1, will lead to groundbreaking beyond state-of-the-art advances in the second half of the project.