Newton001 Sero-surveillance to estimate the burden of Plasmodium vivax and P. falciparum infection in Latin America

Malaria elimination requires that activities focus on reducing parasite carriage within communities in addition to treating those sick with the disease. However, as malaria transmission levels decrease, it becomes harder to identify individuals who might be carrying parasites using conventional methods (microscopy, rapid diagnostic tests), as many of these infections will be of low density and asymptomatic. Therefore, there is a need for innovative and affordable approaches to identify likely parasite carriers and the areas where they reside. One approach is serological surveillance. A malaria infection will leave an antibody 'footprint' in the serum of the human host that will last longer than the infection itself. Detection of these antibodies is an additional sensitive and specific approach to measure a population's level of exposure to infection. Using antibodies in this way has recently been revitalised by researchers at LSHTM as a method to estimate malaria burden with considerable accuracy.

Antibody measures have been shown to correlate with other conventional estimates of malaria burden (entomological, parasitological and clinical). It has also been shown that by evaluating the antibody responses and age of individuals it is possible to recreate the history of exposure to malaria. This facet allows a retrospective examination of the effect of malaria control interventions in a given locality. This work has primarily been conducted in African settings where Plasmodium falciparum is predominant, however a more recent analysis of samples from Para state, Brazil showed the approach was applicable in this setting. Therefore, the aim of this project is to extend this work by assembling the current evidence on sero-epidemiology and antibody dynamics in Latin America and extending this with novel antibody targets and analytical approaches.

The expected results of this project are to promote better understanding of the current landscape of sero-surveillance evidence in Latin America and to identify research needs to be addressed in future studies. These studies will be formulated to further strengthen collaboration between participating institutions in developing reliable sero-surveillance methods to estimate species-specific malaria burden in the region, target control methods and ultimately contribute to malaria elimination in the region. This proposal specifically addresses the need for rapid and reliable tools and strategies to measure malaria burden and we believe it will provide considerable information to guide policy makers in Latin America.

The project comprises four main parts:
1. Systematic review of seroepidemiology studies of malaria in Latin America. Data will be extracted on antigenic targets, serological measurements, malaria transmission intensity, demographic and geographical characteristics and study design. Meta-analysis will evaluate the correlation between serological measurements obtained with malaria transmission data from each location. A preliminary map of malaria sero-surveillance will be generated using geostatistical tools. Further evaluation will be made on studies which could provide data on differing serological patterns between new Pv infection and relapse episodes.
2. Repository of sero-survey samples from Brazil. A library of samples will be collated in Brazil and used to identify a broader range of antibody markers for future study.
3. Evaluation of antigenic targets. We will identify and evaluate antigenic sources previously described for assays in the review and reproduce these and newer candidate antigens using SLIC. Newer antigenic candidates will be identified in existing databases, including next generation sequence data. Purified antigens will be analysed by SDS PAGE and Western blot, using Pv positive control sera, to determine protein integrity and screen for immunoreactivity. Promising candidates will be further assayed primarily by ELISA, later with Luminex, against endemic sera identified above and archived in London.
4. Capacity & partnership strengthening. An initial meeting in Manaus will harmonize study design and methods. A second meeting will be held in November to: present and discuss results of the systematic review and sample repository; identify knowledge gaps in sero-surveillance in Latin America and plan future studies; and exchange knowledge and technology between research groups. Exchange of postdoctoral and PhD students from both countries will enable technology transfer on measurement and analysis of malaria sero-surveillance studies.

N/A