Genomic epidemiology of Plasmodium vivax malaria in Latin America and the Caribbean

Abstract

Plasmodium vivax is the main cause of malaria outside of Africa. Each year, between 6 and 7 million cases are reported, and in the Americas, this parasite represents over 70% of all malaria cases. Despite efforts to reduce malaria, P. vivax persists. Progress in reducing cases across the region has been uneven. Between 2010 and 2018, Panama, Honduras, and Guatemala succeeded in reducing, or at least containing, the number of cases per year within their territories. However, starting in 2019, this progress stalled. By 2023, Panama was reporting more than 9,000 cases, and beginning in 2021, Honduras and Guatemala began to follow the same trend. This increase coincides with the intensification of the Venezuelan exodus and other demographic displacements in the region. In this way, genetic relatedness from parasite populations in LAC could allow us to test if the increment on cases is due to the introduction of new parasite populations or the expansion of local populations that are resilient to control and elimination strategies. In Chapter One, we review P. vivax transmission in Latin America and the Caribbean over the past 15 years. We also discuss the close relationship between transmission intensity and the genetic relatedness among parasite populations, and how these relationships can help classify infections as either imported or locally acquired. In Chapter Two, I introduce two new Illumina-based multiplexed PCR amplicon sequencing panels for P. vivax: PvGTSeq and PvCRiSP. The PvGTSeq panel incorporates 249 amplicons, covering candidate genes associated with drug resistance as well as amplicons capturing polymorphic regions particularly useful for finescale spatial resolution of parasite populations in Latin America. PvCRiSP consists of only four highly-polymorphic and ultra-sensitive amplicons to estimate complexity of infection (COI) and identify instances of clonal transmission, without a costly and effort-intensive pre-amplification step. Both panels reliably generate genotypic data for patient samples with parasitemia levels as low as five parasites/μL and do not use proprietary reagents. These panels are suited for use in diverse geographic regions, with particular utility for studying P. vivax in the Americas—a region that is facing significant challenges in malaria control and elimination. At the time of submitting this thesis, the results presented in Chapter Two had been accepted for publication in the scientific journal PLOS Neglected Tropical Diseases, and the work will be published under the Creative Commons Attribution (CC BY) 4.0 license. In Chapter Three, by using PvGTSeq and whole genome sequencing data I evaluate whether the increase in P. vivax cases in Panama, Honduras and Guatemala from 2020 onwards is due to the resilience of local parasite populations or the introduction of foreign parasite populations. Our results suggest that despite the presence of imported and introduced cases in Guatemala and Panama, the P. vivax parasite population remains largely unchanged, with the increase in cases primarily attributed to clonal lineages that have proven resilient to existing control measures. Finally, in Chapter Four I discuss the challenges posed by the epidemiological characteristics of Latin America to generating large-scale genomic data cost-effectively and interpreting it correctly. These findings are crucial for guiding local authorities in managing migrant populations, who often become vulnerable to local parasite strains.