AUTHOR=Ruybal-Pesántez Shazia , Sáenz Fabián E. , Deed Samantha L. , Johnson Erik K. , Larremore Daniel B. , Vera-Arias Claudia A. , Tiedje Kathryn E. , Day Karen P. 

TITLE=Molecular epidemiology of continued Plasmodium falciparum disease transmission after an outbreak in Ecuador

JOURNAL=Frontiers in Tropical Diseases

VOLUME=4

YEAR=2023

URL=https://www.frontiersin.org/journals/tropical-diseases/articles/10.3389/fitd.2023.1085862

DOI=10.3389/fitd.2023.1085862

ISSN=2673-7515

ABSTRACT=<p>To better understand the factors underlying the continued incidence of clinical episodes of falciparum malaria in E-2025 countries targeting elimination, we characterized the molecular epidemiology of <italic>Plasmodium falciparum</italic> disease transmission after a clonal outbreak in Ecuador. Here we study disease transmission by documenting the diversity and population structure of the major variant surface antigen of the blood stages of <italic>P. falciparum</italic> encoded by the <italic>var</italic> multigene family. We used a high-resolution genotyping method, “<italic>var</italic>coding”, involving targeted amplicon sequencing to fingerprint the DBLα encoding region of <italic>var</italic> genes to describe both antigenic <italic>var</italic> diversity and <italic>var</italic> repertoire similarity or relatedness in parasite isolates from clinical cases. We identified nine genetic <italic>var</italic>codes in 58 <italic>P. falciparum</italic> isolates causing clinical disease in 2013-2015. Network analyses revealed that four of the <italic>var</italic>codes were highly related to the outbreak <italic>var</italic>code, with identification of possible diversification of the outbreak parasites by recombination as seen in three of those <italic>var</italic>codes. The majority of clinical cases in Ecuador were associated with parasites with highly related or recombinant <italic>var</italic>codes to the outbreak clone and due to local transmission rather than recent importation of parasites from other endemic countries. Sharing of types in Ecuadorian <italic>var</italic>codes to those sampled in South American <italic>var</italic>codes reflects historical parasite importation of some <italic>var</italic>codes, especially from Colombia and Peru. Our findings highlight the translational application of <italic>var</italic>coding for outbreak surveillance in epidemic/unstable malaria transmission, such as in E-2025 countries, and point to the need for surveillance of local reservoirs of infection in Ecuador to achieve the malaria elimination goal by 2025.</p>