Influx of diverse, drug resistant and transmissible Plasmodium falciparum into a malaria-free setting in Qatar

Abstract

Background: Successful control programs have impeded local malaria transmission in almost all Gulf Cooperation Council (GCC) countries: Qatar, Bahrain, Kuwait, Oman, the United Arab Emirates (UAE) and Saudi Arabia. Nevertheless, a prodigious influx of imported malaria via migrant workers sustains the threat of local transmission. Here we examine the origin of imported malaria in Qatar, assess genetic diversity and the prevalence of drug resistance genes in imported Plasmodium falciparum, and finally, address the potential for the reintroduction of local transmission.

Methods: This study examined imported malaria cases reported in Qatar, between 2013 and 2016. We focused on P. falciparum infections and estimated both total parasite and gametocyte density, using qPCR and qRT-PCR, respectively. We also examined ten neutral microsatellites and four genes associated with drug resistance, Pfmrp1, Pfcrt, Pfmdr1, and Pfkelch13, to assess the genetic diversity of imported P. falciparum strains, and the potential for propagating drug resistance genotypes respectively.

Results: The majority of imported malaria cases were P. vivax, while P. falciparum and mixed species infections (P. falciparum / P. vivax) were less frequent. The primary origin of P. vivax infection was the Indian subcontinent, while P. falciparum was mostly presented by African expatriates. Imported P. falciparum strains were highly diverse, carrying multiple genotypes, and infections also presented with early- and late-stage gametocytes. We observed a high prevalence of mutations implicated in drug resistance among these strains, including novel SNPs in Pfkelch13.

Conclusions: The influx of genetically diverse P. falciparum, with multiple drug resistance markers and a high capacity for gametocyte production, represents a threat for the reestablishment of drug-resistant malaria into GCC countries. This scenario highlights the impact of mass international migration on the reintroduction of malaria to areas with absent or limited local transmission.

Keywords: Gametocytes; Gulf cooperation council (GCC) countries; Imported malaria; Malaria elimination; P. falciparum; Qatar.

Fig. 1

Correlation between total parasite density with both early gametocyte and late gametocyte density. a log total parasitaemia (X axis) and log early gametocyte density (Y axis), the fit line in scatter plot shows a weak/non-significant correlation coefficient (r = 0.031, p = 0.835). b log total parasitaemia (X axis) and log late gametocyte density (Y axis), the fit line in scatter plot shows a weak/non-significant correlation coefficient (r = 0.008, p = 0.946)

Fig. 2

Principal Co-ordinates Analysis (PCoA) of P. falciparum populations from two regions (the Indian Subcontinent [black square] and Africa [transparent rectangular]). Values within parenthesis after the coordinate number are the percentage of variation explained by the coordinate