Malaria in Venezuela: changes in the complexity of infection reflects the increment in transmission intensity

Abstract

Background Malaria incidence has reached staggering numbers in Venezuela. Commonly, Bolívar State accounted for approximately 70% of the country cases every year. Most cases cluster in the Sifontes municipality, a region characterized by an extractive economy, including gold mining. An increase in migration to Sifontes, driven by gold mining, fueled a malaria spillover to the rest of the country and the region. Here samples collected in 2018 were compared with a previous study of 2003/2004 to describe changes in the parasites population structures and the frequency of point mutations linked to anti-malarial drugs. Methods A total of 88 Plasmodium falciparum and 94 Plasmodium vivax isolates were collected in 2018 and compared with samples from 2003/2004 (106 P. falciparum and 104 P. vivax). For P. falciparum, mutations linked to drug resistance (Pfdhfr, Pfdhps, and Pfcrt) and the Pfk13 gene associated with artemisinin delayed parasite clearance, were analysed. To estimate the multiplicity of infection (MOI), and perform P. falciparum and P. vivax population genetic analyses, the parasites were genotyped by using eight standardized microsatellite loci. Results The P. falciparum parasites are still harbouring drug-resistant mutations in Pfdhfr, Pfdhps, and Pfcrt. However, there was a decrease in the frequency of highly resistant Pfdhps alleles. Mutations associated with artemisinin delayed parasite clearance in the Pfk13 gene were not found. Consistent with the increase in transmission, polyclonal infections raised from 1.9% in 2003/2004 to 39% in 2018 in P. falciparum and from 16.3 to 68% in P. vivax. There is also a decrease in linkage disequilibrium. Bayesian clustering yields two populations linked to the time of sampling, showing that the parasite populations temporarily changed. However, the samples from 2003/2004 and 2018 have several alleles per locus in common without sharing multi-locus genotypes. Conclusions The frequency of mutations linked with drug resistance in P. falciparum shows only changes in Pfdhps. Observations presented here are consistent with an increase in transmission from the previously circulating parasites. Following populations longitudinally, using molecular surveillance, provides valuable information in cases such as Venezuela with a fluid malaria situation that is affecting the regional goals toward elimination.

Changes in the frequencies of Plasmodium falciparum dhps and dhfr drug-resistant mutations in children from Western Kenya from 2005 to 2018: the rise of Pfdhps S436H

“…Unlike mutations linked to chloroquine resistance, SP resistant mutations have shown to be resilient in Africa even after the drug is no longer the first-line anti-malarial treatment [ 13 , 30 , 31 ]. A possibility in Africa is that mutations conferring resistance to SP may not have a relative fitness cost because of the lack of wild-type alleles in the population that can outcompete the resistant ones in the absence of drug pressure, as has been suggested in South America [ 32 , 33 ]. However, the significant increase in the frequencies of the Pfdhfr triple mutant and the Pfdhps allele with the S436 H mutation is consistent with selective drug pressure.…”

Identification of tyrosine kinase inhibitors that halt Plasmodium falciparum parasitemia

“…Ninety percent of these cases occurred in sub-Saharan Africa where one child dies every two minutes from the parasitemia [7,8]. With multi-drug resistant strains emerging in Southeast Asia [9][10][11][12][13][14][15], and rates of infection beginning to increase again [8], interest in finding new cures for the disease is escalating [16][17][18]. Indeed, according to the World Health Organization, $2.7 billion was invested in malaria research in 2018 alone [7,19].…”

Genetic diversity and complexity of Plasmodium falciparum infections in the microenvironment among siblings of the same household in North-Central Nigeria

“…Plasmodium falciparum exhibits enormous genetic diversity in natural populations, and this is evident in the number of antigenically diverse parasite populations found among infected individuals in malaria-endemic regions. Genetic diversity in the parasite population is characteristically a reflection of the transmission intensity in an area and is required for the acquisition of protective immunity against malaria [ 9 – 12 ]. Individuals living in areas of high or intense malaria transmission are frequently infected with several complex mixtures of distinct parasite clones [ 13 – 17 ].…”