Kelch13 mutations in Plasmodium falciparum and risk of spreading in Amazon basin countries.

BACKGROUND: The first potential focus for artemisinin resistance in South America was recently confirmed with the presence of the C580Y mutation in the Plasmodium falciparum kelch 13 gene (pfk13) in Guyana. OBJECTIVES: This study aimed to strengthen pfk13 monitoring in the Amazon basin countries, to compile the available data and to evaluate the risk of spreading of mutations. METHODS: Sanger sequencing was done on 862 samples collected between 1998 and 2019, and a global map of pfk13 genotypes available for this region was constructed. Then, the risk of spreading of mutations based on P. falciparum case importation between 2015 and 2018 within countries of the Amazon basin was evaluated. RESULTS: No additional pfk13 C580Y foci were identified. Few mutations (0.5%, 95% CI = 0.3%-0.8%) in the propeller domain were observed in the general parasite population of this region despite a high proportion of K189T mutations (49.1%, 95% CI = 46.2%-52.0%) in the non-propeller domain. Case information revealed two patterns of intense human migration: Venezuela, Guyana and the Roraima State in Brazil; and French Guiana, Suriname and the Amapá State in Brazil. CONCLUSIONS: There are few pfk13 mutant foci, but a high risk of dispersion in the Amazon basin, mainly from the Guiana Shield, proportionate to mining activities. Therefore, access to prompt diagnosis and treatment, and continuous molecular monitoring is essential in these geographical areas.

The association between gold mining and malaria in Guyana: a statistical inference and time-series analysis.

BACKGROUND: Guyana reported a significant rise in malaria between 2008 and 2014. As there was no evidence of impairment of national malaria control strategies, public health authorities attributed the surge to a temporal increase in gold mining activity in forested regions. However, systematic analysis of this association is lacking because of the difficulties associated with collecting reliable data for both malaria and mining. We aimed to investigate the association between the international gold price and Plasmodium falciparum malaria transmission in Guyana between 2007 and 2019. We also aimed to evaluate the association between P falciparum cases and the El Niño-Southern Oscillation pattern, which has previously been suggested as a major driver of malaria. METHODS: We used national malaria surveillance data from Guyana to estimate the correlation over time between the international gold price and reported P falciparum infections in individuals who were likely to be involved in mining activities (ie, men and boys aged between 15 and 50 years who were living in mining regions) for each month between 2007 and 2019. We compared the estimates with those obtained from individuals who were unlikely to be directly involved in mining activities (ie, women, children aged 12 years and younger, and adults aged over 70 years) and estimates obtained from individuals living in non-mining regions. We also evaluated the correlation between P falciparum infections and the El Niño-Southern Oscillation pattern in the same subpopulations and time period. Lastly, we evaluated the performance of a statistical model formulated to estimate P falciparum infections in real time using the international gold price as the predictor variable. FINDINGS: The proportion of P falciparum malaria cases in temporary residents, which was used as a proxy for circulating individuals involved in gold mining, was highest during the years of peak gold price (ie, between 2008 and 2014). Cases of malaria in all demographic groups showed a strong positive correlation with the gold price, but only in regions with mining camps (0·88 [95% CI 0·84-0·89] for boys and men aged between 15 and 50 years and 0·80 [0·73-0·85] for the aggregated population of women, children aged 12 years and younger, and adults older than 70 years). The highest correlation occurred earlier in men and boys aged between 15 and 50 years, the demographic most likely to be miners, suggesting that transmission in mining camps is followed by infections in the community. On the basis of these findings, we were able to reliably forecast P falciparum malaria trends using only the gold price as the predictor variable. A 1% increase in gold price was associated with a 2·13% increase in P falciparum infections after 1 month in the mining populations, and with a 1·63% increase after 2 months in the non-mining populations. Lastly, La Niña climatic events showed an additional, smaller positive correlation with malaria transmission. INTERPRETATION: Our analysis provides evidence that the P falciparum malaria surge observed in Guyana between 2008 and 2014 was likely to have been driven mainly by an increase in gold mining, while climate factors might have contributed synergistically. We propose that the international gold price over time is a useful indicator of malaria trends. We conclude that the feasibility of malaria elimination in Guyana, and in other areas in the Amazon where malaria and gold mining overlap, should be evaluated against the challenges posed by rapidly rising gold prices. FUNDING: Ramón Areces Foundation, National Institutes of Health, and National Institute of General Medical Sciences.