Describing the current status of Plasmodium falciparum population structure and drug resistance within mainland Tanzania using molecular inversion probes
| Autor: | Robert Verity, Rashid A. Madebe, Linda Mlunde, Erik Reaves, Billy Ngasala, Abdunoor M. Kabanywanyi, Frank Chaky, Patrick W Marsh, Ozkan Aydemir, Madeline Denton, Deus S. Ishengoma, Susan F. Rumisha, Ritha Njau, Chonge Kitojo, Erasmus Kamugisha, Marian Warsame, Oliver J Watson, Sigsbert Mkude, Reginald A. Kavishe, George Greer, Fabrizio Molteni, Celine I. Mandara, Jonathan J. Juliano, Dunstan Bishanga, Muhidin K. Mahende, Kara A. Moser, Mercy G. Chiduo, Maimuna Ahmed, Ally Mohamed, Jeffrey A. Bailey, Renata Mandike |
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| Rok vydání: | 2020 |
| Předmět: |
0106 biological sciences
0301 basic medicine Plasmodium falciparum 030231 tropical medicine Population Drug Resistance Drug resistance Biology 010603 evolutionary biology 01 natural sciences Tanzania Plasmodium Article 03 medical and health sciences 0302 clinical medicine parasitic diseases Genetics medicine Humans Parasite hosting Malaria Falciparum education Ecology Evolution Behavior and Systematics Isolation by distance 030304 developmental biology 0303 health sciences Genetic diversity education.field_of_study medicine.disease biology.organism_classification 3. Good health 030104 developmental biology Evolutionary biology Molecular Probes Malaria |
| Zdroj: | Mol Ecol |
| DOI: | 10.1101/2020.05.09.085225 |
| Popis: | High-throughput Plasmodium genomic data is increasingly useful in assessing prevalence of clinically important mutations and malaria transmission patterns. Understanding parasite diversity is important for identification of specific human or parasite populations that can be targeted by control programs, and to monitor the spread of mutations associated with drug resistance. An up-to-date understanding of regional parasite population dynamics is also critical to monitor the impact of control efforts. However, this data is largely absent from high-burden nations in Africa, and to date, no such analysis has been conducted for malaria parasites in Tanzania country-wide. To this end, over 1,000 P. falciparum clinical isolates were collected in 2017 from 13 sites in seven administrative regions across Tanzania, and parasites were genotyped at 1,800 variable positions genome-wide using molecular inversion probes. Population structure was detectable among Tanzanian P. falciparum parasites, roughly separating parasites from the northern and southern districts and identifying genetically admixed populations in the north. Isolates from geographically close districts were more likely to be genetically related compared to parasites sampled from more distant districts. Known drug resistance mutations were seen at increased frequency in northern districts, and additional variants with undetermined significance for antimalarial resistance also varied by geography. Malaria Indicator Survey (2017) data corresponded with genetic findings, including average region-level complexity-of-infection and malaria prevalence estimates. The parasite populations identified here provide important information on extant spatial patterns of genetic diversity of Tanzanian parasites, to which future surveys of genetic relatedness can be compared.SIGNIFICANCEDocumenting dynamics of malaria parasite genomics in high-transmission settings at scale in sub-Saharan Africa is critical for policy and decision making to support ongoing malaria elimination initiatives. Using molecular inversion probes, we genotyped over 1,000 Tanzanian Plasmodium falciparum samples collected country-wide in 2017 at hundreds of variable polymorphic positions across the genome. Frequencies of known drug resistance mutations were higher in northern districts of the country compared to the south. Results also showed a distinct isolation-by-distance pattern (whereby increasing geographic distance was correlated with decreasing genetic relatedness), as well as signals of higher genetic sharing between several southern districts. These results provide, for the first time, a picture of current within-country diversity of Tanzanian P. falciparum populations. |
| Databáze: | OpenAIRE |
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