Dataset Information

Kelch 13-propeller polymorphisms in Plasmodium falciparum from Jazan region, southwest Saudi Arabia.

ABSTRACT: BACKGROUND:Artemisinin-based combination therapy (ACT) is recommended at the initial phase for treatment of Plasmodium falciparum, to reduce morbidity and mortality in all countries where malaria is endemic. Polymorphism in portions of P. falciparum gene encoding kelch (K13)-propeller domains is associated with delayed parasite clearance after ACT. Of about 124 different non-synonymous mutations, 46 have been identified in Southeast Asia (SEA), 62 in sub-Saharan Africa (SSA) and 16 in both the regions. This is the first study designed to analyse the prevalence of polymorphism in the P. falciparum k13-propeller domain in the Jazan region of southwest Saudi Arabia, where malaria is endemic. METHODS:One-hundred and forty P. falciparum samples were collected from Jazan region of southwest Saudi Arabia at three different times: 20 samples in 2011, 40 samples in 2016 and 80 samples in 2020 after the implementation of ACT. Plasmodium falciparum kelch13 (k13) gene DNA was extracted, amplified, sequenced, and analysed using a basic local alignment search tool (BLAST). RESULTS:This study obtained 51 non-synonymous (NS) mutations in three time groups, divided as follows: 6 single nucleotide polymorphisms (SNPs) '11.8%' in samples collected in 2011 only, 3 (5.9%) in 2011and 2016, 5 (9.8%) in 2011 and 2020, 5 (9.8%) in 2016 only, 8 (15.7%) in 2016 and 2020, 14 (27.5%) in 2020 and 10 (19.6%) in all the groups. The BLAST revealed that the 2011 isolates were genetically closer to African isolates (53.3%) than Asian ones (46.7%). Interestingly, this proportion changed completely in 2020, to become closer to Asian isolates (81.6%) than to African ones (18.4%). CONCLUSIONS:Despite the diversity of the identified mutations in the k13-propeller gene, these data did not report widespread artemisinin-resistant polymorphisms in the Jazan region where these samples were collected. Such a process would be expected to increase frequencies of mutations associated with the resistance of ACT.

SUBMITTER: Dafalla OM

PROVIDER: S-EPMC7653757 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Kelch 13-propeller polymorphisms in Plasmodium falciparum from Jazan region, southwest Saudi Arabia.

Dafalla Ommer Mohammed OM Alzahrani Mohammed M Sahli Ahmed A Al Helal Mohammed Abdulla MA Alhazmi Mohammad Mohammad MM Noureldin Elsiddig Mohammed EM Mohamed Waheed Sideeg WS Hamid Tajeldin Bashir TB Abdelhaleem Aymen Awad AA Hobani Yahya Ali YA Arif Ommar Ali OA Bokar Ibrahim Munagi IM Hakami Abdulazai Mohammed AM Eisa Zaki Manawar ZM

Malaria journal 20201110 1

<h4>Background</h4>Artemisinin-based combination therapy (ACT) is recommended at the initial phase for treatment of Plasmodium falciparum, to reduce morbidity and mortality in all countries where malaria is endemic. Polymorphism in portions of P. falciparum gene encoding kelch (K13)-propeller domains is associated with delayed parasite clearance after ACT. Of about 124 different non-synonymous mutations, 46 have been identified in Southeast Asia (SEA), 62 in sub-Saharan Africa (SSA) and 16 in bo ...[more]

PMID: 33168025

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Project description:For a long time, the people of Saudi Arabia have been using medicinal plants (MPs) as conventional medicine to heal diverse human and livestock diseases. The present work is the first study on ethnobotanical uses of 124 MPs species used by the local tribal communities of Jazan province in the Southwest of Saudi Arabia. Ethnobotanical data were collected by interviewing 174 local informants using semistructured interviews. Informants of different ages, from several settlements belonging to several tribal communities, were interviewed. It is worth noticing that the age of informants and their knowledge of MPs were positively correlated, whereas the educational level and MP knowledge of participants were negatively correlated. To find out if there was agreement in the use of certain plants in the treatment of given ailments, we used Informant Consensus Factor (ICF). To determine the most frequently used plant species for treating a particular ailment category by local people we used the fidelity level (FL%). The Relative Frequency of Citation (RFC) was used to indicate the local importance of a species and the relative importance (RI) level was used to check the therapeutic potentials of the cited plants. A total of 124 MPs belonging to 103 genera and 48 families were collected and identified. The majority of these plants were shrubs (45%), perennial herbs (21%), annual herbs (19%), or trees (18%). The Asteraceae (10.48%), Fabaceae (7.25%), and Apocynaceae (7.25%) families were the most represented. Leaves, fruits, and whole plant (24%, 18%, and 16%, respectively) were the most used plant parts in formulating traditional medicines. Ziziphus spina-christi and Calotropis procera with the highest RI level (2.0) were found to have the highest range of therapeutic uses. They were followed by Datura stramonium (1.86), Withania somnifera, and Aloe vera (1.81). The ICF ranged from 0.02 to 0.42 covering 12 disease categories with a prevalence of disease categories related to skin and hair problems (ICF=0.42) having 75 species cited, while 73 species were cited for gastrointestinal tract (GIT) disorders (ICF = 0.40). Senna alexandrina (67%), Tribulus terrestris (64%), Pulicaria undulata (60%), Leptadenia pyrotechnica (55%), and Rumex nervosus (55%) had the highest FL which indicates their good healing potential against specific diseases. The high-FL species are the most promising candidate plants for in-depth pharmacological screening and merit further consideration. Accordingly, Jazan flora has good ethnobotanical potential. Unfortunately, many MP species are endangered by drought, overgrazing, and overexploitation. Some protection measures should be undertaken to prevent these species from becoming extinct. Natural reserves and wild nurseries are typical settings to retain medically important plants in their natural habitats, while botanic gardens and seed banks are important paradigms for ex situ conservation.

Project description:BackgroundDespite significant progress in eliminating malaria from the Kingdom of Saudi Arabia, the disease is still endemic in the southwestern region of the country. Artesunate plus sulfadoxine-pyrimethamine (AS + SP) has been used in Saudi Arabia since 2007 as a first-line treatment for uncomplicated Plasmodium falciparum malaria. This study aimed to investigate the prevalence of mutations associated with resistance to artemisinin and sulfadoxine-pyrimethamine (SP) resistance in P. falciparum parasites circulating in Jazan region, southwestern Saudi Arabia.MethodsA total of 151 P. falciparum isolates were collected between April 2018 and March 2019 from 12 of the governorates in Jazan region. Genomic DNA was extracted from dried blood spots and amplified using nested PCR. Polymorphisms in the propeller domain of the P. falciparum k13 (pfkelch13) gene and point mutations in the P. falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes were identified by sequencing.ResultsNo mutations in the pfkelch13 propeller domain were found in any of the 151 isolates. However, point mutations in the pfdhfr and pfdhps genes were detected in 90.7% (137/151) of the isolates. The pfdhfr double mutations N51I + S108N (i.e. ACICNI haplotype) and triple mutations N51I + C59R + S108N (i.e. ACIRNI haplotype) were detected in 47% and 37.8% of the isolates, respectively. Moreover, the pfdhps single mutation at codon A437G and double mutations A437G + K540E (i.e. SGEAAI haplotype) were observed in 4.6% and 51.7% of the isolates, respectively. Interestingly, 23.8%, 25.1 and 12.6% of the isolates had quintuple, quadruple and triple mutated combined pfdhfr-pfdhps genotypes, respectively. Furthermore, significant associations were found between the prevalence of mutant haplotypes and the age, gender and nationality of the patients (P < 0.05).ConclusionThis study revealed a high prevalence of point mutations in the pfdhfr and pfdhps genes of P. falciparum isolates from Jazan region, with quintuple and quadruple mutant pfdhfr-pfdhps genotypes reported for the first time in Saudi Arabia and the Arabian Peninsula. Despite the absence of the pfkelch13 mutation in the isolates examined, the pfdhfr and pfdhps mutations undermine the efficacy of SP partner drug, thereby threatening the main falciparum malaria treatment policy in Saudi Arabia, i.e. the use of AS + SP. Therefore, the continuous molecular and in-vivo monitoring of ACT efficacy in Jazan region is highly recommended.

Project description:The conventional morphological characterization of mosquito species remains heavily used for species identification in Jazan, Saudi Arabia. It requires substantial expertise and time, as well as having difficulty in confirming identity of morphologically similar species. Therefore, to establish a reliable and accurate identification system that can be applied to understanding spatial distribution of local mosquito species from the Jazan region, DNA barcoding was explored as an integrated tool for mosquito species identification. In this study, 44 adult mosquito specimens were analyzed, which contain 16 species belong to three genera of potential mosquito disease vectors (Aedes, Anopheles, and Culex). The specimens were collected from the Jazan region located in southwest Saudi Arabia. These included old and preserved mosquito voucher specimens. In addition, we assessed the genetic distance based on the generated mitochondrial partial COI DNA barcodes to detect cryptic diversity across these taxa. Nine mosquito species belonging to three genera were successfully barcoded and submitted to GenBank, namely: Aedes aegypti, Aedes caspius, Aedes vexans, Aedes vittatus, Anopheles arabiensis, Culex pipiens, Culex quinquefasciatus, Culex sitiens, and Culex tritaeniorhynchus. Of these nine species, Aedes vexans, Aedes vittatus, Culex sitiens, and Culex tritaeniorhynchus were registered in GenBank for the first time from Saudi Arabia. The DNA barcodes generated a 100% match to known barcodes of these mosquito species, that also matched with the morphological identification. Ae. vexans was found to be either a case of cryptic species (subspecies) or a new species from the region. However, more research has to be conducted to prove the latter. This study directly contributes to the development of a molecular reference library of mosquito species from the Jazan region and Saudi Arabia. The library is essential for confirmation of species in support of existing mosquito surveillance and control programmes.

Project description:BackgroundSaudi Arabia and Yemen are the only two countries in the Arabian Peninsula that are yet to achieve malaria elimination. Over the past two decades, the malaria control programme in Saudi Arabia has successfully reduced the annual number of malaria cases, with the lowest incidence rate across the country reported in 2014. This study aims to investigate the distribution of residual malaria in Jazan region and to identify potential climatic drivers of autochthonous malaria cases in the region.MethodsA cross-sectional study was carried out from 1 April 2018 to 31 January 2019 in Jazan region, southwestern Saudi Arabia, which targeted febrile individuals attending hospitals and primary healthcare centres. Participants' demographic data were collected, including age, gender, nationality, and residence. Moreover, association of climatic variables with the monthly autochthonous malaria cases reported during the period of 2010-2017 was retrospectively analysed.ResultsA total of 1124 febrile subjects were found to be positive for malaria during the study period. Among them, 94.3 and 5.7% were infected with Plasmodium falciparum and Plasmodium vivax, respectively. In general, subjects aged 18-30 years and those aged over 50 years had the highest (42.7%) and lowest (5.9%) percentages of malaria cases. Similarly, the percentage of malaria-positive cases was higher among males than females (86.2 vs 13.8%), among non-Saudi compared to Saudi subjects (70.6 vs 29.4%), and among patients residing in rural rather than in urban areas (89.8 vs 10.2%). A total of 407 autochthonous malaria cases were reported in Jazan region between 2010 and 2017. Results of zero-inflated negative binomial regression analysis showed that monthly average temperature and relative humidity were the significant climatic determinants of autochthonous malaria in the region.ConclusionMalaria remains a public health problem in most governorates of Jazan region. The identification and monitoring of malaria transmission hotspots and predictors would enable control efforts to be intensified and focused on specific areas and therefore expedite the elimination of residual malaria from the whole region.

Project description:BackgroundTimely molecular surveillance of Plasmodium falciparum kelch 13 (k13) gene mutations is essential for monitoring the emergence and stemming the spread of artemisinin resistance. Widespread artemisinin resistance, as observed in Southeast Asia, would reverse significant gains that have been made against the malaria burden in Africa. The purpose of this study was to assess the prevalence of k13 polymorphisms in western Kenya and Ethiopia at sites representing varying transmission intensities between 2018 and 2022.MethodsDried blood spot samples collected through ongoing passive surveillance and malaria epidemiological studies, respectively, were investigated. The k13 gene was genotyped in P. falciparum isolates with high parasitaemia: 775 isolates from four sites in western Kenya (Homa Bay, Kakamega, Kisii, and Kombewa) and 319 isolates from five sites across Ethiopia (Arjo, Awash, Gambella, Dire Dawa, and Semera). DNA sequence variation and neutrality were analysed within each study site where mutant alleles were detected.ResultsSixteen Kelch13 haplotypes were detected in this study. Prevalence of nonsynonymous k13 mutations was low in both western Kenya (25/783, 3.19%) and Ethiopia (5/319, 1.57%) across the study period. Two WHO-validated mutations were detected: A675V in three isolates from Kenya and R622I in four isolates from Ethiopia. Seventeen samples from Kenya carried synonymous mutations (2.17%). No synonymous mutations were detected in Ethiopia. Genetic variation analyses and tests of neutrality further suggest an excess of low frequency polymorphisms in each study site. Fu and Li's F test statistic in Semera was 0.48 (P > 0.05), suggesting potential population selection of R622I, which appeared at a relatively high frequency (3/22, 13.04%).ConclusionsThis study presents an updated report on the low frequency of k13 mutations in western Kenya and Ethiopia. The WHO-validated R622I mutation, which has previously only been reported along the north-west border of Ethiopia, appeared in four isolates collected from eastern Ethiopia. The rapid expansion of R622I across Ethiopia signals the need for enhanced monitoring of the spread of drug-resistant P. falciparum parasites in East Africa. Although ACT remains currently efficacious in the study areas, continued surveillance is necessary to detect early indicators of artemisinin partial resistance.

Dataset Information

Kelch 13-propeller polymorphisms in Plasmodium falciparum from Jazan region, southwest Saudi Arabia.

Publications

Kelch 13-propeller polymorphisms in Plasmodium falciparum from Jazan region, southwest Saudi Arabia.

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