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Fulltext Increased prevalence of pfdhfr and pfdhps mutations associated with sulfadoxine-pyrimethamine resistance in Plasmodium falciparum isolates from Jazan Region, Southwestern Saudi Arabia: important implications for malaria treatment policy

Madkhali AM, Al-Mekhlafi HM, Atroosh WM, Ghzwani AH, Zain KA, Abdulhaq AA, et al.

Malar J, 2020 Dec 02;19(1):446.
PMID: 33267841 DOI: 10.1186/s12936-020-03524-x

BACKGROUND: Despite 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.
METHODS: A 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.
RESULTS: No 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
Fulltext Residual malaria in Jazan region, southwestern Saudi Arabia: the situation, challenges and climatic drivers of autochthonous malaria

Al-Mekhlafi HM, Madkhali AM, Ghailan KY, Abdulhaq AA, Ghzwani AH, Zain KA, et al.

Malar J, 2021 Jul 13;20(1):315.
PMID: 34256757 DOI: 10.1186/s12936-021-03846-4

BACKGROUND: Saudi 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.
METHODS: A 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.
RESULTS: A 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.
CONCLUSION: Malaria 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.
The return of chloroquine-sensitive Plasmodium falciparum parasites in Jazan region, southwestern Saudi Arabia over a decade after the adoption of artemisinin-based combination therapy: analysis of genetic mutations in the pfcrt gene

Madkhali AM, Abdulhaq AA, Atroosh WM, Ghzwani AH, Zain KA, Ghailan KY, et al.

Parasitol Res, 2021 Nov;120(11):3771-3781.
PMID: 34561749 DOI: 10.1007/s00436-021-07323-4

This study investigated the polymorphism in the P. falciparum chloroquine resistance transporter (pfcrt) gene 11 years after chloroquine (CQ) cessation in Jazan region, southwestern Saudi Arabia. Two hundred and thirty-five P. falciparum isolates were amplified to detect mutations in the pfcrt gene. The pfcrt 76 T molecular marker for CQ resistance was detected in 66.4% (156/235) of the isolates, while the K76 CQ-sensitive wild type was detected in 33.6%. The pfcrt 74I and pfcrt 75E point mutations were each found to be present in 56.2% of isolates, while only four isolates (1.7%) were found to carry the pfcrt 72S mutation. Moreover, four pfcrt haplotypes were identified as follows: the CVIET triple-allele (56.2%), SVMET double-allele (1.7%) and CVMNT single-allele (8.5%) mutant haplotypes and the CVMNK wild haplotype (33.6%). The analysis also revealed significant associations between the prevalence of mutant pfcrt alleles and haplotypes and the age group, governorate and nationality of the patients as well as the parasitaemia level (p
Fulltext Microsatellite-based analysis reveals Aedes aegypti populations in the Kingdom of Saudi Arabia result from colonization by both the ancestral African and the global domestic forms

Mashlawi AM, Alqahtani H, Abuelmaali SA, Gloria-Soria A, Saingamsook J, Kaddumukasa M, et al.

Evol Appl, 2024 Feb;17(2):e13661.
PMID: 38405337 DOI: 10.1111/eva.13661

The Aedes aegypti (Linnaeus, 1762) mosquito is the main vector of dengue, chikungunya and Zika and is well established today all over the world. The species comprises two forms: the ancestral form found throughout Africa and a global domestic form that spread to the rest of the tropics and subtropics. In Saudi Arabia, A. aegypti has been known in the southwest since 1956, and previous genetic studies clustered A. aegypti from Saudi Arabia with the global domestic form. The purpose of this study was to assess the genetic structure of A. aegypti in Saudi Arabia and determine their geographic origin. Genetic data for 17 microsatellites were collected for A. aegypti ranging from the southwestern highlands of Saudi Arabia on the border of Yemen to the north-west in Madinah region as well as from Thailand and Uganda populations (as representatives of the ancestral African and global domestic forms, respectively). The low but significant level of genetic structuring in Saudi Arabia was consistent with long-distance dispersal capability possibly through road connectivity and human activities, that is, passive dispersal. There are two main genetic groupings in Saudi Arabia, one of which clusters with the Ugandan population and the other with the Thailand population with many Saudi Arabian individuals having mixed ancestry. The hypothesis of genetic admixture of the ancestral African and global domestic forms in Saudi Arabia was supported by approximate Bayesian computational analyses. The extent of admixture varied across Saudi Arabia. African ancestry was highest in the highland area of the Jazan region followed by the lowland Jazan and Sahil regions. Conversely, the western (Makkah, Jeddah and Madinah) and Najran populations corresponded to the global domesticated form. Given potential differences between the forms in transmission capability, ecology and behaviour, the findings here should be taken into account in vector control efforts in Saudi Arabia.
Fulltext Polymorphism analysis of pfmdr1 gene in Plasmodium falciparum isolates 11 years post-adoption of artemisinin-based combination therapy in Saudi Arabia

Al-Mekhlafi HM, Madkhali AM, Abdulhaq AA, Atroosh WM, Ghzwani AH, Zain KA, et al.

Sci Rep, 2022 01 11;12(1):517.
PMID: 35017593 DOI: 10.1038/s41598-021-04450-x

A total of 227 Plasmodium falciparum isolates from Jazan region, southwestern Saudi Arabia were amplified for the P. falciparum multi-drug resistance 1 (pfmdr1) gene to detect point mutations 11 years after the introduction of artemisinin-based combination therapy (ACT) in Saudi Arabia. The pfmdr1 86Y mutation was found in 11.5% (26/227) of the isolates while the N86 wild allele was detected in 88.5%. Moreover, 184F point mutations dominated (86.3%) the instances of pfmdr1 polymorphism while no mutation was observed at codons 1034, 1042 and 1246. Three pfmdr1 haplotypes were identified, NFSND (74.9%), NYSND (13.7%) and YFSND (11.4%). Associations of the prevalence of 86Y mutation and YFSND haplotype with participants' nationality, residency and parasitaemia level were found to be significant (P