An insight to better understanding cross border malaria in Saudi Arabia.

BACKGROUND: Border malaria is a major obstacle for the malaria elimination in Saudi Arabia. Today, the southern border of Saudi Arabia is a region where malaria cases are resurging, and malaria control is dwindling mainly due to the humanitarian crisis and the conflict in Yemen. This study analyses the current border malaria epidemiology along the southern border of Saudi Arabia from 2015 to 2018. METHODS: All reported cases maintained by the malaria elimination centres in Aledabi and Baish, Jazan Province, Saudi Arabia, from 2015 to 2018 were analysed to examine the epidemiological changes over time. Pearson's Chi-Square test of differences was utilized to assess differences between the characteristics of imported and local causes and between border cases. A logistic regression model was used to predict imported status was related to living along side of the border area. RESULTS: A total of 3210 malaria cases were reported in Baish and Aledabi malaria centres between 2015 and 2018, of which 170 were classified as local cases and 3040 were classified as imported cases. Reported malaria cases were mainly among males, within the imported cases 61.5% (1868/3039) were residents of the border areas. CONCLUSIONS: Given the complexity of cross-border malaria, creating a malaria buffer zone that covers a certain margin from both sides of the border would allow for a joint force, cross-border malaria elimination programme. To initiate a malaria elimination activity and cases reported as belonging to this zone, rather than being pushed from one country to the other, would allow malaria elimination staff to work collaboratively with local borderland residents and other stakeholders to come up with innovative solutions to combat malaria and reach malaria-free borders.

Livelihood activities, human mobility, and risk of malaria infection in elimination settings: a case-control study.

BACKGROUND: Livelihood activities and human movements participate in the epidemiology of vector-borne diseases and influence malaria risk in elimination settings. In Saudi Arabia, where malaria transmission intensity varies geographically, it is vital to understand the components driving transmission within specific areas. In addition, shared social, behavioural, and occupational characteristics within communities may provoke the risk of malaria infection. This study aims to understand the relationship between human mobility, livelihood activities, and the risk of malaria infection in the border region of Jazan to facilitate further strategic malaria interventions. In addition, the study will complement and reinforce the existing efforts to eliminate malaria on the Saudi and Yemen border by providing a deeper understanding of human movement and livelihood activities. METHODS: An unmatched case-control study was conducted. A total of 261 participants were recruited for the study, including 81 cases of confirmed malaria through rapid diagnostic tests (RDTs) and microscopy and 180 controls in the Baish Governorate in Jazan Provinces, Saudi Arabia. Individuals who received malaria tests were interviewed regarding their livelihood activities and recent movement (travel history). A questionnaire was administered, and the data was captured electronically. STATA software version 16 was used to analyse the data. Bivariate and multivariate analyses were conducted to determine if engaging in agricultural activities such as farming and animal husbandry, recent travel history outside of the home village within the last 30 days and participating in spiritual gatherings were related to malaria infection status. RESULTS: A logistical regression model was used to investigate components associated with malaria infection. After adjusting several confounding factors, individuals who reported travelling away from their home village in the last 30 days OR 11.5 (95% CI 4.43-29.9), and those who attended a seasonal night spiritual gathering OR 3.04 (95% CI 1.10-8.42), involved in animal husbandry OR 2.52 (95% CI 1.10-5.82), and identified as male OR 4.57 (95% CI 1.43-14.7), were more likely to test positive for malaria infection. CONCLUSION: Human movement and livelihood activities, especially at nighttime, should be considered malaria risk factors in malaria elimination settings, mainly when the targeted area is limited to a confined borderland area.

Integrated Network Pharmacology Approach to Evaluate Bioactive Phytochemicals of Acalypha indica and Their Mechanistic Actions to Suppress Target Genes of Tuberculosis.

Mycobacterium tuberculosis is responsible for tuberculosis (TB) all over the world. Despite tremendous advancements in biomedical research, new treatment approaches, and preventive measures, TB incidence rates continue to ascend. The herbaceous plant Acalypha indica, also known as Indian Nettle, belongs to the Euphorbiaceae family and is known as one of the most important sources of medicines and pharmaceuticals for the medical therapy for a range of ailments. However, the precise molecular mechanism of its therapeutic action is still unknown. In this study, an integrated network pharmacology approach was employed to explore the potential mechanism of A. indica phytochemicals against TB. The active chemical components of A. indica were collected from two independent databases and published sources, whereas SwissTargetPrediction was used to identify the target genes of these phytochemicals. GeneCards and DisGeNET databases were employed to retrieve tuberculosis-related genes and variants. Following the evaluation of overlapped genes, gene enrichment analysis and PPI network analysis were performed using the DAVID and STRING databases, respectively. Later, to identify the potential target(s) for the disease, molecular docking was performed. A. indica revealed 9 active components with 259 potential therapeutic targets; TB attributed 694 intersecting genes from the two data sets; and both TB and A. indica overlapped 44 potential targets. The in-depth analysis based on the degree revealed that AKT1 and EGFR formed the foundation of the PPI network. Moreover, docking analysis followed by molecular dynamics simulations revealed that phytosterol and stigmasterol have higher binding affinities to AKT1 and EGFR to suppress tuberculosis. This study provides a convincing proof that A. indica can be exploited to target TB after experimental endorsement; further, it lays the framework for more experimental research on A. indica's anti-TB activity.

Plasmodium AdoMetDC/ODC bifunctional enzyme is essential for male sexual stage development and mosquito transmission.

Polyamines are positively-charged organic molecules that are important for cellular growth and division. Polyamines and their synthesizing enzymes are particularly abundant in rapidly proliferating eukaryotic cells such as parasitic protozoa and cancer cells. Polyamine biosynthesis inhibitors, such as Elfornithine, are now being considered for cancer prevention and have been used effectively against Trypanosoma brucei Inhibitors of polyamine biosynthesis have caused growth arrest of Plasmodium falciparum blood stages in vitro, but in P. berghei only partial inhibition has been observed. While polyamine biosynthesis enzymes are characterized and conserved in Plasmodium spp., little is known on the biological roles of these enzymes inside malaria parasite hosts. The bifunctional polyamine biosynthesis enzyme S-adenosyl methionine decarboxylase/ornithine decarboxylase (AdoMetDC/ODC) was targeted for deletion in P. yoelii Deletion of AdoMetDC/ODC significantly reduced blood stage parasitemia but Anopheles transmission was completely blocked. We showed that male gametocytogenesis and male gamete exflagellation were abolished and consequently no ookinetes or oocyst sporozoites could be generated from adometdc/odc(-) parasites. Supplementation of putrescine and spermidine did not rescue the defective phenotypes of male gametocytes and gametes of the knockout parasites. These results highlight the crucial role of polyamine homeostasis in the development and functions of Plasmodium erythrocytic stages in the blood and in the mosquito vector and validate polyamine biosynthesis pathway enzymes as drug targeting candidates for malaria parasite transmission blocking.