Malaria during COVID-19 Travel Restrictions in Makkah, Saudi Arabia.

Malaria is a parasitic infection that may result in an acute, life-threatening illness. It is a major public health problem in the tropical world. The disease is caused by the parasites of the genus Plasmodium and is transmitted by female Anopheles mosquitoes. Saudi Arabia is in the elimination phase of malaria control. Several parts of Saudi Arabia report cases of imported malaria among travelers and visitors. The city of Makkah in Saudi Arabia has a population of about 2.3 million. Moreover, over 6 million religious visitors from different parts of the world visit Makkah annually. During the COVID-19 outbreak, travel restrictions were enforced in Makkah to contain the spread of COVID-19. We compare the total reported cases of malaria in Makkah before, during, and after COVID-19 travel restrictions in this retrospective cross-sectional study. Data on demographics, clinical data, and laboratory parameters were collected from the medical records of the Ministry of Health, Saudi Arabia. The annual malaria incidence rates in Makkah were 29.13/million people (2018), 37.82/million people (2019), 15.65/million people (2020), 12.61/million people (2021), and 48.69/million people (2022). Most of the malaria cases in Makkah were caused by Plasmodium falciparum, followed by P. vivax. Sudan, Nigeria, Yamen, Pakistan, and India are the top five countries contributing to malaria cases in Makkah. Weekly malaria case analyses revealed that COVID-19-related travel restrictions resulted in zero malaria cases in Makkah, indicating the magnitude of the travel-related malaria burden in the city.

High Seroprevalence of SARS-CoV-2 IgG and RNA among Asymptomatic Blood Donors in Makkah Region, Saudi Arabia.

The gold-standard approach for diagnosing and confirming Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) infection is reverse transcription-polymerase chain reaction (RT-PCR). This method, however, is inefficient in detecting previous or dormant viral infections. The presence of antigen-specific antibodies is the fingerprint and cardinal sign for diagnosis and determination of exposure to infectious agents including Corona virus disease-2019 (COVID-19). This cross-sectional study examined the presence of SARS-CoV-2 spike-specific immunoglobulin G (IgG) among asymptomatic blood donors in Makkah region. A total of 4368 asymptomatic blood donors were enrolled. They were screened for spike-specific IgG using ELISA and COVID-19 RNA by real-time PCR. COVID-19 IgG was detected among 2248 subjects (51.5%) while COVID-19-RNA was detected among 473 (10.8%) subjects. The IgG frequency was significantly higher among males and non-Saudi residents (p < 0.001 each) with no significant variation in IgG positivity among blood donors with different blood groups. In addition, COVID-19 RNA frequency was significantly higher among donors below 40-years old (p = 0.047, χ2 = 3.95), and non-Saudi residents (p = 0.001, χ2 = 304.5). The COVID-19 IgG levels were significantly higher among the RNA-positive donors (p = 001), and non-Saudi residents (p = 0.041), with no variations with age or blood group (p > 0.05). This study reveals a very high prevalence of COVID-19 IgG and RNA among asymptomatic blood donors in Makkah, Saudi Arabia indicating a high exposure rate of the general population to COVID-19; particularly foreign residents. It sheds light on the spread on COVID-19 among apparently healthy individuals at the beginning of the pandemic and could help in designing various control measures to minimize viral spread.

In Silico Prediction of Plasmodium falciparum Cytoadherence Inhibitors That Disrupt Interaction between gC1qR-DBLß12 Complex.

Malaria causes about half a million deaths per year, mainly in children below 5 years of age. Cytoadherence of Plasmodium falciparum infected erythrocytes in brain and placenta has been linked to severe malaria and malarial related deaths. Cytoadherence is mediated by binding of human receptor gC1qR to the DBLß12 domain of a P. falciparum erythrocyte membrane protein family 1 (PfEMP1) protein. In the present work, molecular dynamic simulation was extensively studied for the gC1qR-DBLß12 complex. The stabilized protein complex was used to study the protein-protein interface interactions and mapping of interactive amino acid residues as hotspot were performed. Prediction of inhibitors were performed by using virtual protein-protein inhibitor database Timbal screening of about 15,000 compounds. In silico mutagenesis studies, binding profile and protein ligand interaction fingerprinting were used to strengthen the screening of the potential inhibitors of gC1qR-DBLß12 interface. Six compounds were selected and were further subjected to the MAIP analysis and ADMET studies. From these six compounds, the compounds 3, 5, and 6 were found to outperform on all screening criteria from the rest selected compounds. These compounds may provide novel drugs to treat and manage severe falciparum malaria. Additionally. the identified hotspots can be used in future for designing novel interventions for disruption of interface interactions, such as through peptides or vaccines. Futher in vitro and in vivo studies are required for the confirmation of these compounds as potential inhibitors of gC1qR-DBLß12 interaction.

Dihydrofolate reductase, thymidylate synthase, and serine hydroxy methyltransferase: successful targets against some infectious diseases.

Parasitic diseases have a serious impact on the world in terms of health and economics and are responsible for worldwide mortality and morbidity. The present review features the hybrid targeting involving three main enzymes for the treatment of different parasitic diseases. The enzymes Dihydrofolate reductase, thymidylate synthase, and Serine hydroxy methyltransferase play an essential role in the folate pathway. The present review focuses on these enzymes, which can be targeted against several diseases. It shed light on the past, present, and future of these targets, and it can be assessed that these targets can play a significant role against several infectious diseases. For combating viral and protozoal infectious diseases, these targets in combination should be addressed.

The epidemiology and incidence of dengue in Makkah, Saudi Arabia, during 2017-2019.

OBJECTIVES: To study the epidemiology of dengue incidence and understand the dynamics of dengue transmission in Makkah, Kingdom of Saudi Arabia (KSA), between 2017-2019. METHODS: This is a cross-sectional study. Health and demographic data was obtained for all confirmed dengue cases in Makkah, KSA, in the years 2017-2019 from the Vector-Borne and Zoonotic Diseases Administration (VBZDA) in Makkah and the Makkah Regional Laboratory, KSA. In addition, entomological data about Aedes density was obtained from the VBZDA. Descriptive epidemiological methods were used to determine the occurrence and distribution of dengue cases. RESULTS: Laboratory-confirmed dengue cases were higher in 2019 as compared to 2017 and 2018, suggesting an outbreak of dengue in Makkah, KSA, in 2019. The incidence of confirmed dengue cases was 204 in 2017, 163 in 2018 and 748 in 2019. Dengue mostly affected people in the 25-44 age group, accounting for approximately half of the annual dengue cases each year. Men were at a higher dengue incidence risk when compared to women, and Saudi women had a higher risk rate for dengue cases when compared to non-Saudi women in all 3 years studied. There was no dengue related death in these 3 years. CONCLUSION: The dengue incidence increased in Makkah, KSA, in 2019 as compared to the previous 2 years, owing to heavy rainfall in 2019. Post-rainfall Vector control efforts may help contain the disease in Makkah, KSA.

Computational Insights into the Interaction between Cytoadherence Receptor gC1qR and the DBLß12 Domain of a Plasmodium falciparum PfEMP1 Ligand.

Human receptor gC1qR is a 32 kD protein that mediates the cytoadherence of Plasmodium falciparum-infected erythrocytes (IEs) to human brain microvascular endothelial cells (HBMEC) and platelets. The cytoadherence of IEs to gC1qR has been associated with severe malaria symptoms. The cytoadherence to gC1qR is mediated by the Duffy binding-like ß12 (DBLß12) domain of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), PFD0020c. Here, we report the structural insights into the binding of the DBLß12 domain of PfEMP1 with the human receptor gC1qR using computational methods. A molecular model of the DBLß12 domain was generated and used for protein-protein docking with the host receptor gC1qR. The protein-protein docking revealed that the DBLß12 asymmetrically interacts with two subunits of the gC1qR trimer at the solution face of gC1qR. A total of 21 amino acid residues of DBLß12 interact with 26 amino acid residues in the gC1qR trimer through 99 nonbonding interactions and 4 hydrogen bonds. Comparative analysis of binding sites on the DBL domain fold for the two receptors gC1qR and ICAM1 showed that the two sites are distinct. This is the first study that provides structural insights into DBLß12 binding with its receptor gC1qR and may help in designing novel antisevere malaria interventions.

Antiprotozoal potential of Salvadora persica against three virulent subtypes of Blastocystis sp.

Blastocystis sp. is a group of anaerobic protozoa parasitizing the gastrointestinal tract of humans and a broad variety of animals. Evidences of Blastocystis parasites resistance development to antiprotozoal drugs urge the exploration of new therapeutics. Antiprotozoal potential of Salvadora persica, a medicinal plant traditionally used for oral hygiene, was evaluated in vitro against Blastocystis sp. human isolates. Until now, no study has described the effect of S. persica extracts on this parasitic protozoa. Blastocystis sp. positive stool samples collected from patients with gastrointestinal complaints and asymptomatic individuals diagnosed by microscopy were furthermore cultured in vitro and characterized by PCR and multiplex-PCR using sequence-tagged-site primers to determine their subtypes. Out of 21 Blastocystis sp. isolates, five were determined as ST1, 14 as ST3, and two as ST5 subtypes. Antiprotozoal activity of untreated and heat-treated S. persica roots aqueous extracts was evaluated in vitro by serial dilutions on three Blastocystis sp. subtypes; ST1, ST3, and ST5 isolated from symptomatic patients. A significant killing activity was observed with both, untreated and heat-treated aqueous extracts of S. persica at minimal concentration of 2.5 µl/ml compared to parasites' growth controls (P < 0.05). Maximal antiprotozoal effect was reached at a concentration of 20 µl/ml of S. persica aqueous extract. Means of growth inhibition effect obtained with untreated and heat-treated extracts at 40 µl/ml against the three subtypes of Blastocystis sp. were 80% (SD 2.3) and 82% (SD 1.1), respectively. No significant difference was observed in the inhibitory effect of S. persica extracts between the three Blastocystis sp. subtypes. Aqueous extract of S. persica roots contains therefore heat-stable components with significant antiprotozoal activity against Blastocystis sp. subtypes ST1, ST3, and ST5 in vitro. Further investigations are required to determine and characterize the active antiprotozoal components of S. persica roots and their evaluation in vivo.

Subtyping of Blastocystis sp. isolated from symptomatic and asymptomatic individuals in Makkah, Saudi Arabia.

BACKGROUND: Blastocystis is a group of cosmopolitan gastrointestinal parasite of humans and a wide variety of animals. These anaerobic protozoans include more than 17 specific small-subunit ribosomal RNA subtypes, of which nine are found in humans with a variable geographical distribution. Until now, no study has described the Blastocystis subtypes present in Saudi Arabia. METHODS: In total, 1,262 faecal samples were collected from patients with gastrointestinal complaints and asymptomatic individuals visiting two major hospitals. All samples were analysed by F1/R1 diagnostic PCR, microscopy and culture methods. The subtypes of Blastocystis sp. isolates were determined by the sequenced-tagged site (STS)-based method. RESULTS: One-hundred-thirty-three positive cases were detected by F1/R1 diagnostic PCR, of which 122 were also positive by the culture method and 83 by direct microscopy. The sensitivities of direct microscopy and the culture method were 62% and 92%, respectively. Subtype (ST3) was the most prevalent (80.5%), followed by ST1 (14.5%) and ST2 (5%). ST4, ST5, ST6 and ST7 were not detected in this study. ST3 infections were significantly predominant (P < 0.05) among symptomatic patients. CONCLUSIONS: To our knowledge, this study provides the first run-through information on Blastocystis sp. epidemiology in Makkah city, revealing a rather moderate prevalence of 10.5% and the presence of three subtypes, ST1, ST2, and ST3. ST3 was the most predominant, particularly among symptomatic patients.