Malaria, Dengue and Chikungunya are vector borne diseases with shared endemic profiles and symptoms. Coinfections with any of these diseases could have fatal outcomes if left undiagnosed. Understanding the prevalence and distribution of coinfections is necessary to improve diagnosis and designing therapeutic interventions. We have carried out a systematic search of the published literature based on PRISMA guidelines to identify cases of Malaria, Dengue and Chikungunya coinfections. We systematically reviewed the literature to identify eligible studies and extracted data regarding cases of coinfection from cross sectional studies, case reports, retrospective studies, prospective observational studies and surveillance reports. Care full screening resulted in 104 publications that met the eligibility criteria and reported Malaria/Dengue, Dengue/Chikungunya, Malaria/Chikungunya and Malaria/Dengue/Chikungunya coinfections. These coinfections were spread over six geographical locations and 42 different countries and are reported more frequently in the last 15 years possibly due to expanding epidemiology of Dengue and Chikungunya. Few of these reports have also analysed distinguishing features of coinfections. Malaria/Dengue coinfections were the most common coinfection followed by Dengue/Chikungunya, Malaria/Chikungunya and Malaria/Dengue/Chikungunya coinfections. P. falciparum and P. vivax were the commonest species found in cases of malaria coinfections and Dengue serotype-4 commonest serotype in cases of dengue coinfections. Most studies were reported from India. Nigeria and India were the only two countries from where all possible combinations of coinfections were reported. We have comprehensively reviewed the literature associated with cases of coinfections of three important vector borne diseases to present a clear picture of their prevalence and distribution across the globe. The frequency of coinfections presented in the study suggests proper diagnosis, surveillance and management of cases of coinfection to avoid poor prognosis of the underlying etiology.

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.

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.

Dengue fever is caused by four common serotypes of the dengue virus (DENV-1, DENV-2, DENV-3, and DENV-4). Patients infected with one serotype may develop lifelong serotype-specific protective immunity. However, they remain susceptible to reinfection with the other serotypes, often increasing the risk of severe forms of dengue. This cross-sectional study investigates the prevalence of the four dengue serotypes in patients who presented with dengue fever at Makkah hospitals between April 2023 and May 2024. Data were collected from the medical records of the Regional Laboratory in Makkah, Saudi Arabia. The 238 positive dengue samples included 185 samples (77.73%) from male patients. The average age of the patients was 37.65 years (SD = 15.05). Dengue type 2 was the most common serotype, followed by type 1, type 3, and type 4. Most of the dengue patients were Saudi nationals, followed by Egyptians. There were 11 dengue-positive samples that were not diagnosed with any of the four dengue serotypes. Since Makkah receives numerous international travelers, these samples might contain novel dengue serotypes circulating in different parts of the world. This study underscores the need for the continuous monitoring of dengue serotypes to predict potential outbreaks and mitigate the risk of severe dengue in susceptible populations.

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 DBLβ12 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-DBLβ12 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-DBLβ12 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-DBLβ12 interaction.

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 β12 (DBLβ12) domain of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), PFD0020c. Here, we report the structural insights into the binding of the DBLβ12 domain of PfEMP1 with the human receptor gC1qR using computational methods. A molecular model of the DBLβ12 domain was generated and used for protein–protein docking with the host receptor gC1qR. The protein–protein docking revealed that the DBLβ12 asymmetrically interacts with two subunits of the gC1qR trimer at the solution face of gC1qR. A total of 21 amino acid residues of DBLβ12 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 DBLβ12 binding with its receptor gC1qR and may help in designing novel antisevere malaria interventions.