Mosquito-borne Infectious Disease Research Articles

Phytochemicals of Different Medicinal Herbs as Potential Inhibitors Against Dengue Serotype 2 Virus: A Computational Approach.

Dengue is one of the major mosquito-borne infectious diseases of the present century, reported to affect about 100-400 million people globally. The lack of effective therapeutic options has inspired several in vitro and in silico studies for the search of antivirals. Our previous study revealed the anti-dengue activity of different plant extracts from Plumeria alba, Bacopa monnieri, Vitex negundo, and Ancistrocladus heyneanus. Therefore, the current in silico study was designed to identify the phytochemicals present in the aforementioned plants, which are possibly responsible for the anti-dengue activity. Different plant databases as well as relevant literature were explored to find out the major compounds present in the above-stated plants followed by screening of the retrieved phytochemicals for the assessment of their binding affinity against different dengue viral proteins via molecular docking. The best poses of protein-ligand complexes obtained after molecular docking were selected for the calculation of binding free energy via MM-GBSA method. Based on the highest docking score and binding energy, six complexes were considered for further analysis. To analyze the stability of the complex, 100ns molecular dynamics (MD) simulations were carried out using Desmond module in the Schrodinger suite. The MD simulation analysis showed that four compounds viz. liriodendrin, bacopaside VII, isoorientin, and cynaroside exhibited stability with viral targets including the RdRp, NS3 helicase, and E protein indicating their potential as novel anti-dengue antivirals.

Dynamic analysis and optimal control of a mosquito-borne infectious disease model under the influence of biodiversity dilution effect

In this paper, biodiversity and a saturation treatment rate are introduced into a type of mosquito-borne infectious disease model with an incubation time delay. Through the dynamical analysis of the model, conditions for the existence and stability of disease-free and endemic equilibria are determined. The basic reproduction number of the model is calculated, and the condition for the existence of backward bifurcation is outlined. The study finds that under the dual influence of biodiversity and saturation treatment, the threshold characteristic of the basic reproduction number becomes invalidated. When R0\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$R_{0}$\\end{document} is less than 1, the model may exhibit four equilibrium states, with both the disease-free equilibrium and the endemic equilibrium being locally stable. In this scenario, whether the virus will become extinct depends on the initial conditions. The study also finds that when the basic reproduction number R0\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$R_{0}$\\end{document} is greater than 1, the stability of the model is influenced by the time delay, with Hopf bifurcation occurring at a specific time delay. In addition, another novel contribution of this paper is the formulation of an optimal control problem that takes into account the minimization of damage caused by humans to biodiversity. Based on the Pontryagin’s maximum principle, the specific characteristics of the optimal control measures are given, and the optimal strategy is derived by comparing five groups of control strategies. The optimal control results highlight the synergistic effect of multiple control measures with biodiversity. Under optimal control, a significant complementary effect between medical inputs and the dilution effect of biodiversity is evident. The findings imply that maintaining high biodiversity levels can decrease the demand for medical resources in mosquito-borne disease control efforts.

A multistage Plasmodium CRL4WIG1 ubiquitin ligase is critical for the formation of functional microtubule organization centers in microgametocytes.

Malaria is a mosquito-borne infectious disease caused by unicellular eukaryotic parasites of the Plasmodium genus. Protein ubiquitination by E3 ligases is a critical post-translational modification required for various cellular processes during the lifecycle of Plasmodium parasites. However, little is known about the repertoire and function of these enzymes in Plasmodium. Here, we show that Plasmodium expresses a conserved cullin RING E3 ligase (CRL) complex that is functionally related to CRL4 in other eukaryotes. In P. falciparum asexual blood stages, a cullin-4 scaffold interacts with the RING protein RBX1, the adaptor protein DDB1, and a set of putative receptor proteins that may determine substrate specificity for ubiquitination. These receptor proteins contain WD40-repeat domains and include WD-repeat protein important for gametogenesis 1 (WIG1). This CRL4-related complex is also expressed in P. berghei gametocytes, with WIG1 being the only putative receptor detected in both the schizont and gametocyte stages. WIG1 disruption leads to a complete block in microgamete formation. Proteomic analyses indicate that WIG1 disruption alters proteostasis of ciliary proteins and components of the DNA replication machinery during gametocytogenesis. Further analysis by ultrastructure expansion microscopy (U-ExM) indicates that WIG1-dependent depletion of ciliary proteins is associated with impaired the formation of the microtubule organization centers that coordinate mitosis with axoneme formation and altered DNA replication during microgametogenesis. This work identifies a CRL4-related ubiquitin ligase in Plasmodium that is critical for the formation of microgametes by regulating proteostasis of ciliary and DNA replication proteins.IMPORTANCEPlasmodium parasites undergo fascinating lifecycles with multiple developmental steps, converting into morphologically distinct forms in both their mammalian and mosquito hosts. Protein ubiquitination by ubiquitin ligases emerges as an important post-translational modification required to control multiple developmental stages in Plasmodium. Here, we identify a cullin RING E3 ubiquitin ligase (CRL) complex expressed in the replicating asexual blood stages and in the gametocyte stages that mediate transmission to the mosquito. WIG1, a putative substrate recognition protein of this ligase complex, is essential for the maturation of microgametocytes into microgametes upon ingestion by a mosquito. More specifically, WIG1 is required for proteostasis of ciliary proteins and components of the DNA replication machinery during gametocytogenesis. This requirement is linked to DNA replication and microtubule organization center formation, both critical to the development of flagellated microgametes.

Approach from the laboratory to the field: New strategies in the control of mosquito-borne infectious diseases.

Approach from the laboratory to the field: New strategies in the control of mosquito-borne infectious diseases.

The Implications of Malaria in Livestock: Reservoirs, Challenges, and Future Directions

Malaria, a mosquito-borne infectious disease caused by the parasite Plasmodium, has been predominantly associated with humans. However, recent studies have uncovered a potential reservoir for Plasmodium spp., within livestock populations. Malaria, caused by the parasitic protozoan Plasmodium spp., is a deadly disease that affects millions of people worldwide. Although human is the primary host for the malaria parasite, it has been discovered that certain animals can also serve as reservoirs. One such potential reservoir is livestock populations, as they have been found to carry Plasmodium spp. parasites. This article will discuss the implications of livestock being potential reservoirs for malaria and the importance of understanding this relationship for effective disease control. Livestock populations have long been overlooked as potential reservoirs for malaria transmission, but recent advancements in diagnostic techniques and surveillance studies have sparked interest in exploring this field. By prioritizing thorough assessments of zoonotic transmission risks, we can gain valuable insights into the role of livestock in malaria transmission and develop effective strategies to reduce the burden of this devastating disease.

Generation of soluble, immunoreactive recombinant JEV E protein through a simplified inclusion body extraction and refolding approach in vitro

Japanese encephalitis (JE) is a mosquito-borne infectious disease caused by the Japanese encephalitis virus (JEV). There is currently no effective treatment for JE, and all approved Japanese encephalitis vaccine products originated from the JEV genotype III (GIII). In recent years, JEV genotype I (GI) has gradually replaced GIII as the dominant genotype, and a new symptom of peripheral nerve injury (PNI) caused by JEV NX1889 strain has attracted wide attention, in which JEV envelope (E) protein may be involved in early peripheral nerve injury. Here, the envelope (E) gene of JEV GIb, NX1889 strain was cloned into pET-32a (+) plasmid, and then the E protein was successfully expressed as the high-yield inclusion body form in Escherichia coli (E. coli) BL21 (DE3). Subsequently, we successfully developed a simplified approach to generate soluble JEV E protein by solubilization, and a stepwise dialysis refolding approach with the introduction of a redox system. The refolding recombinant E protein was identified by anti-JEV-E polyclonal antibody and the serum anti-E titer of mice immunized with refolded E protein was higher than 1: 409,600, which proves it has highly immunoreactive. Moreover, the recombinant E protein could recognize antibodies in samples of multiple species and types, such as mice, rabbits, and humans. The approach described above is economical and does not require complex eukaryotic expression systems to produce immunoreactive JEV E protein, which may be of great significance for the diagnosis and pathogenesis of JEV GI strain.

Design and evaluation of an efficient mosquito trap.

Vector mosquito control is important for preventing and controlling mosquito-borne infectious diseases. This study designed and developed a mosquito killer (MK) with a specific light wavelength, simulated human body temperature, human odor, and a photocatalyst to stimulate CO2 based on the physiological characteristics and ecological habits of mosquitoes. We tested the trapping effect of individual and multiple mosquito-trapping elements of the MK through two-way selection experiments and compared them with several commercial mosquito traps. The 365 nm wavelength MK was significantly more effective than the 395 nm (Cx. quinquefasciatus: 62.00% vs. 34.25%; Ae. albopictus: 50.75% vs 45.00%, An. sinensis: 49.75% vs 39.00%). Mosquitoes captured by the MK with heaters at 365 nm were significantly more than those captured by the MK without heaters at 365 nm. A trap with a 365 nm wavelength, heating element, and lure showed significantly better capture effectiveness than MK with a 365 nm wavelength, heating element, but without lure (Cx. quinquefasciatus: 67.00% vs. 29.75%, Ae. albopictus: 60.25% vs 36.25%, An. sinensis: 49.75% vs 39.75%). The coated photocatalyst trap with a 365 nm wavelength, heating element, and lure showed significantly better capture effectiveness than the trap without coating (Cx. quinquefasciatus: 54.25% vs. 42.50%; Ae. albopictus: 53.50% vs 44.00%, An. sinensis: 50.00% vs 41.25%). This trap demonstrated a significantly better capture advantage for Cx. quinquefasciatus and Ae. albopictus compared to the three commercial products. The developed mosquito trap with multiple attractant factors significantly enhanced the capture effectiveness of common mosquitoes. © 2024 Society of Chemical Industry.

Long-term effects of climate factors on dengue fever over a 40-year period

BackgroundDengue fever stands as one of the most extensively disseminated mosquito-borne infectious diseases worldwide. While numerous studies have investigated its influencing factors, a gap remains in long-term analysis, impeding the identification of temporal patterns, periodicity in transmission, and the development of effective prevention and control strategies. Thus, we aim to analyze the periodicity of dengue fever incidence and explore the association between various climate factors and the disease over an extended time series.MethodsBy utilizing monthly dengue fever cases and climate data spanning four decades (1978–2018) in Guangdong province, China, we employed wavelet analysis to detect dengue fever periodicity and analyze the time-lag relationship with climate factors. Additionally, Geodetector q statistic was employed to quantify the explanatory power of each climate factor and assess interaction effects.ResultsOur findings revealed a prolonged transmission period of dengue fever over the 40-year period, transitioning from August to November in the 1970s to nearly year-round in the 2010s. Moreover, we observed lags of 1.5, 3.5, and 3 months between dengue fever and temperature, relative humidity, and precipitation, respectively. The explanatory power of precipitation, temperature, relative humidity, and the Oceanic Niño Index (ONI) on dengue fever was determined to be 18.19%, 12.04%, 11.37%, and 5.17%, respectively. Dengue fever exhibited susceptibility to various climate factors, with notable nonlinear enhancement arising from the interaction of any two variables. Notably, the interaction between precipitation and humidity yielded the most significant effect, accounting for an explanatory power of 75.32%.ConclusionsConsequently, future prevention and control strategies for dengue fever should take into account these climate changes and formulate corresponding measures accordingly. In regions experiencing the onset of high temperatures, humidity, and precipitation, it is imperative to initiate mosquito prevention and control measures within a specific window period of 1.5 months.

Green synthesized silver nanoparticles of Terminalia bellirica leaves extract: synthesis, characterization, in-silico studies, and antimalarial activity

Malaria is a mosquito-borne infectious disease that is caused by the Plasmodium parasite. Most of the available medication are losing their efficacy. Therefore, it is crucial to create fresh leads to combat malaria. Green silver nanoparticles (AgNPs) have recently attracted a lot of attention in biomedical research. As a result, green mediated AgNPs from leaves of Terminalia bellirica, a medicinal plant with purported antimalarial effects, were used in this investigation. Initially, cysteine-rich proteins from Plasmodium species were studied in silico as potential therapeutic targets. With docking scores between −9.93 and −11.25 kcal/mol, four leaf constituents of Terminalia bellirica were identified. The green mediated silver nanoparticles were afterward produced using leaf extract and were further examined using UV-vis spectrophotometer, DLS, Zeta potential, FTIR, XRD, and FESEM. The size of synthesized TBL-AgNPs was validated by the FESEM results; the average size of TBL-AgNPs was around 44.05 nm. The zeta potential study also supported green mediated AgNPs stability. Additionally, Plasmodium falciparum (3D7) cultures were used to assess the antimalarial efficacy, and green mediated AgNPs could effectively inhibit the parasitized red blood cells (pRBCs). In conclusion, this novel class of AgNPs may be used as a potential therapeutic replacement for the treatment of malaria.

While the priest climbs a post, the devil climbs ten: major biological threats from parasite and vector to malaria control and elimination

Malaria is one of the most serious mosquito-borne infectious diseases in the world. The global malaria control progress has stalled in recent years, which is largely due to the biological threats from the malaria pathogen Plasmodium and the vector Anopheles mosquitoes. This article provides an overview of biological threats to global malaria elimination, including antimalarial drug resistance, deletions in the malaria rapid diagnostic test target P. falciparum histidine-rich protein 2/3 (Pfhrp2/3) genes, vector insecticide resistance and emergence of invasive vector species, so as to provide insights into malaria and vector research and the formulation and adjustment of the malaria control and elimination strategy.

Medicinal Plants Used in Sri Lankan Traditional Medicine for Dengue Fever

Dengue fever, a mosquito-borne viral infectious disease caused by the dengue virus, is a significant global health concern, especially in tropical and subtropical regions. Despite preventive efforts, Sri Lanka faces recurring dengue outbreaks, with the Western province being the most affected. Current treatments primarily focus on supportive care, as specific antiviral therapies remain elusive. This review presents an overview of dengue, its clinical presentations, the dengue burden in Sri Lanka, and the potential of Sri Lankan medicinal plants used in traditional medicine for treating dengue. Several plants, such as Munronia pinnata, Azardirachta indica, Cissampelos pareira L., Carica papaya, Zingiber officinale, Curcuma longa, and Bambusa vulgaris, show antiviral properties against dengue. The utilization of these medicinal plants in dengue treatment could offer a promising avenue for further research and drug development.

Dengue Hemorrhagic Fever: Risk Factors in Pakistani Cohort

Background: Dengue fever is a mosquito-borne infectious disease with potential complications such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) and has fatality risk of greater than 20% if left untreated. There is lot of heterogeneity in factors predicting development of DHF in different populations. Objective: To determine clinical, biochemical and radiological parameters associated with risk of developing DHF in Pakistani population. Methods: This prospective observational study was conducted in Jinnah Hospital Lahore from October 2022 to December 2022. 180 patients with confirmed Dengue fever were included. Detailed history, clinical examination and laboratory/radiological investigations were performed. Patients were followed for development of DHF. Univariate analysis followed by logistic regression analysis was used to determine independent predictors for DHF. Results: Among 180 patients with Dengue fever with mean age of 33.04 (+14.12) and male to female ratio of 1.53/1 (109/71), we identified presence of mucosal bleeding {OR 4.7 (95% CI 2.05-10.78)p value <0.000}, abdominal pain {OR 2.73 (95% CI 1.17-4.38)p value 0.013}, persistent vomiting {OR 3.09 (95% CI 1.51-6.34)p value 0.002}, tender right hypochondrium {OR 3.98 (95% CI 1.94-8.16) p value <0.000} and presence of peri-cholecystic fluid {OR 7.78 (95% CI 3.25-18.63)p value < 0.000} to be significantly associated with risk of developing DHF with 83.6% accuracy on logistic regression analysis. Conclusion: Mucosal bleeding, right hypochondrium pain, persistent vomiting and presence of peri-cholecystic fluid in a patient of dengue fever predict risk of developing dengue hemorrhagic fever.

Progress in epidemiological characteristics and surveillance and early warning of dengue fever in China

Dengue fever is an acute mosquito-borne infectious disease caused by dengue virus and widely spread worldwide. Many factors, such as pathogens, vector organisms, climate, and social environment, affect its transmission and prevalence. The local dengue fever epidemic caused by imported cases in China shows a trend of increasing epidemic latitude and more widespread epidemic areas. However, the traditional monitoring and early warning models of dengue fever mainly focus on researching a single factor and a single area. Establishing a multi-factor forecast and early warning system is urgent to strengthen the early warning capability for the dengue fever epidemic. This paper mainly discusses the epidemic characteristics, the influencing factors, and the surveillance and early warning models of dengue fever in China to provide a reference for the effective prevention and control of dengue fever in China.

A review of knowledge, attitudes and practices regarding mosquitoes and mosquito-borne infectious diseases in nonendemic regions.

Mosquito-borne infectious diseases (MBIDs) present significant public health risks within tropical and subtropical regions. However, the rapid spread of MBIDs from these areas to temperate regions increase the risk of their emergence in nonendemic regions, i.e., regions where diseases are still sporadic and not sustained in the population. Raising awareness about preventive measures and protective behaviors is of primary importance to face the risks of vector-borne diseases. In this context, the number of studies on knowledge, attitude, and practice (KAP) about mosquitoes and MBIDs has grown rapidly in response to the need to identify knowledge and practices in nonendemic countries to fight mosquito proliferation. Building upon the recent developments in this field, we conducted the first-ever literature review to examine KAP studies conducted in nonendemic regions. Our aim was to identify the community's knowledge and attitudes that shape practices concerning the prevention of MBIDs. We used specific keywords regarding the scope of this review and then selected studies that were performed in nonendemic regions for MBIDs, including regions located in European countries, the USA or Asia. We identified 32 KAP studies, the oldest from 2003. The findings in the reviewed studies show that survey participants generally possessed a rather good understanding of mosquito breeding sites. However, there were notable variations in knowledge and perception of MBIDs, primarily linked to the geographic location of the survey and the prevalence of infectious outbreaks related to mosquito transmission. These findings highlight the significant influence of knowledge and awareness in fostering effective mosquito control practices. Moreover, socioeconomic status, particularly educational attainment, and respondents' gender emerged as key determinants in explaining the variability of appropriate practices. The survey results thus show the crucial role of knowledge, emphasizing the need for widespread awareness and information campaigns, encompassing both appropriate practices and efficient mosquito control methods. Understanding the interaction between these factors could provide good guidelines for implementing awareness plans and ultimately motivate the population to actively fight against mosquito proliferation and MBIDs development.

Pathogenetic mechanisms and treatment targets in cerebral malaria.

Malaria, the most prevalent mosquito-borne infectious disease worldwide, has accompanied humanity for millennia and remains an important public health issue despite advances in its prevention and treatment. Most infections are asymptomatic, but a small percentage of individuals with a heavy parasite burden develop severe malaria, a group of clinical syndromes attributable to organ dysfunction. Cerebral malaria is an infrequent but life-threatening complication of severe malaria that presents as an acute cerebrovascular encephalopathy characterized by unarousable coma. Despite effective antiparasite drug treatment, 20% of patients with cerebral malaria die from this disease, and many survivors of cerebral malaria have neurocognitive impairment. Thus, an important unmet clinical need is to rapidly identify people with malaria who are at risk of developing cerebral malaria and to develop preventive, adjunctive and neuroprotective treatments for cerebral malaria. This Review describes important advances in the understanding of cerebral malaria over the past two decades and discusses how these mechanistic insights could be translated into new therapies.

Spatial analysis and mapping of malaria risk areas using multi-criteria decision making in Ibadan, Oyo state, Nigeria

Malaria is a mosquito-borne infectious disease that affects humans and poses a severe public health problem. Nigeria has the highest number of global cases. Geospatial technology has been widely used to study the risks and factors associated with malaria hazards. The present study is conducted in Ibadan, Oyo State, Nigeria. The objective of this study is to map out areas that are at high risk of the prevalence of malaria by considering a good number of factors as criteria that determine the spread of malaria within Ibadan using open-source and Landsat remote sensing data and further analysis in GIS-based multi-criteria evaluation (MCE). This study considered factors like climate, environmental, socio-economic, and proximity to health centers as criteria for mapping malaria risk. The MCE used a weighted overlay of the factors to produce an element at-risk map, a malaria hazard map, and a vulnerability map. These maps were overlaid to produce the final malaria risk map, which showed that 72% of Ibadan has a risk of malaria prevalence. Identification and delineation of risk areas in Ibadan would help policymakers and decision-makers mitigate the hazards and improve the health status of the state.

Genotype Change in Circulating JEV Strains in Fujian Province, China.

Japanese encephalitis (JE), found in pigs, is a serious mosquito-borne zoonotic infectious disease caused by the Japanese encephalitis virus (JEV). JEV is maintained in an enzootic cycle between mosquitoes and amplifying vertebrate hosts, mainly pigs and wading birds. It is transmitted to humans through the bite of an infected mosquito, allowing the pathogen to spread and cause disease epidemics. However, there is little research on JEV genotype variation in mosquitoes and pigs in Fujian province. Previous studies have shown that the main epidemic strain of JEV in Fujian Province is genotype III. In this study, a survey of mosquito species diversity in pig farms and molecular evolutionary analyses of JEV were conducted in Fujian, China, in the summer of 2019. A total of 19,177 mosquitoes were collected at four sites by UV trap. Four genera were identified, of which the Culex tritaeniorhynchus was the most common mosquito species, accounting for 76.4% of the total (14,651/19,177). Anopheles sinensi (19.25%, 3691/19,177) was the second largest species. High mosquito infection rateswere an important factor in the outbreak. The captured mosquito samples were milled and screened with JEV-specific primers. Five viruses were isolated, FJ1901, FJ1902, FJ1903, FJ1904, and FJ1905. Genetic affinity was determined by analyzing the envelope (E) gene variants. The results showed that they are JEV gene type I and most closely related to the strains SH-53 and SD0810. In this study, it was found through genetic evolution analysis that the main epidemic strain of JE in pig farms changed from gene type III to gene type I. Compared with the SH-53 and SD0810 strains, we found no change in key sites related to antigenic activity and neurovirulence of JEV in Fujian JEV and pig mosquito strains, respectively. The results of the study provide basic data for analyzing the genotypic shift of JEV in Fujian Province and support the prevention and control of JEV.

A recombinant Aspergillus oryzae fungus transmitted from larvae to adults of Anopheles stephensi mosquitoes inhibits malaria parasite oocyst development

The control of malaria parasite transmission from mosquitoes to humans is hampered by decreasing efficacies of insecticides, development of drug resistance against the last-resort antimalarials, and the absence of effective vaccines. Herein, the anti-plasmodial transmission blocking activity of a recombinant Aspergillus oryzae (A. oryzae-R) fungus strain, which is used in human food industry, was investigated in laboratory-reared Anopheles stephensi mosquitoes. The recombinant fungus strain was genetically modified to secrete two anti-plasmodial effector peptides, MP2 (midgut peptide 2) and EPIP (enolase-plasminogen interaction peptide) peptides. The transstadial transmission of the fungus from larvae to adult mosquitoes was confirmed following inoculation of A. oryzae-R in the water trays used for larval rearing. Secretion of the anti-plasmodial effector peptides inside the mosquito midguts inhibited oocyst formation of P. berghei parasites. These results indicate that A. oryzae can be used as a paratransgenesis model carrying effector proteins to inhibit malaria parasite development in An. stephensi. Further studies are needed to determine if this recombinant fungus can be adapted under natural conditions, with a minimal or no impact on the environment, to target mosquito-borne infectious disease agents inside their vectors.

Design and Molecular Docking Studies of N-Mannich Base Derivatives of Primaquine Bearing Isatin on the Targets involved in the Pathophysiology of Cerebral Malaria.

Malaria is considered one of the life-threatening mosquito-borne infectious diseases responsible for approximately more than 4,00,000 deaths every year all over the world. Plasmodium falciparum and Plasmodium vivax are widespread species, but infections caused by the former are of great concern. Among the various forms of infections associated with Plasmodium falciparum, cerebral malaria (CM) is the most severe neurological complication, accounting for almost 13% of all malariarelated mortality. The development of effective therapeutics is urgently needed to overcome the fatality of this dreadful disease. The present work attempted to design and virtually screen a chemical library of 75 molecules (N-Mannich base derivatives of primaquine bearing isatin moiety as heterocyclic) by molecular docking studies against anti-malarial target proteins-Cystein Protease Falcipain-2; Dipeptidyl Aminopeptidase- 1; Dipeptidyl Aminopeptidase-3 and Glycogen synthase Kinase-3β receptors, for evaluating their anti-malarial potential. Among all studied anti-malarial target receptors, the designed molecules showed an overall higher affinity for Dipeptidyl Aminopeptidase-3. Furthermore, the molecules were analyzed for binding affinity and drug-like properties using Lipinski rules, and 30 best hits were shortlisted and analyzed for the pharmacokinetic profile. Two of these hits were found to be more toxic than primaquine, hence were omitted in further analysis. Later, these 28 hits were docked against two target proteins, (a) Plasmodium falciparum erythrocyte membrane protein-1 and (b) Intracellular adhesion molecule-1, to determine their efficiency against cerebral malaria, and the results were recorded. Analysis of docking results led to the identification of the 8 studied molecules as lead molecules which were selected for chemical synthesis, in vivo studies, and further preclinical evaluation. The molecule DSR 11 was predicted as the most appropriate lead molecule for anti-CM activity in the present investigation apart from the other seven molecules (DSR4, DSR26, DSR38, DSR40, DSR49, DSR56, and DSR70).

Analysis and interpretation of Malaria disease model in crisp and fuzzy environment

Malaria is a mosquito-borne infectious disease caused by the Plasmodium parasite. It is prevalent in many regions of the globe, particularly in sub-Saharan Africa, where it is a major cause of illness and death. Mathematical models can aid in understanding the dynamics of malaria transmission and guiding disease-control interventions. The authors discuss a mathematical model and focus on severely infected people of malaria transmission in both crisp and fuzzy environments in this article. A parameter pertaining to the cases where relapse of the disease has occurred is considered. This study discusses the stability of the model in both crisp and fuzzy environments and also considered numerical illustrations to validate the said model.