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Dynamical systems analysis of a reaction-diffusion SIRS model with optimal control for the COVID-19 spread

Salman AM, Mohd MH

Comput Methods Biomech Biomed Engin, 2024 Nov 13.
PMID: 39534924 DOI: 10.1080/10255842.2024.2423879

We examine an SIRS reaction-diffusion model with local dispersal and spatial heterogeneity to study COVID-19 dynamics. Using the operator semigroup approach, we establish the existence of disease-free equilibrium (DFE) and endemic equilibrium (EE), and derive the basic reproduction number, R0. Simulations show that without dispersal, reinfection and limited medical resources problems can cause a plateau in cases. Dispersal and spatial heterogeneity intensify localised outbreaks, while integrated control strategies (vaccination and treatment) effectively reduce infection numbers and epidemic duration. The possibility of reinfection demonstrates the need for adaptable health measures. These insights can guide optimised control strategies for enhanced public health preparedness.
ChatGPT revisited: Using ChatGPT-4 for finding references and editing language in medical scientific articles

Alyasiri OM, Salman AM, Akhtom D, Salisu S

J Stomatol Oral Maxillofac Surg, 2024 Mar 21.
PMID: 38521243 DOI: 10.1016/j.jormas.2024.101842

The attainment of academic superiority relies heavily upon the accessibility of scholarly resources and the expression of research findings through faultless language usage. Although modern tools, such as the Publish or Perish software program, are proficient in sourcing academic papers based on specific keywords, they often fall short of extracting comprehensive content, including crucial references. The challenge of linguistic precision remains a prominent issue, particularly for research papers composed by non-native English speakers who may encounter word usage errors. This manuscript serves a twofold purpose: firstly, it reassesses the effectiveness of ChatGPT-4 in the context of retrieving pertinent references tailored to specific research topics. Secondly, it introduces a suite of language editing services that are skilled in rectifying word usage errors, ensuring the refined presentation of research outcomes. The article also provides practical guidelines for formulating precise queries to mitigate the risks of erroneous language usage and the inclusion of spurious references. In the ever-evolving realm of academic discourse, leveraging the potential of advanced AI, such as ChatGPT-4, can significantly enhance the quality and impact of scientific publications.
The use of transgenic parasites in malaria vaccine research

Othman AS, Marin-Mogollon C, Salman AM, Franke-Fayard BM, Janse CJ, Khan SM

Expert Rev Vaccines, 2017 Jul;16(7):1-13.
PMID: 28525963 DOI: 10.1080/14760584.2017.1333426

INTRODUCTION: Transgenic malaria parasites expressing foreign genes, for example fluorescent and luminescent proteins, are used extensively to interrogate parasite biology and host-parasite interactions associated with malaria pathology. Increasingly transgenic parasites are also exploited to advance malaria vaccine development. Areas covered: We review how transgenic malaria parasites are used, in vitro and in vivo, to determine protective efficacy of different antigens and vaccination strategies and to determine immunological correlates of protection. We describe how chimeric rodent parasites expressing P. falciparum or P. vivax antigens are being used to directly evaluate and rank order human malaria vaccines before their advancement to clinical testing. In addition, we describe how transgenic human and rodent parasites are used to develop and evaluate live (genetically) attenuated vaccines. Expert commentary: Transgenic rodent and human malaria parasites are being used to both identify vaccine candidate antigens and to evaluate both sub-unit and whole organism vaccines before they are advanced into clinical testing. Transgenic parasites combined with in vivo pre-clinical testing models (e.g. mice) are used to evaluate vaccine safety, potency and the durability of protection as well as to uncover critical protective immune responses and to refine vaccination strategies.
Fulltext Scenario analysis of COVID-19 transmission dynamics in Malaysia with the possibility of reinfection and limited medical resources scenarios

Salman AM, Ahmed I, Mohd MH, Jamiluddin MS, Dheyab MA

Comput Biol Med, 2021 Jun;133:104372.
PMID: 33864970 DOI: 10.1016/j.compbiomed.2021.104372

COVID-19 is a major health threat across the globe, which causes severe acute respiratory syndrome (SARS), and it is highly contagious with significant mortality. In this study, we conduct a scenario analysis for COVID-19 in Malaysia using a simple universality class of the SIR system and extensions thereof (i.e., the inclusion of temporary immunity through the reinfection problems and limited medical resources scenarios leads to the SIRS-type model). This system has been employed in order to provide further insights on the long-term outcomes of COVID-19 pandemic. As a case study, the COVID-19 transmission dynamics are investigated using daily confirmed cases in Malaysia, where some of the epidemiological parameters of this system are estimated based on the fitting of the model to real COVID-19 data released by the Ministry of Health Malaysia (MOH). We observe that this model is able to mimic the trend of infection trajectories of COVID-19 pandemic in Malaysia and it is possible for transmission dynamics to be influenced by the reinfection force and limited medical resources problems. A rebound effect in transmission could occur after several years and this situation depends on the intensity of reinfection force. Our analysis also depicts the existence of a critical value in reinfection threshold beyond which the infection dynamics persist and the COVID-19 outbreaks are rather hard to eradicate. Therefore, understanding the interplay between distinct epidemiological factors using mathematical modelling approaches could help to support authorities in making informed decisions so as to control the spread of this pandemic effectively.
Fulltext OX40 Stimulation Enhances Protective Immune Responses Induced After Vaccination With Attenuated Malaria Parasites

Othman AS, Franke-Fayard BM, Imai T, van der Gracht ETI, Redeker A, Salman AM, et al.

Front Cell Infect Microbiol, 2018;8:247.
PMID: 30073152 DOI: 10.3389/fcimb.2018.00247

Protection against a malaria infection can be achieved by immunization with live-attenuated Plasmodium sporozoites and while the precise mechanisms of protection remain unknown, T cell responses are thought to be critical in the elimination of infected liver cells. In cancer immunotherapies, agonistic antibodies that target T cell surface proteins, such as CD27, OX40 (CD134), and 4-1BB (CD137), have been used to enhance T cell function by increasing co-stimulation. In this study, we have analyzed the effect of agonistic OX40 monoclonal antibody treatment on protective immunity induced in mice immunized with genetically attenuated parasites (GAPs). OX40 stimulation enhanced protective immunity after vaccination as shown by an increase in the number of protected mice and delay to blood-stage infection after challenge with wild-type sporozoites. Consistent with the enhanced protective immunity enforced OX40 stimulation resulted in an increased expansion of antigen-experienced effector (CD11ahiCD44hi) CD8+ and CD4+ T cells in the liver and spleen and also increased IFN-γ and TNF producing CD4+ T cells in the liver and spleen. In addition, GAP immunization plus α-OX40 treatment significantly increased sporozoite-specific IgG responses. Thus, we demonstrate that targeting T cell costimulatory receptors can improve sporozoite-based vaccine efficacy.
Fulltext Chimeric Plasmodium falciparum parasites expressing Plasmodium vivax circumsporozoite protein fail to produce salivary gland sporozoites

Marin-Mogollon C, van Pul FJA, Miyazaki S, Imai T, Ramesar J, Salman AM, et al.

Malar J, 2018 Aug 09;17(1):288.
PMID: 30092798 DOI: 10.1186/s12936-018-2431-1

BACKGROUND: Rodent malaria parasites where the gene encoding circumsporozoite protein (CSP) has been replaced with csp genes from the human malaria parasites, Plasmodium falciparum or Plasmodium vivax, are used as pre-clinical tools to evaluate CSP vaccines in vivo. These chimeric rodent parasites produce sporozoites in Anopheles stephensi mosquitoes that are capable of infecting rodent and human hepatocytes. The availability of chimeric P. falciparum parasites where the pfcsp gene has been replaced by the pvcsp would open up possibilities to test P. vivax CSP vaccines in small scale clinical trials using controlled human malaria infection studies.
METHODS: Using CRISPR/Cas9 gene editing two chimeric P. falciparum parasites, were generated, where the pfcsp gene has been replaced by either one of the two major pvcsp alleles, VK210 or VK247. In addition, a P. falciparum parasite line that lacks CSP expression was also generated. These parasite lines have been analysed for sporozoite production in An. stephensi mosquitoes.
RESULTS: The two chimeric Pf-PvCSP lines exhibit normal asexual and sexual blood stage development in vitro and produce sporozoite-containing oocysts in An. stephensi mosquitoes. Expression of the corresponding PvCSP was confirmed in oocyst-derived Pf-PvCSP sporozoites. However, most oocysts degenerate before sporozoite formation and sporozoites were not found in either the mosquito haemocoel or salivary glands. Unlike the chimeric Pf-PvCSP parasites, oocysts of P. falciparum parasites lacking CSP expression do not produce sporozoites.
CONCLUSIONS: Chimeric P. falciparum parasites expressing P. vivax circumsporozoite protein fail to produce salivary gland sporozoites. Combined, these studies show that while PvCSP can partially complement the function of PfCSP, species-specific features of CSP govern full sporozoite maturation and development in the two human malaria parasites.
Fulltext A P. falciparum NF54 Reporter Line Expressing mCherry-Luciferase in Gametocytes, Sporozoites, and Liver-Stages

Marin-Mogollon C, Salman AM, Koolen KMJ, Bolscher JM, van Pul FJA, Miyazaki S, et al.

Front Cell Infect Microbiol, 2019;9:96.
PMID: 31058097 DOI: 10.3389/fcimb.2019.00096

Transgenic malaria parasites expressing fluorescent and bioluminescent proteins are valuable tools to interrogate malaria-parasite biology and to evaluate drugs and vaccines. Using CRISPR/Cas9 methodology a transgenic Plasmodium falciparum (Pf) NF54 line was generated that expresses a fusion of mCherry and luciferase genes under the control of the Pf etramp10.3 gene promoter (line mCherry-luc@etramp10.3). Pf etramp10.3 is related to rodent Plasmodium uis4 and the uis4 promoter has been used to drive high transgene expression in rodent parasite sporozoites and liver-stages. We examined transgene expression throughout the complete life cycle and compared this expression to transgenic lines expressing mCherry-luciferase and GFP-luciferase under control of the constitutive gapdh and eef1a promoters. The mCherry-luc@etramp10.3 parasites express mCherry in gametocytes, sporozoites, and liver-stages. While no mCherry signal was detected in asexual blood-stage parasites above background levels, luciferase expression was detected in asexual blood-stages, as well as in gametocytes, sporozoites and liver-stages, with the highest levels of reporter expression detected in stage III-V gametocytes and in sporozoites. The expression of mCherry and luciferase in gametocytes and sporozoites makes this transgenic parasite line suitable to use in in vitro assays that examine the effect of transmission blocking inhibitors and to analyse gametocyte and sporozoite biology.