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Fulltext Modeling the effect of delay strategy on transmission dynamics of HIV/AIDS disease

Raza A, Ahmadian A, Rafiq M, Salahshour S, Naveed M, Ferrara M, et al.

Adv Differ Equ, 2020;2020(1):663.
PMID: 33250928 DOI: 10.1186/s13662-020-03116-8

In this manuscript, we investigate a nonlinear delayed model to study the dynamics of human-immunodeficiency-virus in the population. For analysis, we find the equilibria of a susceptible-infectious-immune system with a delay term. The well-established tools such as the Routh-Hurwitz criterion, Volterra-Lyapunov function, and Lasalle invariance principle are presented to investigate the stability of the model. The reproduction number and sensitivity of parameters are investigated. If the delay tactics are decreased, then the disease is endemic. On the other hand, if the delay tactics are increased then the disease is controlled in the population. The effect of the delay tactics with subpopulations is investigated. More precisely, all parameters are dependent on delay terms. In the end, to give the strength to a theoretical analysis of the model, a computer simulation is presented.
Molecular evidence of Anaplasma infection in naturally affected domestic cats of Pakistan

Ahmed A, Ijaz M, Ghauri HN, Aziz MU, Ghaffar A, Naveed M, et al.

Comp Immunol Microbiol Infect Dis, 2020 Oct;72:101524.
PMID: 32829184 DOI: 10.1016/j.cimid.2020.101524

Feline anaplasmosis is considered as an emerging tick-borne disease of zoonotic potential. The aim of current study was to investigate the molecular prevalence of anaplasmosis, associated risk factors, and alterations in hematological parameters of domestic cats from Lahore, Pakistan. Blood samples of 100 domestic cats from district Lahore were examined microscopically and the extracted genomic DNA from each sample was processed for the amplification of 16 S rRNA gene of Anaplasma. PCR confirmed isolates were purified for sequencing. The data regarding the risk factors was collected in a predesigned questionnaire and statistically analyzed by logistic regression analysis. The study found a molecular prevalence of 13% (13/100) among analyzed blood samples. The nucleotide analysis of Anaplasmataceae species sequences amplified by PCR showed high resemblance (99%) with isolates from Korea, Japan, Malaysia, Philippines, and India. The potential risk factors found to be significantly associated (p 
Fulltext A Vaccine Construction against COVID-19-Associated Mucormycosis Contrived with Immunoinformatics-Based Scavenging of Potential Mucoralean Epitopes

Naveed M, Ali U, Karobari MI, Ahmed N, Mohamed RN, Abullais SS, et al.

Vaccines (Basel), 2022 Apr 22;10(5).
PMID: 35632420 DOI: 10.3390/vaccines10050664

Mucormycosis is a group of infections, caused by multiple fungal species, which affect many human organs and is lethal in immunocompromised patients. During the COVID-19 pandemic, the current wave of mucormycosis is a challenge to medical professionals as its effects are multiplied because of the severity of COVID-19 infection. The variant of concern, Omicron, has been linked to fatal mucormycosis infections in the US and Asia. Consequently, current postdiagnostic treatments of mucormycosis have been rendered unsatisfactory. In this hour of need, a preinfection cure is needed that may prevent lethal infections in immunocompromised individuals. This study proposes a potential vaccine construct targeting mucor and rhizopus species responsible for mucormycosis infections, providing immunoprotection to immunocompromised patients. The vaccine construct, with an antigenicity score of 0.75 covering, on average, 92-98% of the world population, was designed using an immunoinformatics approach. Molecular interactions with major histocompatibility complex-1 (MHC-I), Toll-like receptors-2 (TLR2), and glucose-regulated protein 78 (GRP78), with scores of -896.0, -948.4, and -925.0, respectively, demonstrated its potential to bind with the human immune receptors. It elicited a strong predicted innate and adaptive immune response in the form of helper T (Th) cells, cytotoxic T (TC) cells, B cells, natural killer (NK) cells, and macrophages. The vaccine cloned in the pBR322 vector showed positive amplification, further solidifying its stability and potential. The proposed construct holds a promising approach as the first step towards an antimucormycosis vaccine and may contribute to minimizing postdiagnostic burdens and failures.
Fulltext Regulation of Host Immune Response against Enterobacter cloacae Proteins via Computational mRNA Vaccine Design through Transcriptional Modification

Naveed M, Jabeen K, Naz R, Mughal MS, Rabaan AA, Bakhrebah MA, et al.

Microorganisms, 2022 Aug 10;10(8).
PMID: 36014038 DOI: 10.3390/microorganisms10081621

Enterobacter cloacae is mainly responsible for sepsis, urethritis, and respiratory tract infections. These bacteria may affect the transcription of the host and particularly their immune system by producing changes in their epigenetics. In the present study, four proteins of Enterobacter cloacae were used to predict the epitopes for the construction of an mRNA vaccine against Enterobacter cloacae infections. In order to generate cellular and humoral responses, various immunoinformatic-based approaches were used for developing the vaccine. The molecular docking analysis was performed for predicting the interaction among the chosen epitopes and corresponding MHC alleles. The vaccine was developed by combining epitopes (thirty-three total), which include the adjuvant Toll-like receptor-4 (TLR4). The constructed vaccine was analyzed and predicted to cover 99.2% of the global population. Additionally, in silico immunological modeling of the vaccination was also carried out. When it enters the cytoplasm of the human (host), the codon is optimized to generate the translated mRNA efficiently. Moreover, the peptide structures were analyzed and docked with TLR-3 and TLR-4. A dynamic simulation predicted the stability of the binding complex. The assumed construct was considered to be a potential candidate for a vaccine against Enterobacter cloacae infections. Hence, the proposed construct is suitable for in vitro analyses to validate its effectiveness.
Fulltext Designing mRNA- and Peptide-Based Vaccine Construct against Emerging Multidrug-Resistant Citrobacter freundii: A Computational-Based Subtractive Proteomics Approach

Naveed M, Hassan JU, Ahmad M, Naeem N, Mughal MS, Rabaan AA, et al.

Medicina (Kaunas), 2022 Sep 27;58(10).
PMID: 36295517 DOI: 10.3390/medicina58101356

Background and Objectives: Citrobacter freundii (C. freundii) is an emerging and opportunistic Gram-negative bacteria of the human gastrointestinal tract associated with nosocomial and severe respiratory tract infections. It has also been associated with pneumonia, bloodstream, and urinary tract infections. Intrinsic and adaptive virulence characteristics of C. freundii have become a significant source of diarrheal infections and food poisoning among immune-compromised patients and newborns. Impulsive usage of antibiotics and these adaptive virulence characteristics has modulated the C. freundii into multidrug-resistant (MDR) bacteria. Conventional approaches are futile against MDR C. freundii. Materials and Methods: The current study exploits the modern computational-based vaccine design approach to treat infections related to MDR C. freundii. A whole proteome of C. freundii (strain: CWH001) was retrieved to screen pathogenic and nonhomologous proteins. Six proteins were shortlisted for the selection of putative epitopes for vaccine construct. Highly antigenic, nonallergen, and nontoxic eleven B-cell, HTL, and TCL epitopes were selected for mRNA- and peptide-based multi-epitope vaccine construct. Secondary and tertiary structures of the multi-epitope vaccine (MEVC) were designed, refined, and validated. Results: Evaluation of population coverage of MHC-I and MHC-II alleles were 72% and 90%, respectively. Docking MEVC with TLR-3 receptor with the binding affinity of 21.46 (kcal/mol) occurred through the mmGBSA process. Further validations include codon optimization with an enhanced CAI value of 0.95 and GC content of about 51%. Immune stimulation and molecular dynamic simulation ensure the antibody production upon antigen interaction with the host and stability of the MEVC construct, respectively. Conclusions: These interpretations propose a new strategy to combat MDR C. freundii. Further, in vivo and in vitro trials of this vaccine will be valuable in combating MDR pathogens.
Fulltext Mapping age- and sex-specific HIV prevalence in adults in sub-Saharan Africa, 2000-2018

Haeuser E, Serfes AL, Cork MA, Yang M, Abbastabar H, Abhilash ES, et al.

BMC Med, 2022 Dec 19;20(1):488.
PMID: 36529768 DOI: 10.1186/s12916-022-02639-z

BACKGROUND: Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15-59 years across SSA.
METHODS: We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units.
RESULTS: We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group.
CONCLUSIONS: As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA.