Antiretroviral therapy of HIV infection using a novel optimal type-2 fuzzy control strategy

Abstract The human immunodeficiency virus (HIV), as one of the most hazardous viruses, causes destructive effects on the human bodies' immune system. Hence, an immense body of research has focused on developing antiretroviral therapies for HIV infection. In the current study, we propose a new control technique for a fractional-order HIV infection model. Firstly, a fractional model of the HIV model is investigated, and the importance of the fractional-order derivative in the modeling of the system is shown. Afterward, a type-2 fuzzy logic controller is proposed for antiretroviral therapy of HIV infection. The developed control scheme consists of two individual controllers and an aggregator. The optimal aggregator modifies the output of each individual controller. Simulations for two different strategies are conducted. In the first strategy, only reverse transcriptase inhibitor (RTI) is used, and the superiority of the proposed controller over a conventional fuzzy controller is demonstrated. Lastly, in the second strategy, both RTI and protease inhibitors (PI) are used simultaneously. In this case, an optimal type-2 fuzzy aggregator is also proposed to modify the output of the individual controllers based on optimal rules. Simulations results demonstrate the appropriate performance of the designed control scheme for the uncertain system

Mathematical model with fractional order derivatives for Tuberculosis taking into account its relationship with HIV/AIDS and Diabetes

In this paper, we present a mathematical model for the study of resistance to tuberculosis treatment using fractional derivatives in the Caputo sense. This model takes into account the relationship between Tuberculosis, HIV/AIDS, and diabetes and differentiates resistance cases into MDR-TB (multidrug-resistant tuberculosis) and XDR-TB (extensively drug-resistant tuberculosis). We present the basic results associated with the model and study the behavior of the disease-free equilibrium points in the different sub-populations, TB-Only, TB-HIV/AIDS, and TB-Diabetes. We performed computational simulations for different fractional orders (α-values) using an Adams-Bashforth-Moulton type predictor-corrector PECE method. Among the results obtained, we have that the MDR-TB cases in all sub-populations decrease at the beginning of the study for the different α-values. In XDR-TB cases in the TB-Only sub-population, there is a decrease in the number of cases. XDR-TB cases in the TB-HIV/AIDS sub-population have differentiated behavior depending on α. This knowledge helps to design an effective control strategy. The XDR-TB cases in diabetics increased throughout the study period and outperformed all resistant compartments for the different α-values. We recommend special attention to the control of this compartment due to this growth

Mathematical Modeling, Analysis and Simulation of COVID-19 Dynamics

COVID-19 is an infectious disease caused by the SAR-COV-2 virus. Globally, as of 21 February 2023, there have been 757,264,511 confirmed cases of COVID-19, including 6,850,594 deaths, reported to the World Health Organization (WHO). \cite{WHO} The disease dynamics have evolved considerably since the initial outbreak in Wuhan, China with multiple variants, diverse public health measures and shifting public perception. Various public health measures have been implemented in order to slow the spread of including; social distancing, masking and several vaccines have been developed and granted emergency use authorization to help quell the spread of COVID-19. \cite{vaxreview}Since the onset of the coronavirus pandemic, researchers have been formulating mathematical models to gain insight into the complex dynamics of disease.In this talk, a model is proposed to study Coronavirus Disease 2019 (COVID-19) with the effect of vaccination with waning immunity. We also consider how hospitalization and COVID-19 specific deaths effect the disease dynamics. Our deterministic model is formulated by a system of ordinary differential equations (ODEs) that is built upon the classical SEIR framework. The local and global dynamics of the disease are analyzed by using the deterministic model with a time dependent vaccination parameter, and the result indicates that the basic reproduction number $\mathcal{R}_0$ serves as a valid disease threshold. Globally the disease dies out if $\mathcal{R}_0 1$. The time dependent vaccination parameter was modeled after the historical vaccination trends. Our results indicate that both the exposed and infected classes as well as vaccination play an important role in shaping the epidemic dynamics of COVID-19.

Incidence of HIV infection in rural KwaZulu-Natal in the context of the epidemiology and impact of HIV/AIDS in South Africa.

Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2007.South Africa has had one of the fastest growing HIV epidemics in the world and almost 30% of women attending public antenatal clinics (ANC) are currently infected with the virus. But as the epidemic is starting to level off and antiretroviral therapy (ART) is becoming increasingly available, few methods exist to determine the impact of ART or other interventions on the epidemic in South Africa. This thesis explores the epidemiology and dynamics of HIV infection and investigates the potential impact of ART. Methods Total and age-specific prevalence data are analysed in time and space and are used to investigate patterns of infection in men and women, urban and rural, and low and high risk populations. Dynamical models are developed to estimate incidence from age-specific prevalence and trends over time and are compared to laboratory-based estimates of recent HIV sero-conversion. Incidence is estimated in different populations in South Africa. A dynamical model is developed to estimate the impact of ART on the future course of the HIV epidemic. Results HIV prevalence varies geographically and by age, sex and race. The average female-tomale HIV prevalence ratio is 1.7 and prevalence peaks at an older age among men than women. The age at which prevalence peaks among women has increased from 23.0 to 26.5 years between 1995 and 2002. Four patterns of infection are identified: among pregnant women attending ANCs, among men and women in the general population, and among migrant workers. HIV incidence among ANC attendees peaked in the mid to late 1990s (at 6.6% per year nationally) with variation between provinces. Current estimates of HIV prevalence and incidence among the general population in South Africa (aged 15-49 year) are 18.8% and 2.4% per year, respectively. Age-specific incidence estimates from dynamical models and laboratory methods are in good agreement provided the window period for the laboratory method is increased. Over the next ten years the provision of ART could avert 1 to 1.5 million deaths depending on whether it is provided when the CD4 cell count falls to 200 or 350 cells/ul. By 2015 about 1.1 million people will be receiving ART but this will have little impact on the incidence of HIV and scaling up of prevention efforts remains urgent. Conclusions The thesis explores some of the determinants and patterns of HIV prevalence and incidence in South Africa in order to find better ways to manage the epidemic of HIV, monitor changes and evaluate progress in control efforts. In order to fight the epidemic we need to mobilize the best possible science in support of those people and communities affected by the epidemic

Innate Factors in Early Clearance of Mycobacterium tuberculosis

Introduction: Early clearance (EC) is the eradication of M. tuberculosis infection by innate immunity, before an adaptive immune response develops. Case contact studies consistently report a group of highly exposed but uninfected contacts that could be early clearers, and genetic loci are associated with the trait. Understanding how early clearers are protected could lead to vaccines or other therapies to prevent M. tuberculosis infection. Methods: In Indonesia, contacts of smear and x-ray positive Tuberculosis (TB) cases were recruited within 2 weeks of the case starting treatment. A Quantiferon Gold In Tube (QFN-GIT) test was performed at baseline, and contacts with a positive test were classified as "baseline positive" (BP), and those with a negative test received a repeat QFN-GIT 14 weeks later. Contacts who continued to test QFN-GIT negative, were classed as "persistently negative" (PN) and those who tested positive were classified as "converters". Cell populations, cytokine responses to stimuli, serum 25-OH vitamin D and the expression of candidate innate immune genes were measured in samples collected at baseline. The primary comparison was of the PN group, putative early clearers, to converters. Measurements collected from the whole cohort (peripheral blood cell counts, 25-OH vitamin D) were modelled for their association with risk of conversion in multi-level models that adjusted for clustering and confounding variables. Sub-studies on cytokine responses, gene expression and M. tuberculosis lineage were performed in subsets of participants. Results: A total of 941 case contacts of 317 index cases were recruited. One hundred and sixty-two (51%) of index cases had lung cavities on x-ray. Of the contacts 544 (57.9%) were BP, 223 (23.6%) were PN, 76 (8.0%) were converters, 18 had indeterminate QFN-GIT results and 22 (2.3%) had TB disease. A further 27 (2.9%) had unevaluated symptoms and 31 (3.1%) were lost to follow up. Risk of conversion was higher for contacts exposed to a 3+ smear grade case than those exposed to a grade 1+ or scanty case (RR=2.63; 95% CI 1.54 - 4.50; P<0.0001), and it was also higher for current smokers versus non smokers (RR=1.63; 95% CI 1.03 - 2.57; P=0.04). Risk of conversion was lower in those who been vaccinated with Bacillus Calmette-Guérin (BCG) compared to those who had not (RR=0.52; 95% CI 0.35 - 0.77; P=0.001). Risk of conversion increased with each additional mg/kg2 increase in body mass index (RR=1.06; 95% CI 1.01 - 1.10; P=0.01), and each 1000 cells per microliter decrease in immature granulocyte count (RR=0.72; 95% CI 0.60 - 0.90; P=0.004) and a neutrophil count in the lowest quartile, relative to the second quartile (RR 1.91 95%CI 1.05 - 3.50; P=0.04). There was no association with risk of conversion and vitamin D insufficiency (RR=1.10; 95% CI 0.65 - 1.85; P=0.7) or deficiency (RR=1.12; 95% CI 0.64 - 1.98; P=0.7). Cytokine responses to whole blood stimulation were analysed for 97 PN contacts and 41 converters. Responses to M. tuberculosis stimulation were not significantly higher for the primary comparison, but the IL-6 response to Streptococcus (RR=1.41; 95% CI 1.09 - 1.84; P=0.01) and the IL-8 responses to E. coli (RR=1.38; 95% CI 1.04 - 1.84; P=0.03) were higher in PN than converters. Restricting the analysis to 111 BCG vaccinated contacts (81 PN, 30 converters) revealed PN had higher IL-1β and IL-6 responses to Mtb lysate (RR=1.43; 95% CI 1.00 - 2.03; P=0.047) and (RR=1.40 95% CI 1.04 - 1.88; P=0.027) respectively and higher IL-6 response to S. pneumoniae (RR=1.52; 95% CI 1.14 - 2.03; P=0.005) and E. coli (RR: 1.26; 95% CI 1.00 - 1.59; P=0.054). Out of 45 candidate genes, the expression of nine genes differed at the P<0.05 threshold and of these only one (CTSD) was higher in PN than converters. Data on the M. tuberculosis lineage of the index case was available for 271 contacts. In this sub-study exposure to an index case with a lineage two isolate was cultured was associated with a positive QFN-GIT at baseline or follow up (RR=1.22; 95% CI 1.02 - 1.46; P=0.03), relative to exposure to M. tuberculosis of another lineage. Conclusions: Higher concentrations of immature granulocytes, neutrophils and pro-inflammatory innate cytokines in the PN group reveal early clearers have a pro-inflammatory phenotype. ECwas associated with BCG vaccination, and a higher innate cytokine responses in vaccinated contacts. This findings suggest BCG mediated protection occurs by trained innate immunity. Lineage two M. tuberculosis could evade EC more successfully than other lineages

Microbiology for Allied Health Students

This open textbook is a remix of Openstax Microbiology, CC-BY 4.0, and created through an Affordable Learning Georgia Round Six Textbook Transformation Grant. The textbook has the following supplemental materials within this repository: This is a collection of instructional materials for the following open textbook and lab manual: Microbiology for Allied Health Students Lab Manual Microbiology for Allied Health Students Instructional Materials Authors\u27 Description: Microbiology for Allied Health Students is designed to cover the scope and sequence requirements for the single semester Microbiology course for non-majors and allied health students. The book presents the core concepts of microbiology with a focus on applications for careers in allied health. The pedagogical features of Microbiology for Allied Health Students make the material interesting and accessible to students while maintaining the career-application focus and scientific rigor inherent in the subject matter. The scope and sequence of Microbiology for Allied Health Students has been developed and vetted with input from numerous instructors at institutions across the U.S. It is designed to meet the needs of most microbiology courses allied health students. With these objectives in mind, the content of this textbook has been arranged in a logical progression from fundamental to more advanced concepts. The opening chapters present an overview of the discipline, with individual chapters focusing on cellular biology as well as each of the different types of microorganisms and the various means by which we can control and combat microbial growth. The focus turns to microbial pathogenicity, emphasizing how interactions between microbes and the human immune system contribute to human health and disease. The last several chapters of the text provide a survey of medical microbiology, presenting the characteristics of microbial diseases organized by body system. Accessible files with optical character recognition (OCR) and auto-tagging provided by the Center for Inclusive Design and Innovation.https://oer.galileo.usg.edu/biology-textbooks/1015/thumbnail.jp

Renal Failure

The book "Renal Failure - The Facts" consists of some facts about diagnosis, etiopathogenis and treatment of acute and chronic renal failure. Acute, as well as chronic renal failure is great medical problems and their treatment is a burden for the budget of each government. The purpose of the chapters is to present some important issues of diagnosis and causes of AKI, as well as caused by snakes and arthropods, after cardiac surgery, as well as some therapeutic achievements in AKI. Well presented are the psychological condition in patients on haemodialysis, as well as the treatment of diabetic uremics. The book is aimed at clinicians with a special interest in nephrology, but it should also prove to be a valuable resource for any generalists who encounter a nephrological problems in their day-to-day practice