Mapping baroreceptor function to genome: a mathematical modeling approach

To gain information about the genetic basis of a complex disease such as hypertension, blood pressure averages are often obtained and used as phenotypes in genetic mapping studies. In contrast, direct measurements of physiological regulatory mechanisms are not often obtained, due in large part to the time and expense required. As a result, little information about the genetic basis of physiological controlling mechanisms is available. Such information is important for disease diagnosis and treatment. In this article, we use a mathematical model of blood pressure to derive phenotypes related to the baroreceptor reflex, a short-term controller of blood pressure. The phenotypes are then used in a quantitative trait loci (QTL) mapping study to identify a potential genetic basis of this controller.     

Understanding cyclical thrombocytopenia: a mathematical modeling approach

Cyclical thrombocytopenia (CT) is a rare hematological disease characterized by periodic oscillations in the platelet count. Although first reported in 1936, the pathogenesis and an effective therapy remain to be identified. Since besides fluctuations in platelet levels the patients hematological profile have been consistently normal, a destabilization of a peripheral control mechanism might play an important role in the genesis of this disorder. In this paper, we investigate through computer simulations the mechanisms underlying the platelet oscillations observed in CT. First, we collected the data published in the last 40 years and quantified the significance of the platelet fluctuations using Lomb-Scargle periodograms. Our analysis reveals that the incidence of the statistically significant periodic data is equally distributed in men and women. The mathematical model proposed in this paper captures the essential features of hematopoiesis and successfully duplicates the characteristics of CT. With the same parameter changes, the model is able to fit the platelet counts and to qualitatively reproduce the TPO oscillations (when data is available). Our results indicate that a variation in the megakaryocyte maturity, a slower relative growth rate of megakaryocytes, as well as an increased random destruction of platelets are the critical elements generating the platelet oscillations in CT.     

Chancroid transmission dynamics: a mathematical modeling approach

Mathematical models have long been used to better understand disease transmission dynamics and how to effectively control them. Here, a chancroid infection model is presented and analyzed. The disease-free equilibrium is shown to be globally asymptotically stable when the reproduction number is less than unity. High levels of treatment are shown to reduce the reproduction number suggesting that treatment has the potential to control chancroid infections in any given community. This result is also supported by numerical simulations which show a decline in chancroid cases whenever the reproduction number is less than unity.     

The use of operational modeling of HIV/AIDS in a systems approach to public health decision making.

Compartmental models of infectious diseases readily represent known biological and epidemiological processes, are easily understood in flow-chart form by administrators, are simple to adjust to new information, and lend themselves to routine statistical analysis such as parameter estimation and model fitting. Technical results are immediately interpretable in epidemiological and public health terms. Deterministic models are easily stochasticized where this is important for practical purposes. With HIV/AIDS, serial data on both HIV prevalence and AIDS morbidity have been available from San Francisco. Assuming the distribution of the incubation period to be biologically stable, statistical analysis is quite feasible in other regions, even those with no reliable HIV data. Transmission rates must be estimated locally. It is also often possible to estimate the effective size of a population subgroup at risk, from population data on AIDS morbidity only. Computer simulation provides estimates of the evolving pattern of both HIV prevalence and AIDS morbidity. Some public health questions can be answered only by appropriately formulated stochastic models.     

Long-lasting insecticidal nets and the quest for malaria eradication: a mathematical modeling approach

Journal of Mathematical Biology - Recent dramatic declines in global malaria burden and mortality can be largely attributed to the large-scale deployment of insecticidal-based measures, namely...     

Role of environmental persistence in pathogen transmission: a mathematical modeling approach

Although diseases such as influenza, tuberculosis and SARS are transmitted through an environmentally mediated mechanism, most modeling work on these topics is based on the concepts of infectious contact and direct transmission. In this paper we use a paradigm model to show that environmental transmission appears like direct transmission in the case where the pathogen persists little time in the environment. Furthermore, we formulate conditions for the validity of this modeling approximation and we illustrate them numerically for the cases of cholera and influenza. According to our results based on recently published parameter estimates, the direct transmission approximation fails for both cholera and influenza. While environmental transmission is typically chosen over direct transmission in modeling cholera, this is not the case for influenza.     

HIV/AIDS的细胞治疗

获得性免疫缺陷综合征（AIDS）是由人类免疫缺陷病毒（HIV）感染引起的危险性极高的慢性传染病。高效抗逆转录病毒疗法（HAART）能够阻断正在进行的病毒复制而不能清除潜伏的病毒,目前尚无有效根治AIDS方法。免疫细胞在HIV/AIDS发展过程的不同阶段发挥着十分复杂的作用。细胞治疗是通过筛选表达抗HIV基因型的细胞或转染抗HIV基因、受体基因等方法获得抗HIV免疫细胞,并在体外进行扩增,将其转输给HIV/AIDS患者。细胞疗法与HAART等疗法有协同作用,促进HIV/AIDS的治疗。本文综述抗HIV-CAR T细胞、aTCR T细胞、负载HIV抗原的树突状细胞等在HIV/AIDS治疗中的应用及其疗效。     

Hospitalizations for HIV/AIDS: Differences between sexes

Background: Women are especially vulnerable to HIV infection because of biological, social, cultural, and economic factors. In Brazil, AIDS was initially seen predominantly in homosexual men, but the epidemic gradually reached a gender balance as increasing numbers of women became infected with HIV.Objective: The aim of the present study was to identify the clinical and epidemiologic characteristics of hospitalized patients with HIV/AIDS of both sexes and compare the differences between them.Methods: This epidemiologic cross-sectional study evaluated gender differences in demographic, social, clinical, and epidemiologic characteristics of patients diagnosed with HIV/AIDS who were admitted for any reason to the Public Hospital of the Medical School of the Federal University of Triângulo Mineiro, Uberaba, Minas Gerais State, Brazil.Results: A total of 363 patients were included in the analysis, with a male/female ratio of 1.1:1.0. Forty-one percent of women were pregnant. Mean age at hospitalization and duration of hospitalization were significantly greater among men (P<0.05). Men and nonpregnant women were admitted because of infection significantly more often than were pregnant women (P<0.05). Significantly more single men who reported homosexual, bisexual, or heterosexual behavior associated with drug use were admitted compared with women (P<0.05). Women admitted for treatment were significantly more likely than men to be employed (P<0.05). Adherence to antiretroviral treatment and T CD4+ lymphocyte count indicated important differences between the sexes, with better parameters observed among nonpregnant and pregnant women compared with men.Conclusions: In the present study, women with HIV/AIDS who were admitted to the hospital for any reason were in better clinical condition compared with men. This observation may be partially explained by the proportion of pregnant women in the study population. These findings suggest that future studies should examine pregnant women with HIV/AIDS as a separate population group to avoid bias in analysis.     

HIV/AIDS eradication

Antiretroviral therapy can inhibit HIV replication in patients and prevent progression to AIDS. However, it is not curative. Here we provide an overview of what antiretroviral drugs do and how the virus persists during therapy in rare reservoirs, such as latently infected CD4+ T cells. We also outline several innovative methods that are currently under development to eradicate HIV from infected individuals. These strategies include gene therapy approaches intended to create an HIV-resistant immune system, and activation/elimination approaches directed towards flushing out latent virus. This latter approach could involve the use of novel chemically synthesized analogs of natural activating agents.     

The role of screening and treatment in the transmission dynamics of HIV/AIDS and tuberculosis co-infection: a mathematical study

In this paper, we present a deterministic non-linear mathematical model for the transmission dynamics of HIV and TB co-infection and analyze it in the presence of screening and treatment. The equilibria of the model are computed and stability of these equilibria is discussed. The basic reproduction numbers corresponding to both HIV and TB are found and we show that the disease-free equilibrium is stable only when the basic reproduction numbers for both the diseases are less than one. When both the reproduction numbers are greater than one, the co-infection equilibrium point may exist. The co-infection equilibrium is found to be locally stable whenever it exists. The TB-only and HIV-only equilibria are locally asymptotically stable under some restriction on parameters. We present numerical simulation results to support the analytical findings. We observe that screening with proper counseling of HIV infectives results in a significant reduction of the number of individuals progressing to HIV. Additionally, the screening of TB reduces the infection prevalence of TB disease. The results reported in this paper clearly indicate that proper screening and counseling can check the spread of HIV and TB diseases and effective control strategies can be formulated around ‘screening with proper counseling’.     

A mathematical model of vaccination against HIV to prevent the development of AIDS.

Vaccination and post-exposure immunization against the human immunodeficiency viruses (HIV-1 and HIV-2) faces the problem of the extensive genetic and antigenic variability of these viruses. This raises the question of what fraction of all possible antigen strains of the virus must be recognized by the immune response to a vaccine to prevent development of acquired immunodeficiency disease (AIDS). The success of a vaccine can depend on the variability of the target epitopes. The different HIV variants must be suppressed faster than new escape mutants can be produced. In this paper the antigenic variation of HIV during an individual infection is described by a stochastic process. The central assumption is that antigenic drift is important for the virus to survive immunological attack and to establish a persistent infection that leads to the development of AIDS after a long incubation period. The mathematical analysis reveals that the fraction of antigenic variants recognized by the immune response, that is induced by a successful immunogen, must exceed 1-1/R, where R is the diversification rate of the virus population. This means that if each HIV strain can produce, on average, five new escape mutants, then more than 80% of the possible variants must be covered by the immunogen. A generic result of the model is that, no matter how immunogenic a vaccine is, it will fail if it does not enhance immune attack against a sufficiently large fraction of strains. Furthermore, it is shown that the timing of the application of post-exposure immunization is important.     

Animal models for HIV AIDS: a comparative review

Human immunodeficiency virus (HIV), the causative agent for acquired immune deficiency syndrome, was described over 25 y ago. Since that time, much progress has been made in characterizing the pathogenesis, etiology, transmission, and disease syndromes resulting from this devastating pathogen. However, despite decades of study by many investigators, basic questions about HIV biology still remain, and an effective prophylactic vaccine has not been developed. This review provides an overview of the viruses related to HIV that have been used in experimental animal models to improve our knowledge of lentiviral disease. Viruses discussed are grouped as causing (1) nonlentiviral immunodeficiency-inducing diseases, (2) naturally occurring pathogenic infections, (3) experimentally induced lentiviral infections, and (4) nonpathogenic lentiviral infections. Each of these model types has provided unique contributions to our understanding of HIV disease; further, a comparative overview of these models both reinforces the unique attributes of each agent and provides a basis for describing elements of lentiviral disease that are similar across mammalian species.