Biomedical subjects

N I Stilianakis

Publications and source records attributed to N I Stilianakis.

10 recordsLinked to original sources

PubMed2004

Influenza-associated excess mortality from monthly total mortality data for Germany from 1947 to 2000.

OBJECTIVES: Death attributable to influenza is noted under various causes in the mortality statistics. Therefore, excess of total mortality is frequently used for the estimation of the entire impact of influenza on mortality. Various models for the estimation of the expected mortality are in use but are rather complex which hampers their routine use. A simple and hence transparent model was developed and applied to the total mortality in Germany from 1947 to 2000. METHODS: The method is based on the pattern of the distribution of the mortality over the months. Additional trends over the time could be included with simple factors. In this manner the model was applicable over the total observation period. RESULTS: The fit for the months where influenza was not epidemic was good and comparable to other models (R2 = 0.91). The estimated excess mortality is plausible and congruent with estimates based on other models. CONCLUSION: This method is applicable to long time series of any duration and obvious trends could be considered by simple factors in a readily identifiable and plausible way. Possible reductions in precision due to the consideration of a given monthly distribution pattern of the annual mortality seem tolerable with respect to the goodness of fit of the model. The estimation includes the pandemics of 1957/58 and 1968 to 1970.

Germany↗

PubMed2003

Effects of bioaerosol polluted outdoor air on airways of residents: a cross sectional study.

BACKGROUND: Bioaerosol pollution of workplace and home environments mainly affects airways and mucous membranes. The effect of environmental outdoor residential bioaerosol pollution, for example, livestock holdings, farming, and waste disposal plants, is unclear. AIMS: To investigate the perceived health of residents living in areas with measurable outdoor bioaerosol pollution (for example, spores of Aspergillus fumigatus and actinomycetes), and effects of accompanying odours. METHODS: In a cross sectional study, double blinded to ongoing microbial measurements, doctors collected 356 questionnaires from residents near a large scale composting site, and from unexposed controls in 1997. Self reported prevalence of health complaints during the past year, doctors' diagnoses, as well as residential odour annoyance were assessed. Microbiological pollution was measured simultaneously in residential outdoor air. RESULTS: Concentrations of >10(5) colony forming units of thermophilic actinomycetes, moulds, and total bacteria/m(3) air were measured 200 m from the site, dropping to near background concentrations within 300 m. Positive adjusted associations were observed for residency within 150-200 m from the site versus unexposed controls for self reported health complaints: "waking up due to coughing", odds ratio (OR) 6.59 (95% confidence interval (CI) 2.57 to 17.73); "coughing on rising or during the day", OR 3.18 (95% CI 1.24 to 8.36); "bronchitis", OR 3.59 (95% CI 1.40 to 9.4); and "excessive tiredness", OR 4.27 (95% CI 1.56 to 12.15). Reports of irritative airway complaints were associated with residency in the highest bioaerosol exposure, 150-200 m (versus residency >400-500 m) from the site, and period of residency more than five years, but not residential odour annoyance. Lifetime prevalence of self reported diseases did not differ with exposure. CONCLUSIONS: Bioaerosol pollution of residential outdoor air can occur in concentrations found in occupational environments. For the first time residents exposed to bioaerosol pollution were shown to report irritative respiratory complaints similar to mucous membrane irritation independently of perceived odours.

Aerosols↗

PubMed2001

Persistence of infectious HIV on follicular dendritic cells.

Follicular dendritic cells (FDCs) trap Ags and retain them in their native state for many months. Shortly after infection, HIV particles are trapped on FDCs and can be observed until the follicular network is destroyed. We sought to determine whether FDCs could maintain trapped virus in an infectious state for long periods of time. Because virus replication would replenish the HIV reservoir and thus falsely prolong recovery of infectious virus, we used a nonpermissive murine model to examine maintenance of HIV infectivity in vivo. We also examined human FDCs in vitro to determine whether they could maintain HIV infectivity. FDC-trapped virus remained infectious in vivo at all time points examined over a 9-mo period. Remarkably, as few as 100 FDCs were sufficient to transmit infection throughout the 9-mo period. Human FDCs maintained HIV infectivity for at least 25 days in vitro, whereas virus without FDCs lost infectivity after only a few days. These data indicate that HIV retained on FDCs can be long lived even in the absence of viral replication and suggest that FDCs stabilize and protect HIV, thus providing a long-term reservoir of infectious virus. These trapped stores of HIV may be replenished with replicating virus that persists even under highly active antiretroviral therapy and would likely be capable of causing infection on cessation of drug therapy.

Animals↗

PubMed2000

Influence of follicular dendritic cells on decay of HIV during antiretroviral therapy.

Drug treatment of HIV type 1 (HIV-1) infection leads to a rapid initial decay of plasma virus followed by a slower second phase of decay. To investigate the role of HIV-1 retained on follicular dendritic cells (FDCs) in this process, we have developed and analyzed a mathematical model for HIV-1 dynamics in lymphoid tissue (LT) that includes FDCs. Analysis of clinical data using this model indicates that decay of HIV-1 during therapy may be influenced by release of FDC-associated virus. The biphasic character of viral decay can be explained by reversible multivalent binding of HIV-1 to receptors on FDCs, indicating that the second phase of decay is not necessarily caused by long-lived or latently infected cells. Furthermore, viral clearance and death of short-lived productively infected cells may be faster than previously estimated. The model, with reasonable parameter values, is consistent with kinetic measurements of viral RNA in plasma, viral RNA on FDCs, productively infected cells in LT, and CD4(+) T cells in LT during therapy.

Dendritic Cells↗

PubMed2000

Influence of follicular dendritic cells on HIV dynamics.

In patients infected with human immunodeficiency virus type 1 (HIV-1), a large amount of virus is associated with follicular dendritic cells (FDCs) in lymphoid tissue. To assess the influence of FDCs on viral dynamics during antiretroviral therapy we have developed a mathematical model for treatment of HIV-1 infection that includes FDCs. Here, we use this model to analyse measurements of HIV-1 dynamics in the blood and lymphoid tissue of a representative patient, who was treated with a combination of HIV-1 reverse transcriptase and protease inhibitors. We show that loss of virus from FDCs during therapy can make a much larger contribution to plasma virus than production of virus by infected cells. This result challenges the notion that long-lived infected cells are a significant source of HIV-1 during drug therapy. Due to release of FDC-associated virus, we find that it is necessary to revise upward previous estimates of c, the rate at which free virus is cleared, and delta, the rate at which productively infected cells die. Furthermore, we find that potentially infectious virus, present before treatment, is released from FDCs during therapy and that the persistence of this virus can be affected by whether therapy includes reverse transcriptase inhibitors.

Anti-HIV Agents↗

PubMed1998

Emergence of drug resistance during an influenza epidemic: insights from a mathematical model.

A model was developed for the emergence of drug-resistant influenza viruses during a closed population influenza epidemic that occurs in a single wave. The model was used to consider several treatment and chemoprophylaxis strategies and to determine their effects on the spread of the infection. The model predicts frequent emergence and transmission of drug-resistant viruses with certain treatment scenarios. According to the model, chemoprophylaxis of susceptible persons (without treatment of those who are symptomatic) may be the best way to reduce the force of an epidemic and to keep development of drug resistance low. The model predictions indicate that the relative transmissibility of resistant variants compared with wild type virus and the choice of the treatment or chemoprophylaxis strategy can be decisive for the spread of drug-resistant viruses, a feature that may be crucial in a pandemic.

Amantadine↗

PubMed1997

Analysis of a model for the pathogenesis of AIDS.

According to a previously proposed mathematical model, the pathogenesis of acquired immunodeficiency syndrome (AIDS) could be explained by two phenomena: direct human immunodeficiency virus (HIV) infection of CD4+ T-cell populations and ongoing generation and selection of HIV mutants with increasing replicative capacity. In the present paper, the results obtained with this model are described in more detail. For different values of biologically interpretable parameters, the model predicts very different patterns of CD4+ T-cell decline after primary infection. With the assumption of a variability of 10% to 25% of three parameters between infected individuals, the model yields a realistic distribution curve of the incubation period to AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Clinical data sets of human immunodeficiency virus type 1 reverse transcriptase-resistant mutants explained by a mathematical model.

Treatment of human immunodeficiency virus type 1 (HIV-1) infection during the clinical latency phase with drugs inhibiting reverse transcriptase (RT) reduces the HIV-1 RNA load and increases the CD4+ T-cell count. Typically, however, the virus evolves mutations in the RT gene that circumvent the drugs. We develop a mathematical model for this situation. The model distinguishes quiescent from activated CD4+ T cells, incorporates the fact that only activated cells can become productively infected by HIV-1, embodies empirical estimates for the drug resistance and the mutation frequency for each of the HIV-1 drug-resistant mutants, and assumes the antiviral immune response to remain constant over the course of the experiments. We analyze clinical data on the evolution of drug-resistant mutants for the RT inhibitors lamivudine and zidovudine. The results show that the evolutionary sequence of the drug-resistant mutants in both data sets is accounted for by our model, given that lamivudine is more effective than zidovudine. Thus, current empirical estimates of the mutation frequencies and the drug resistances of the mutants suffice for explaining the data. We derive a critical treatment level below which the wild-type HIV-1 RNA load can rebound before the first drug-resistant mutant appears. Our zidovudine data confirm this to be the case. Thus, we demonstrate in the model and the data that the rebound of the HIV-1 RNA load in the case of zidovudine is due to the outgrowth of wild-type virus and the first drug-resistant mutant, whereas that in the case of lamivudine can only be due to the drug-resistant mutants. The evolution of drug resistance proceeds slower in the case of zidovudine because (i) zidovudine is not as effective as lamivudine and (ii) the first zidovudine drug-resistant mutant is competing with the rebounding wild-type virus.

Drug Resistance, Microbial↗

PubMed1996

Host-parasite dynamics and outgrowth of virus containing a single K70R amino acid change in reverse transcriptase are responsible for the loss of human immunodeficiency virus type 1 RNA load suppression by zidovudine.

The association between human immunodeficiency virus type I (HIV-1) RNA load changes and the emergence of resistant virus variants was investigated in 24 HIV-1-infected asymptomatic persons during 2 years of treatment with zidovudine by sequentially measuring serum HIV-1 RNA load and the relative amounts of HIV-1 RNA containing mutations at reverse transcriptase (RT) codons 70 (K-->R), 41 (M-->L), and 215 (T-->Y/F). A mean maximum decline in RNA load occurred during the first month, followed by a resurgence between 1 and 3 months, which appeared independent of drug-resistance. Mathematical modeling suggests that this resurgence is caused by host-parasite dynamics, and thus reflects infection of the transiently increased numbers of CD4+ lymphocytes. Between 3 and 6 months of treatment, the RNA load returned to baseline values, which was associated with the emergence of virus containing a single lysine to arginine amino acid change at RT codon 70, only conferring an 8-fold reduction in susceptibility. Despite the relative loss of RNA load suppression, selection toward mutations at RT codons 215 and 41 continued. Identical patterns were observed in the mathematical model. While host-parasite dynamics and outgrowth of low-level resistant virus thus appear responsible for the loss of HIV-1 RNA load suppression, zidovudine continues to select for alternative mutations, conferring increasing levels of resistance.

Base Sequence↗

PubMed1994

On the antigenic diversity threshold model for AIDS.

In this paper stochastic simulations of a model for AIDS pathogenesis developed by Nowak and coworkers are presented. The results reveal a strong dependency on initial conditions, and the model predicts a nonmonotonic hazard rate for the transition to AIDS. Doubts are raised concerning the significance of the "antigenic diversity threshold," since it only partially characterizes the model dynamics.

Acquired Immunodeficiency Syndrome↗