Seroprevalence of Hepatitis B and C Genotypes Among Young Apparently Healthy Females of Karachi-Pakistan

INTRODUCTION: Although the prevalence of hepatitis virus infections in Pakistan is still unknown, limited data indicate that the exposure rate to HBV is 35-38% with 4% being carriers and 32% having anti-HBV surface antibodies through natural conversion [1,2,3]. Studies in Pakistan have shown that the prevalence rate of HCV is 4.8-14% for, and that it is continuously increasing. Hence there is an urgent need to create awareness about the prevalence of both hepatitis B and C, and to develop preventive measures aimed at minimizing the prevalence of these diseases in the country.Study Design: Prospective, descriptive study. The study took place from March 2002 till October 2006 at two university campuses in Karachi.MATERIALS AND METHODS: A total of 4000 healthy female students were screened for HBs Ag, anti-HBs antibodies and anti-HCV antibodies by rapid immunochromatography, ELISA and PCR.RESULTS: A total of 3820 volunteers (95.5%) were negative by all three methods, 181 (4.5%) tested positive for HB surface antigen and 20 (0.5%) were positive for anti HB surface antibodies; 208 volunteers (5.2%) were positive for HCV. Double infection with HBV and HCV was found in only one patient (0.025%). Out of 180 HBs antigen positive samples 151 (83.89%) were genotype D, 28 (15.56%) showed mixed infection with genotypes B and D, and one patient (0.56%) showed mixed infection with genotypes C and D. Out of 208 samples positive for HCV antibodies, 107 (51.44%) were genotype 3a, 50 (24.04%) were mix of genotype 3a and 3b, 33 (15.87%) were genotype 3b, 10 (4.81%) were genotype 1b while, 8 (3.84%) samples could not be typed.CONCLUSION: Although the presence of these pathogenic viruses was not very high in our young healthy female population, it is still a matter of concern to control the unregulated spread of these deadly infections by promoting increased awareness and regular immunization programs in the community. Local manufacturing of vaccines and related products may reduce these infections

The effects of symmetry on the dynamics of antigenic variation

In the studies of dynamics of pathogens and their interactions with a host immune system, an important role is played by the structure of antigenic variants associated with a pathogen. Using the example of a model of antigenic variation in malaria, we show how many of the observed dynamical regimes can be explained in terms of the symmetry of interactions between different antigenic variants. The results of this analysis are quite generic, and have wider implications for understanding the dynamics of immune escape of other parasites, as well as for the dynamics of multi-strain diseases.Comment: 21 pages, 4 figures; J. Math. Biol. (2012), Online Firs

Games of Incomplete Information and Myopic Equilibria

A new concept of an equilibrium in games is introduced that solves an open question posed by A. Neyman

On the general theory of the origins of retroviruses

<p>Abstract</p> <p>Background</p> <p>The order retroviridae comprises viruses based on ribonucleic acids (RNA). Some, such as HIV and HTLV, are human pathogens. Newly emerged human retroviruses have zoonotic origins. As far as has been established, both repeated infections (themselves possibly responsible for the evolution of viral mutations <b>(Vm) </b>and host adaptability <b>(Ha)</b>); along with interplay between <it>inhibitors </it>and <it>promoters </it>of cell tropism, are needed to effect retroviral cross-species transmissions. However, the exact <it>modus operadi </it>of intertwine between these factors at molecular level remains to be established. Knowledge of such intertwine could lead to a better understanding of retrovirology and possibly other infectious processes. This study was conducted to derive the mathematical equation of a general theory of the origins of retroviruses.</p> <p>Methods and results</p> <p>On the basis of an arbitrarily non-Euclidian geometrical "thought experiment" involving the cross-species transmission of simian foamy virus (sfv) from a non-primate species <it>Xy </it>to <it>Homo sapiens </it>(<it>Hs</it>), initially excluding all social factors, the following was derived. At the port of exit from <it>Xy </it>(where the species barrier, SB, is defined by the <it>Index of Origin</it>, IO), sfv shedding is (1) enhanced by two transmitting tensors <b>(Tt)</b>, (i) virus-specific immunity (VSI) and (ii) evolutionary defenses such as APOBEC, RNA interference pathways, and (when present) expedited therapeutics (denoted e²D); and (2) opposed by the five accepting scalars <b>(At)</b>: (a) genomic integration hot spots, gIHS, (b) nuclear envelope transit <b>(</b>NMt) vectors, (c) virus-specific cellular biochemistry, VSCB, (d) virus-specific cellular receptor repertoire, VSCR, and (e) pH-mediated cell membrane transit, (↓_pHCMat). Assuming <b>As </b>and <b>Tt </b>to be independent variables, <b>IO = Tt/As</b>. The same forces acting in an opposing manner determine SB at the port of sfv entry (defined here by the <it>Index of Entry</it>, <b>IE = As/Tt</b>). Overall, If sfv encounters no unforeseen effects on transit between X<it>y </it>and <it>Hs</it>, then the square root of the combined index of sfv transmissibility (√<b>|RTI|) </b>is proportional to the product IO* IE (or ~Vm* Ha* ∑Tt*∑As*<b>Ω</b>), where <b>Ω </b>is the retrovirological constant and ∑ is a function of the ratio Tt/As or As/Tt for sfv transmission from <it>Xy </it>to <it>Hs</it>.</p> <p>Conclusions</p> <p>I present a mathematical formalism encapsulating the general theory of the origins of retroviruses. It summarizes the choreography for the intertwined interplay of factors influencing the probability of retroviral cross-species transmission: <b>Vm, Ha, Tt, As, </b>and <b>Ω</b>.</p

Gender Differences in HIV Disease Progression and Treatment Outcomes among HIV Patients One Year after Starting Antiretroviral Treatment (ART) in Dar es Salaam, Tanzania.

We investigated gender differences in treatment outcome during first line antiretroviral treatment (ART) in a hospital setting in Tanzania, assessing clinical, social demographic, virological and immunological factors. We conducted a cohort study involving HIV infected patients scheduled to start ART and followed up to 1 year on ART. Structured questionnaires and patients file review were used to collect information and blood was collected for CD4 and viral load testing. Gender differences were assessed using Kruskal-Wallis test and chi-square test for continuous and categorical data respectively. Survival distributions for male and female patients were estimated using the Kaplan-Meier method and compared using Cox proportional hazards models. Of 234 patients recruited in this study, 70% were females. At baseline, women had significantly lower education level; lower monthly income, lower knowledge on ARV, less advanced HIV disease (33% women; 47% men started ART at WHO stage IV, p = 0.04), higher CD4 cell count (median 149 for women, 102 for men, p = 0.02) and higher BMI (p = 0.002). After 1 year of standard ART, a higher proportion of females survived although this was not significant, a significantly higher proportion of females had undetectable plasma viral load (69% women, 45% men, p = 0.003), however females ended at a comparable CD4 cell count (median CD4, 312 women; 321 men) signifying a worse CD4 cell increase (p = 0.05), even though they still had a higher BMI (p = 0.02). The unadjusted relative hazard for death for men compared to women was 1.94. After correcting for confounding factors, the Cox proportional hazards showed no significant difference in the survival rate (relative hazard 1.02). We observed women were starting treatment at a less advanced disease stage, but they had a lower socioeconomical status. After one year, both men and women had similar clinical and immunological conditions. It is not clear why women lose their immunological advantage over men despite a better virological treatment response. We recommend continuous follow up of this and more cohorts of patients to better understand the underlying causes for these differences and whether this will translate also in longer term differences

Production of Transgenic Pigs Mediated by Pseudotyped Lentivirus and Sperm

Sperm-mediated gene transfer can be a very efficient method to produce transgenic pigs, however, the results from different laboratories had not been widely repeated. Genomic integration of transgene by injection of pseudotyped lentivirus to the perivitelline space has been proved to be a reliable route to generate transgenic animals. To test whether transgene in the lentivirus can be delivered by sperm, we studied incubation of pseudotyped lentiviruses and sperm before insemination. After incubation with pig spermatozoa, 62±3 lentiviral particles were detected per 100 sperm cells using quantitative real-time RT-PCR. The association of lentivirus with sperm was further confirmed by electron microscopy. The sperm incubated with lentiviral particles were artificially inseminated into pigs. Of the 59 piglets born from inseminated 5 sows, 6 piglets (10.17%) carried the transgene based on the PCR identification. Foreign gene and EGFP was successfully detected in ear tissue biopsies from two PCR-positive pigs, revealed via in situ hybridization and immunohistochemistry. Offspring of one PCR-positive boar with normal sows showed PCR-positive. Two PCR-positive founders and offsprings of PCR-positive boar were further identified by Southern-blot analysis, out of which the two founders and two offsprings were positive in Southern blotting, strongly indicating integration of foreign gene into genome. The results indicate that incubation of sperm with pseudotyped lentiviruses can incorporated with sperm-mediated gene transfer to produce transgenic pigs with improved efficiency

HIV-1 Nef increases astrocyte sensitivity towards exogenous hydrogen peroxide

<p>Abstract</p> <p>Background</p> <p>HIV-1 infected individuals are under chronic exposure to reactive oxygen species (ROS) considered to be instrumental in the progression of AIDS and the development of HIV-1 associated dementia (HAD). Astrocytes support neuronal function and protect them against cytotoxic substances including ROS. The protein HIV-1 Nef, a progression factor in AIDS pathology is abundantly expressed in astrocytes in patients with HAD, and thus may influence its functions.</p> <p>Results</p> <p>Endogenous expressed HIV-1 Nef leads to increased sensitivity of human astrocytes towards exogenous hydrogen peroxide but not towards TNF-alpha. Cell death of <it>nef</it>-expressing astrocytes exposed to 10 μM hydrogen peroxide for 30 min occurred within 4 h.</p> <p>Conclusion</p> <p>HIV-1 Nef may contribute to neuronal dysfunction and the development of HAD by causing death of astrocytes through decreasing their tolerance for hydrogen peroxide.</p