The effect of sexual transmission on Zika virus dynamics.

Zika virus is a human disease that may lead to neurological disorders in affected individuals, and may be transmitted vectorially (by mosquitoes) or sexually. A mathematical model of Zika virus transmission is formulated, taking into account mosquitoes, sexually active males and females, inactive individuals, and considering both vector transmission and sexual transmission from infectious males to susceptible females. Basic reproduction numbers are computed, and disease control strategies are evaluated. The effect of the incidence function used to model sexual transmission from infectious males to susceptible females is investigated. It is proved that for such functions that are sublinear, if the basic reproduction [Formula: see text], then the disease dies out and [Formula: see text] is a sharp threshold. Moreover, under certain conditions on model parameters and assuming mass action incidence for sexual transmission, it is proved that if [Formula: see text], there exists a unique endemic equilibrium that is globally asymptotically stable. However, under nonlinear incidence, it is shown that for certain functions backward bifurcation and Hopf bifurcation may occur, giving rise to subthreshold equilibria and periodic solutions, respectively. Numerical simulations for various parameter values are displayed to illustrate these behaviours.

A Mathematical Model of Anthrax Transmission in Animal Populations.

A general mathematical model of anthrax (caused by Bacillus anthracis) transmission is formulated that includes live animals, infected carcasses and spores in the environment. The basic reproduction number [Formula: see text] is calculated, and existence of a unique endemic equilibrium is established for [Formula: see text] above the threshold value 1. Using data from the literature, elasticity indices for [Formula: see text] and type reproduction numbers are computed to quantify anthrax control measures. Including only herbivorous animals, anthrax is eradicated if [Formula: see text]. For these animals, oscillatory solutions arising from Hopf bifurcations are numerically shown to exist for certain parameter values with [Formula: see text] and to have periodicity as observed from anthrax data. Including carnivores and assuming no disease-related death, anthrax again goes extinct below the threshold. Local stability of the endemic equilibrium is established above the threshold; thus, periodic solutions are not possible for these populations. It is shown numerically that oscillations in spore growth may drive oscillations in animal populations; however, the total number of infected animals remains about the same as with constant spore growth.

Estimation of Zika virus prevalence by appearance of microcephaly.

BACKGROUND: There currently is a severe Zika Virus (ZIKV) epidemic in Brazil and other South American countries. Due to international travel, this poses severe public health risk of ZIKV importation to other countries. We estimate the prevalence of ZIKV in an import region by the time a microcephaly case is detected, since microcephaly is presently the most significant indication of ZIKV presence. METHODS: We establish a mathematical model to describe ZIKV spread from a source region to an import region. This model incorporates both vector transmission (between humans and mosquitoes) and sexual transmission (from males to females). We take account of population structure through a contact network for sexually active individuals. Parameter values of our model are either taken from the literature or estimated from travel data. RESULTS: This model gives us the probability distribution of time until detection of the first microcephaly case. Based on current field observations, our results also indicate that the percentage of infected pregnant women that results in fetal abnormalities is more likely to be on the smaller end of the 1%-30% spectrum that is currently hypothesized. Our model predicts that for import regions with at least 250,000 people, on average 1,000-12,000 will have been infected by the time of the first detection of microcephaly, and on average 200-1,500 will be infectious at this time. Larger population sizes do not significantly change our predictions. CONCLUSIONS: By the first detection of a microcephaly case, a sizable fraction of the population will have been infected by ZIKV. It is thus clear that adequate surveillance, isolation, and quarantine are needed in susceptible import regions to stop the dissemination of a Zika epidemic.

Models of bovine babesiosis including juvenile cattle.

Bovine Babesiosis in cattle is caused by the transmission of protozoa of Babesia spp. by ticks as vectors. Juvenile cattle (<9 months of age) have resistance to Bovine Babesiosis, rarely show symptoms, and acquire immunity upon recovery. Susceptibility to the disease varies between breeds of cattle. Models of the dynamics of Bovine Babesiosis transmitted by the cattle tick that include these factors are formulated as systems of ordinary differential equations. Basic reproduction numbers are calculated, and it is proved that if these numbers are below the threshold value of one, then Bovine Babesiosis dies out. However, above the threshold number of one, the disease may approach an endemic state. In this case, control measures are suggested by determining target reproduction numbers. The percentage of a particular population (for example, the adult bovine population) needed to be controlled to eradicate the disease is evaluated numerically using Columbia data from the literature.

Functional transplant of megabase human immunoglobulin loci recapitulates human antibody response in mice.

We constructed two megabase-sized YACs containing large contiguous fragments of the human heavy and kappa (kappa) light chain immunoglobulin (Ig) loci in nearly germline configuration, including approximately 66 VH and 32 V kappa genes. We introduced these YACs into Ig-inactivated mice and observed human antibody production which closely resembled that seen in humans in all respects, including gene rearrangement, assembly, and repertoire. Diverse Ig gene usage together with somatic hypermutation enables the mice to generate high affinity fully human antibodies to multiple antigens, including human proteins. Our results underscore the importance of the large Ig fragments with multiple V genes for restoration of a normal humoral immune response. These mice are likely to be a valuable tool for the generation of therapeutic antibodies.

A mathematical model of syphilis transmission in an MSM population.

Syphilis is caused by the bacterium Treponema pallidum subspecies pallidum, and is a sexually transmitted disease with multiple stages. A model of transmission of syphilis in an MSM population (there has recently been a resurgence of syphilis in such populations) that includes infection stages and treatment is formulated as a system of ordinary differential equations. The control reproduction number is calculated, and it is proved that if this threshold parameter is below one, syphilis dies out; otherwise, if it is greater than one, it is shown that there exists a unique endemic equilibrium and that for certain special cases, this equilibrium is globally asymptotically stable. Using data from the literature on MSM populations, numerical methods are used to determine the variation and robustness of the control reproduction number with respect to the model parameters, and to determine adequate treatment rates for syphilis eradication. By assuming a closed population and no return to susceptibility, an epidemic model is obtained. Final outbreak sizes are numerically determined for various parameter values, and its variation and robustness to parameter value changes is also investigated. Results quantify the importance of early treatment for syphilis control.

Analysis of a model of gambiense sleeping sickness in humans and cattle.

Human African Trypanosomiasis (HAT) and Nagana in cattle, commonly called sleeping sickness, is caused by trypanosome protozoa transmitted by bites of infected tsetse flies. We present a deterministic model for the transmission of HAT caused by Trypanosoma brucei gambiense between human hosts, cattle hosts and tsetse flies. The model takes into account the growth of the tsetse fly, from its larval stage to the adult stage. Disease in the tsetse fly population is modeled by three compartments, and both the human and cattle populations are modeled by four compartments incorporating the two stages of HAT. We provide a rigorous derivation of the basic reproduction number R0. For R0 < 1, the disease free equilibrium is globally asymptotically stable, thus HAT dies out; whereas (assuming no return to susceptibility) for R0 >1, HAT persists. Elasticity indices for R0 with respect to different parameters are calculated with baseline parameter values appropriate for HAT in West Africa; indicating parameters that are important for control strategies to bring R0 below 1. Numerical simulations with R0 > 1 show values for the infected populations at the endemic equilibrium, and indicate that with certain parameter values, HAT could not persist in the human population in the absence of cattle.

Fully human anti-interleukin-8 monoclonal antibodies: potential therapeutics for the treatment of inflammatory disease states.

Interleukin-8 (IL-8) is a potent chemotactic cytokine implicated in the pathogenesis of a number of inflammatory disease states. Agents that block the binding of IL-8 to its receptor have been shown to block inflammation in animal models of disease. This suggests that drugs specifically targeting IL-8 may prove efficacious in treating multiple human diseases. To this end, we developed a panel of fully human anti-IL-8 monoclonal antibodies (mAbs). These human antibodies were generated from XenoMouse strains, mice created by introducing megabase-size unrearranged human immunoglobulin heavy and kappa light chain loci into a mouse genome in which the corresponding endogenous loci have been inactivated. From the panel of more than 50 mAbs, two antibodies, K4.3 and K2.2, were further characterized and evaluated for their specificity, productivity, affinity, and biological activity. Both K4.3 and K2.2 bind human IL-8 with high affinity (Kd of K4.3 = 2.1x10(10) M; Kd of K2.2 = 2.5x10(-10) M). In vitro, in addition to blocking IL-8 binding to human neutrophils, K4.3 and K2.2 blocked a number of IL-8-dependent cellular functions including neutrophil activation, up-regulation of the cell adhesion receptor CD11b/CD18, and neutrophil chemotaxis, suggesting that the fully human anti-IL-8 mAbs derived from XenoMouse strains are potent anti-inflammatory agents. This was further supported by in vivo studies in which K4.3 and K2.2 significantly inhibited IL-8-induced skin inflammation in rabbits. A pharmacokinetic study in Cynomolgus monkeys demonstrated that the alpha phase half-life is 9.4 h and the beta phase 10.9 days, typical of human mAbs in monkeys. These data support advancing a fully human anti-IL-8 mAb into clinical trials to treat inflammatory diseases.

The involvement of people living with HIV/AIDS in community-based organizations: contributions and constraints.

An important feature of the social and organizational response to the HIV epidemic has been that many people living with HIV/AIDS have demanded to have a say in the development of policies and the delivery of services. Surprisingly little attention has been paid in the literature to this involvement. This paper is based on a participatory action research project that involved 70 people with HIV/AIDS in 15 focus group discussions. Findings from the study show the complexities of translating organizational commitments to involve people with HIV/AIDS into practice. This paper outlines the organizational contributions of people with HIV, and examines the difficulties and obstacles to their meaningful involvement. The paper concludes with a discussion of the challenges of user empowerment and with recommendations for policy and practice.