On the efficiency of HIV transmission: Insights through discrete time HIV models.

There are different views on which of the two forms of viral spread is more efficient in vivo between cell-free and cell-associated virus. In this study, discrete time human immunodeficiency virus models are formulated and analysed with the goal of determining the form of viral spread that is more efficient in vivo. It is shown that on its own, cell-free viral spread cannot sustain an infection owing to the low infectivity of cell-free virus and cell-associated virus can sustain an infection because of the high infectivity of cell-associated virus. When acting concurrently, cell-associated virus is more efficient in spreading the infection upon exposure to the virus. However, in the long term, the two forms of viral spread contribute almost equally. Both forms of viral spread are shown to be able to initiate an infection.

Projecting the impact of anal intercourse on HIV transmission among heterosexuals in high HIV prevalence settings.

Whereas penile vaginal intercourse (VI) is thought to be the dominant mode of HIV transmission in sub-Saharan Africa, cross-sectional studies in the region indicate the preponderance of heterosexual anal intercourse (AI) among high activity groups. A dynamic, heterosexual core group model with risk of infection through both vaginal and anal pathways is formulated and comprehensively analysed. The model is coupled to a general population model and fitted to HIV prevalence data for Zimbabwe in order to explore the parameter space related to heterosexual AI. The model fit supports a core group size ranging between 5-20% and exposure risk to AI in excess of 50%. The control effort quantified by the reproductive number (RA) at commencement of the epidemic corresponds to R0=4.40. With the contribution of heterosexual AI to Zimbabwe's (and that of the sub-Saharan African region) epidemic unknown, the study apportioned infections between the two infection pathways. New infections due to VI ranged from 2-4.5% and 0.5-2.7% from heterosexual AI. The study estimates infection probabilities ranging from 0.15 to 0.35 for both receptive and infective AI. By quantifying the incidence due to VI and AI risks, we put emphasis on the necessity for targeted interventions. To project the potential impact of heterosexual AI in high HIV prevalence settings, we raised the core group size to 20% in the year 2010 coinciding with reported heterosexual AI prevalence outside of Africa and allowed the proportion of infection risk associated with AI to vary. Prevalence and incidence projections were made up to the year 2020 starting from a baseline value of zero exposure to AI transmission risk per sex act, progressively increasing exposure to 50% and 70% respectively. A 50% exposure to AI would result in HIV prevalence scaling up by 23% from the baseline values in year 2020. Increasing exposure to 70% was projected to increase HIV prevalence by 38% in year 2020. The HIV infection risks associated with AI are recognised and inform HIV policy for men who have sex with men, yet the same risks are ignored in HIV intervention programmes for heterosexuals. This study highlights the potential danger of increasing prevalence of heterosexual AI in settings with high HIV prevalence. Evolving and globally cross pollinating sexual behaviors compel for dovetailing HIV policy making with sexology.

Assessing the Potential Impact of Hormonal-Based Contraceptives on HIV Transmission Dynamics Among Heterosexuals.

HIV susceptibility linked to hormonal contraception (HC) has been studied before, but with mixed results. Reports from some of the recent findings have prompted the World Health Organisation to encourage women who use HC to concurrently use condoms in order to prevent HIV infection in the light of possible increased HIV risk of infection associated with hormone-based contraceptives. A two-sex HIV model classifying women into three risk groups consisting of individuals who use condoms, natural methods, and hormone-based contraceptives is formulated and analysed to assess the possible effects of various birth control strategies on the transmission dynamics of the disease. Our model results showed that women who use HC could be key drivers of the epidemic and that their increased infectivity may be critical in driving the epidemic. Women who use hormone-based contraceptives potentially act as a core group from which men get infected and in turn transmit the disease to other population groups. We fitted the model to HIV prevalence data for Zimbabwe reported by UNAIDS and Zimbabwe Ministry of Health and Child Care and used the model fit to project HIV prevalence. Predictions using HIV data for Zimbabwe suggest that a hypothesised increase in susceptibility and infectivity of two-, three-, and fourfold would result in a 25, 50, and 100% increase in baseline HIV prevalence projection, respectively, thus suggesting possible increased disease burden even in countries reporting plausible HIV prevalence declines. Although a possible causal relationship between HIV susceptibility and HC use remains subject of continuing scientific probe, its inclusion as part of birth control strategy has been shown in this study, to possibly increase HIV transmission. If proven, HC use may potentially explain the inordinate spread of HIV within the sub-Saharan Africa region and therefore compel for urgent assessment with a view to reorienting birth control methods in use in settings with generalised epidemics.

A comparison of elasticities of viral levels to specific immune response mechanisms in human immunodeficiency virus infection.

BACKGROUND: The presence of an asymptomatic phase in an HIV infection indicates that the immune system can partially control the infection. Determining the immune mechanisms that contribute significantly to the partial control of the infection enhance the HIV infection intervention strategies and is important in vaccine development. Towards this goal, a discrete time HIV model, which incorporates the life cycle aspects of the virus, the antibody (humoral) response and the cell-mediated immune response is formulated to determine immune system components that are most efficient in controlling viral levels. Ecological relationships are used to model the interplay between the immune system components and the HIV pathogen. Model simulations and transient elasticity analysis of the viral levels to immune response parameters are used to compare the different immune mechanisms. RESULTS: It is shown that cell-mediated immune response is more effective in controlling the viral levels than the antibody response. Killing of infected cells is shown to be crucial in controlling the viral levels. Our results show a negative correlation between the antibody response and the viral levels in the early stages of the infection, but we predicted this immune mechanism to be positively correlated with the viral levels in the late stage of the infection. A result that suggests lack of relevance of antibody response with infection progression. On the contrary, we predicted the cell-mediated immune response to be always negatively correlated with viral levels. CONCLUSION: Neutralizing antibodies can only control the viral levels in the early days of the HIV infection whereas cell-mediated immune response is beneficial during all the stages of the infection. This study predicts that vaccine design efforts should also focus on stimulating killer T cells that target infected cells.

Impact of New Water Sources on the Overall Water Network: An Optimisation Approach.

A mathematical programming problem is formulated for a water network with new water sources included. Salinity and water hardness are considered in the model, which is later solved using the Max-Min Ant System (MMAS) to assess the impact of new water sources on the total cost of the existing network. It is efficient to include new water sources if the distances to them are short or if there is a high penalty associated with failure to meet demand. Desalination unit costs also significantly affect the decision whether to install new water sources into the existing network while softening costs are generally negligible in making such decisions. Experimental results show that, in the example considered, it is efficient to reduce number of desalination plants to remain with one central plant. The Max-Min Ant System algorithm seems to be an effective method as shown by least computational time as compared to the commercial solver Cplex.

Cost-Effectiveness Analysis of Hospitalization and Home-Based Care Strategies for People Living with HIV/AIDS: The Case of Zimbabwe.

The model of care of people living with HIV/AIDS (PLWHA) has shifted from hospital care to community home-based care (CHBC) because of shortage of space in hospitals and lack of resources. We evaluate the costs and benefits of home-based care and other HIV/AIDS intervention strategies in Zimbabwe, using an interdisciplinary approach which weaves together the techniques of an epidemic transmission model and economic evaluation concepts. The intervention strategies considered are voluntary counselling and testing (VCT), VCT combined with hospitalization (H), VCT combined with CHBC, and all the interventions implemented concurrently. The results of the study indicate that implementing all the strategies concurrently is the most cost-effective, a result which also agrees with the epidemiological model. Our results also show that the effectiveness of a strategy in the epidemiological model does not necessarily imply cost-effectiveness of the strategy and behaviour change, modelled by the parameters p and m, that accompanied the strategies, influencing both the cost-effectiveness of an intervention strategy and dynamics of the epidemic. This study shows that interdisciplinary collaborations can help in improving the accuracy of predictions of the course and cost of the epidemic and help policy makers in implementing the correct strategies.

From heroin epidemics to methamphetamine epidemics: modelling substance abuse in a South African province.

The global rise in the use of methamphetamine has been documented to have reached epidemic proportions. Researchers have focussed on the social implications of the epidemic. A typical drug use cycle consists of concealed drugs use after initiation, addiction, treatment-recovery-relapse cycle, whose dynamics are not well understood. The model by White and Comiskey [41], on heroin epidemics, treatment and ODE modelling, is modified to model the dynamics of methamphetamine use in a South African province. The analysis of the model is presented in terms of the methamphetamine epidemic threshold R(0). It is shown that the model has multiple equilibria and using the center manifold theory, the model exhibits the phenomenon of backward bifurcation where a stable drug free equilibrium co-exists with a stable drug persistent equilibrium for a certain defined range of R(0). The stabilities of the model equilibria are ascertained and persistence conditions established. Furthermore, numerical simulations are performed; these include fitting the model to the available data on the number of patients with methamphetamine problems. The implications of the results to drug policy, treatment and prevention are discussed.

Theoretical analysis of mixed Plasmodium malariae and Plasmodium falciparum infections with partial cross-immunity.

A deterministic model for assessing the dynamics of mixed species malaria infections in a human population is presented to investigate the effects of dual infection with Plasmodium malariae and Plasmodium falciparum. Qualitative analysis of the model including positivity and boundedness is performed. In addition to the disease free equilibrium, we show that there exists a boundary equilibrium corresponding to each species. The isolation reproductive number of each species is computed as well as the reproductive number of the full model. Conditions for global stability of the disease free equilibrium as well as local stability of the boundary equilibria are derived. The model has an interior equilibrium which exists if at least one of the isolation reproductive numbers is greater than unity. Among the interesting dynamical behaviours of the model, the phenomenon of backward bifurcation where a stable boundary equilibrium coexists with a stable interior equilibrium, for a certain range of the associated invasion reproductive number less than unity is observed. Results from analysis of the model show that, when cross-immunity between the two species is weak, there is a high probability of coexistence of the two species and when cross-immunity is strong, competitive exclusion is high. Further, an increase in the reproductive number of species i increases the stability of its boundary equilibrium and its ability to invade an equilibrium of species j. Numerical simulations support our analytical conclusions and illustrate possible behaviour scenarios of the model.