Search

In this paper a mathematical model is proposed for the interaction of the immune system with HIV viruses and malaria parasites in an individual host. It consists of a system of three coupled ordinary differential equations, which represents the rate of change in the concentration of malaria parasites, HIV viruses and immunity effector within a host, respectively. The theoretical model gives insight into the biological balance between pathogen replication and the immune response to the pathogen: persistence versus elimination of the pathogen, which determines the outcome of infection. Dynamical analysis shows that the outcomes of the interactions between the immune system of the host with either malaria parasites or HIV viruses are dramatic such as malaria infection promoting proliferation of HIV virus, HIV infection increasing the risk from malaria and the immune system of the host failing to keep the diseases under control, etc. The results provide a new perspective for understanding of the complexity mechanisms of the co-infection (or dual infection) with malaria and HIV in a host.

The within-host and between-host dynamics of malaria are linked in myriad ways, but most obviously by gametocytes, the parasite blood forms transmissible from human to mosquito. Gametocyte dynamics depend on those of non-transmissible blood forms, which stimulate immune responses, impeding transmission as well as within-host parasite densities. These dynamics can, in turn, influence antigenic diversity and recombination between genetically distinct parasites. Here, we embed a differential-equation model of parasite-immune system interactions within each of the individual humans represented in a discrete-event model of Plasmodium falciparum transmission, and examine the effects of human population turnover, parasite antigenic diversity, recombination, and gametocyte production on the dynamics of malaria. Our results indicate that the local persistence of P. falciparum increases with turnover in the human population and antigenic diversity in the parasite, particularly in combination, and that antigenic diversity arising from meiotic recombination in the parasite has complex differential effects on the persistence of founder and progeny genotypes. We also find that reductions in the duration of individual human infectivity to mosquitoes, even if universal, produce population-level effects only if near-absolute, and that, in competition, the persistence and prevalence of parasite genotypes with gametocyte production concordant with data exceed those of genotypes with higher gametocyte production. This new, integrated approach provides a framework for investigating relationships between pathogen dynamics within an individual host and pathogen dynamics within interacting host and vector populations.

We present the first mathematical model of the within-host dynamics of a mixed-species malaria infection in a human: the blood-stage population dynamics of a dual infection with Plasmodium malariae and Plasmodium falciparum. Our results reproduce several important features of such infections in nature, including the asymmetry of species asexual-form densities, inter-specific suppression through interactions with the human immune system, and seasonal alternations in species prevalence. Most importantly, our results suggest that an existing P. malariae infection can reduce the peak parasitemia of a subsequent P. falciparum superinfection by as much as 50%. This result integrates numerous empirical observations and supports the hypothesis that clinical outcomes of P. falciparum infections may be influenced by the presence of a congener., (Copyright 1999 Academic Press.)