Single Infection Models Research Articles

Virulence Comparison of Four Porcine Circovirus Type 2 (PCV2) Genotypes (2a, 2b, 2d and 2e) in Pigs Single-Infected with PCV2 and Pigs Dual-Infected with PCV2 and Mycoplasma hyopneumoniae

The objective of this study was to compare the virulence of four porcine circovirus type 2 (PCV2) genotypes (2a, 2b, 2d and 2e). Pigs were infected with one of these four genotypes. Pigs were also dually infected with Mycoplasma hyopneumoniae and one of the four PCV2 genotypes. Virulence was determined based on the amount of PCV2 loads in the blood and lymph nodes and the severity of lymphoid lesions. Marked differences in virulence were found among the four genotypes. Within the single infection model, PCV2a, PCV2b and PCV2d were more virulent than PCV2e, while significant differences in virulence were not found among the PCV2a, PCV2b and PCV2d groups. Within the dual infection model, PCV2d was more virulent than the other three PCV2 genotypes. Mycoplasma hyopneumoniae potentiated the severity of PCV2-associated lymphoid lesions and increased the amount of PCV2 loads in the blood and lymph nodes, regardless of the PCV2 genotype. By contrast, PCV2 was not able to potentiate the severity of mycoplasmal-induced lung lesions or the level of M. hyopneumoniae laryngeal load. The results of this study demonstrate that PCV2d is of major clinical importance, while PCV2e is of minor clinical importance.

In vivo pharmacodynamics of lascufloxacin and levofloxacin against Streptococcus pneumoniae and Prevotella intermedia in a pneumonia mixed-infection mouse model

This study aimed to evaluate the antimicrobial activity of a new quinolone, lascufloxacin, for the treatment of complicated pneumonia caused by Streptococcus pneumoniae and Prevotella intermedia using a neutropenic mice pneumonia mixed-infection model. In this study, one S. pneumoniae and four P. intermedia isolates were utilized. Antimicrobial efficacy was calculated for each isolate as the reduction of the bacterial count comparatively to the non-treated mice (log10 colony forming units (cfu)/mL) obtained in the lungs of the treated mice after 24 h. Consequently, the bacterial densities of S. pneumoniae (KY-9) and P. intermedia (335) in the lungs of control animals were 8.20 ± 0.19 log10 cfu/mL and 5.26 ± 1.50 log10 cfu/mL, respectively. At human-simulated doses, lascufloxacin and levofloxacin showed high antimicrobial activities against not only S. pneumoniae (lascufloxacin: 1.88 ± 0.43 log10 cfu/mL, p < 0.001; levofloxacin 4.30 ± 0.75 log10 cfu/mL, p < 0.001), but also P. intermedia (lascufloxacin: 1.54 ± 0.57 log10 cfu/mL, p < 0.001; levofloxacin: 2.79 ± 0.55 log10 cfu/mL, p = 0.0102). Additionally, levofloxacin demonstrated attenuated antimicrobial efficacies against S. pneumoniae in the mixed-infection model compared with that in the single infection model. In contrast, lascufloxacin showed enhanced antimicrobial activities against S. pneumoniae and P. intermedia in the mixed-infection model. In conclusion, lascufloxacin resulted in enhanced efficacies against S. pneumoniae and P. intermedia, in both the single and mixed-infection models used. These data support the clinical utility of lascufloxacin for use against S. pneumoniae and P. intermedia in the treatment of pneumonia.

ON THE DYNAMICS MALARIA-DYSENTERY CO-INFECTION MODEL

In this paper, a mathematical model for malaria-dysentery co-infection was formulated in order to study and examine its dynamic relationship in the presence of malaria and dysentery preventive and treatment measures. First, analysis of the single infection steady states was done and then the basic reproduction number was obtained. Furthermore, investigation into the existence and stability of equilibria carried out. The single infection models were found to exhibit the possibility of backward bifurcation. Thereafter, the impact of malaria on the dynamics of dysentery is further investigated. Second, incorporating time-dependent controls, using Pontryagin’s Maximum Principle, the necessary conditions for the optimal control of the disease was derived. It is found that malaria infection may be associated with an increased risk of dysentery. Also, that dysentery infection may be associated with an increased risk for malaria. Therefore, to effectively control malaria, the malaria intervention strategies by policy makers must at the same time it also includes effective prevention and control measures for dysentery. Policy makers should take efforts on preventive strategies in combating dysentery and malaria.

Optimal control analysis of malaria-schistosomiasis co-infection dynamics.

This paper presents a mathematical model for malaria--schistosomiasis co-infection in order to investigate their synergistic relationship in the presence of treatment. We first analyse the single infection steady states, then investigate the existence and stability of equilibria and then calculate the basic reproduction numbers. Both the single-infection models and the co-infection model exhibit backward bifurcations. We carrying out a sensitivity analysis of the co-infection model and show that schistosomiasis infection may not be associated with an increased risk of malaria. Conversely, malaria infection may be associated with an increased risk of schistosomiasis. Furthermore, we found that effective treatment and prevention of schistosomiasis infection would also assist in the effective control and eradication of malaria. Finally, we apply Pontryagin's Maximum Principle to the model in order to determine optimal strategies for control of both diseases.

ToRCH “co‐infections” are associated with increased risk of abortion in pregnant women

ToRCH infections (toxoplasmosis, rubella, cytomegalovirus and Herpes simplex virus) have long been known to be associated with bad obstetric outcomes. However, little information is available about the impact of ToRCH co-infections on the outcome of pregnancy. Hence, we tested the IgG and IgM antibodies to Toxoplasma gondii, Rubella, Cytomegalovirus and Herpes Simplex Virus among 81 pregnant women with abortion (case group) and 98 pregnant women with normal delivery (control group). In the single-infection model, only CMV-IgM seropositivity was significantly increased in case than control group (25.9% in case and 12.2 % in control, OR = 2.5, P = 0.019). In the co-infection model, 14 patterns were recognized, but two patterns were significantly increased in the case than the control group. Co-infection of T. gondii IgG + CMV IgM was 9.1-fold increased in the case than the control group (8.6% in the case and 1% in control, OR = 9.1; P = 0.024). Also, co-infection of T. gondii IgG + HSV IgG + CMV IgM was 7.7-fold increased in case than the control group (7.4% in case and 1 % in control, OR = 7.7; P = 0.04). Although the OR of other co-infections was higher in the case than the control group, the difference was not statistically significant. These findings indicate that ToRCH co-infections are associated with increased risk of abortion than single infection. Hence, the rates of co-infections should be considered in prenatal screening of ToRCH infections.

TcI/TcII co-infection can enhance Trypanosoma cruzi growth in Rhodnius prolixus

BackgroundRhodnius prolixus is an obligate haematophagous insect and one of the most important vectors of Trypanosoma cruzi, the causative agent of Chagas disease in the Americas. T. cruzi is a highly variable parasite which is not transmitted in the same efficiency by the different triatomine vectors. Because different T. cruzi genotypes are aetiopathologically divergent, further elucidation of the transmission abilities of different Chagas disease vectors is extremely important.FindingsIn the present study, the growth behaviour of two T. cruzi isolates, MDID/BR/1993/C45 (TcI) and TBRA/BR/1999/JCA3 (TcII), sharing the same microhabitat (intestinal tract) in single and mixed infections, was examined. The distribution patterns and parasite population densities were evaluated at 7, 14 and 21 days after feeding (daf) by quantification of parasites using Neubauer haemocytometric measurements and mini-exon PCR to identify TcI and TcII subpopulations. Parasitic colonization in the small intestine was more successful in the mixed infection model than the single infection models at 21 daf. In the rectal lumen and wall, the growth behaviour of the mixed infection was similar to that of the TcI group, although the total parasite number was lower. In the TcII group, no metacyclic trypomastigote forms were found. PCR analysis of the contents of each dissected region showed different genotype fractions in the mixed infection model, in which TcI seemed to be the predominant isolate.ConclusionThe different growth behaviour of the TcI and TcII isolates in single and mixed infection models demonstrated that possibly an intraspecific factor modulates parasitic development in the intestine of R. prolixus.

Network Model of Immune Responses Reveals Key Effectors to Single and Co-infection Dynamics by a Respiratory Bacterium and a Gastrointestinal Helminth

Co-infections alter the host immune response but how the systemic and local processes at the site of infection interact is still unclear. The majority of studies on co-infections concentrate on one of the infecting species, an immune function or group of cells and often focus on the initial phase of the infection. Here, we used a combination of experiments and mathematical modelling to investigate the network of immune responses against single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminth Trichostrongylus retortaeformis. Our goal was to identify representative mediators and functions that could capture the essence of the host immune response as a whole, and to assess how their relative contribution dynamically changed over time and between single and co-infected individuals. Network-based discrete dynamic models of single infections were built using current knowledge of bacterial and helminth immunology; the two single infection models were combined into a co-infection model that was then verified by our empirical findings. Simulations showed that a T helper cell mediated antibody and neutrophil response led to phagocytosis and clearance of B. bronchiseptica from the lungs. This was consistent in single and co-infection with no significant delay induced by the helminth. In contrast, T. retortaeformis intensity decreased faster when co-infected with the bacterium. Simulations suggested that the robust recruitment of neutrophils in the co-infection, added to the activation of IgG and eosinophil driven reduction of larvae, which also played an important role in single infection, contributed to this fast clearance. Perturbation analysis of the models, through the knockout of individual nodes (immune cells), identified the cells critical to parasite persistence and clearance both in single and co-infections. Our integrated approach captured the within-host immuno-dynamics of bacteria-helminth infection and identified key components that can be crucial for explaining individual variability between single and co-infections in natural populations.

Evolutionary branching of virulence in a single-infection model

This study explores the evolutionary dynamics of pathogen virulence in a single-infection model with density-dependent mortality. Although virulence is not an adaptation of the pathogen per se, it is generally believed to be an inevitable by-product of a pathogen's need to propagate and transmit to new hosts: an increase in virulence will parallel an increase in transmission efficacy. The exact characteristics of the trade-off curve defined by this relationship are important with respect to possible evolutionary scenarios. We conduct a critical function analysis, a method that exposes the evolutionary outcome resulting from trade-offs of arbitrary shape, and find that this simple model can display a wide variety of evolutionary dynamics; comprising multiple stable attractors, evolutionary repellors, and most notably, evolutionary branching points. We identify the conditions under which the different evolutionary outcomes are realised. Our analysis furthermore considers the evolution of coexisting strains, and identifies the trade-off characteristics that will support an evolutionarily stable dimorphic state. We find that an evolutionarily stable dimorphism may exist also in the absence of a branching point in the monomorphic state. The analysis reveals that an evolutionarily stable dimorphism will always be attracting and that no further branching is possible under this model. We discuss our results in relation to the dimension of the environmental feedback inherent in the model, and to results from previous studies and models of evolution of virulence.

THE EVOLUTION OF VIRULENCE IN A PLANT VIRUS

The evolution of virulence is a rapidly growing field of research, but few reports deal with the evolution of virulence in natural populations of parasites. We present here an observational and experimental analysis of the evolution of virulence of the plant virus Cucumber mosaic virus (CMV) during an epidemic on tomato in eastern Spain. Three types of CMV isolates were found that caused in tomato plants either a systemic necrosis (N isolates), stunting and a severe reduction of leaf lamina (Y isolates), or stunting and leaf curl (A isolates). These phenotypes were due to the presence of satellite RNAs (satRNAs) necrogenic (in N isolates) or attenuative (in A isolates) of the symptoms caused by CMV without satRNA (Y isolates). For these three types of isolates, parameters of virulence and transmission were estimated experimentally. For virulence the ranking of isolates was N > Y > A, for transmissibility, Y > A > N. The predictions of theoretical models for the evolution of virulence were analyzed with these parameters and compared with observations from the field. A single-infection model predicted adequately the observed long-term evolution of the CMV population to intermediate levels of virulence. A coinfection model that considered competition between isolates with an effect on transmission explained the invasion of the CMV population by N isolates at the beginning of the epidemic, and its predictions also agreed with field data on the long-term evolution of the CMV population. An important conclusion from both models was that the density of the aphid vector's population is a major factor in the evolution of CMV virulence. This may be relevant for the design of control strategies for CMV-induced diseases.

Evolution of Virulence: a Unified Framework for Coinfection and Superinfection

Models of the evolution of parasite virulence have focused on computing the evolutionarily stable level of virulence favored by tradeoffs within a host and by competition for hosts, and deriving conditions under which strains with different virulence levels can coexist. The results depend on the type of interaction between disease strains, such as single infection (immunity of infected individuals to other strains), coinfection (simultaneous infection by two strains), and superinfection (instantaneous takeover of host by the more virulent strain). We present a coinfection model with two strains and derive the superinfection model as the limit where individuals are rapidly removed from the doubly-infectious class. When derived in this way, the superinfection model includes not only the takeover of hosts infected by the less virulent strain, but new terms which take into account the possibility of increased mortality of doubly-infected individuals. Coinfection tends to favor higher virulence and support more coexistence than the single infection model, but the detailed results depend sensitively on two factors: (1) whether and how the model is near the superinfection limit, and (2) the shape of the coinfection function (the function describing the rate at which a more virulent strain can infect a host). If the superinfection limit arises due to rapid mortality of doubly-infected hosts, there is a region of uninvadable virulence levels rather than coexistence. When the coinfection function is discontinuous, as in many previous models, neither the coinfection model nor the superinfection limit can support an evolutionarily stable virulence level. Piecewise differentiable and differentiable coinfection functions produce qualitatively different results, and we propose that these more general cases should be used to study evolution of virulence when other mechanisms like space, population dynamics, and stochasticity interact.