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Co-infections determine patterns of mortality in a population exposed to parasite infection.

Woolhouse ME, Thumbi SM, Jennings A, Chase-Topping M, Callaby R, Kiara H, Oosthuizen MC, Mbole-Kariuki MN, Conradie I, Handel IG, Poole EJ, Njiiri E, Collins NE, Murray G, Tapio M, Auguet OT, Weir W, Morrison WI, Kruuk LE, Bronsvoort BM, Hanotte O, Coetzer K, Toye PG - Sci Adv (2015)

Bottom Line: Using infections with Theileria parva (a tick-borne protozoan, related to Plasmodium) in indigenous African cattle [where it causes East Coast fever (ECF)] as a model system, we obtain the first quantitative estimate of the effects of heterologous reactivity for any parasitic disease.In individual calves, concurrent co-infection with less pathogenic species of Theileria resulted in an 89% reduction in mortality associated with T. parva infection.Across our study population, this corresponds to a net reduction in mortality due to ECF of greater than 40%.

View Article: PubMed Central - PubMed

Affiliation: Centre for Immunity, Infection and Evolution, University of Edinburgh, Ashworth Laboratories, Kings Buildings, West Mains Road, Edinburgh EH9 3JT, UK.

ABSTRACT
Many individual hosts are infected with multiple parasite species, and this may increase or decrease the pathogenicity of the infections. This phenomenon is termed heterologous reactivity and is potentially an important determinant of both patterns of morbidity and mortality and of the impact of disease control measures at the population level. Using infections with Theileria parva (a tick-borne protozoan, related to Plasmodium) in indigenous African cattle [where it causes East Coast fever (ECF)] as a model system, we obtain the first quantitative estimate of the effects of heterologous reactivity for any parasitic disease. In individual calves, concurrent co-infection with less pathogenic species of Theileria resulted in an 89% reduction in mortality associated with T. parva infection. Across our study population, this corresponds to a net reduction in mortality due to ECF of greater than 40%. Using a mathematical model, we demonstrate that this degree of heterologous protection provides a unifying explanation for apparently disparate epidemiological patterns: variable disease-induced mortality rates, age-mortality profiles, weak correlations between the incidence of infection and disease (known as endemic stability), and poor efficacy of interventions that reduce exposure to multiple parasite species. These findings can be generalized to many other infectious diseases, including human malaria, and illustrate how co-infections can play a key role in determining population-level patterns of morbidity and mortality due to parasite infections.

No MeSH data available.


Related in: MedlinePlus

Age-related variation in risks of T. parva infection, clinical illness, and death from ECF.(A) Empirical estimates of (i) hazard of seroconversion to T. parva (18), with censoring of non–T. parva–related deaths and adjusted for a 14-day delay between infection and a detectable antibody response; (ii) case fatality rate (probability of death conditional on infection, CF); (iii) net clinical rate (probability of death or ECF-like illness conditional on infection, CL). In contrast to hazard, CF and CL both decrease with age (Poisson regression: F1,8 = 10.4, P = 0.012 and F1,8 = 57.7, P < 0.001, respectively). (B) Model-predicted estimates for hazard and corresponding predictions for CF and CL with age. Model equations are given in Materials and Methods; parameter estimates are as in Table 3.
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Figure 2: Age-related variation in risks of T. parva infection, clinical illness, and death from ECF.(A) Empirical estimates of (i) hazard of seroconversion to T. parva (18), with censoring of non–T. parva–related deaths and adjusted for a 14-day delay between infection and a detectable antibody response; (ii) case fatality rate (probability of death conditional on infection, CF); (iii) net clinical rate (probability of death or ECF-like illness conditional on infection, CL). In contrast to hazard, CF and CL both decrease with age (Poisson regression: F1,8 = 10.4, P = 0.012 and F1,8 = 57.7, P < 0.001, respectively). (B) Model-predicted estimates for hazard and corresponding predictions for CF and CL with age. Model equations are given in Materials and Methods; parameter estimates are as in Table 3.

Mentions: Twenty-four ECF deaths (77%) were classified as acute, that is, occurred within 35 days of first infection with T. parva. Of the remainder, five were attributed to secondary reinfection with T. parva, and two had uncertain infection dates, so these could not be categorized. Of calves surviving infection, 75 (18%) experienced clinical illness consistent with acute ECF but, for the majority, no clinical signs were detected. As previously reported (14), surviving first infection with T. parva (using seroconversion as a marker of previous exposure) strongly protects against subsequent ECF mortality [hazard ratio, 0.12; 95% confidence interval (CI), 0.07 to 0.22] through the development of T cell–mediated adaptive immunity (17). The rate of exposure to T. parva estimated from serology data (18) was near constant over the first year of life (Fig. 2A). In contrast, both the case fatality rate (proportion dying of acute ECF among those infected) and the net clinical ECF rate (proportion dying and/or experiencing clinical illness) declined with age (Fig. 2A). These patterns are consistent with mathematical model predictions described below (see Fig. 2B).


Co-infections determine patterns of mortality in a population exposed to parasite infection.

Woolhouse ME, Thumbi SM, Jennings A, Chase-Topping M, Callaby R, Kiara H, Oosthuizen MC, Mbole-Kariuki MN, Conradie I, Handel IG, Poole EJ, Njiiri E, Collins NE, Murray G, Tapio M, Auguet OT, Weir W, Morrison WI, Kruuk LE, Bronsvoort BM, Hanotte O, Coetzer K, Toye PG - Sci Adv (2015)

Age-related variation in risks of T. parva infection, clinical illness, and death from ECF.(A) Empirical estimates of (i) hazard of seroconversion to T. parva (18), with censoring of non–T. parva–related deaths and adjusted for a 14-day delay between infection and a detectable antibody response; (ii) case fatality rate (probability of death conditional on infection, CF); (iii) net clinical rate (probability of death or ECF-like illness conditional on infection, CL). In contrast to hazard, CF and CL both decrease with age (Poisson regression: F1,8 = 10.4, P = 0.012 and F1,8 = 57.7, P < 0.001, respectively). (B) Model-predicted estimates for hazard and corresponding predictions for CF and CL with age. Model equations are given in Materials and Methods; parameter estimates are as in Table 3.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4643819&req=5

Figure 2: Age-related variation in risks of T. parva infection, clinical illness, and death from ECF.(A) Empirical estimates of (i) hazard of seroconversion to T. parva (18), with censoring of non–T. parva–related deaths and adjusted for a 14-day delay between infection and a detectable antibody response; (ii) case fatality rate (probability of death conditional on infection, CF); (iii) net clinical rate (probability of death or ECF-like illness conditional on infection, CL). In contrast to hazard, CF and CL both decrease with age (Poisson regression: F1,8 = 10.4, P = 0.012 and F1,8 = 57.7, P < 0.001, respectively). (B) Model-predicted estimates for hazard and corresponding predictions for CF and CL with age. Model equations are given in Materials and Methods; parameter estimates are as in Table 3.
Mentions: Twenty-four ECF deaths (77%) were classified as acute, that is, occurred within 35 days of first infection with T. parva. Of the remainder, five were attributed to secondary reinfection with T. parva, and two had uncertain infection dates, so these could not be categorized. Of calves surviving infection, 75 (18%) experienced clinical illness consistent with acute ECF but, for the majority, no clinical signs were detected. As previously reported (14), surviving first infection with T. parva (using seroconversion as a marker of previous exposure) strongly protects against subsequent ECF mortality [hazard ratio, 0.12; 95% confidence interval (CI), 0.07 to 0.22] through the development of T cell–mediated adaptive immunity (17). The rate of exposure to T. parva estimated from serology data (18) was near constant over the first year of life (Fig. 2A). In contrast, both the case fatality rate (proportion dying of acute ECF among those infected) and the net clinical ECF rate (proportion dying and/or experiencing clinical illness) declined with age (Fig. 2A). These patterns are consistent with mathematical model predictions described below (see Fig. 2B).

Bottom Line: Using infections with Theileria parva (a tick-borne protozoan, related to Plasmodium) in indigenous African cattle [where it causes East Coast fever (ECF)] as a model system, we obtain the first quantitative estimate of the effects of heterologous reactivity for any parasitic disease.In individual calves, concurrent co-infection with less pathogenic species of Theileria resulted in an 89% reduction in mortality associated with T. parva infection.Across our study population, this corresponds to a net reduction in mortality due to ECF of greater than 40%.

View Article: PubMed Central - PubMed

Affiliation: Centre for Immunity, Infection and Evolution, University of Edinburgh, Ashworth Laboratories, Kings Buildings, West Mains Road, Edinburgh EH9 3JT, UK.

ABSTRACT
Many individual hosts are infected with multiple parasite species, and this may increase or decrease the pathogenicity of the infections. This phenomenon is termed heterologous reactivity and is potentially an important determinant of both patterns of morbidity and mortality and of the impact of disease control measures at the population level. Using infections with Theileria parva (a tick-borne protozoan, related to Plasmodium) in indigenous African cattle [where it causes East Coast fever (ECF)] as a model system, we obtain the first quantitative estimate of the effects of heterologous reactivity for any parasitic disease. In individual calves, concurrent co-infection with less pathogenic species of Theileria resulted in an 89% reduction in mortality associated with T. parva infection. Across our study population, this corresponds to a net reduction in mortality due to ECF of greater than 40%. Using a mathematical model, we demonstrate that this degree of heterologous protection provides a unifying explanation for apparently disparate epidemiological patterns: variable disease-induced mortality rates, age-mortality profiles, weak correlations between the incidence of infection and disease (known as endemic stability), and poor efficacy of interventions that reduce exposure to multiple parasite species. These findings can be generalized to many other infectious diseases, including human malaria, and illustrate how co-infections can play a key role in determining population-level patterns of morbidity and mortality due to parasite infections.

No MeSH data available.


Related in: MedlinePlus