The mathematical model used describes the evolution of the parasite distribution in different host age groups and the impact of periodic chemotherapy on host burdens, incorporating the key epidemiological and biological processes influencing transmission. Building on past research
[15 (link),16 ], it includes the observed features of sexual reproduction by the dioecious helminths, heterogeneity in exposure to infection by host age, variation in the intensity of transmission in different human communities, aggregated distributions of worm numbers per host and a decline in fecundity as a function of worm burden (density dependence)
[16 -18 (link)]. The dynamics of transmission under repeated rounds of treatment is examined for the three main intestinal nematodes, Ascaris lumbricoides, Trichuris trichuria and hookworms (Necator americanus and Ancylostoma duodenale). The model is described in detail in the Additional file
1 available online.
Although a full age distribution is embedded in the model, we employ the key age groupings described above to define intervention coverage levels and illustrate their effect. These are infants (0–1 years of age) who cannot be treated under current licensure of the main anthelmintic drugs in wide use (e.g. albendazole and mebendazole), pre-school aged children (pre-SAC, 2–4 years of age), school aged children (SAC, 5–14 years of age) and adults (15+ years of age). Varying combinations of the fraction treated in each age grouping, treatment frequency and duration of treatment are explored. The fraction in each grouping effectively treated is a product of the fraction given treatment and drug efficacy (defined as the proportion of worms expelled). Within the current model, these two aspects of treatment are inseparable, and coverage of the population is represented as a proportion of worms treated. Drug efficacy is typically in the region of 90% or more for Ascaris and hookworms, but somewhat less for Trichuris[19 (link)-22 (link)]. It should be noted that the fraction treated is effectively chosen at random from the subpopulation. This model does not address systematic non-compliance.
The life cycles of these parasites involve free living stages that are passed in the faeces of the human host and mature to infective stages in the external habitat (eggs for Ascaris and Trichuris and larvae for hookworms). The infective stages of the parasite in the environment are represented in the model by a common pool of infectious material. The life span of these stages is typically weeks to months under favourable environmental conditions, and they are excreted in very large numbers
[23 -26 (link)]. Although this duration is short by comparison with adult worm life expectancies in the human host, infectious material in the environment acts as a reservoir which is unaffected by chemotherapy and can play a significant role in the dynamics of treatment. Dynamics of a range of parasites within the host population can be represented by the same model, with distinct parameter ranges for different species (See Additional file
1 : Table S1).
Different age groups are thought to both contribute to, and be exposed to, this infective pool to varying degrees. An indication of this is provided by the changes in the intensity of infection by age; the patterns are typically convex for Ascaris and Trichuris, but continue to rise for hookworms as individuals age
[27 (link)-29 (link)] (Figure
2 ). The respective roles of age related exposure to infection versus acquired immunity remains uncertain, but rapid re-infection by all three parasites post treatment points to the former as the main driver of age-intensity of infection profiles. On this basis, MCMC methods
[30 ] are employed to fit the model to these age related patterns of infection, to estimate both transmission intensity (measured by the basic reproductive number R0 - the average number of offspring produced by one female worm that survive to reproductive maturity) and age related exposure. We have endeavoured to choose typical or characteristic infection profiles for the parasite species investigated in the hope that our results will be broadly applicable.
[15 (link),16 ], it includes the observed features of sexual reproduction by the dioecious helminths, heterogeneity in exposure to infection by host age, variation in the intensity of transmission in different human communities, aggregated distributions of worm numbers per host and a decline in fecundity as a function of worm burden (density dependence)
[16 -18 (link)]. The dynamics of transmission under repeated rounds of treatment is examined for the three main intestinal nematodes, Ascaris lumbricoides, Trichuris trichuria and hookworms (Necator americanus and Ancylostoma duodenale). The model is described in detail in the Additional file
Although a full age distribution is embedded in the model, we employ the key age groupings described above to define intervention coverage levels and illustrate their effect. These are infants (0–1 years of age) who cannot be treated under current licensure of the main anthelmintic drugs in wide use (e.g. albendazole and mebendazole), pre-school aged children (pre-SAC, 2–4 years of age), school aged children (SAC, 5–14 years of age) and adults (15+ years of age). Varying combinations of the fraction treated in each age grouping, treatment frequency and duration of treatment are explored. The fraction in each grouping effectively treated is a product of the fraction given treatment and drug efficacy (defined as the proportion of worms expelled). Within the current model, these two aspects of treatment are inseparable, and coverage of the population is represented as a proportion of worms treated. Drug efficacy is typically in the region of 90% or more for Ascaris and hookworms, but somewhat less for Trichuris[19 (link)-22 (link)]. It should be noted that the fraction treated is effectively chosen at random from the subpopulation. This model does not address systematic non-compliance.
The life cycles of these parasites involve free living stages that are passed in the faeces of the human host and mature to infective stages in the external habitat (eggs for Ascaris and Trichuris and larvae for hookworms). The infective stages of the parasite in the environment are represented in the model by a common pool of infectious material. The life span of these stages is typically weeks to months under favourable environmental conditions, and they are excreted in very large numbers
[23 -26 (link)]. Although this duration is short by comparison with adult worm life expectancies in the human host, infectious material in the environment acts as a reservoir which is unaffected by chemotherapy and can play a significant role in the dynamics of treatment. Dynamics of a range of parasites within the host population can be represented by the same model, with distinct parameter ranges for different species (See Additional file
Different age groups are thought to both contribute to, and be exposed to, this infective pool to varying degrees. An indication of this is provided by the changes in the intensity of infection by age; the patterns are typically convex for Ascaris and Trichuris, but continue to rise for hookworms as individuals age
[27 (link)-29 (link)] (Figure
[30 ] are employed to fit the model to these age related patterns of infection, to estimate both transmission intensity (measured by the basic reproductive number R0 - the average number of offspring produced by one female worm that survive to reproductive maturity) and age related exposure. We have endeavoured to choose typical or characteristic infection profiles for the parasite species investigated in the hope that our results will be broadly applicable.
Free full text: Click here
