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Transmission dynamics of Taenia solium and potential for pig-to-pig transmission
Parasitology International 55 (2006) S131 – S135 www.elsevier.com/locate/parint
Transmission dynamics of Taenia solium and potential for pig-to-pig transmission Armando E. Gonzalez a,*, Teresa Lopez-Urbina a, Byron Tsang b, Cesar Gavidia a, H. Hugo Garcia c,d, Maria E. Silva a, Daphne D. Ramos a, Rafael Manzanedo a, Lelia Sanchez-Hidalgo a, Robert H. Gilman e, Victor C.W. Tsang b The cysticercosis working group in Peru a
b
School of Veterinary Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru Immunology Branch, Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control, Atlanta, GA, USA c Universidad Peruana Cayetano Heredia, Lima, Peru d Cysticercosis Unit, Instituto Nacional de Ciencias Neurolo´gicas, Lima, Peru e Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA Available online 13 December 2005
Abstract Taenia solium taeniasis/cysticercosis is one of few potentially eradicable infectious diseases and is the target of control programs in several countries. The larval stage of this zoonotic cestode invades the human brain and is responsible for most cases of adult-onset epilepsy in the world. Our current understanding of the life cycle implicates humans as the only definitive host and tapeworm carrier, and thus the sole source of infective eggs that are responsible for cysticercosis in both human and pigs through oral – faecal transmission. Here we review transmission dynamics of porcine cysticercosis including an alternative pig-to-pig route of transmission, previously not suspected to exist. Second-hand transmission of T. solium eggs could explain the overdispersed pattern of porcine cysticercosis, with few pigs harbouring heavy parasite burdens and many more harbouring small numbers of parasites. D 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Taenia solium; Porcine cysticercosis; Transmission dynamics
1. Introduction Taenia solium cysticercosis is a common disease in pig raising areas of resource-poor countries [1]. This parasitic infection causes severe neurological disease in humans and economic losses in the poorest communities. The life cycle involves humans as the sole definitive host, harbouring the adult tapeworm in the intestine, and pigs as the intermediate host, harbouring the larval form or cysticerci. The larval stage of this zoonotic cestode also invades the human brain, causing morbidity and mortality. Although control measures have been described and tested, sustainable cysticercosis control remains
* Corresponding author. Tel.: +51 1 4368938; fax: +51 1 431027. E-mail address: [email protected] (A.E. Gonzalez). 1383-5769/$ - see front matter D 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.parint.2005.11.021
elusive. The idea that every pig with antibodies has the potential to continue the life cycle of the parasite represents a risky assumption. Likewise, any successful control program may interrupt transmission temporarily, but decreased herd immunity will eventually return the infection rates to their original levels. 2. Endemic stability Endemic stability describes a dynamic epidemiological state in which clinical disease is rare in spite of a high incidence of infection within a population [2]. The concept of ‘‘endemic stability’’ (herd immunity), where the rate of transmission of infection is low enough as to not result in clinical disease yet sufficiently high to immunize susceptible animals, has been an accepted epidemiologic concept for decades [3]. The endemic
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A.E. Gonzalez et al. / Parasitology International 55 (2006) S131 – S135
stability of an organism is influenced by the organism’s basic reproductive ratio (or number) and density dependent constraints. For macroparasites, the basic reproductive ratio is defined as the average number of offspring produced through the reproductive life-span of the mature parasite [4]. Densitydependent constraints are mechanisms that regulate the abundance of parasite populations, the effects of which are less obvious when the parasite is first introduced into the host population [5]. Once the density-dependent constraint is present, a regulated population size fluctuates considerably less. Density dependence and the basic reproductive ratio govern the rate of recovery of the parasite population following treatment or chemotherapy. Removing parasites should reduce the average density dependent effect. It follows that the effective reproduction ratio, in this case, the average number of infective cysts per pig, will increase above its equilibrium value and the adult parasite population will grow [6]. This will cease when density dependence is again at its equilibrium value, which generally will be when the parasite population has re-attained its previous density [7]. This helps explain how a regulated population, one that had persisted at a consistent population size for a long period of time, can return to its original population size after having been perturbed. Our group produced the key piece of evidence suggesting that population regulation occurs in T. solium cysticercosis. A cohort study was performed to evaluate the effect of a combined intervention (human and porcine mass chemotherapy) on the prevalence and incidence of porcine cysticercosis in treated versus control areas. Although the combined intervention controlled the parasite, the effect only lasted for 2 years after treatment [8]. Parasite recrudescence has been demonstrated again in a T. solium elimination program in Tumbes (Peru) and whenever similar strategies have been employed [9]. 3. Aggregation The population distributions of helminths invariably indicate a tendency towards aggregation, meaning that the majority of parasites are harboured by a minority of hosts [10]. Aggregation is generally recognized as an important factor in the dynamics of host – macroparasite interactions, and it has been found to be relevant in stabilizing population dynamics in a coexisting equilibrium [11]. Aggregation tends to influence the interactions that regulate parasite numbers, such that the interactions influence a larger proportion of the parasite population [7]. The impact of macroparasites upon host populations is critically dependent upon parasite frequency distributions [12,13]. Understanding the nature of parasite frequency distributions enhances our understanding of the patterns that we see in the field [6]. As demonstrated using simulation models, the mechanism producing aggregation in parasite populations has a strong influence on the stability of the system [11]. Despite their relevance, the aggregated nature of parasite frequency distributions and the complexities
introduced by the incorporation of acquired immunity and its relationship to endemic stability are two features of macroparasite systems that have been dealt with only superficially, if not ignored [6]. Differences among hosts in terms of predisposition to infection and acquired immunity influence density-dependent constraint and aggregation. The variability in host predisposition to infection has been seen with Taenia saginata and Taenia taeniaeformis in cattle and rodents, respectively [14]. In addition, it has been observed that immunity to super infection by Echinococcus granulosus, Taenia hydatigena and Taenia ovis can be acquired or induced in sheep [15,16]. This evidence suggests that aggregation in porcine cysticercosis infection may be partly explained by different levels of immunity against the parasite. In epidemiological terms, in porcine populations with high herd immunity, aggregation will work as a negative feedback system, operating as a density-dependent constraint, thus limiting the population size of T. solium larvae. A serosurvey for porcine cysticercosis was conducted in the district of Quilcas, a highly endemic area in Huancayo, in the Peruvian Central Highlands [17]. Presence of antibodies against T. solium was determined using a specific immunoblot test (EITB) as previously described by Tsang and others [18]. Serology was performed within 24 h and a sample of the EITB positive pigs were then selected according to age and number of bands and purchased for necropsy studies. A subset of 84 EITB positive pigs were bought, humanely killed and necropsied to determine burden of infection. Table 1 summarizes the necropsy results organized by age and serological response to the EITB assay. It was found that the burden of infection was clearly aggregated. Also, that the probability of being necropsy positive increased with the number of reactive antibody bands to T. solium antigens, and age. No statistical association was found between the infection burden and age. A recent experiment in Peru, performed under the aegis of a control program against T. solium cysticercosis (see description below in the experiments section), have shown that from 325 pigs culled from an endemic area, 40 were infected with cysts. Ten of them had viable cysts, allegedly capable of continuing with the life cycle. Interestingly enough, just one pig was infected with more than 10 viable cysts. Besides corroborating aggregation in porcine cysticercosis, the data hints on interesting similarities. Apparently, the rate of heavy infections
Table 1 Distribution of necropsied pigs according to EITB number of bands, infection burden and age in categories Infection burden
Less or equal to 8 months Older than 8 months EITB bands 1–2
Negative 13 Low (1 – 10) 3 Moderate (11 – 100) 1 Heavy (100+) 2 Total 19
3
4+
6 5 0 1 12
1 1 0 1 3
Subtotal
EITB bands Subtotal 1–2 3
4+
20 9 1 4 34
14 3 1 1 19
1 0 0 3 4
6 10 5 6 27
21 13 6 10 50
Total
41 22 7 14 84
A.E. Gonzalez et al. / Parasitology International 55 (2006) S131 – S135
in pigs is about the rate of tapeworm infections in the human population (A. Gonzalez, unpublished). Our group also showed that incidence of T. solium in humans measured by specific antibodies was greater than previously expected. The discordance between the extremely high sero-prevalence of T. solium antibodies in diseaseendemic populations, relatively few symptomatic cases of neurocysticercosis, and high background levels of putatively inactive brain lesions (mainly calcifications) in sero-negative controls have confused researchers, clinicians, and epidemiologists in the last decade [19]. Just a short time ago it was assumed that the incidence of human cysticercosis was very low and closely related to mortality in the exposed group. Longitudinal serologic data from 3 different cysticercosisendemic areas of Peru and Colombia showed that approximately 40% of sero-positive people reverted to sero-negative when re-sampled after 1 year (3 surveys) or after 3 years (1 survey). In this case, transient antibodies may have significant implications for disease immunity and epidemiology. 4. Egg dispersal Taenia eggs are dispersed in different ways, and therefore the ways in which they may be ingested by their corresponding intermediate host differ. Although most of T. hydatigena and T. ovis eggs remain within about 180 m of the site of deposition, some may rapidly disperse in all directions [20]. In T. saginata, the other human tapeworm, proglottids are motile and often continue to move after passage from the body [21 – 24]. By contracting and expanding longitudinally, the proglottid can move away from the feces and towards areas where the worm’s eggs may be likely to be ingested by a suitable host [20]. T. solium proglottids, however, are not motile and eggs and proglottids are almost always ingested directly at the site of
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deposition. Random dispersion of T. solium proglottids and eggs is also less likely due to the intermittent nature of proglottid and egg release [21]. Although the life cycle is known, a thorough explanation of transmission dynamics at the village level remains elusive. The mechanisms of egg dispersal depicted above do not correlate with the spatial distribution of T. solium. Fig. 1 depicts a GPS/GIS map with the location of tapeworms and pigs according to its EITB reaction. Just 1% of the total human population is infected with the adult tapeworm, yet there is evidence of disease or at least exposure in the whole community. Even though pig-to-pig transmission was not systematically proven or characterized yet, it still represents an issue that should not be easily disregarded. Whether or not secondary infection is only attributable to coprophagic habits under field conditions has yet to be demonstrated. Additionally, the effect of coprophagia in parasitic infections has been documented for nematodes such as Ascaris suum [25], Trichuris suis [26] and Parascaris equorum [27]. Also, coprophagia was described as a transmission mechanism in cestode, Hymenolepis nana [28]. Studies with T. hydatigena and T. ovis in sheep and dogs demonstrated that immunity is acquired after the ingestion of as few as 10 eggs, is life-long in the presence of eggs, does not depend on the presence of larvae from a previous infection, and can be lost between 6 and 12 months in the absence of eggs [14]. Perhaps the only feature missing in the human/pig relationship is just another means to disperse eggs in a manner that immunity would become a density-dependent constraint and produce the aggregation shown in porcine cysticercosis. After all, it has been suggested that endemic stability arises if the force of infection is high enough that acquisition of functional immunity occurs in the population at a relatively young age [2].
Fig. 1. Matapalo Village, Tumbes, Peru´. Map showing the distribution of tapeworm carriers and pigs positive to EITB-C with 1 – 2 bands, 3 or more bands and negative pigs.
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5. Coprophagia and egg dispersion
References
Coprophagia in domestic animals other than pigs, dogs, guinea pigs, and rabbits is a rarely observed behaviour. Older sucking pigs have been observed to rush towards and consume the recently voided faeces of their dam [21,29]. This behaviour has adaptive importance as newborn piglets, while usually having adequate haemoglobin levels, typically have limited iron stores. Since a sow’s milk is low in iron, commercial farms will give piglets iron supplementation [30]. Under free-range conditions, the piglets get their iron requirement from the environment. It has been demonstrated that piglets born to sows housed in solid-floored farrowing pens get their iron from the dam faeces [31,32]. Knowing the relationship between foraging habits and social behaviour in free ranging pigs is helpful in understanding how pig infection with T. solium eggs may occur [33]. Copado and others [33] demonstrated that pig herds have a stable hierarchy, strong group cohesion, and social dynamics which may influence parasite transmission and aggregation. They observed that the frequency in which the pigs were seen consuming human faeces was different among age groups. In addition, the pigs moved with a definite hierarchical order and the dominant pigs were the first to ingest human faecal material. Adult alfa pigs and their lieutenants, therefore, eat a greater proportion of faeces, leaving very little for the rest of the herd. A major breakthrough was recently published that may help to explain egg dispersal [34]. A series of experiments were devised to investigate if a single dose of an infective T. solium proglottid administered to an index, or primary, pig is capable of passing the infection to a second pig. Three 1-month-old piglets, each infected with one proglottid, were housed with two 1month-old naı¨ve piglets. Both naı¨ve piglets developed antibodies to cyst antigen and one of them was cyst positive at necropsy. In a subsequent experiment, two naı¨ve 1-month-old sentinel piglets were housed in the same pen with six other piglets that had been infected 1 day prior with one proglottid each. Both sentinel piglets became seropositive and developed cysts. In a third experiment, four sows and their litters were housed together in the same pen. One was a tongue-positivenaturally infected sow, another was EITB positive, and the others were naı¨ve, EITB negative sows. Both dams received orally, two proglottids each, when the piglets were 1 week old. Six weeks after infection of the dams, three of the piglets from the EITB-C positive dam showed cysts at necropsy. Finally, a pilot experiment was conducted to evaluate when secondary infections occur. Fourteen 1-month-old piglets from a cysticercosis-free farm were housed with a single pig infected with one proglottid. Piglets were divided into four homogenous groups. Groups were exposed at different times to the primarily infected pig i) from day 1 to 6, ii) from day 7 to 12 and iii) from day 13 to 18. Piglets were humanely killed 8 weeks after exposure. Cysts were found up to the third week, demonstrating that pig-to-pig infections not only dilute the infective dose, but may also dilate the time of infection. The phenomenon of endemic stability may be partially explained by parasite egg dispersal in the environment and/or host susceptibility (herd immunity). Both egg dispersal and herd immunity may be related to pig-to-pig infection.
[1] Acha P, Szyfres B. Zoonosis y enfermedades transmisibles comunes al hombre y los animales. Washington’ Pan American Health Organization; 1986. [2] Coleman PG, Perry BD, Woolhouse ME. Endemic stability—a veterinary idea applied to human public health. Lancet 2001;357:1284 – 6. [3] Smith RD. Epidemiology of babesiosis. In: Ristic M, Ambroise-Thomas P, editors. Malaria and babesiosis research findings and control measures. Dordrecht’ Nijhoff; 1984. p. 207 – 32. [4] Anderson RM, May RM. Biology of host – macroparasite associations in infectious diseases of humans dynamics and control. Oxford’ Oxford University Press; 1991. [5] Smith G. Parasite population density is regulated. In: Scott ME, Smith G, editors. Parasitic and infectious diseases. San Diego’ Academic Press; 1994. p. 47 – 63. [6] Smith G, Basan˜ez M-G, Dietz K, Gemmell MA, Grenfell BT, Gulland FMD, et al. Macroparasite group report: problems in modelling the dynamics of macroparasitic systems. In: Grenfell BT, Dobson AP, editors. Ecology of infectious diseases in natural populations. Cambridge’ Cambridge University Press; 1995. p. 209 – 29. [7] Hudson PJ, Dobson AP. Macroparasites: observed patterns in naturally fluctuating animal populations. In: Grenfell BT, Dobson AP, editors. Ecology of infectious diseases in natural populations. Cambridge’ Cambridge University Press; 1995. p. 144 – 76. [8] Garcia H. Effectiveness of a control program for human and porcine Taenia solium cysticercosis in field conditions. PhD dissertation. Johns Hopkins University, Baltimore; 2002. [9] Medley GF. Chemotherapy. In: Scott ME, Smith G, editors. Parasitic and infectious diseases. Epidemiology and Ecology. San Diego’ Academic Press; 1994. p. 141 – 57. [10] Anderson RM, Gordon DM. Processes influencing the distribution of parasite numbers within host populations with special emphasis on parasite-induced host mortalities. Parasitology 1982;85:373 – 98. [11] Rosa R, Pugliese A. Aggregation, stability, and oscillations in different models for host – macroparasite interactions. Theor Popul Biol 2002;61: 319 – 34. [12] Gulland FMD. Impact of infectious diseases on wild animal populations. In: Grenfell BT, Dobson AP, editors. Ecology of infectious diseases in natural populations. Cambridge’ Cambridge University Press; 1995. p. 20 – 51. [13] Roberts MG, Smith G, Grenfell BT. Mathematical models for macroparasites of wildlife. In: Grenfell BT, Dobson AP, editors. Ecology of infectious diseases in natural populations. Cambridge’ Cambridge Academic Press; 1995. p. 177 – 208. [14] Gemmell MA. Current knowledge of the epidemiology of the family taenidae: operational research needs in planning control of Taenia solium. In: Garcia H, Martinez M, editors. Taenia solium taeniasis/cysticercosis. Lima’ Editorial Universo; 1999. p. 219 – 54. [15] Gemmell MA, Macnamara FN. Immune response to tissue parasites: II. Cestodes. In: Soulsby EJL, editor. Immunity to animal parasites. London’ Academic Press; 1999. p. 235 – 72. [16] Lightowlers MW. Vaccination against cestode parasites. Int J Parasitol 1996;26:819 – 24. [17] Garcia HH, Gonzalez AE, Gavidia C, Falcon N, Bernal T, Verastegui M, et al. Seroincidence of porcine Taenia solium infection in the Peruvian highlands. Prev Vet Med 2003;57:227 – 36. [18] Tsang VC, Brand JA, Boyer AE. An enzyme-linked immunoelectrotransfer blot assay and glycoprotein antigens for diagnosing human cysticercosis (Taenia solium). J Infect Dis 1989;159:50 – 9. [19] Garcia HH, Gonzalez AE, Gilman RH, Palacios LG, Jimenez I, Rodriguez S, et al. Short report: transient antibody response in Taenia solium infection in field conditions—a major contributor to high seroprevalence. Am J Trop Med Hyg 2001;65:31 – 2. [20] Gemmell MA, Johnstone PD, Boswell CC. Factors regulating tapeworm populations: dispersion patterns of Taenia hydatigena eggs on pasture. Res Vet Sci 1978;24:334 – 8. [21] Cordero-del-Campillo M, Hidalgo-Arguello MR. Cisticercosis (C. cellulosae). In: Cordero-del-Campillo M, Rojo-Vazquez FA, editors. Para-
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sitologia veterinaria. Madrid’ McGraw Hill – Interamericana; 1999. p. 493 – 5. Roman G, Sotelo J, Del BO, Flisser A, Dumas M, Wadia N, et al. A proposal to declare neurocysticercosis an international reportable disease. Bull WHO 2000;78:399 – 406. Sanchez-Acedo C. Cisticercosis bovina. Cisticercosis de los pequen˜os rumiantes. In: Cordero-del-Campillo M, Rojo-Vazquez FA, editors. Parasitologia veterinaria. Madrid’ McGraw Hill – Interamericana; 1999. p. 350 – 62. Soulsby EJL. Helminths, arthropods and protozoa of domesticated animals. London’ Baillia´ere Tindall; 1982. Boes J, Nansen P, Stephenson LS. False-positive Ascaris suum egg counts in pigs. Int J Parasitol 1997;27:833 – 8. Boes J, Johansen MV, Eriksen L, Bogh HO, Nansen P, Stephenson LS. False-positive Trichuris suis egg counts in pigs in relation to coprophagia. Parasite 1998;5:91 – 3. Lyons ET, Swerczek TW, Tolliver SC, Drudge JH. Natural superinfection of Parascaris equorum in a stall-confined orphan horse foal. Vet Parasitol 1996;66:119 – 23.
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[28] Ghazal AM, Avery RA. Observations on coprophagy and the transmission of Hymenolepis nana infections in mice. Parasitology 1976;73:39 – 45. [29] Smith WJ, Penny RHC. Behavioral problems. In: Leman AD, Straw B, Glock RD, Mengeling WL, Penny RHC, Scholl E, editors. Diseases of swine. Ames, IA’ Iowa State University Press; 1984. p. 762 – 71. [30] Becker HN. Castration, vasectomy, hernia repair and baby pig processing. In: Leman AD, Straw B, Glock RD, Mengeling WL, Penny RHC, Scholl E. Ames, IA’ Iowa State University Press; 1986. p. 852 – 65. [31] Gleed PT, Sansom BF. Ingestion of iron in sow’s faeces by piglets reared in farrowing crates with slotted floors. Br J Nutr 1982;47:113 – 7. [32] Sansom BF, Gleed PT. The ingestion of sow’s faeces by suckling piglets. Br J Nutr 1981;46:451 – 6. [33] Copado F, Aluja AS, Mayagoitia L, Galindo F. The behavior of free ranging pigs in the Mexican tropics and its relationship with human faeces consumption. Me´xico; 2004: 243 – 52. [34] Gonzalez AE, Lopez-Urbina MT, Tsang B, Gavidia C, Garcia HH, Silva ME, et al. Short report: secondary transmission in Porcine Cysticercosis: description and their potential implications for control sustainability. Am J Trop Med Hyg 2005;73:501 – 3.
Transmission dynamics of Taenia solium and potential for pig-to-pig transmission Armando E. Gonzalez a,*, Teresa Lopez-Urbina a, Byron Tsang b, Cesar Gavidia a, H. Hugo Garcia c,d, Maria E. Silva a, Daphne D. Ramos a, Rafael Manzanedo a, Lelia Sanchez-Hidalgo a, Robert H. Gilman e, Victor C.W. Tsang b The cysticercosis working group in Peru a
b
School of Veterinary Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru Immunology Branch, Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control, Atlanta, GA, USA c Universidad Peruana Cayetano Heredia, Lima, Peru d Cysticercosis Unit, Instituto Nacional de Ciencias Neurolo´gicas, Lima, Peru e Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA Available online 13 December 2005
Abstract Taenia solium taeniasis/cysticercosis is one of few potentially eradicable infectious diseases and is the target of control programs in several countries. The larval stage of this zoonotic cestode invades the human brain and is responsible for most cases of adult-onset epilepsy in the world. Our current understanding of the life cycle implicates humans as the only definitive host and tapeworm carrier, and thus the sole source of infective eggs that are responsible for cysticercosis in both human and pigs through oral – faecal transmission. Here we review transmission dynamics of porcine cysticercosis including an alternative pig-to-pig route of transmission, previously not suspected to exist. Second-hand transmission of T. solium eggs could explain the overdispersed pattern of porcine cysticercosis, with few pigs harbouring heavy parasite burdens and many more harbouring small numbers of parasites. D 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Taenia solium; Porcine cysticercosis; Transmission dynamics
1. Introduction Taenia solium cysticercosis is a common disease in pig raising areas of resource-poor countries [1]. This parasitic infection causes severe neurological disease in humans and economic losses in the poorest communities. The life cycle involves humans as the sole definitive host, harbouring the adult tapeworm in the intestine, and pigs as the intermediate host, harbouring the larval form or cysticerci. The larval stage of this zoonotic cestode also invades the human brain, causing morbidity and mortality. Although control measures have been described and tested, sustainable cysticercosis control remains
* Corresponding author. Tel.: +51 1 4368938; fax: +51 1 431027. E-mail address: [email protected] (A.E. Gonzalez). 1383-5769/$ - see front matter D 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.parint.2005.11.021
elusive. The idea that every pig with antibodies has the potential to continue the life cycle of the parasite represents a risky assumption. Likewise, any successful control program may interrupt transmission temporarily, but decreased herd immunity will eventually return the infection rates to their original levels. 2. Endemic stability Endemic stability describes a dynamic epidemiological state in which clinical disease is rare in spite of a high incidence of infection within a population [2]. The concept of ‘‘endemic stability’’ (herd immunity), where the rate of transmission of infection is low enough as to not result in clinical disease yet sufficiently high to immunize susceptible animals, has been an accepted epidemiologic concept for decades [3]. The endemic
S132
A.E. Gonzalez et al. / Parasitology International 55 (2006) S131 – S135
stability of an organism is influenced by the organism’s basic reproductive ratio (or number) and density dependent constraints. For macroparasites, the basic reproductive ratio is defined as the average number of offspring produced through the reproductive life-span of the mature parasite [4]. Densitydependent constraints are mechanisms that regulate the abundance of parasite populations, the effects of which are less obvious when the parasite is first introduced into the host population [5]. Once the density-dependent constraint is present, a regulated population size fluctuates considerably less. Density dependence and the basic reproductive ratio govern the rate of recovery of the parasite population following treatment or chemotherapy. Removing parasites should reduce the average density dependent effect. It follows that the effective reproduction ratio, in this case, the average number of infective cysts per pig, will increase above its equilibrium value and the adult parasite population will grow [6]. This will cease when density dependence is again at its equilibrium value, which generally will be when the parasite population has re-attained its previous density [7]. This helps explain how a regulated population, one that had persisted at a consistent population size for a long period of time, can return to its original population size after having been perturbed. Our group produced the key piece of evidence suggesting that population regulation occurs in T. solium cysticercosis. A cohort study was performed to evaluate the effect of a combined intervention (human and porcine mass chemotherapy) on the prevalence and incidence of porcine cysticercosis in treated versus control areas. Although the combined intervention controlled the parasite, the effect only lasted for 2 years after treatment [8]. Parasite recrudescence has been demonstrated again in a T. solium elimination program in Tumbes (Peru) and whenever similar strategies have been employed [9]. 3. Aggregation The population distributions of helminths invariably indicate a tendency towards aggregation, meaning that the majority of parasites are harboured by a minority of hosts [10]. Aggregation is generally recognized as an important factor in the dynamics of host – macroparasite interactions, and it has been found to be relevant in stabilizing population dynamics in a coexisting equilibrium [11]. Aggregation tends to influence the interactions that regulate parasite numbers, such that the interactions influence a larger proportion of the parasite population [7]. The impact of macroparasites upon host populations is critically dependent upon parasite frequency distributions [12,13]. Understanding the nature of parasite frequency distributions enhances our understanding of the patterns that we see in the field [6]. As demonstrated using simulation models, the mechanism producing aggregation in parasite populations has a strong influence on the stability of the system [11]. Despite their relevance, the aggregated nature of parasite frequency distributions and the complexities
introduced by the incorporation of acquired immunity and its relationship to endemic stability are two features of macroparasite systems that have been dealt with only superficially, if not ignored [6]. Differences among hosts in terms of predisposition to infection and acquired immunity influence density-dependent constraint and aggregation. The variability in host predisposition to infection has been seen with Taenia saginata and Taenia taeniaeformis in cattle and rodents, respectively [14]. In addition, it has been observed that immunity to super infection by Echinococcus granulosus, Taenia hydatigena and Taenia ovis can be acquired or induced in sheep [15,16]. This evidence suggests that aggregation in porcine cysticercosis infection may be partly explained by different levels of immunity against the parasite. In epidemiological terms, in porcine populations with high herd immunity, aggregation will work as a negative feedback system, operating as a density-dependent constraint, thus limiting the population size of T. solium larvae. A serosurvey for porcine cysticercosis was conducted in the district of Quilcas, a highly endemic area in Huancayo, in the Peruvian Central Highlands [17]. Presence of antibodies against T. solium was determined using a specific immunoblot test (EITB) as previously described by Tsang and others [18]. Serology was performed within 24 h and a sample of the EITB positive pigs were then selected according to age and number of bands and purchased for necropsy studies. A subset of 84 EITB positive pigs were bought, humanely killed and necropsied to determine burden of infection. Table 1 summarizes the necropsy results organized by age and serological response to the EITB assay. It was found that the burden of infection was clearly aggregated. Also, that the probability of being necropsy positive increased with the number of reactive antibody bands to T. solium antigens, and age. No statistical association was found between the infection burden and age. A recent experiment in Peru, performed under the aegis of a control program against T. solium cysticercosis (see description below in the experiments section), have shown that from 325 pigs culled from an endemic area, 40 were infected with cysts. Ten of them had viable cysts, allegedly capable of continuing with the life cycle. Interestingly enough, just one pig was infected with more than 10 viable cysts. Besides corroborating aggregation in porcine cysticercosis, the data hints on interesting similarities. Apparently, the rate of heavy infections
Table 1 Distribution of necropsied pigs according to EITB number of bands, infection burden and age in categories Infection burden
Less or equal to 8 months Older than 8 months EITB bands 1–2
Negative 13 Low (1 – 10) 3 Moderate (11 – 100) 1 Heavy (100+) 2 Total 19
3
4+
6 5 0 1 12
1 1 0 1 3
Subtotal
EITB bands Subtotal 1–2 3
4+
20 9 1 4 34
14 3 1 1 19
1 0 0 3 4
6 10 5 6 27
21 13 6 10 50
Total
41 22 7 14 84
A.E. Gonzalez et al. / Parasitology International 55 (2006) S131 – S135
in pigs is about the rate of tapeworm infections in the human population (A. Gonzalez, unpublished). Our group also showed that incidence of T. solium in humans measured by specific antibodies was greater than previously expected. The discordance between the extremely high sero-prevalence of T. solium antibodies in diseaseendemic populations, relatively few symptomatic cases of neurocysticercosis, and high background levels of putatively inactive brain lesions (mainly calcifications) in sero-negative controls have confused researchers, clinicians, and epidemiologists in the last decade [19]. Just a short time ago it was assumed that the incidence of human cysticercosis was very low and closely related to mortality in the exposed group. Longitudinal serologic data from 3 different cysticercosisendemic areas of Peru and Colombia showed that approximately 40% of sero-positive people reverted to sero-negative when re-sampled after 1 year (3 surveys) or after 3 years (1 survey). In this case, transient antibodies may have significant implications for disease immunity and epidemiology. 4. Egg dispersal Taenia eggs are dispersed in different ways, and therefore the ways in which they may be ingested by their corresponding intermediate host differ. Although most of T. hydatigena and T. ovis eggs remain within about 180 m of the site of deposition, some may rapidly disperse in all directions [20]. In T. saginata, the other human tapeworm, proglottids are motile and often continue to move after passage from the body [21 – 24]. By contracting and expanding longitudinally, the proglottid can move away from the feces and towards areas where the worm’s eggs may be likely to be ingested by a suitable host [20]. T. solium proglottids, however, are not motile and eggs and proglottids are almost always ingested directly at the site of
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deposition. Random dispersion of T. solium proglottids and eggs is also less likely due to the intermittent nature of proglottid and egg release [21]. Although the life cycle is known, a thorough explanation of transmission dynamics at the village level remains elusive. The mechanisms of egg dispersal depicted above do not correlate with the spatial distribution of T. solium. Fig. 1 depicts a GPS/GIS map with the location of tapeworms and pigs according to its EITB reaction. Just 1% of the total human population is infected with the adult tapeworm, yet there is evidence of disease or at least exposure in the whole community. Even though pig-to-pig transmission was not systematically proven or characterized yet, it still represents an issue that should not be easily disregarded. Whether or not secondary infection is only attributable to coprophagic habits under field conditions has yet to be demonstrated. Additionally, the effect of coprophagia in parasitic infections has been documented for nematodes such as Ascaris suum [25], Trichuris suis [26] and Parascaris equorum [27]. Also, coprophagia was described as a transmission mechanism in cestode, Hymenolepis nana [28]. Studies with T. hydatigena and T. ovis in sheep and dogs demonstrated that immunity is acquired after the ingestion of as few as 10 eggs, is life-long in the presence of eggs, does not depend on the presence of larvae from a previous infection, and can be lost between 6 and 12 months in the absence of eggs [14]. Perhaps the only feature missing in the human/pig relationship is just another means to disperse eggs in a manner that immunity would become a density-dependent constraint and produce the aggregation shown in porcine cysticercosis. After all, it has been suggested that endemic stability arises if the force of infection is high enough that acquisition of functional immunity occurs in the population at a relatively young age [2].
Fig. 1. Matapalo Village, Tumbes, Peru´. Map showing the distribution of tapeworm carriers and pigs positive to EITB-C with 1 – 2 bands, 3 or more bands and negative pigs.
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5. Coprophagia and egg dispersion
References
Coprophagia in domestic animals other than pigs, dogs, guinea pigs, and rabbits is a rarely observed behaviour. Older sucking pigs have been observed to rush towards and consume the recently voided faeces of their dam [21,29]. This behaviour has adaptive importance as newborn piglets, while usually having adequate haemoglobin levels, typically have limited iron stores. Since a sow’s milk is low in iron, commercial farms will give piglets iron supplementation [30]. Under free-range conditions, the piglets get their iron requirement from the environment. It has been demonstrated that piglets born to sows housed in solid-floored farrowing pens get their iron from the dam faeces [31,32]. Knowing the relationship between foraging habits and social behaviour in free ranging pigs is helpful in understanding how pig infection with T. solium eggs may occur [33]. Copado and others [33] demonstrated that pig herds have a stable hierarchy, strong group cohesion, and social dynamics which may influence parasite transmission and aggregation. They observed that the frequency in which the pigs were seen consuming human faeces was different among age groups. In addition, the pigs moved with a definite hierarchical order and the dominant pigs were the first to ingest human faecal material. Adult alfa pigs and their lieutenants, therefore, eat a greater proportion of faeces, leaving very little for the rest of the herd. A major breakthrough was recently published that may help to explain egg dispersal [34]. A series of experiments were devised to investigate if a single dose of an infective T. solium proglottid administered to an index, or primary, pig is capable of passing the infection to a second pig. Three 1-month-old piglets, each infected with one proglottid, were housed with two 1month-old naı¨ve piglets. Both naı¨ve piglets developed antibodies to cyst antigen and one of them was cyst positive at necropsy. In a subsequent experiment, two naı¨ve 1-month-old sentinel piglets were housed in the same pen with six other piglets that had been infected 1 day prior with one proglottid each. Both sentinel piglets became seropositive and developed cysts. In a third experiment, four sows and their litters were housed together in the same pen. One was a tongue-positivenaturally infected sow, another was EITB positive, and the others were naı¨ve, EITB negative sows. Both dams received orally, two proglottids each, when the piglets were 1 week old. Six weeks after infection of the dams, three of the piglets from the EITB-C positive dam showed cysts at necropsy. Finally, a pilot experiment was conducted to evaluate when secondary infections occur. Fourteen 1-month-old piglets from a cysticercosis-free farm were housed with a single pig infected with one proglottid. Piglets were divided into four homogenous groups. Groups were exposed at different times to the primarily infected pig i) from day 1 to 6, ii) from day 7 to 12 and iii) from day 13 to 18. Piglets were humanely killed 8 weeks after exposure. Cysts were found up to the third week, demonstrating that pig-to-pig infections not only dilute the infective dose, but may also dilate the time of infection. The phenomenon of endemic stability may be partially explained by parasite egg dispersal in the environment and/or host susceptibility (herd immunity). Both egg dispersal and herd immunity may be related to pig-to-pig infection.
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