A stochastic mathematical model of methicillin resistant Staphylococcus aureus transmission in an intensive care unit: predicting the impact of interventions

OBJECTIVES: To estimate the transmission rate of MRSA in an intensive care unit (ICU) in an 800 bed Australian teaching hospital and predict the impact of infection control interventions. METHODS: A mathematical model was developed which consisted of four compartments: colonised and uncolonised patients and contaminated and uncontaminated health-care workers (HCWs). Patient movements, MRSA acquisition and daily prevalence data were collected from an ICU over 939 days. Hand hygiene compliance and the probability of MRSA transmission from patient to HCW per discordant contact were measured during the study. Attack rate and reproduction ratio were estimated using Bayesian methods. The impact of a number of interventions on attack rate was estimated using both stochastic and deterministic versions of the model. RESULTS: The mean number of secondary cases arising from the ICU admission of colonised patients, also called the ward reproduction ratio, R(w), was estimated to be 0.50 (95% CI 0.39-0.62). The attack rate was one MRSA transmission per 160 (95% CI 130-210) uncolonised-patient days. Results were not sensitive to uncertainty in measured model parameters (hand hygiene rate and transmission probability per contact). Hand hygiene was predicted to be the most effective intervention. Decolonisation was predicted to be relatively ineffective. Increasing HCW numbers was predicted to increase MRSA transmission, in the absence of patient cohorting. The predictions of the stochastic model differed from those of the deterministic model, with lower levels of colonisation predicted by the stochastic model. CONCLUSIONS: The number of secondary cases of MRSA colonisation within the ICU in this study was below unity. Transmission of MRSA was sustained through admission of colonised patients. Stochastic model simulations give more realistic predictions in hospital ward settings than deterministic models. Increasing staff does not necessarily lead to reduced transmission of nosocomial pathogens.     

Renewed hope for a vaccine against the intestinal adult Taenia solium

Review of experimental and observational evidence about various cestode infections of mammalian hosts revives hope for the development of an effective vaccine against adult intestinal tapeworms, the central protagonists in their transmission dynamics. As for Taenia solium, there are abundant immunological data regarding cysticercosis in humans and pigs, but information about human taeniasis is scarce. A single publication reporting protection against T. solium taeniasis by experimental primo infection and by vaccination of an experimental foster host, the immunocompetent female hamster, kindles the hope of a vaccine against the tapeworm to be used in humans, its only natural definitive host.     

A Bayesian approach for estimating values for prevalence and diagnostic test characteristics of porcine cysticercosis

Several diagnostic techniques are used to estimate the prevalence of the zoonotic tapeworm Taenia solium in pigs, but none of these tests are perfect, making interpretation of results difficult. A Bayesian approach was used to estimate values for the prevalence and diagnostic test characteristic of porcine cysticercosis by combining results of four imperfect tests. Village pigs (N = 868) slaughtered in Lusaka (Zambia), were bled, and tongue and routine meat inspected; and serum antibody and parasite antigen concentrations were determined by ELISA. A model, based on a multinomial distribution and including all possible interactions between the individual tests required 31 parameters to be estimated, but actually allowed only 15 parameters (i.e. had 15 degrees of freedom) to be estimated. Therefore, prior expert opinion on specificity and (in)-dependence of the tests was entered in the model, resulting in a reduction of the number of parameters to be estimated. The estimated prevalence of porcine cysticercosis was 0.642 (95% confidence interval 0.54-0.91). The performances of the tests were (sensitivity (se)-specificity (sp)): tongue inspection (se 0.210-sp 1.000), meat inspection (se 0.221-sp 1.000), Ab-ELISA (se 0.358-sp 0.917), Ag-ELISA (se 0.867-sp 0.947). To validate the estimates obtained from the model we performed a second study: 65 randomly purchased Zambian village pigs were bled for serum antibody and antigen determination, their tongue and meat inspected; and in addition, the carcasses were dissected for total cysticercus counts (gold standard). Cysticerci were found in 31 pigs (prevalence 0.477, 95% confidence interval 0.35-0.60), overlapping with the estimated prevalence in the first study. Sensitivity and specificity values obtained for the aforementioned tests in this study were in agreement with those estimated. A Bayesian analysis framework offers the possibility to combine prior opinion with experimental data to more accurately estimate the real prevalence of porcine cysticercosis in the absence of a gold standard.     

A Periodically-Forced Mathematical Model for the Seasonal Dynamics of Malaria in Mosquitoes

We describe and analyze a periodically-forced difference equation model for malaria in mosquitoes that captures the effects of seasonality and allows the mosquitoes to feed on a heterogeneous population of hosts. We numerically show the existence of a unique globally asymptotically stable periodic orbit and calculate periodic orbits of field-measurable quantities that measure malaria transmission. We integrate this model with an individual-based stochastic simulation model for malaria in humans to compare the effects of insecticide-treated nets (ITNs) and indoor residual spraying (IRS) in reducing malaria transmission, prevalence, and incidence. We show that ITNs are more effective than IRS in reducing transmission and prevalence though IRS would achieve its maximal effects within 2 years while ITNs would need two mass distribution campaigns over several years to do so. Furthermore, the combination of both interventions is more effective than either intervention alone. However, although these interventions reduce transmission and prevalence, they can lead to increased clinical malaria; and all three malaria indicators return to preintervention levels within 3 years after the interventions are withdrawn.     

Toxoplasma gondii: from animals to humans

Toxoplasmosis is one of the more common parasitic zoonoses world-wide. Its causative agent, Toxoplasma gondii, is a facultatively heteroxenous, polyxenous protozoon that has developed several potential routes of transmission within and between different host species. If first contracted during pregnancy, T. gondii may be transmitted vertically by tachyzoites that are passed to the foetus via the placenta. Horizontal transmission of T. gondii may involve three life-cycle stages, i.e. ingesting infectious oocysts from the environment or ingesting tissue cysts or tachyzoites which are contained in meat or primary offal (viscera) of many different animals. Transmission may also occur via tachyzoites contained in blood products, tissue transplants, or unpasteurised milk. However, it is not known which of these routes is more important epidemiologically. In the past, the consumption of raw or undercooked meat, in particular of pigs and sheep, has been regarded as a major route of transmission to humans. However, recent studies showed that the prevalence of T. gondii in meat-producing animals decreased considerably over the past 20 years in areas with intensive farm management. For example, in several countries of the European Union prevalences of T. gondii in fattening pigs are now <1%. Considering these data it is unlikely that pork is still a major source of infection for humans in these countries. However, it is likely that the major routes of transmission are different in human populations with differences in culture and eating habits. In the Americas, recent outbreaks of acute toxoplasmosis in humans have been associated with oocyst contamination of the environment. Therefore, future epidemiological studies on T. gondii infections should consider the role of oocysts as potential sources of infection for humans, and methods to monitor these are currently being developed. This review presents recent epidemiological data on T. gondii, hypotheses on the major routes of transmission to humans in different populations, and preventive measures that may reduce the risk of contracting a primary infection during pregnancy.     

Risk factors of porcine cysticercosis in the Eastern Cape Province, South Africa

There is a high prevalence of Taenia solium taeniosis/cysticercosis in humans and pigs in the Eastern Cape Province (ECP) of South Africa. The objective of this study was to identify risk factors of porcine cysticercosis in select districts of the ECP. Data were collected in 2003 by interviewing 217 pig producers from the area. Blood samples were collected from 261 of their pigs, which were tested using two enzyme-linked immunosorbent assays (ELISA) for the presence of antibodies to cysticercosis. Frequencies of both owner- and pig-level characteristics were determined. For pig-level analysis, all bivariable and multivariable associations were determined using the surveylogistic procedure of the SAS/STAT? software to accommodate for the intraclass correlation that exists for clusters of pigs within one owner and for clusters of owners within a district. All tests for significance were performed at the α?=?0.05 level, and adjusted odds ratios (aOR) and 95% confidence intervals (CI) were determined. Among the respondents, 48% of their households lacked a latrine, 98% slaughtered pigs at home, and 99% indicated that meat inspection services were not available. On bivariable analysis, there was a significant association between porcine infection and district (p?=?0.003), breed (p?=?0.041) and the absence of a latrine (p?=?0.006). On multivariable analysis, the absence of a latrine was the only variable significantly associated with porcine infection (aOR?=?1.89; 95% CI?=?1.07, 3.35) (p?=?0.028). The increased odds of porcine infection with households lacking a latrine contributes to our understanding of the transmission of this parasite in the ECP. Determining and addressing the risk factors for T. solium infection can potentially lower the very high prevalence in humans and pigs in this endemic area.     

How should pathogen transmission be modelled?

Host-pathogen models are essential for designing strategies for managing disease threats to humans, wild animals and domestic animals. The behaviour of these models is greatly affected by the way in which transmission between infected and susceptible hosts is modelled. Since host-pathogen models were first developed at the beginning of the 20th century, the 'mass action' assumption has almost always been used for transmission. Recently, however, it has been suggested that mass action has often been modelled wrongly. Alternative models of transmission are beginning to appear, as are empirical tests of transmission dynamics.     

Eradication of Taenia solium cysticercosis: A role for vaccination of pigs

Taenia solium is the causative agent of neurocysticercosis, a disease responsible for substantial human morbidity and mortality. It is a zoonotic parasite, involving pigs as intermediate hosts. The parasite’s full life cycle is restricted to poor people in developing countries. Attempts to date to control transmission of the parasite have been relatively poorly effective and not sustainable. Over the past decade research has been undertaken to develop practical vaccines for use in pigs to prevent transmission of T. solium. The most effective of these vaccines in controlled experimental trials has been the TSOL18 vaccine. More recently, TSOL18 has been proven to be highly effective against naturally acquired infection with T. solium in pigs. Application of TSOL18 together with a single treatment of pigs with oxfendazole achieved the complete elimination of transmission of the parasite by pigs involved in the field trial. This strategy may provide a relatively low cost and sustainable control tool which could assist towards the goal of achieving eradication of the parasite. An assessment is made of the potential value of various control measures that are available for T. solium, and two options are suggested as potential parasite control programs.     

Dogs as alternative intermediate hosts of Taenia solium in Papua (Irian Jaya), Indonesia confirmed by highly specific ELISA and immunoblot using native and recombinant antigens and mitochondrial DNA analysis

Serology (ELISA and immunoblot) using native glycoproteins, affinity purified glycoproteins, and a recombinant antigen is known to be highly specific to Taenia solium cysticercosis in humans and pigs. These techniques were applied for dogs in the highly endemic area of cysticercosis in Papua (Irian Jaya), Indonesia. Analysis of dog sera by both ELISA and immunoblot revealed 7 of 64 dogs were highly positive. Examination of two sero-positive dogs revealed cysticerci of T. solium in the brain and heart of these dogs. Mitochondrial DNA analysis confirmed that they were the same as T. solium previously confirmed from pigs and biopsies from local people from Irian Jaya. It is suggested that the life cycle of T. solium may be completed not only between humans and pigs but also between humans and dogs.     

A seroepidemiological survey of Taenia solium cysticercosis in Nabo, Guangxi Zhuang Autonomous Region, China

We have observed the seropositive rate of Taenia solium cysticercosis in residents at Nabo Village, Tiandong County, Guangxi Zhuang Autonomous Region, China by enzyme linked immunosorbent assay. The village had been found to be a relatively high endemic area of porcine cysticercosis among roaming pigs. Of 202 persons examined four males aged 15, 25, 35 and 41 year-old exhibited absorbance (abs) at 0.18, 0.20, 0.35 and 0.55, respectively. In addition, two females whose ages were 35 and 39 years revealed specific antibody levels of abs 0.26 and 0.41 in their sera. Overall positive rate among the people was 2.97%. All of these persons agreed that they had ingested the pork infected with T. solium metacestode (TsM), while history of proglottid discharge was not noticed from all of them. Three males and one female complained of intermittent headache. Our findings reinforced not only that the prevalence of cysticercosis might be related with roaming pigs infected with TsM but also that behavioral and environmental practices in local community constituted risk factors for transmission of the infection.     

Control of Taenia solium taeniasis/cysticercosis: from research towards implementation

Theoretically, considering the biology of its transmission and reservoirs, global eradication of Taenia solium taeniasis and cysticercosis is feasible. Recently much progress has been made in research on diagnosis, treatment and prevention of human taeniasis and porcine cysticercosis, although more operational research is still needed. In spite of this, global eradication of T. solium infection is still unlikely in the near future. Major obstacles to practical implementation of control measures include low levels of sanitation and health education amongst endemic populations, ineffective health services infrastructure and inadequate socioeconomic development in these areas. The continued public health impact of neurocysticercosis, especially fatalities and epilepsy, force us to identify improved options for control. In order to implement control measures in highly endemic areas the active involvement of medical services in controlling T. solium infection and more effective collaboration between medical and veterinary services is necessary. A switch is suggested from total reliance on meat inspection to active diagnosis and treatment of human taeniasis, protection of pigs against infection, promotion of health education and improved surveillance preparing chemotherapeutic and/or sanitary interventions. This could be implemented in areas where active transmission causes substantial morbidity and mortality provided there is the political will, social support, better financing and an effective organizational framework.     

The Asian Taenia and the possibility of cysticercosis

In certain Asian countries, a third form of human Taenia, also known as the Asian Taenia, has been discovered. This Asian Taenia seems to be an intermediate between Taenia solium and T. saginata since in morphological terms it is similar to T. saginata, yet biologically, as it uses the same intermediate host (pigs), it is more akin to T. solium. Taenia solium causes human cysticercosis, while T. saginata does not. It is not known whether the Asian taeniid is able to develop to the larval stage in humans or not. The arguments proposed by those authors who consider it unlikely that the Asian Taenia causes human cysticercosis are: (a) its molecular similarities with T. saginata; (b) the absence of cases of human cysticercosis in populations where the Asian adult is highly prevalent; and (c) the unsupporting results derived from an experimental infestation study. These three arguments are debated, although bearing in mind that at present there is still no clear scientific data to support that human cysticercosis can be caused by the Asian Taenia.     

Dynamics of Japanese Encephalitis Virus Transmission among Pigs in Northwest Bangladesh and the Potential Impact of Pig Vaccination

Background

Japanese encephalitis (JE) virus infection can cause severe disease in humans, resulting in death or permanent neurologic deficits among survivors. Studies indicate that the incidence of JE is high in northwestern Bangladesh. Pigs are amplifying hosts for JE virus (JEV) and a potentially important source of virus in the environment. The objectives of this study were to describe the transmission dynamics of JEV among pigs in northwestern Bangladesh and estimate the potential impact of vaccination to reduce incidence among pigs.

Methodology/Principal Findings

We conducted a comprehensive census of pigs in three JE endemic districts and tested a sample of them for evidence of previous JEV infection. We built a compartmental model to describe JEV transmission dynamics in this region and to estimate the potential impact of pig vaccination. We identified 11,364 pigs in the study area. Previous JEV infection was identified in 30% of pigs with no spatial differences in the proportion of pigs that were seropositive across the study area. We estimated that JEV infects 20% of susceptible pigs each year and the basic reproductive number among pigs was 1.2. The model suggest that vaccinating 50% of pigs each year resulted in an estimated 82% reduction in annual incidence in pigs.

Conclusions/Significance

The widespread distribution of historic JEV infection in pigs suggests they may play an important role in virus transmission in this area. Future studies are required to understand the contribution of pig infections to JE risk in humans and the potential impact of pig vaccination on human disease.     

Serological responses in porcine cysticercosis: a link with the parasitological outcome of infection

An oral infection model with Taenia solium whole proglottids was used to study host-parasite relationships and the mechanisms underlying resistance to infection in pigs. In addition, an attempt was made to link the parasitological findings to serological data. Groups of six piglets aged 1, 3 and 5 months were infected and slaughtered 3 months p.i. Circulating antibody and antigen levels were monitored weekly. At autopsy total cyst counts were performed. Although the detailed carcass dissection at necropsy revealed a high variation in the number of cysts, the trend was that the number of viable cysts decreased with the age at which the animals were infected. The kinetics of the antigen levels throughout the course of the infection differed markedly between the three age groups of the experimental infection model. In the younger animals, a fast increase in titres of circulating antigen was observed in most animals, reaching a plateau as early as 2 weeks p.i. Besides its faster increase, antigen levels in pigs infected at younger ages also reached higher levels than in older animals and were associated with weaker antibody responses. Results also demonstrated that a relationship exists between the number of cysts and the titre of circulating antigen. This is promising in view of the development of an assay to quantify the progress of an active T. solium infection and would be a useful tool in epidemiological studies to assess the infection burden and the risk of transmission of the disease. The use of specific antibody-detection assays combined with circulating antigen detection could improve our understanding of this relationship.     

Geographic Correlation between Tapeworm Carriers and Heavily Infected Cysticercotic Pigs

Background

Neurocysticercosis is a leading cause of preventable epilepsy in the developing world. Sustainable community-based interventions are urgently needed to control transmission of the causative parasite, Taenia solium. We examined the geospatial relationship between live pigs with visible cysticercotic cysts on their tongues and humans with adult intestinal tapeworm infection (taeniasis) in a rural village in northern Peru. The objective was to determine whether tongue-positive pigs could indicate high-risk geographic foci for taeniasis to guide targeted screening efforts. This approach could offer significant benefit compared to mass intervention.

Methods

We recorded geographic coordinates of all village houses, collected stool samples from all consenting villagers, and collected blood and examined tongues of all village pigs. Stool samples were processed by enzyme-linked immunosorbent assay (ELISA) for presence of Taenia sp. coproantigens indicative of active taeniasis; serum was processed by enzyme-linked immunoelectrotransfer blot for antibodies against T. solium cysticercosis (EITB LLGP) and T. solium taeniasis (EITB rES33).

Findings

Of 548 pigs, 256 (46.7%) were positive for antibodies against cysticercosis on EITB LLGP. Of 402 fecal samples, 6 (1.5%) were positive for the presence of Taenia sp. coproantigens. The proportion of coproantigen-positive individuals differed significantly between residents living within 100-meters of a tongue-positive pig (4/79, 5.1%) and residents living >100 meters from a tongue-positive pig (2/323, 0.6%) (p = 0.02). The prevalence of taeniasis was >8 times higher among residents living within 100 meters of a tongue-positive pig compared to residents living outside this range (adjusted PR 8.1, 95% CI 1.4–47.0).

Conclusions

Tongue-positive pigs in endemic communities can indicate geospatial foci in which the risk for taeniasis is increased. Targeted screening or presumptive treatment for taeniasis within these high-risk foci may be an effective and practical control intervention for rural endemic areas.     

Population genetic structure of Taenia solium from Madagascar and Mexico: implications for clinical profile diversity and immunological technology

Taenia solium is a cestode parasitic of humans and pigs that strongly impacts on public health in developing countries. Its larvae (cysticercus) lodge in the brain, causing neurocysticercosis, and in other tissues, like skeletal muscle and subcutaneous space, causing extraneuronal cysticercosis. Prevalences of these two clinical manifestations vary greatly among continents. Also, neurocysticercosis may be clinically heterogeneous, ranging from asymptomatic forms to severely incapacitating and even fatal presentation. Further, vaccine design and diagnosis technology have met with difficulties in sensitivity, specificity and reproducibility. Parasite diversity underlying clinical heterogeneity and technological difficulties is little explored. Here, T. solium genetic population structure and diversity was studied by way of random amplified polymorphic DNA in individual cysticerci collected from pigs in Madagascar and two regions in Mexico. The amplification profiles of T. solium were also compared with those of the murine cysticercus Taenia crassiceps (ORF strain). We show significant genetic differentiation between Madagascar and Mexico and between regions in Mexico, but less so between cysticerci from different localities in Mexico and none between cysticerci from different tissues from the same pig. We also found restricted genetic variability within populations and gene flow was estimated to be low between populations. Thus, genetic differentiation of T. solium suggests that different evolutionary paths have been taken and provides support for its involvement in the differential tissue distribution of cysticerci and varying degrees of severity of the disease. It may also explain difficulties in the development of vaccines and tools for immunodiagnosis.     

Protein and antigen diversity in the vesicular fluid of Taenia solium cysticerci dissected from naturally infected pigs

Cysticercosis caused by Taenia solium is a health threat for humans and pigs living in developing countries, for which there is neither a flawless immunodiagnostic test nor a totally effective vaccine. Suspecting of individual diversity of hosts and parasites as possible sources of the variations of the parasite loads among cysticercotic animals and of the limited success of such immunological applications as well as, we explored and measured both in nine cases of naturally acquired porcine cysticercosis. For this purpose, 2-Dimensional IgG immunoblots were performed by reacting the sera of each cysticercotic pig with the antigens contained in the vesicular fluid (VF) of their own cysticerci. We found an unexpectedly large diversity among the proteins and antigens contained in each of the nine VFs. Also diverse were the serum IgG antibody responses of the nine pigs, as none of their 2D- immunoblot images exhibited the same number of spots and resembled each other in only 6.3% to 65.3% of their features. So large an individual immunological diversity of the cysticercal antigens and of the infected pigs′ IgG antibody response should be taken into account in the design of immunological tools for diagnosis and prevention of cysticercosis and should also be considered as a possibly significant source of diversity in Taenia solium′s infectiveness and pathogenicity.     

Portrait of human tapeworms

The tapeworms of the genus Taenia that infect human beings are T. solium, T. saginata and T. saginata asiatica. Taenia solium and T. saginata exhibit unequivocal features that characterize them; in contrast, only recent DNA studies, morphological characteristics, and epidemiological and sanitary aspects indicate that T. saginata asiatica is a subspecies of T. saginata. These 3 tapeworms occur in humans in their adult stage, and the intermediate hosts are pigs for T. solium and T. saginata asiatica and cows for T. saginata. Their identification is crucial considering the migratory increase from Asia to the Western Hemisphere and the fact that these tapeworms coexist in the same environment in Asia; furthermore, it is estimated that movement in both directions across the United States-Mexico border exceeds 200 million persons per yr, and thus, opportunities for acquiring and transporting T. solium infections are multiplied. It is not easy to distinguish among these tapeworms; therefore, a comparative diagram of the 3 parasites is shown in this article, which will facilitate their identification. All morphological features, some of which allow for identification, are clear and can be easily distinguished among the 3 tapeworms.     

Taeniasis-cysticercosis in Southern Ecuador: assessment of infection status using multiple laboratory diagnostic tools

Taenia solium-taeniasis and cysticercosis were studied in the human and porcine populations of a rural community in the Southern Ecuadorian Andes. From the 1059 inhabitants, 800 serum samples and 958 stool samples could be collected. In addition, 646 from the estimated 1148 pigs were tongue inspected. Circulating antigen was detected by enzyme linked immunosorbent assay (Ag-ELISA) in 2.25% of the human population, whereas intestinal taeniasis was detected in 1.46% by the formalin-ether technique. Following treatment and recovery of tapeworm fragments these were all identified as T. solium. Porcine cysticercosis was diagnosed in 3.56% of the pigs by tongue inspection. In addition, enzyme linked immunoelectrotransfer blot (EITB) was performed on a subset group of 100 humans to confirm the results of the Ag-ELISA. One hundred serum samples from pigs were also analysed by EITB. It appeared that 43 and 74% of humans and pigs had antibodies against T. solium cysticerci, respectively. It is concluded that contrary to the high exposure of the human population to T. solium that is suggested by EITB, the number of active cysticercosis cases, diagnosed by Ag-ELISA, was low, which may indicate endemic stability. The further use of complementary diagnostic methods for a better understanding of the epidemiology of T. solium is suggested.     

Progesterone induces mucosal immunity in a rodent model of human taeniosis by Taenia solium

More than one quarter of human world's population is exposed to intestinal helminth parasites. The Taenia solium tapeworm carrier is the main risk factor in the transmission of both human neurocysticercosis and porcine cysticercosis. Sex steroids play an important role during T. solium infection, particularly progesterone has been proposed as a key immunomodulatory hormone involved in susceptibility to human taeniosis in woman and cysticercosis in pregnant pigs. Thus, we evaluated the effect of progesterone administration upon the experimental taeniosis in golden hamsters (Mesocricetus auratus). Intact female adult hamsters were randomly divided into 3 groups: progesterone-subcutaneously treated; olive oil-treated as the vehicle group; and untreated controls. Animals were treated every other day during 4 weeks. After 2 weeks of treatment, all hamsters were orally infected with 4 viable T. solium cysticerci. After 2 weeks post infection, progesterone-treated hamsters showed reduction in adult worm recovery by 80%, compared to both vehicle-treated and non-manipulated infected animals. In contrast to control and vehicle groups, progesterone treatment diminished tapeworm length by 75% and increased proliferation rate of leukocytes from spleen and mesenteric lymph nodes of infected hamsters by 5-fold. The latter exhibited high expression levels of IL-4, IL-6 and TNF-α at the duodenal mucosa, accompanied with polymorphonuclear leukocytes infiltration. These results support that progesterone protects hamsters from the T. solium adult tapeworm establishment by improving the intestinal mucosal immunity, suggesting a potential use of analogues of this hormone as novel inductors of the gut immune response against intestinal helminth infections and probably other bowel-related disorders.