Acquired immune heterogeneity and its sources in human helminth infection

Similarities in the immunobiology of different parasitic worm infections indicate that co-evolution of humans and helminths has shaped a common anti-helminth immune response. However, recent in vitro and immuno-epidemiological studies highlight fundamental differences and plasticity within host-helminth interactions. The 'trade-off' between immunity and immunopathology inherent in host immune responses occurs on a background of genetic polymorphism, variable exposure patterns and infection history. For the parasite, variation in life-cycle and antigen expression can influence the effector responses directed against them. This is particularly apparent when comparing gastrointestinal and tissue-dwelling helminths. Furthermore, insights into the impact of anti-helminthic treatment and co-infection on acquired immunity suggest that immune heterogeneity arises not from hosts and parasites in isolation, but also from the environment in which immune responses develop. Large-scale differences observed in the epidemiology of human helminthiases are a product of complex host-parasite-environment interactions which, given potential for exposure to parasite antigens in utero, can arise even before a parasite interacts with its human host. This review summarizes key differences identified in human acquired immune responses to nematode and trematode infections of public health importance and explores the factors contributing to these variations.     

Different patterns of intestinal helminth infection among young workers in urban and rural areas of Alexandria Governorate, Egypt.

The process of urbanisation taking place in most developing countries is creating favourable conditions for an increase in prevalence of infections, especially with intestinal parasites, in the marginal areas of the towns. The present study was implemented in 1996 to assess the varying prevalence and intensity of infection among young workers in urban and rural areas of the same Governorate (Alexandria, Egypt). The sample comprised 408 male subjects, 8 to 19 years of age, in various occupations: 308 from urban areas, 67 from an industrialised village close to the desert, and 33 from a rural village. A quantitative diagnosis of intestinal helminth infections was made using the Kato-Katz technique, with a double reading of each slide. The results showed a higher prevalence (> 50%) and intensity of infection (indirectly measured as number of eggs per gram of faeces) than in previous studies. Furthermore, a higher prevalence and intensity of infection with Ascaris lumbricoides and Trichuris trichiura was detected in urban districts, as compared to rural areas. This difference was statistically significant. High crowding index, latrine shared with other families and no piped water inside the household, were more common in urban areas as compared with rural settlements and also associated with a higher intensity of infection by soil-transmitted helminths. The trend toward urbanisation seems to have caused deterioration of living conditions and sanitation standards in some areas of Alexandria city, with the most vulnerable people experiencing an increase in intestinal parasitic infections.     

Population ecology of intestinal helminth infections in human communities

The distribution of worm burdens in human populations is a major determinant of both the dynamics of transmission and the level of community morbidity. The distribution exhibits convexity with host age, which appears to correlate with exposure in the young age-classes but not in adults, and may be evidence for the development of an acquired immune response. The distribution between individuals is typically overdispersed. Individuals are predisposed to high (or low) intensity of infection and to a correspondingly high (or low) rate of acquisition of infection. A major epidemiological question is whether this reflects individual differences in environmental exposure or susceptibility. Environmental studies that have observed clustering of intense infection in particular households are supportive of either mechanism. Individual host behaviours that predispose to infection have an overdispersed distribution and may alone, or as compounding factors, generate the observed distribution of infection intensity. Factors such as host nutrition and physiology may modify host immune-responsiveness and hence susceptibility. Preliminary evidence suggests correlates between infection intensity and HLA class II antigens, and tentatively implies a genetic factor in susceptibility. These findings suggest that further understanding of the relative importance of environmental factors and resistance to the acquisition of intense infection is dependent upon a multidisciplinary approach to epidemiological field study.     

Airborne fungal spores in urban and rural environments in Poland

The concentrations of airborne fungal spores were measured during 2001–2002 in two sites in Poland—one in the city and the other in the countryside. The sites differed in habitat characteristics, such as urbanisation level, vegetation and microclimate. The aim of the study was to determine if, and in which way, land use type would affect spore occurrence. The volumetric method was used, and ten easily identifiable spore types were sampled and anyalysed: Alternaria, Botrytis, Cladosporium, Epiccocum, Ganoderma, Pithomyces, Polythrincium, Stemphylium, Torula and Drechslera. The season of spore occurrence was determined using the 90% method. The fungal spores studied were very frequent in the air (in most instances at a frequency higher than 50%). The most common spores were those of Cladosporium, with a frequency range of 83.1–90.5%. In both years the proportion of Cladosporium spores was statistically significantly higher in the city. In both 2001 and 2002 the total seasonal sum of all the spores was higher in the countryside than in the city as was the Seasonal Fungal Index (SFI) values and average concentrations of Botrytis, Ganoderma and Torula. These latter three genera are usually represented as pathogens of plants. The mean spore concentrations of most taxa were significantly higher in the rural environment. Correlation coefficients between daily concentrations at both sites for most of the taxa studied were significant, but with lower correlation values between variables. Such results indicate that the values from the sites are weakly interdependent. The study confirms that land use type may very likely have an impact on the course of spore occurrence, the mean daily concentrations of spores as well as SFI values.     

Sandflies (Diptera: Psychodidae) in rural and urban environments in an endemic area of cutaneous leishmaniasis in southern Brazil

The high proportion of cases of cutaneous leishmaniasis reported amongst residents in the city of Bandeirantes, in the state of Paraná, Brazil, led the authors to investigate the phlebotomine fauna in both urban and rural environments. The sandflies were captured with automatic light traps from 07:00 pm-07:00 am fortnightly in 11 urban peridomiciles from April 2008-March 2009 and monthly in three ecotopes within four rural localities from April 2009-March 2010. In one of these latter localities, sandfly capture was conducted with white/black Shannon traps during each of three seasons: spring, summer and fall. A total of 5,729 sandflies of 17 species were captured. Nyssomyia neivai (46.7%) and Nyssomyia whitmani (35.3%) were the predominant species. In this study, 3,865 specimens were captured with automatic light traps: 22 (0.083 sandflies/trap) in the urban areas and 3,843 (26.69 sandflies/trap) in the rural areas. Ny. neivai was predominant in urban (68.2%) and rural (42.8%) areas. A total of 1,864 specimens were captured with the white/black Shannon traps and Ny. neivai (54.5%) and Ny. whitmani (31.4%) were the predominant species captured. The small numbers of sandflies captured in the urban areas suggest that the transmission of Leishmania has occurred in the rural area due to Ny. neivai and Ny. whitmani as the probable vectors.     

In vitro parasite antigen-induced antibody responses in human helminth infections

Helminth parasites characteristically induce vigorous antibody responses in human infections, but the immunoregulatory mechanisms determining the level of these responses are not at all understood. To investigate these mechanisms, peripheral blood mononuclear cells were obtained from 10 patients with parasitic helminth infections (three with schistosomiasis, three with onchocerciasis, and four with loiasis), along with six normal controls. These cells were then cultured in vitro and the capacity of the cells to respond to a specific parasite antigenic stimulus was examined by measuring the amount of parasite-specific antibody produced. Parasite antigen alone, without exogenous mitogen, induced an IgG anti-parasite antibody response in vitro. Optimal responses were obtained at extremely low antigen concentrations--concentrations at which little if any polyclonal immunoglobulin production occurred. Additionally, the in vitro induction of parasite-specific antibody was antigen dose-dependent, requiring much lower antigen concentrations than those necessary to induce lymphocyte blastogenesis. Antibody production was shown to require the cooperative interaction of B and T cells. These studies demonstrate that in vitro responses to antigens from naturally acquired parasitic infections, like those in individuals postimmunization, can be utilized to dissect the cellular and humoral factors that regulate antibody production to naturally acquired human pathogens.     

A small-scale survey on the status of intestinal parasite infections in rural villages in Nepal

The status of intestinal parasite infections was investigated in two rural villages (Chitrasar, Jerona) in Chitwan District, Nepal in 1999. Stool examination was performed with a total of 300 specimens from schoolchildren by formalin-ether sedimentation technique. The prevalence rate of intestinal parasite infections in the surveyed areas was 44.0%. The prevalence rate in Jerona was slightly higher than that in Chitrasar. The prevalence rate of intestinal parasite infections in female was slightly higher than that in male without statistically significant difference. Entamoeba coli was the most commonly found protozoan parasite (21.0%) followed by Giardia lamblia (13.7%) and others (5.3%). Hookworm was the most prevalent intestinal helminth (13.0%) followed by Trichuris trichiura (3.0%) and others (5.0%). Forty-three specimens (14.3%) showed mixed infections. It is necessary to implement large-scale treatment with anthelminthics, health education and sanitary improvement for intestinal parasite control in the surveyed areas.     

On the solution of mathematical models of herd immunity in human helminth infections

The general solution of the mathematical model of herd immunity to human helminth infections recently proposed by Anderson and May [3] is obtained. The numerical solution of a more accurate biological model is indistinguishable from the corresponding exact solution of a more tractable mathematical model. Computer simulations of some particular cases of this model support the notion that both ecological and immunological factors determine the observed convex patterns of age-prevalence and age-intensity curves of human helminth infections.This work was made thanks to the advise and support of Dr. Robert M. May while the author was Postdoctoral Fellow at Princeton University     

Parallel regulation of IL-4 and IL-5 in human helminth infections.

To investigate the relationship between cytokine production and the increased levels of serum IgE and peripheral eosinophilia commonly accompanying human helminth infections, we studied the ability of PBMC of normal (N1) (n = 18) and eosinophilic individuals with helminth infections (H1) (n = 9) to produce IL-3, IL-4, IL-5, granulocyte-macrophage-CSF, and IFN-gamma in vitro after stimulation with PMA (50 ng/ml) and ionomycin (1 microgram/ml). The two groups differed in both the levels of serum IgE and eosinophilia. For mitogen-induced production of granulocyte-macrophage-CSF and IFN-gamma, there was no difference in cytokine production between the two groups. In marked contrast, supernatants from PBMC of infected individuals had significantly higher levels of IL-4 (mean = 213 pg/ml for N1 and 944 pg/ml for H1, p less than 0.02), IL-5 (mean = 180 pg/ml for N1 and 1118 pg/ml for HL, p less than 0.001), and IL-3 (mean = 13900 pg/ml for N1, 28029 pg/ml for H1, p less than 0.05). In addition, helminth-infected patients had approximately 5-fold greater numbers of T cells capable of producing IL-5 and 2.5-fold greater frequency of IL-4-secreting cells than did normal individuals; GM-CSF- and IFN-gamma-producing T cell numbers were not significantly different in the two groups. IL-3-producing cell frequencies could not be evaluated by this method. There was a direct correlation between IL-4 production and IL-5 production at the level of both protein production and frequency of T cells capable of producing these cytokines. These data indicate that individuals with reactive eosinophilia and elevated serum IgE have an expanded population of lymphocytes producing IL-4 and IL-5 and the association of the two suggests that the regulation of IL-4 and IL-5 may be linked.     

Social mixing patterns in rural and urban areas of southern China

A dense population, global connectivity and frequent human–animal interaction give southern China an important role in the spread and emergence of infectious disease. However, patterns of person-to-person contact relevant to the spread of directly transmitted infections such as influenza remain poorly quantified in the region. We conducted a household-based survey of travel and contact patterns among urban and rural populations of Guangdong, China. We measured the character and distance from home of social encounters made by 1821 individuals. Most individuals reported 5–10 h of contact with around 10 individuals each day; however, both distributions have long tails. The distribution of distance from home at which contacts were made is similar: most were within a kilometre of the participant''s home, while some occurred further than 500 km away. Compared with younger individuals, older individuals made fewer contacts which tended to be closer to home. There was strong assortativity in age-based contact rates. We found no difference between the total number or duration of contacts between urban and rural participants, but urban participants tended to make contacts closer to home. These results can improve mathematical models of infectious disease emergence, spread and control in southern China and throughout the region.     

Monospecific helminth and arthropod infections in an urban population of brown rats from Doha, Qatar

Parasitic infections were studied for the first time in an urban population of brown rats (Rattus norvegicus) from Doha. Only one species of helminth was found, the cestode Hymenolepis diminuta, and one ectoparasite, the flea Xenopsylla astia, from a sample size of 136 rats (52 males and 84 females). The prevalence of H. diminuta was 17.6%, increasing with host age but not in relation to host sex nor season of capture. Host age was a key factor in influencing abundance of infection, although there was a significant three-way interaction with season and host sex arising through heavy infections in juvenile male rats in the summer. The prevalence of X. astia was 45.6%, although both prevalence and abundance of infestations were season and host age dependent. In the winter prevalence and abundance were similar in both host age and sex groups, but in the summer both parameters of infestation were markedly higher among juveniles compared with adults. We found evidence for some association between these two species: H. diminuta was more prevalent among rats with fleas than among those without, although this association was season-, and independently sex- and age-dependent. There were no quantitative interactions and reasons for this are discussed in relation to the foraging and breeding behaviour of the brown rat in Qatar.     

Contrasting effects of acute and chronic gastro-intestinal helminth infections on a heterologous immune response in a transgenic adoptive transfer model

We have previously found that co-immunisation with ovalbumin (OVA) and the body fluid of the helminth Ascaris suum inhibited an OVA-specific delayed type hypersensitivity (DTH) response by reducing OVA-specific CD4+ T lymphocyte proliferation via an IL-4 independent mechanism. In the present study, we determined whether parasite infections themselves could induce similar changes to peripheral immunisation by examining the modulation of OVA-specific immune responses during acute and chronic helminth infections. Surprisingly, an acute infection with Trichinella spiralis, but not a chronic infection with Heligmosomoides polygyrus, inhibited the OVA-specific DTH reaction. Correspondingly, the T helper 1 (Th1) OVA-specific response was decreased in mice infected with T. spiralis, but not with H. polygyrus. Inhibition of the Th1 response may be a result of a shift in the Th1/Th2 balance as although both H. polygyrus and T. spiralis infected mice induced a Th2 OVA-specific response, that exhibited by T. spiralis was more potent. Furthermore, although IL-10 secretion upon OVA restimulation was similarly increased by both infections, production of this immunoregulatory cytokine may play a role in the suppression of immune responses observed with T. spiralis infection depending on the context of its release. Interestingly, analysis of the OVA-specific T lymphocyte division by carboxyfluorescein diacetate succinimidyl ester (CFSE) staining revealed that gastro-intestinal infection with the acute helminth T. spiralis, but not with chronic H. polygyrus, inhibited the systemic immune response by significantly inhibiting the antigen-specific T cell proliferation during the primary response, a mechanism similar to that observed when A. suum parasite extracts were directly mixed with the OVA during immunisation in our previous studies.     

Immunology and immunopathology of helminth infections.

A short review is presented describing the novel immunological concepts related to vaccine development. Trichinella is used as an example.     

Non-native species in urban environments: patterns,processes, impacts and challenges

Although urban ecosystems are hotspots for biological invasions, the field of invasion science has given scant attention to invasion dynamics and the challenges facing managers in towns and cities. This paper provides an introduction to the growing challenges of understanding and managing invasive species in urban systems, and the context for a special issue of Biological Invasions, comprising 17 papers, that arose from a workshop on “Non-native species in urban environments: patterns, processes, impacts and challenges” held in Stellenbosch, South Africa, in November 2016. Contributions explore the following key questions: Are patterns and processes of urban invasions different from invasions in other contexts? Why is it important to manage non-native species in urban ecosystems? What are the special management needs in an urban context? How can we bridge the gaps between science, management, and policy with regards to biological invasions in urban ecosystems? The papers in this special issue show that patterns and processes of urban invasions differ in many ways from invasions in other contexts, and that managing invasive species in cities poses unique and increasingly complex challenges. Progress in urban invasion science requires further work to: (1) address key limitations that hinder our understanding of invasion dynamics in cities; (2) clarify whether fundamental concepts in the field of invasion science are appropriate for urban ecosystems; (3) integrate insights from invasion science with those from the burgeoning literature on the “Anthropocene biosphere”, novel ecosystems, social–ecological systems, human–wildlife conflicts, urban green infrastructure, urban planning and design, and ecosystem services/disservices.     

The mycorrhizal status and colonization of 26 tree species growing in urban and rural environments

Urban environments are highly disturbed and fragmented ecosystems that commonly have lower mycorrhizal fungal species richness and diversity compared to rural or natural ecosystems. In this study, we assessed whether the mycorrhizal status and colonization of trees are influenced by the overall environment (rural vs. urban) they are growing in. Soil cores were collected from the rhizosphere of trees growing in urban and rural environments around southern Ontario. Roots were extracted from the soil cores to determine whether the trees were colonized by arbuscular mycorrhizal fungi, ectomycorrhizal fungi, or both, and to quantify the percent colonization of each type of mycorrhizal fungi. All 26 tree species were colonized by arbuscular mycorrhizal fungi, and seven tree species were dually colonized by arbuscular mycorrhizal and ectomycorrhizal fungi. Overall, arbuscular mycorrhizal and ectomycorrhizal fungal colonization was significantly (p < 0.001) lower in trees growing in urban compared to rural environments. It is not clear what ‘urban’ factors are responsible for the reduction in mycorrhizal fungal colonization; more research is needed to determine whether inoculating urban trees with mycorrhizal fungi would increase colonization levels and growth of the trees.     

Serological evidence of hantavirus infection in rural and urban regions in the state of Amazonas, Brazil

Hantavirus disease is caused by the hantavirus, which is an RNA virus belonging to the family Bunyaviridae. Hantavirus disease is an anthropozoonotic infection transmitted through the inhalation of aerosols from the excreta of hantavirus-infected rodents. In the county of Itacoatiara in the state of Amazonas (AM), Brazil, the first human cases of hantavirus pulmonary and cardiovascular syndrome were described in July 2004. These first cases were followed by two fatal cases, one in the municipality of Maués in 2005 and another in Itacoatiara in 2007. In this study, we investigated the antibody levels to hantavirus in a population of 1,731 individuals from four different counties of AM. Sera were tested by IgG/IgM- enzyme-linked immune-sorbent assay using a recombinant nucleocapsid protein of the Araraquara hantavirus as an antigen. Ten sera were IgG positive to hantavirus (0.6%). Among the positive sera, 0.8% (1/122), 0.4% (1/256), 0.2% (1/556) and 0.9% (7/797) were from Atalaia do Norte, Careiro Castanho, Itacoatiara and Lábrea, respectively. None of the sera in this survey were IgM-positive. Because these counties are distributed in different areas of AM, we can assume that infected individuals are found throughout the entire state, which suggests that hantavirus disease could be a local emerging health problem.