The zoonotic transmission of Giardia and Cryptosporidium

The molecular characterisation of Giardia and Cryptosporidium has given rise to a more epidemiological meaningful and robust taxonomy. Importantly, molecular tools are now available for 'typing' isolates of the parasites directly from clinical and environmental samples. As a consequence, information on zoonotic potential has been obtained although the frequency of zoonotic transmission is still poorly understood. Analysis of outbreaks and case-control studies, especially when coupled with genotyping data, is slowly providing information on the public health significance of zoonotic transmission. Such studies support the hypothesis that Cryptosporidium hominis is spread only between humans but that the major reservoir for Cryptosporidium parvum is domestic livestock, predominantly cattle, and that direct contact with infected cattle is a major transmission pathway along with indirect transmission through drinking water. The situation is less clearcut for Giardia duodenalis but the evidence does not, in general, support zoonotic transmission as a major risk for human infections. However, for both parasites there is a need for molecular epidemiological studies to be undertaken in well-defined foci of transmission in order to fully determine the frequency and importance of zoonotic transmission.     

Enterocytozoon bieneusi in human and animals, focus on laboratory identification and molecular epidemiology

Human microsporidian infections have emerged following the onset of the AIDS pandemic. Microsporidia are unicellular eukaryotic parasites that form spores. They are an exceptionally diverse group of parasites that infect a wide range of eukaryotic cells in numerous invertebrate and vertebrate hosts. Of the 14 species newly described as pathogens in human, Enterocytozoon bieneusi, which causes gastrointestinal diseases, is the most common agent of human infections. In the past fifteen years, E. bieneusi was also identified in environmental sources, especially in surface water, as well as in wild, domestic and farm animals. These findings raised concerns for waterborne, foodborne and zoonotic transmission. Molecular analyses of the 243-bp internal Transcribed spacer-(ITS) of the rRNA gene have revealed a considerable genetic variation within E. bieneusi isolates of human and animal origins, supporting the potential for zoonotic transmission. The focus of this revue is to present and discuss recent advances in diagnosis and zoonotic potential of E. bieneusi infections.     

Zoonotic cryptosporidiosis

The widespread usages of molecular epidemiological tools have improved the understanding of cryptosporidiosis transmission. Much attention on zoonotic cryptosporidiosis is centered on Cryptosporidium parvum. Results of genotype surveys indicate that calves are the only major reservoir for C. parvum infections in humans. The widespread presence of human-adapted C. parvum, especially in developing countries, is revealed by recent subtyping and multilocus typing studies, which have also demonstrated the anthroponotic transmission of C. parvum subtypes shared by humans and cattle. Developing and industrialized countries differ significantly in disease burdens caused by zoonotic species and in the source of these parasites, with the former having far fewer human infections caused by C. parvum and little zoonotic transmission of this species. Exclusive anthroponotic transmission of seemingly zoonotic C. parvum subtypes was seen in Mid-Eastern countries. Other zoonotic Cryptosporidium spp. are also responsible for substantial numbers of human infections in developing countries, many of which are probably transmitted by anthroponotic pathways. The lower pathogenicity of some zoonotic species in some populations supports the occurrence of different clinical spectra of Cryptosporidium spp. in humans. The use of a new generation of molecular diagnostic tools is likely to produce a more complete picture of zoonotic cryptosporidiosis.     

Molecular characterisation of species and genotypes of Cryptosporidium and Giardia and assessment of zoonotic transmission

The molecular characterisation of species and genotypes of Cryptosporidium and Giardia is essential for accurately identifying organisms and assessing zoonotic transmission. Results of recent molecular epidemiological studies strongly suggest that zoonotic transmission plays an important role in cryptosporidiosis epidemiology. In such cases the most prevalent zoonotic species is Cryptosporidium parvum. Genotyping and subtyping data suggest that zoonotic transmission is not as prevalent in the epidemiology of giardiasis. Molecular characterisation of Cryptosporidium and Giardia is a relatively recent application that is evolving as new genes are found that increase the accuracy of identification while discovering a greater diversity of species and yet unnamed taxa within these two important genera. As molecular data accumulate, our understanding of the role of zoonotic transmission in epidemiology and clinical manifestations is becoming clearer.     

Tracing the future of epidemics: Coincident niche distribution of host animals and disease incidence revealed climate-correlated risk shifts of main zoonotic diseases in China

Climate has critical roles in the origin, pathogenesis and transmission of infectious zoonotic diseases. However, large-scale epidemiologic trend and specific response pattern of zoonotic diseases under future climate scenarios are poorly understood. Here, we projected the distribution shifts of transmission risks of main zoonotic diseases under climate change in China. First, we shaped the global habitat distribution of main host animals for three representative zoonotic diseases (2, 6, and 12 hosts for dengue, hemorrhagic fever, and plague, respectively) with 253,049 occurrence records using maximum entropy (Maxent) modeling. Meanwhile, we predicted the risk distribution of the above three diseases with 197,098 disease incidence records from 2004 to 2017 in China using an integrated Maxent modeling approach. The comparative analysis showed that there exist highly coincident niche distributions between habitat distribution of hosts and risk distribution of diseases, indicating that the integrated Maxent modeling is accurate and effective for predicting the potential risk of zoonotic diseases. On this basis, we further projected the current and future transmission risks of 11 main zoonotic diseases under four representative concentration pathways (RCPs) (RCP2.6, RCP4.5, RCP6.0, and RCP8.5) in 2050 and 2070 in China using the above integrated Maxent modeling with 1,001,416 disease incidence records. We found that Central China, Southeast China, and South China are concentrated regions with high transmission risks for main zoonotic diseases. More specifically, zoonotic diseases had diverse shift patterns of transmission risks including increase, decrease, and unstable. Further correlation analysis indicated that these patterns of shifts were highly correlated with global warming and precipitation increase. Our results revealed how specific zoonotic diseases respond in a changing climate, thereby calling for effective administration and prevention strategies. Furthermore, these results will shed light on guiding future epidemiologic prediction of emerging infectious diseases under global climate change.     

Giardiasis as a re-emerging infectious disease and its zoonotic potential

The reasons for considering giardiasis as a re-emerging infectious disease are presented, with emphasis on Giardia infections in child care centres, livestock and pets, and the role of zoonotic transmission. However, the aetiology and control of giardiasis is complicated by the genetic and phenotypic variability of Giardia species infective to mammals. Of particular significance has been the uncertainty about host specificity and the question of zoonotic transmission. The recent application of molecular characterisation procedures based on PCR has made an enormous contribution to an understanding of the genetic structure of Giardia populations, and this is reviewed in the context of the zoonotic transmission and molecular epidemiology of Giardia infections.     

Effects of environmental change on emerging parasitic diseases

Ecological disturbances exert an influence on the emergence and proliferation of malaria and zoonotic parasitic diseases, including, Leishmaniasis, cryptosporidiosis, giardiasis, trypanosomiasis, schistosomiasis, filariasis, onchocerciasis, and loiasis. Each environmental change, whether occurring as a natural phenomenon or through human intervention, changes the ecological balance and context within which disease hosts or vectors and parasites breed, develop, and transmit disease. Each species occupies a particular ecological niche and vector species sub-populations are distinct behaviourally and genetically as they adapt to man-made environments. Most zoonotic parasites display three distinct life cycles: sylvatic, zoonotic, and anthroponotic. In adapting to changed environmental conditions, including reduced non-human population and increased human population, some vectors display conversion from a primarily zoophyllic to primarily anthrophyllic orientation. Deforestation and ensuing changes in landuse, human settlement, commercial development, road construction, water control systems (dams, canals, irrigation systems, reservoirs), and climate, singly, and in combination have been accompanied by global increases in morbidity and mortality from emergent parasitic disease. The replacement of forests with crop farming, ranching, and raising small animals can create supportive habitats for parasites and their host vectors. When the land use of deforested areas changes, the pattern of human settlement is altered and habitat fragmentation may provide opportunities for exchange and transmission of parasites to the heretofore uninfected humans. Construction of water control projects can lead to shifts in such vector populations as snails and mosquitoes and their parasites. Construction of roads in previously inaccessible forested areas can lead to erosion, and stagnant ponds by blocking the flow of streams when the water rises during the rainy season. The combined effects of environmentally detrimental changes in local land use and alterations in global climate disrupt the natural ecosystem and can increase the risk of transmission of parasitic diseases to the human population.     

Novel Insights into Cell Entry of Emerging Human Pathogenic Arenaviruses

Viral hemorrhagic fevers caused by emerging RNA viruses of the Arenavirus family are among the most devastating human diseases. Climate change, global trade, and increasing urbanization promote the emergence and re-emergence of these human pathogenic viruses. Emerging pathogenic arenaviruses are of zoonotic origin and reservoir-to-human transmission is crucial for spillover into human populations. Host cell attachment and entry are the first and most fundamental steps of every virus infection and represent major barriers for zoonotic transmission. During host cell invasion, viruses critically depend on cellular factors, including receptors, co-receptors, and regulatory proteins of endocytosis. An in-depth understanding of the complex interaction of a virus with cellular factors implicated in host cell entry is therefore crucial to predict the risk of zoonotic transmission, define the tissue tropism, and assess disease potential. Over the past years, investigation of the molecular and cellular mechanisms underlying host cell invasion of human pathogenic arenaviruses uncovered remarkable viral strategies and provided novel insights into viral adaptation and virus–host co-evolution that will be covered in the present review.     

Zoonotic Disease Risk and the Bushmeat Trade: Assessing Awareness Among Hunters and Traders in Sierra Leone

The bushmeat industry has been a topic of increasing importance among both conservationists and public health officials for its influence on zoonotic disease transmission and animal conservation. While the association between infectious diseases and the bushmeat trade is well established in the research community, risk perception among bushmeat hunters and traders has not been well characterized. I conducted surveys of 123 bushmeat hunters and traders in rural Sierra Leone to investigate hunting practices and awareness of zoonotic disease risk associated with the bushmeat trade. Twenty-four percent of bushmeat hunters and traders reported knowledge of disease transmission from animals to humans. Formal education did not significantly affect awareness of zoonotic disease transmission. Individuals who engaged exclusively in preparation and trading of bushmeat were more likely to accidentally cut themselves compared to those who primarily engaged in bushmeat hunting (P < 0.001). In addition, women involved in the bushmeat trade were at greater risk of exposing themselves to potential zoonotic pathogens through accidental self-cutting compared to men (P < 0.01). This study collected preliminary information on risk perception among bushmeat hunters that could guide the creation of a future public health-based education program to minimize zoonotic disease transmission risk among vulnerable communities.     

Advances in molecular epidemiology of cryptosporidiosis in dogs and cats

The use of molecular tools has led to the identification of several zoonotic Cryptosporidium spp. in dogs and cats. Among them, Cryptosporidium canis and Cryptosporidium felis are dominant species causing canine and feline cryptosporidiosis, respectively. Some Cryptosporidium parvum infections have also been identified in both groups of animals. The identification of C. canis, C. felis and C. parvum in both pets and owners suggests the possible occurrence of zoonotic transmission of Cryptosporidium spp. between humans and pets. However, few cases of such concurrent infections have been reported. Thus, the cross-species transmission of Cryptosporidium spp. between dogs or cats and humans has long been a controversial issue. Recently developed subtyping tools for C. canis and C. felis should be very useful in identification of zoonotic transmission of both Cryptosporidium spp. Data generated using these tools have confirmed the occurrence of zoonotic transmission of these two Cryptosporidium spp. between owners and their pets, but have also shown the potential presence of host-adapted subtypes. Extensive usage of these subtyping tools in epidemiological studies of human cryptosporidiosis is needed for improved understanding of the importance of zoonotic transmission of Cryptosporidium spp. from pets.     

Does Cryptosporidium parvum have a clonal population structure?

Cryptosporidiosis, the disease caused in humans by the opportunistic parasite Cryptosporidium parvum, is the result of zoonotic or anthroponotic transmission. Molecular characterization of different isolates from humans and other mammalian species has recently shown this species to be heterogeneous; this heterogeneity has been linked to the host of isolation, suggesting that the parasites causing zoonotic cryptosporidiosis and those propagated by anthroponotic transmission are genetically distinct. Here, Fatih Awad-El-Kariem provides an update on the taxonomic and epidemiological significance of these observations, and discusses evidence for and against the clonality hypothesis as a model to explain strain variation in this species.     

Bat Predation by <Emphasis Type="Italic">Cercopithecus</Emphasis> Monkeys: Implications for Zoonotic Disease Transmission

The relationship between bats and primates, which may contribute to zoonotic disease transmission, is poorly documented. We provide the first behavioral accounts of predation on bats by Cercopithecus monkeys, both of which are known to harbor zoonotic disease. We witnessed 13 bat predation events over 6.5 years in two forests in Kenya and Tanzania. Monkeys sometimes had prolonged contact with the bat carcass, consuming it entirely. All predation events occurred in forest-edge or plantation habitat. Predator–prey relations between bats and primates are little considered by disease ecologists, but may contribute to transmission of zoonotic disease, including Ebolavirus.     

Tracing the source of campylobacteriosis

Campylobacter jejuni is the leading cause of bacterial gastro-enteritis in the developed world. It is thought to infect 2–3 million people a year in the US alone, at a cost to the economy in excess of US $4 billion. C. jejuni is a widespread zoonotic pathogen that is carried by animals farmed for meat and poultry. A connection with contaminated food is recognized, but C. jejuni is also commonly found in wild animals and water sources. Phylogenetic studies have suggested that genotypes pathogenic to humans bear greatest resemblance to non-livestock isolates. Moreover, seasonal variation in campylobacteriosis bears the hallmarks of water-borne disease, and certain outbreaks have been attributed to contamination of drinking water. As a result, the relative importance of these reservoirs to human disease is controversial. We use multilocus sequence typing to genotype 1,231 cases of C. jejuni isolated from patients in Lancashire, England. By modeling the DNA sequence evolution and zoonotic transmission of C. jejuni between host species and the environment, we assign human cases probabilistically to source populations. Our novel population genetics approach reveals that the vast majority (97%) of sporadic disease can be attributed to animals farmed for meat and poultry. Chicken and cattle are the principal sources of C. jejuni pathogenic to humans, whereas wild animal and environmental sources are responsible for just 3% of disease. Our results imply that the primary transmission route is through the food chain, and suggest that incidence could be dramatically reduced by enhanced on-farm biosecurity or preventing food-borne transmission.     

Zoonotic enterohemorrhagic Escherichia coli: A One Health perspective

Escherichia coli O157 and other enterohemorrhagic E. coli (EHEC) are food- and waterborne zoonotic pathogens that cause diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome in humans but little or no discernible disease in their animal reservoirs. Like other zoonotic infections, EHEC are illustrative of the One Health concept as they embody the complex ecology of agricultural animals, wildlife, and the environment in zoonotic transmission of EHEC O157. But compared to the detailed epidemiological and clinical information available for EHEC infection in humans, there is an incomplete understanding of the ecology of EHEC infection in animals and the persistence of EHEC bacteria in the environment. Significant aspects of the microbiology, epidemiology, and host-pathogen interactions of EHEC in animals remain undefined. This review highlights the nature of EHEC infection in humans, provides a One Health perspective on what is known about EHEC in animal and environmental reservoirs, and proposes interventions targeted at pathways of transmission to optimize effective prevention and control measures.     

Cryptosporidium: Detection in water and food

Water and food are major environmental transmission routes for Cryptosporidium, but our ability to identify the spectrum of oocyst contributions in current performance-based methods is limited. Determining risks in water and foodstuffs, and the importance of zoonotic transmission, requires the use of molecular methods, which add value to performance-based morphologic methods. Multi-locus approaches increase the accuracy of identification, as many signatures detected in water originate from species/genotypes that are not infectious to humans. Method optimisation is necessary for detecting small numbers of oocysts in environmental samples consistently, and further work is required to (i) optimise IMS recovery efficiency, (ii) quality assure performance-based methods, (iii) maximise DNA extraction and purification, (iv) adopt standardised and validated loci and primers, (v) determine the species and subspecies range in samples containing mixtures, and standardising storage and transport matrices for validating genetic loci, primer sets and DNA sequences.     

A comparison of bats and rodents as reservoirs of zoonotic viruses: are bats special?

Bats are the natural reservoirs of a number of high-impact viral zoonoses. We present a quantitative analysis to address the hypothesis that bats are unique in their propensity to host zoonotic viruses based on a comparison with rodents, another important host order. We found that bats indeed host more zoonotic viruses per species than rodents, and we identified life-history and ecological factors that promote zoonotic viral richness. More zoonotic viruses are hosted by species whose distributions overlap with a greater number of other species in the same taxonomic order (sympatry). Specifically in bats, there was evidence for increased zoonotic viral richness in species with smaller litters (one young), greater longevity and more litters per year. Furthermore, our results point to a new hypothesis to explain in part why bats host more zoonotic viruses per species: the stronger effect of sympatry in bats and more viruses shared between bat species suggests that interspecific transmission is more prevalent among bats than among rodents. Although bats host more zoonotic viruses per species, the total number of zoonotic viruses identified in bats (61) was lower than in rodents (68), a result of there being approximately twice the number of rodent species as bat species. Therefore, rodents should still be a serious concern as reservoirs of emerging viruses. These findings shed light on disease emergence and perpetuation mechanisms and may help lead to a predictive framework for identifying future emerging infectious virus reservoirs.     

Rapid host switching in generalist Campylobacter strains erodes the signal for tracing human infections

Campylobacter jejuni and Campylobacter coli are the biggest causes of bacterial gastroenteritis in the developed world, with human infections typically arising from zoonotic transmission associated with infected meat. Because Campylobacter is not thought to survive well outside the gut, host-associated populations are genetically isolated to varying degrees. Therefore, the likely origin of most strains can be determined by host-associated variation in the genome. This is instructive for characterizing the source of human infection. However, some common strains, notably isolates belonging to the ST-21, ST-45 and ST-828 clonal complexes, appear to have broad host ranges, hindering source attribution. Here whole-genome sequencing has the potential to reveal fine-scale genetic structure associated with host specificity. We found that rates of zoonotic transmission among animal host species in these clonal complexes were so high that the signal of host association is all but obliterated, estimating one zoonotic transmission event every 1.6, 1.8 and 12 years in the ST-21, ST-45 and ST828 complexes, respectively. We attributed 89% of clinical cases to a chicken source, 10% to cattle and 1% to pig. Our results reveal that common strains of C. jejuni and C. coli infectious to humans are adapted to a generalist lifestyle, permitting rapid transmission between different hosts. Furthermore, they show that the weak signal of host association within these complexes presents a challenge for pinpointing the source of clinical infections, underlining the view that whole-genome sequencing, powerful though it is, cannot substitute for intensive sampling of suspected transmission reservoirs.     

Research Commentary: Association of Zoonotic Pathogens with Fresh, Estuarine, and Marine Macroaggregates

Aquatic macroaggregates (flocs ≥0.5 mm) provide an important mechanism for vertical flux of nutrients and organic matter in aquatic ecosystems, yet their role in the transport and fate of zoonotic pathogens is largely unknown. Terrestrial pathogens that enter coastal waters through contaminated freshwater runoff may be especially prone to flocculation due to fluid dynamics and electrochemical changes that occur where fresh and marine waters mix. In this study, laboratory experiments were conducted to evaluate whether zoonotic pathogens (Cryptosporidium, Giardia, Salmonella) and a virus surrogate (PP7) are associated with aquatic macroaggregates and whether pathogen aggregation is enhanced in saline waters. Targeted microorganisms showed increased association with macroaggregates in estuarine and marine waters, as compared with an ultrapure water control and natural freshwater. Enrichment factor estimations demonstrated that pathogens are 2–4 orders of magnitude more concentrated in aggregates than in the estuarine and marine water surrounding the aggregates. Pathogen incorporation into aquatic macroaggregates may influence their transmission to susceptible hosts through settling and subsequent accumulation in zones where aggregation is greatest, as well as via enhanced uptake by invertebrates that serve as prey for marine animals or as seafood for humans.     

Risk factors for human disease emergence

A comprehensive literature review identifies 1415 species of infectious organism known to be pathogenic to humans, including 217 viruses and prions, 538 bacteria and rickettsia, 307 fungi, 66 protozoa and 287 helminths. Out of these, 868 (61%) are zoonotic, that is, they can be transmitted between humans and animals, and 175 pathogenic species are associated with diseases considered to be 'emerging'. We test the hypothesis that zoonotic pathogens are more likely to be associated with emerging diseases than non-emerging ones. Out of the emerging pathogens, 132 (75%) are zoonotic, and overall, zoonotic pathogens are twice as likely to be associated with emerging diseases than non-zoonotic pathogens. However, the result varies among taxa, with protozoa and viruses particularly likely to emerge, and helminths particularly unlikely to do so, irrespective of their zoonotic status. No association between transmission route and emergence was found. This study represents the first quantitative analysis identifying risk factors for human disease emergence.     

Comparative pathogenesis of three human and zoonotic SARS-CoV strains in cynomolgus macaques

The severe acute respiratory syndrome (SARS) epidemic was characterized by increased pathogenicity in the elderly due to an early exacerbated innate host response. SARS-CoV is a zoonotic pathogen that entered the human population through an intermediate host like the palm civet. To prevent future introductions of zoonotic SARS-CoV strains and subsequent transmission into the human population, heterologous disease models are needed to test the efficacy of vaccines and therapeutics against both late human and zoonotic isolates. Here we show that both human and zoonotic SARS-CoV strains can infect cynomolgus macaques and resulted in radiological as well as histopathological changes similar to those seen in mild human cases. Viral replication was higher in animals infected with a late human phase isolate compared to a zoonotic isolate. While there were significant differences in the number of host genes differentially regulated during the host responses between the three SARS-CoV strains, the top pathways and functions were similar and only apparent early during infection with the majority of genes associated with interferon signaling pathways. This study characterizes critical disease models in the evaluation and licensure of therapeutic strategies against SARS-CoV for human use.