Arthropods: Vectors of Disease Agents | Laboratory Medicine | Oxford Academic
An insect that transmits a disease is known as a vector, and the disease is referred to as a vector-borne disease. Insects can act as mechanical. This includes the biology of human-arthropod interactions, as well as ecological considerations. Thus vector transmitted parasites exhibit. Numerous diseases are transmitted by arthropod vectors, and for many of those a workshop with experts in parasite immunology, vector biology, and .. () Relationship between exposure to vector bites and antibody.
Vector saliva proteins that can be produced by recombinant expression methods have a variety of potential applications: Saliva components that function to skew immune responses either to a Th1 or Th2 phenotype may be useful as immunomodulators, for example, in the treatment of autoimmunity, or as vaccine adjuvants.
Several saliva proteins exhibit immunosuppressive activity, such as Sialostatin L2, which suppresses inflammatory responses and could be used for the treatment of inflammatory diseases [ 14 — 16 ].
Salivary glands of sand flies are the source of several anti-inflammatory molecules, such as LJM from saliva of members of the genus Lutzomyia [ 17 ], or nucleosides from the saliva of Phlebotomus, which impair dendritic cell functions [ 18 ]. Such molecules may find applications in the treatment of arthritis and other inflammatory diseases. Similarly, clinical applications can be envisioned for the many vasodilators, anticoagulants, cytokine modulators, histamine-binding proteins, complement inhibitors, or Ig-binding proteins found in the saliva of blood-feeding arthropods.
A specific example cited at the workshop was the treatment of pulmonary arterial hypertension with inhibitors of tissue factor such as Ixolaris Table 2 from ticks [ 1920 ]. This particular molecule has also shown potential as a tumor therapeutic agent and for treating macular degeneration and arthritis.
The potential for using vector saliva factors to combat autoimmune disease or as immunosuppressive agents after organ transplantation should also be considered and explored. What are the potential disadvantages of using saliva protein-based therapeutic agents? Unlike most small molecules, such foreign proteins will eventually trigger the induction of neutralizing antibodies, which will limit the duration of their use in an individual patient.
This may be circumvented by taking advantage of the broad variety of evolutionarily and structurally unrelated saliva proteins from different vectors, which have the same or similar biological functions. This approach would mimic the strategy of blood-feeding ticks, which are capable of using multiple gene-loci-encoding saliva proteins with overlapping functions, but which are immunologically not cross-reactive.
Therefore, despite the extended exposure of the host to tick saliva proteins, no neutralizing antibodies are induced. Field studies suggest that antibody responses against saliva proteins triggered by mosquito bites are short-lived [ 21 ], but it is not known yet whether this phenomenon is related to the nature of these proteins or to the small amounts delivered during a blood meal.
However, both approaches have significant limitations. Insecticides can be quite effective in eliminating a vector species temporarily and locally, but this approach is expensive. Long-term application of pesticides harms other species e. Bed nets protect against blood-feeding by vectors during peak times of transmission only when properly used and maintained.
Environmental modifications such as the draining of swamps are not feasible everywhere and are extremely costly, in addition to having potentially devastating effects on the environment. Finally, repellants only work as long as they are used properly i. Similarly, pathogen-directed therapeutic and preventative measures have numerous limitations.
Drugs targeting the pathogen eventually and inevitably result in the selection of drug-resistant pathogen strains. They are expensive particularly for developing countriesand frequently have undesirable side effects. Vaccines are the most attractive of all strategies, based on a cost-benefit calculation and the potential to protect against infection for extended periods of time. However, vaccines against vector-borne diseases have been largely unsuccessful so far due to insufficient immunogenicity and efficacy.
Furthermore, immune responses against many pathogen-derived antigens are unexpectedly short-lived. Other reasons for failure in field trials include an insufficient understanding of the targeted antigen.
Arthropod Vectors and Disease Transmission: Translational Aspects
For example, AMA-1 was thought to be an essential protein for the invasion of host cells by apicomplexan parasites such as Plasmodium or Toxoplasma [ 23 ], and became the focus of intense vaccine research. However, subsequent studies demonstrated that the antigen is dispensable for host cell invasion.
The sheer complexity of host-pathogen interactions, including manipulation of the host immune response, represents a formidable, though not insurmountable, challenge to design effective vaccination strategies. A valuable lesson learned from trials with the RTS.
S malaria vaccine has been that the efficacy of a vaccine against a vector-borne disease could be dramatically improved by simply changing the vaccination regimen [ 24 ]. Workshop participants discussed an alternative approach to control vector-borne pathogens, one focusing on a stage of the transmission cycle which has received little attention until recently—the time a pathogen spends inside the vector.
A major obstacle in developing such strategies is the highly limited understanding of the arthropod immune system. A recommended solution was to enhance integration of research on the immune system of vectors and Drosophila, with the latter being significantly more advanced.
What approaches could be used to make vectors pathogen-resistant?
Two strategies were discussed: First, it is possible to engineer vectors that constitutively over-express immune defense genes. Unfortunately, the constitutive expression of such genes results in a variety of issues that affect the health and survival of such animals in the field.
Any negative impact on those parameters, even if very minor, will prevent the modified vectors from replacing the wild type population and potentially doom the success of an expensive release of these organisms. Inevitably, this requirement will raise safety concerns, since the modified population could no longer be controlled after release, which raises the bar for safety studies and increases regulatory scrutiny. This approach has already been explored in field trials.
Replacement microbiota may represent unmodified microbial species that normally do not colonize a particular vector species, or genetically engineered symbiotic bacteria [ 26 ]. Various distinct mechanisms can mediate the inability of the vector to transmit pathogens: The first two phenomena are not restricted to arthropods, but have also been observed in vertebrates, including humans.
The potential for blocking disease transmission by altering the vector microbiome has received considerable attention in recent years, following the high-profile releases of vectors carrying modified microbiota; specifically, Aedes aegypti mosquitos infected with a mosquito-adapted Wolbachia strain obtained from Drosophila have been successfully released in Australia and other countries to control dengue transmission.
This strategy successfully interferes with the transmission of Plasmodium [ 29 ] as well as other vector-borne pathogens. Data from large-scale releases indicate that the approach appears to be safe and does not appear to have unintended negative side effects. Since Wolbachia is a ubiquitous microorganism, no new organism is being introduced into the environment by this strategy.
The latter approach is particularly useful for microbiota, which are not or only poorly transmitted horizontally, or vertically. The bait has to be cheap and designed for a particular vector species e. Alternatively, lab-generated paratransgenic colonies of vectors are released with the objective of eventually pushing out the naturally-occurring populations. The latter approach, while technically more attractive, faces significant hurdles in part because the necessary regulatory framework does not yet exist, and because of public resistance when the released vector species is perceived to be a genetically modified organism.
However, there are likely many more useful microbial species that simply have not yet been explored. The analysis of novel microbiota that prevent the pathogen colonization of vector species may also accelerate the identification of novel therapeutic agents, such as an antifungal cyclic dehydropeptide lactone isolated from Aeromonas [ 30 ].
This approach to identify novel therapeutics against infectious diseases may be more attractive than the currently used screening of existing libraries of chemical compounds for several reasons.
First, compounds produced by bacteria with antimicrobial activity have been evolutionarily selected and optimized and, second, a highly relevant and relatively inexpensive in vivo screening system is already available in the form of the vector animal [ 3132 ].
Numerous non-scientific aspects need to be considered and addressed before advancing a promising scientific discovery, such as those discussed above, into the pathway for product development. Most of these translational considerations are pragmatic ones and require a fundamentally different mindset than that found in basic research, which often seeks to explore and pursue new ideas.
By contrast, business development is driven by cycles of planning and risk assessment designed to anticipate known problems that are often encountered by product developers.
There are a few basic guidelines that may be helpful to those seeking to go beyond the bench and into the world of translational development. For example, for a vector saliva-based product, the considerations may include the following: Is the target population humans or an animal host which serves as a reservoir for the pathogen e.
Is the salivary antigen highly variable between vector species from different geography areas? Is it enough to include one protein in the vaccine or should multiple antigens be targeted to increase efficacy and overcome potential variability? What vaccine adjuvant is required to obtain an effective immune response, and has that adjuvant previously been used in humans?
Although potentially essential for obtaining adequate immunogenicity, a human vaccine that includes both a novel antigen i. The latter two significantly complicate deployment and delivery. Second, it is crucial to identify a suitable customer or a collection of stakeholders for the novel product, since the end-users inhabitants of endemic areas in developing countries, for most of the innovations discussed here may not be able to afford even reasonably priced products.
Third, a major consideration influencing product feasibility is the regulatory path that will be required. In some cases adequate precedent exists, based on similar products and their intended uses. In the case of saliva-based vaccines, challenges include the fact that there are no licensed human vaccines yet that are based on vector saliva, although a veterinary vaccine against tick-borne pathogens TickGARD has been on the market for many years.
Although the initial production of a diagram requires a long-term study of the parasite in any region, once the conditions for establishment and optimal development have been described, then extrapolations may be made to other regions for which only the climate data are available. Thus Gordon was able to use his data for H. Levine reviewed and extended the use of bioclimatographs to define and explain the distribution and seasonal incidence of a variety of gastrointestinal parasites of sheep and cattle.
Being based on mean temperature and rainfall data, bioclimatographs are usually only partially successful in predicting parasite outbreaks in any specific year. Similarly, bioclimatographs are seldom derived from laboratory determinations of a parasite's development constraints, because the climate conditions experienced by the parasite larvae in the soil are often different from those measured by the local weather station.
However, bioclimatographs remain useful tools for determining whether a parasite will establish in a region. They may prove invaluable in determining whether long-term climatic changes will permit specific parasites of domestic livestock to establish in regions where they are not at present a problem. Effect of Temperature on Transmission Stages of Microparasites Our focus so far on parasitic helminths reflects the available literature.
Vector (epidemiology) - Wikipedia
Data on the effects of temperature, humidity, and ultraviolet light on the survival and infectivity of viral and bacterial transmission stages have been hard to locate, possibly because work with this material is beset with technical difficulties.
There are, however, data suggesting that the development time of microparasite infections depends on ambient temperature, and there is evidence that the infectivity of some vector-transmitted pathogens is determined by the temperature at which their insect hosts are raised Ford Temperature may also indirectly affect transmission rates by altering the behavior of insect vectors. The disease is of particular importance to conservation in Africa as its presence may exclude humans and their domestic livestock from areas where wild animals act as a reservoir of the disease MolyneuxRogers and Randolph The pathogen may be classified as a microparasite; it is transmitted by an insect vector, the tsetse fly Glossina spp.
E Randolph have made an extensive study of the meteorological conditions that determine the distribution of three species of tsetse flies, Glossina morsitans, G.
Their study is complemented by two models of the dynamics of the different Trypanosoma species, one by Rogers and one by P. Milligan and R D. The former derives expressions for Ro and HT that provide some useful general insights into the processes that are most important in determining the conditions that allow the pathogen to establish; the latter develops a more specific analytical model for trypanosomiasis based on detailed parameter estimates from a study of Trypanosoma vivax in Tanzania.
Rogers's analysis of the bioclimatic tolerances of tsetse flies may be used to determine how predicted patterns of climate change in tropical Africa might affect the distribution of tsetse flies and trypanosomiasis.
Using data from several long-term studies of two subspecies of tsetse flies in Nigeria Glossina morsitans submorstans and Zambia G. Those analyses allow Rogers to identify an environmental optimum for each subspecies of G. These data can be used to compare the present distribution of G. Because the bioclimatic data correlate better with the presence of G.
Keeping that in mind, the analysis suggests that G. From a conservation perspective it remains important to determine to what extent trypanosomiasis is at present maintaining areas as refuges for wild animals by excluding humans and their livestock MolyneuxRogers and Randolph If a change of climate reduces tsetse levels, then pressure for the exploitation of the areas would increase with their subsequent loss as a wildlife refuge.
The diversity of such a community and the abundance of its constituent parasite species are intimately linked not only to the density of the host population but also to the presence of other host species that act as reservoirs for other parasite species. Communities with One Host and Many Parasite Species It is possible to extend the basic one-host, one-parasite models to examine the dynamics of more complex communities fig.
Preliminary analysis of models for such communities suggests that parasite species diversity is a direct function of host density and that the relative abundance of each parasite species is determined more by the parasite's life-history attributes that determine its transmission success than by interactions with other parasite species Dobson This suggests that changes in host density due to changes in meteorological conditions will be crucial in determining the diversity of the community of parasites supported by the hosts.
Increases in the density of some hosts will allow them to support a more diverse parasite fauna, while decreases in the density of other hosts will reduce the diversity of their parasite community. A study comparing the effects of artificial heating on the parasite fauna of an aquatic snail presents some corroborative evidence in support of this model.
Holmes a,b studied a population of Physa gyrina and its parasites and commensals in Lake Wabamun in Alberta, Canada. A section of the lake was used for cooling by a power station and consequently was warmer than the rest of the lake and relatively free of ice in winter.Brood Parasites
The effects on the population of snails were pronounced when both density and population structure are compared for heated and control sites, with population density often several orders of magnitude higher in the heated areas fig. That, and the continual presence of the vertebrate definitive hosts in the parasites life cycle, allowed a considerable increase in both the prevalence and diversity of the parasite community living in the snail population fig.
The increased water temperature also had a detrimental effect on the two species of commensal chaetogasters that live in the mantle of the snails. Laboratory experiments showed that these commensals live as predators, attacking and ingesting the infective stages of parasites that try to infect their snail host Sankurathi and Holmes b.
When the temperature rises, the chaetogasters abandon the snail and die, leading to further increases in the rates of parasitism of the snail hosts. Communities with Two Hosts and Many Parasite Species A more complex pattern emerges if we consider the community structure of parasites in two host species that share parasites. When parasites are able to use more than one species as a definitive host, their ability to establish in any one host species depends on the density of all the potential host species present in an area Because different host species may have different susceptibilities to the parasite and different parasite species may reproduce at different rates in different host species, the density of different host species will be crucial to the composition of the parasite assemblage Dobson Variations in the population density of different host species may thus lead to variations in the parasite burdens of other host species; in some cases this may allow pathogenic parasites to establish in populations of hosts that would otherwise be too small to sustain them.
Climate changes could lead to changes in the composition of host communities, which will lead to changes in the structure of the parasite community that the hosts support and the possible introduction of parasites not previously present in the host population.
Where members of the parasite community are important in mediating competition between hosts, this may lead to further changes in the structure of the host community and the possible extinction of particularly susceptible hosts. Although developmental rates in vertebrate hosts may be comparatively unaffected by changes in environmental temperature, the available evidence suggests that the free-living stages of parasites and those that live in invertebrate poikilothermic hosts are susceptible to prevailing meteorological conditions.
Gillett suggests that many vector-transmitted diseases are limited in their range because the development time of the parasite exceeds the average life expectancy of the insect vector. But increases in environmental temperature are likely to speed up development for those stages in the parasite life cycle, so long-term increases in temperature are likely to lead to increases in the ranges of many diseases transmitted by insects, such as malaria and flariasis.
Up until the mids parasitologists believed that temperature and moisture were the dominant meteorological factors determining disease outbreaks. Curiously, this area of parasitology has been relatively neglected for the last ten to fifteen years. In part, that may be because anthelmintic drugs have been developed that can be readily administered to livestock.
It may also be because models for parasites now emphasize the previously neglected nonlinear components of parasite dynamics Anderson and MayMay and Anderson Finally, it may also reflect the emergence of molecular immunology and the search for vaccines for parasites of domestic livestock. However, parasites are now showing serious levels of resistance to many anthelmintic drugs Anderson and Wallerand the development of vaccines is progressing more slowly than was originally anticipated.
If long-term climatic changes lead to the introduction of parasites into new areas at a time when our ability to control them is rapidly diminishing, many types of domestic livestock will face major disease problems. In some cases this will lead to the abandonment of present pasture lands, which may then be set aside for nature reserves. In other regions an increasingly hungry human population will exert pressure to utilize present reserves as grazing areas.
It seems unlikely that the net result of this exchange will favor wildlife. A considerable body of literature is already available that deals with the climatic responses of a variety of parasites KatesLevineWilson et al. We now also have much better models for examining the dynamics of parasites at all stages of their life cycles Anderson and May; May and Anderson Although there are problems of scale associated with extrapolating between the physiological processes of parasites measured under controlled laboratory conditions and the coarser predictions available for longer-term climate change, it should be possible to merge these various sources of information to produce a quantitative synthesis of the way global climate change may affect the distribution of many parasites.
It thus seems likely that global warming will give new prominence to an area of parasitology that had fallen into relative neglect. The examples given above are mainly from well-studied species in little danger of extinction. Assessment of the potential effects of global warming on the parasites of endangered species can really only be undertaken by extrapolation from these examples and the models used to explain the more general features of parasite-host population dynamics.
A number of possible scenarios are likely to arise as host populations respond to long-term climate changes.
Consider first an endangered species whose population density has declined to such low levels that it is present only in a single nature reserve. Under these conditions it seems likely that a further decline in population size due to global warming will reduce the effects of the parasites already present in that population.
Vectors of Protozoan Parasites
However, the immigration of new host species into the area, as a response to climate change, may lead to the introduction of novel pathogens.
If the endangered host has had no previous contact with these parasites, they may fail to establish, if the host is sufficiently novel, or they may establish and produce significant levels of mortality.
Under these conditions, increases in the density of the immigrant hosts will lead to increases in the rates of parasite transmission. Where endangered species are tolerant to increases in temperature and humidity, they are still likely to face increased assault by parasites whose transmission efficiency improves with increases in temperature and humidity e.
Furthermore, those host populations that increase as temperatures rise are likely to suffer an increase in parasite prevalence and diversity. If the population sizes of host species decline because of climatic changes, their rarer species of parasites and mutualists may become extinct. These species have their own intrinsic value, and they often perform a valuable function, such as the commensal chaetogasters living in the snail mantles discussed above. The absence of a parasite may be as important as its presence; some species of hosts may grow to become pests in the absence of pathogens that are now regulating their numbers.
Parasites and disease will do well on a warming earth. They are, by definition, organisms that colonize and exploit.
Those species of parasite that are already common will be able to spread and perhaps colonize new susceptible hosts that may have no prior genetic resistance to them. Parasite species that are rare and have more specialized requirements may be driven to extinction. In general, these effects are likely to be worse in the temperate zone, where parasites from the tropics can colonize new hosts, than in the tropics, where parasites will have to adapt or evolve.
Rare parasites that are adapted to extreme temperature, however, may become common; changes in the ranges and sizes of some host populations may allow some hitherto unimportant pathogens to become more widespread. Long term studies on the population biology of Diplostomum scheuringi in a thermally altered reservoir. Population biology of infectious diseases: Helminth infections of humans: Mathematical models, population dynamics and control.
Resistance in Nematodes to Anthelmintic Drugs. Arrested larval development in cattle nematodes. A long-term study on various aspects of the population biology of Ornithodiplostomum ptychocheilus in a South Carolina cooling reservoir.
The population dynamics of competition between parasites. The population biology of parasite-induced changes in host behavior.
Models for multi-species parasite-host communities. New York and London: An analysis of the relationship between stress and parasitism. The influence of environmental temperature upon transmission of the cercariae of Echinostoma liei Digenea: Direct and indirect influences of temperature on the transmission of parasites from insects to man.
The epidemiology of parasitic diseases, with special reference to studies with nematode parasites of sheep. The transmission of human bilharziasis in Sierra Leone, with an account of the life cycle of the schstosomes concerned, S. Ecological aspects of helminth transmission in domesticated animals. Weather, climate and the bionomics of ruminant nematode larvae. How many species are there on earth? The population biology of infectious diseases: A model for tsetse-transmitted animal trypanosomiasis.