What are house dust mites
House dust mites (HDMs) are arachnoids and have existed for longer than insects. HDMs are present in every household, living within dust, textile, carpets, beds and upholster furniture (Colloff, 2009) and are considered to be the most common cause of asthma and allergic symptoms worldwide. Due to their very small size and translucent bodies they are barely visible to the eye.
HDMs belong to the Pyroglyphidae family. The most familiar and common known house dust mite species are:
- Dermatophagoides pteronyssinus (European house dust mite)
- Dermatophagoides farinae (American house dust mite)
- Euroglyphus maynei (Mayne’s house dust mite)
These three species are commonly found in homes of humans. In homes, these mites are most prevalent in high-use areas, where shed skin scales collect and serve as their food. Dust contains three fundamental macromolecules which are derived from human and animal dander. These three fundamental macromolecules are chitin, cellulose and keratin. The diet of the HDMs contain these macromolecules. Success of the HDMs is depending on their diet. House dust mites do also feed on mould, spores of micro-organism, yeast, fibres, pollen, fungal mycelia and bacteria (Calderon et al., 2015).
Humans get exposed the most to HDMs allergens and other indoor allergens. In response to the allergen humans can become sensitized. As a result of activities like dusting, bed making, vacuuming or any other activities HDM faeces and other small allergen carrying particles become temporarily airborne. Free-floating allergens can be inhaled by humans. Humans who are atopic can react on this exposure. Atopic human will make IgE antibodies, which bind to the active immune cells which will stimulate mediators, such as histamine, which causes a local inflammation. Allergic responses can result in eczema, conjunctivitis, asthma symptoms and rhinitis (Colloff, 2009).
Geography of house dust mites
The distribution of different sorts of HDMs vary between countries, but also on a global level differences are found (Colloff, 2009). Ambient relative humidity is the key factor that determines the prevalence and geographical distribution of these mites. This is because water vapor in humid air is the main source of water for their survival. They survive and thrive well at relative humidities above 50% but desiccate and die at relative humidities below this. In humid climates, HDM populations are larger in comparison with dry climates (Colloff, 2009). Therefore, dust mites and the allergies they cause are a significant problem only for people who live in humid, tropical, and temperate geographical areas. D. farinae and/or D. pteronyssinus are prevalent in homes in the United States, Europe, South America, and Asia. Most homes are co inhabited by multiple species. However, the most prevalent species varies both between homes in a geographical area and between geographical areas
- D. farinae is found worldwide but it is more abundant in North America than in Europe. It seems to prefer more continental (drier areas) and barren climates than D. pteronyssinus does. The prevalence of allergic reactions to the mite species D. farinae is shown to be extremely high in North America and Japan. However, large numbers of this species have also been found in parts of Italy and Turkey, and in the Far East outside Japan.
- D. pteronyssinus, though it has a worldwide distribution, seems to be more abundant in Europe than in America. It prefers more humid climates than D. farinae does. However, in South America, D. pteronyssinus is prevalent in homes, whereas D. farinae is not.
HDM populations fluctuate throughout the season. In general, the size of the HDM populations within the north of Europe are the largest at the end of the summer and autumn. HDM population size declines during winter when relative humidity is low in homes. In autumn, a larger population correlates with increased production of allergens and therefore increased frequency of disease symptoms.
The life-cycle of house dust mites
HDMs are poikilothermic and cannot regulate their own body temperature. Therefore their duration of life may vary, depending on the temperature of their habitat. The life cycle of HDMs comprise of five different stages: egg, 6-legged larva, protonymph, tritonymph and the final stage is an adult individual. The development from egg to adult, at an optimal laboratory condition, takes 3-4 weeks. Adult HDMs live for approximately 4-6 weeks, depending on the temperature and humidity of the habitat. Female HDMs can produce 40-80 eggs in their life time (Colloff, 2009).
In each stage, there is an active period followed by another, shorter, quiescent stage, before a new stadium emerges from the old exoskeleton. The quiescent period protonymph in dust mites can be long lasting as it is resistant to drying and allows mites to survive long dry periods (several months). This stage remains attached to the substrate and cannot be removed by vacuuming. The life cycle of the mites is directly dependent on the temperature. Microhabitats where mites are found in homes are not uniform in temperature and relative humidity and the temperature fluctuates within a microhabitat. Thus, their development at low-temperature (on the floor) is lower as compared to their development in warmer conditions (mattresses, or sofas).
HDM populations fluctuate throughout the season. In general, the size of the HDM populations within the north of Europe are the largest at the end of the summer and autumn. HDM population size declines in the winter. In autumn, a larger population correlates with increased production of allergens and therefore increased frequency of disease symptoms. In humid climates, HDM populations are larger in comparison with dry climates (Colloff, 2009).
Why do house dust mites produce allergens?
Within HDMs allergens contain a biological functional protein. The paired allergen working is incidental; a bad consequence of the abundant presence of HDM populations within houses. The association of Der p 1 (Group 1 allergens) with the intestinal tract and faecal pellets of HDMs indicate a digestive function. The amino acid sequence of Der p 1 confirms the digestive function (Colloff, 2009). Some other HDM faeces contain other functional enzymes, like amylase. These allergen enzymes were found in faecal pellets extract. Because of this, these enzymes are linked to digestion. Group 2 allergens, like Der p 2, are not present in high concentration in the faecal pellets, therefore they might have another origin (Colloff, 2009).
How do house dust mites produce allergens?
During digestion, cells peel off from the wall of the midgut, together with the swallowed food particles they travel through the intestinal lumen, where food particles are digested. Products of the digestion are absorbed through the intestinal epithelium towards the haemolymph. When cells are at the last part of the intestine, cells are dehydrated and go into apoptose. The faecal pallets are packed in a peritrophic membrane. The peritrophic membrane protects the last part of the intestine for abrasion. The process of digestion results in a high enzyme concentration within the faecal pellets. The faecal pellets have a diameter of approximately 20-50 μm and accumulate within textile where the HDMs live. Proteins are immunogenic (also called allergens) (Colloff, 2009). An allergen is a (non) protein or substance which can induce an allergic response (Galli et al., 2008). Therefore the allergens can trigger an immune reaction when humans are exposed to them. Der p 1 is the first HDM allergen which was discovered and purified, this protein is predominantly present in the faecal pellets. Currently, 23 HDM allergens are known (Colloff, 2009).
Group 1 allergens
Group 1 allergens have a molecular weight of 25 kDa, as monomer, neutral slightly acidic, and polymorph proteins. They belong to the cysteine group of proteolytic enzymes which also contain the mammal enzymes cathepsin B and H, and plant enzymes actinidin and papain. At least 70% of allergic individuals recognize group 1 allergens. These allergens are identified in a lot of HDMs, some of these HDM species are D. pteronyssinus, D. farinae, D. microceras and E. maynei. The allergens can be conceded through the whole body and the faecal pellets. Thereby, allergens get synthesized by cells in the gastrointestinal tract (Colloff, 2009).
Amino acid sequences of group 1 allergens of the pyroglyphids (Dermatophagoides) contains a signal protein of 18/19 residues, followed by a pro-protein of 79/80 residues, the mature protein contains 222-223 amino acids. Other cysteine proteases contain in between transient pre- and pro-forms. The enzyme is produced as inactive and becomes active by cleavage of the pro-protein by autocatalysis (Colloff, 2009).
Mature Der p 1 is a spherical molecule which is folded into two domains, these domains are separated by a surface chasm. The left domain (contains N-terminus and residues: 21-116) is prevailingly an alpha-helix. The right domain (contains C-terminus and residues 117-223) is prevailingly a beta sheet (Colloff, 2009). The final active form of Der p 1 dimerises at a pH of 8, but is a monomer at a pH of 1.5. Authors think that the concentration of Der p 1 within faecal pellets is highly sufficient to exist as a dimer under neutral conditions. Dimerized Der p 1 is more allergenic than the monomeric form. Interestingly, the midgut of the HDM where digestive hydrolysis takes place is slightly acid. Therefore Der p 1 exists as a monomer. In the hindgut were faecal pellets accumulate the environment is neutral to slightly basic. Therefore dimers of Der p 1 are formed in the hind gut. It is known that HDMs have only one Der p 1 gene (Colloff, 2009).
Group 2 allergens
Group 2 allergens are neutral to slightly basic and polymorph. The majority of allergic individuals recognize the 14kDa non-glycosylated allergens. Group 2 allergens are likely to play a role in lipid binding. The exact function remains unknown, it is not likely that group 2 allergens are enzymes. Group 2 allergens are identified in a large number of HDMs compared to other allergens. In D. pteronyssinus, D. farinae, D. siboney, Psoreoptes ovis, Turophagus putrescentiae group 2 allergens are identified (Colloff, 2009).
Complete amino acid sequence of group 2 allergens indicates that allergens get sensitized as pre-proteins with signal proteins of 16-17 residues. Mature protein consists of 125-129 residues. Group 2 allergens are highly conserved. Homolog sequences are not concentrated around the active site and cysteine residues like in group 1 allergens. Group 2 allergens are evenly distributed over the whole molecule. Differences reflect on the phylogenetic relationship of HDM species (Colloff, 2009).
Crystal structure shows a cylindrical molecule that exists of 10 beta strands and a short alpha-helix. It looks like an immunoglobulin like folding which exist of two anti-parallel beta sheets, one exist out of three beta strands, the other of five. The strands overlap each other with an angle of 30° and form a beta-sandwich. Between the different sheets is a central pit where hydrophobic and aromatic residues are lined up. This structure is comparable with other structures found in lipid-binding proteins. Therefore, the structure suggests that group 2 allergens have a lipid-binding function (Colloff, 2009).
Diseases associated with HDMs
Over the years, HDMs were regularly linked to different diseases. Most of those diseases have an allergic foundation. The different diseases human suffer from HDMs are, among other things, allergic rhinitis, keratoconjunctivitis, otitis media, allergic asthma, atopic eczema, anaphylaxis, nettle-rash, and gastrointestinal allergy (Colloff, 2009).
Allergic rhinitis hits 10-30% of the population. The majority (40%) of the population is sensitized to one or more proteins of the environment. In 2012, 9% of all children in the USA were diagnosed with allergic rhinitis the past year. This accounts for 7.5% of the adults within the USA (American Academy of Allergy, Allergy Statistics, 2016). World Health Organization states that 400 million people suffer from allergic rhinitis (WAO, 2011). Most common symptoms of allergic rhinitis are constipated, itchy and or running nose and sneezing (Anafylaxis, 2015). Different investigations show that prevalence rates are increasing over the years, worldwide. Allergic rhinitis is an allergic disease which contains inflammation of the nasal mucosa due to IgE-mediated inflammation. Allergic rhinitis is also a precursor of allergic asthma. Otitis media, sleep disorders, sinusitis, conjunctivitis and sinusitis are some of the co-existing illnesses in line with allergic rhinitis. Controlling the disease includes pharmacotherapy, environmental control measures, patient education and in some cases specific immunotherapy. In Europe the prevalence is approximately 4-32%. The prevalence in Latin America is shown in table 2 below of an ISAAC study (Pawankar et al., 2011).
Table 2. Prevalence of Allergic Rhinitis in Latin America. Light yellow = minimal %, dark yellow = maximal %. % of the total population (Pawankar et al., 2011).
Allergic asthma is a life-long chronic inflammatory disorder within the airways. At severe disease structural changes and remodelling of the airway wall takes place (figure 6). Allergic asthma is a common disease among children and adults (Pawankar et al., 2011). Symptoms of asthma include wheezing, shortness of breath, coughing (especially at night), less energy and chest tightness, pain or pressure (Longfonds, 2015). Asthma is associated with airflow obstruction and hyper responsiveness which is most of the time reversible, sometimes medication is needed to reverse the effects. Corticosteroids which need to be inhaled are currently the most effective treatment. The highest identifiable susceptible factor to develop asthma is atopy. Atopy is a genetic marker to develop IgE mediated sensitivity to allergens. Quality of life can get worse for patients with asthma. Asthma is a serious public health problem in the whole world, especially in middle and low income countries. The problem with asthma is that there is no curing therapy yet on the market and there is no worldwide control (Pawankar et al., 2011).
Asthma Statistics, the prevalence of asthma varies globally. Approximately 300 million people have asthma (WAO, 2011). Estimated, 250.000 people die related to asthma each year, these deaths might be unnecessary (American Academy of Allergy, Asthma Statistics, 2016).
HDM allergen concentrations exposure linked to sensitization
There is some, but not consistent, evidence that levels of exposure are linked to the risk to get sensitized by HDMs within childhood. This is not valid for other types of allergens. The levels of exposure associated with sensitization may vary geographically. Exposure to HDM allergens varies enormously around the world. Where HDM allergen levels are high, atopic sensitization will be more abundantly present. The prevalence of asthma and atopic sensitization are in general not consistently linked to dust HDM exposure in infants and children. Research, where only allergen prevention was used to prevent children from developing asthma, gave disappointing results. Levels of allergen exposure are associated with asthma within atopic adults who are sensitized to HDMs (Colloff, 2009).
Population densities of HDMs
The spread and quantity of HDMs is dependent on their favourable microclimate where they can live and reproduce. HDM population densities influence allergen levels, human exposure and, with a certain reach, prevention of severity of disease. Microclimates indoor are influenced, at least for a certain part in the year, due to the outside climate, also within good isolated houses. The influences of macroclimate on HDM populations appear, on regional and global scales, to overwrite the indoor microclimate. Still, some HDM species do not differ around the world. The most common HDMs and their allergens like D. pteronyssinus and D. farinae are common globally. In houses were the outdoor climate is beneficial for the largest part of the year (like moist and high temperatures) all houses contain HDMs (Colloff, 2009). Humidity is an important factor for the prevalence of HDMs, inside and outside the house. High concentrations of HDMs are found within damped houses. The most favourite place to stay of the HDMs is the bed. The bed is relative humid and this increases rapidly when an individual goes to sleep (Calderon et al., 2015).
Easy HDM control methods
Some HDM control methods are: impermeable mattress covers, ventilate mattress daily by taken off sheets and open window and door, monthly wash bed in hot water, tea tree-oil can be added (minimalizes bacterial growth) when cold wash, remove carpet from bedroom, vacuum weekly all carpets and upholstered furniture with a HEPA filter, or use a steam cleaner. When living in a climate where the summer is hot and sunny and the winters cold and dry: put outside upholstered furniture, mattresses, sheets, carpets and textile for 12 hours, after this vacuum-clean (Colloff, 2009).
Why are HDMs still a problem?
It is difficult to control HDMs and their allergens. Many methods, mentioned above, seem not effective and do not work to reduce the allergen exposure (Colloff, 2009). A review of P. C. Gøtzsche et al. (2008), covered 54 trials which included control measures to reduce the exposure to HDMs and their allergens. Looking at the 54 trials there was no beneficial effect demonstrated by using any of the used control measures. The numbers of the control group and number of the patients who had less symptoms after the investigation where similar. The asthma symptom scores and medication usage where similar for both the control and the treated group. There was no difference measured in severity of asthma between both groups. Therefore, physical and chemical methods are both found to be ineffective (Gøtzsche et al., 2008).
F.M.D. Fu-Sheng Wu et al (2012). investigated daily vacuuming of mattresses, thereby decreasing numbers of HDM allergens, β-glucan and endotoxin. Daily vacuuming of mattresses has shown to reduce exposure to bio-contaminants. Combining vacuuming with other methods, like encasing the mattress, it probably will reduce the exposure to allergens even more. The problem of vacuum mattresses is that non-sensitized human need to do the vacuuming. Due to airborne particles, sensitized human are not able to enter the room for at least half an hour after cleaning (Fu-Sheng Wu et al., 2012).
Regarding a meta-analysis of W.D. Arroyave et al. (2014), impermeable HDM covers did not primary prevent allergic diseases and or tertiary prevent respiratory symptoms of diagnosed allergic patients. Although nasal symptoms scored slightly better in the tertiary prevention experiments, it was not significant. The trend in nasal symptoms was not sufficient when lower-quality studies were removed. Even if the quantity of HDMs in mattresses was decreased significantly, there was no evidence that health improved in atopic human. To conclude, impermeable HDM covers are not effective in reducing symptoms or preventing the development of allergic diseases (Arroyave et al., 2014).
The determination of reduction of allergen exposure remains difficult, a reduction might work for one patient, but may be too frail for another. Another problem is that HDMs are everywhere, and every human carries them (Colloff, 2009). HDMs and humans are indissolubly linked due to the fact that HDMs feed on human skin. The human skin indirectly influences the habitat of the HDMs (Calderon et al., 2015). The positive side is that more methods are developed to measure personal allergen exposure. There is an increase in knowledge of behaviour and dynamic processes of allergens indoor (Colloff, 2009).
Supplier of HDM allergens
Our main focus is the production of house dust mites (HDMs) and their allergens. Citeq was born based on a passion for mites and the research for how mites influence our daily lives. Our founders and leading scientists have pharmaceutical, biological and biochemical backgrounds. With over 25 years of experience and an extensive knowledge about mites Citeq is more than just a supplier of allergen source material. We strive for an academic collaboration with our customers in order to achieve the best possible results in research, diagnostics and immunotherapy.
We deliver house dust mites source material in different forms such as whole culture, purified form (Der p 1/ Der p 2/ Der f 1/ Der f 2) and extracts. Please click on the type of house dust mite that you are interested in for more information and the available forms.