**3. Chiggers and dermatitis**

Currently, effective chemoprophylaxis or vaccination approaches for dealing with *O. tsutsu‐ gamushi* infection are still not available [42]. A prophylactic vaccine to scrub typhus is a public health priority because of its high incidence, high mortality, nonspecific clinical presentation, lack of sensitive diagnostic tests, and emergence of antibiotic resistance. The development of an effective and safe vaccine has to be strongly focused on T cell-mediated immunity, empirical testing of the immunogenicity of proteins encoded by conserved genes, and assessment of protection in relevant animal models that truly mimic human scrub typhus resistance [57]. Therefore, prevention of scrub typhus is based mainly on avoiding the chigger bites and the use of repellents during travel in rural areas of endemic countries [61]. Wearing protective clothing and self-examination after visiting arthropod-vector infested areas are also recom‐

Nowadays, *O. tsutsugamushi* remains as the unique agent whose transmission by chigger bites has been confirmed. Nevertheless, trombiculid mites inhabit areas where the presence of several arthropod-borne microorganisms, their vectors, and reservoirs has been demonstrated.

There are a lot of references in the old scientific literature that associate chiggers with the transmission of several pathogens, being *N. autumnalis* the most reported species. However, the majority of them correspond to secondary anecdotal information and present poor or no details [87]. In the 2000s, *Anaplasma phagocytophilum*-DNA was detected in unfed *N. autumna‐ lis* chiggers collected on vegetation in a mountainous area from the North of Spain [88]. This finding remains doubtful taking into consideration that the infection occurred in unfed larvae, so chiggers are speculated to be true carriers of the bacteria and inherited it through transo‐ varial transmission. The presence of rickettsiae was also investigated in chiggers of the same mountainous area of Spain. Amplicons compatible with infection by *Rickettsia* spp. were detected by molecular techniques in *Neotrombicula inopinata* collected over vegetation [89]. Up to date, these results remain unconfirmed. The vector competence of *N. autumnalis* chiggers for the transmission of *Borrelia burgdorferi* sensu lato (s.l.) has been also investigated. This bacterium was screened by PCR and further DNA hybridization in questing larvae collected on vegetation and feeding larvae removed from trapped micromammals in Germany [87]. Borrelial DNA was amplified in chiggers from 1 larva feeding on a white-toothed shrew (*Crocidura russula*), from a pool of 4 larvae feeding on a *Borrelia garinii*-infected laboratory mouse, and from 1 nymph that had previously fed as a larva on a *Borrelia afzelii*-positive laboratory gerbil. Therefore, the vector competence of *N. autumnalis* remains unclear. The presence of *B. burgdorferi* s.l. and *A. phagocytophilum* DNA was also been investigated by PCR and reverse line blotting in chiggers found on wild birds captured in the western Carpathian Mountains (Czech Republic) [24]. *B. garinii* and *B. valaisiana* were found in a pool of 5 chiggers from the genus *Neotrombicula* collected from a Eurasian Blackcap (*Sylvia atricapilla*). Regarding *A. phagocytophilum*, DNA was detected in none of the samples [87]. Trombiculid mites have also been associated to *Bartonella* spp. A new strain of *Bartonella* sp. was isolated from the gray squirrels *Sciurus carolinensis* in Georgia [90]. Then this bacterium was studied in ectoparasites

Thus, the vector competence of chiggers has long been investigated worldwide.

mended [86].

186 An Overview of Tropical Diseases

**2.2. Other chigger-borne infectious diseases**

"Trombiculiasis," also called "trombiculosis," "trombidiosis," "chigger dermatitis," "scrub itch," or "seasonal dermatitis" is defined as an skin allergic reaction (dermatitis) caused by the salivary secretion of biting chiggers [1,99]. In our experience, as well as it is described in the literature, trombiculiasis is a common but underreported ectoparasitosis that is probably often misdiagnosed [100]. In many cases, trombiculiasis was primarily confused with a plant allergy [29], as it was the case in our country. The better understanding of trombiculid mites' life cycle and their interaction with humans have made possible a proper knowledge of this disease.

### **3.1. Etiology and epidemiology**

Although not often reported in the literature, trombiculiasis is prevalent all over the world, except for the Arctic region [20]. However, it can be easily missed because it is normally transient and no systemic signs are present.

In nontropical areas, bites are particularly common in the late summer and early autumn, when outdoor activities are maximal and the peak of abundance of chiggers occurs [19,20,26,28,101]. Thus, trombiculiasis is also an important threat to travelers that visit infested areas being unaware of chiggers [37].

Mite islands are usually found in cleared land and scrub bush with grassy vegetation, warm soil temperatures, and high humidity. Suitable habitats also require the presence of potential hosts [31]. Trombiculids are also found in parks, gardens, lawns, and moist areas alongside lakes and streams [1]. Clusters of chiggers are usually waiting at elevated points of the groundlevel vegetation, such as the end of grass stalk or on dried tree branches, until an animal or human passes by [8] (Figure 5).

**Figure 5.** Cluster of unfed chiggers. Original contribution.

People are usually bitten during outdoor activities for recreational or professional purposes such as hunting, hiking, mushroom picking, forestry work, etc. [8,28,101]. Although the rate of people bitten is very high, apparently some persons are preferred by the chiggers, resulting in massive parasitization, while others remain unmolested even in highly infested areas [26,28].

More than 3,000 species of chiggers are known, but about 15 frequently bite humans and domestic animals causing cutaneous reactions [102] (Table 2). Species currently considered as the most frequent cause of trombiculiasis are *E. alfreddugesi* in the Americas, *N. autumnalis* in Europe, *Eutrombicula batatas*in South America, and *Eutrombicula wichmanni* in Southeast Asia, Australia, and the Pacific Islands [4,28,37,103].

*E. alfreddugesi* is the most common and widespread trombiculiasis-producing species in the New World. The larvae are present in the late summer and early autumn in temperate regions of its geographical range and throughout the year in the tropics and subtropics. It is particularly common in areas of secondary growth, along margins of swamps, and ecotones between woodlands and open fields or grasslands [1]. *E. splendens* is the second most common chigger attacking human in North America. This species is especially abundant in moist habitats such as swamps, bogs, and low-lying areas with rotting stumps and fallen trees. The seasonality is similar to *E. alfreddugesi* ones [1]. In addition, another mite causing trombiculiasis in the United States is *Eutrombicula lipovsky.* It is present in moist habitats, generally characterized by an abundance of decaying logs and stumps bordering swamps and streams [1].

Mite islands are usually found in cleared land and scrub bush with grassy vegetation, warm soil temperatures, and high humidity. Suitable habitats also require the presence of potential hosts [31]. Trombiculids are also found in parks, gardens, lawns, and moist areas alongside lakes and streams [1]. Clusters of chiggers are usually waiting at elevated points of the groundlevel vegetation, such as the end of grass stalk or on dried tree branches, until an animal or

People are usually bitten during outdoor activities for recreational or professional purposes such as hunting, hiking, mushroom picking, forestry work, etc. [8,28,101]. Although the rate of people bitten is very high, apparently some persons are preferred by the chiggers, resulting in massive parasitization, while others remain unmolested even in highly infested areas

More than 3,000 species of chiggers are known, but about 15 frequently bite humans and domestic animals causing cutaneous reactions [102] (Table 2). Species currently considered as the most frequent cause of trombiculiasis are *E. alfreddugesi* in the Americas, *N. autumnalis* in Europe, *Eutrombicula batatas*in South America, and *Eutrombicula wichmanni* in Southeast Asia,

*E. alfreddugesi* is the most common and widespread trombiculiasis-producing species in the New World. The larvae are present in the late summer and early autumn in temperate regions

human passes by [8] (Figure 5).

188 An Overview of Tropical Diseases

**Figure 5.** Cluster of unfed chiggers. Original contribution.

Australia, and the Pacific Islands [4,28,37,103].

[26,28].

*E. alfreddugesi* and *E. batatas* are the main species implicated in South-America. However, trombiculiasis attributed to *N. autumnalis* (isango) is well-known in Peru [21]. Recently, a "pest" called "Qhapa," with the same clinical features than trombiculiasis, has been associated with *E. batatas* in Bolivia [104]. In Venezuela, it is possible that a high percentage of the diagnosed scabies may actually be trombiculiasis [22]. Recently, *E. alfreddugesi* was implicated in a case of trombiculiasis in a tourist after a vacation in Brazil [20].

Seven chigger species are proven to cause trombiculiasis in Europe: *N. japonica*, *Neotrombicula zachvatkini*, *Euschoengastia xerothermobia*, *N. autumnalis*, *Kepkatrombicula desaleri*, *Blankaartia acuscutellaris*, and *Trombicula toldti* [6,29,105]. Recently, *N. inopinata* has been reported as a possible causative agent of trombiculiasis in Spain [8]. As stated above, it is generally accepted that *N. autumnalis* is the most common cause of trombiculiasis in Europe and the British Islands [1]. However, in many cases, the role of "harvest mite" has been attributed to *N. autumnalis* without enough taxonomic criteria. Therefore, other species may be causative agents of trombiculiasis, as occurred with *N. inopinata* in Spain [8] (Figure 6).

**Figure 6.** *Neotrombicula inopinata* (photo provided by Dr. Stekolnikov).

Although well known in many European regions, the scientific description of trombiculiasis cases have been only reported from Italy [36] and Spain [28]. Moreover, four different cases suspected of trombiculiasis caused by *N. autumnalis* were described in Croatia [106], and one case attributed to harvest mites was informed in the United Kingdom [107]. In Europe, trombiculiasis is associated with the late summer and early autumn [26,28,36,101]. In fact, *N. autumnalis* is known as the "European harvest mite" due to the seasonality of the disease [87]. Nevertheless, in the last years, trombiculiasis-like skin reactions have been reported in Germany not only in summer and autumn but also in early spring and in winter [31].

In Southeast Asia, Australia, and the Pacific Islands, the main involved mite is *E. wichmanni.* Nevertheless, *E. sarcina* and species of genera *Odontacarus* and *Schoengastia* are also causative agents of trombiculiasis [4]. In addition, *Neotrombicula nagayoi* was involved in human trombiculiasis in Japan [5].

A single case of trombiculiasis has been reported in Africa. *L. subquadratum* was described as a cause of severe itching and dermatitis in humans and dogs in South Africa [108].

It is generally accepted that to suffer from trombiculiasis, the antecedent of direct contact with vegetation is required. Nevertheless, it is important to remark that one of the patients reported in Guarneri *et al*., 2005 [36] was not in contact with vegetation but presented similar clinical features than the one that was hunting with the dogs. The authors speculated that trombicu‐ liasis was transmitted by direct contact with the infected dogs. The hypothesis is supported in the fact that the dogs were frequently allowed to sit on the legs of the patients, and the patient's lesions were concentrated on the abdomen and thighs. Dogs can be affected by chigger bites and suffer neurological and digestive forms that may be fatal. In our experience, massive infections are more frequents, and untreated dogs finally die. Dogs usually began with diarrhea, irritation, and ataxia. The precedent of visiting infested areas and the presence of "red points" in the dog's eyes are essential clues to guide the diagnosis [25]

Another example of disease caused by chiggers but without direct contact to vegetation is also a case of conjunctivitis induced by *N. autumnalis*, reported in a patient with no history of travelling, hill walking, gardening, or contact with vegetation [109]. There, the authors suggested mite infestation occurred by direct contact with the patient's cat. Nevertheless, there is no data about the cat in the manuscript. These cases suggested that close human contact with infected pets should be considered as an unusual route of trombiculiasis, so chigger transmission is possible without direct contact with infested soil or vegetation [36,109].

Previously, patients were rarely referred for dermatologist review unless symptoms were severe. Over the last 15 years, cases of severe trombiculiasis have increased in western Germany and in the United Kingdom [31,107]. The influence of climate and environmental variations, changes in leisure habits, and broader environmental awareness in the population have been speculated as possible explanations of this increase [26].

#### **3.2. Clinical manifestation**

Chigger bites are initially painless, and frequently the only sign of exposure is a severe itching. Then small, red bite like lesions appears on the skin [1,19]. Typical 1–2 mm diameter, pruritic, erythematous papules appear at the sites of the bites 3–24 h after exposure (Figure 7). [10,28,37,101,103].

**Figure 7.** Typical papules of trombiculiasis in a patient bitten in La Rioja, Spain. Original contribution.

case attributed to harvest mites was informed in the United Kingdom [107]. In Europe, trombiculiasis is associated with the late summer and early autumn [26,28,36,101]. In fact, *N. autumnalis* is known as the "European harvest mite" due to the seasonality of the disease [87]. Nevertheless, in the last years, trombiculiasis-like skin reactions have been reported in

In Southeast Asia, Australia, and the Pacific Islands, the main involved mite is *E. wichmanni.* Nevertheless, *E. sarcina* and species of genera *Odontacarus* and *Schoengastia* are also causative agents of trombiculiasis [4]. In addition, *Neotrombicula nagayoi* was involved in human

A single case of trombiculiasis has been reported in Africa. *L. subquadratum* was described as

It is generally accepted that to suffer from trombiculiasis, the antecedent of direct contact with vegetation is required. Nevertheless, it is important to remark that one of the patients reported in Guarneri *et al*., 2005 [36] was not in contact with vegetation but presented similar clinical features than the one that was hunting with the dogs. The authors speculated that trombicu‐ liasis was transmitted by direct contact with the infected dogs. The hypothesis is supported in the fact that the dogs were frequently allowed to sit on the legs of the patients, and the patient's lesions were concentrated on the abdomen and thighs. Dogs can be affected by chigger bites and suffer neurological and digestive forms that may be fatal. In our experience, massive infections are more frequents, and untreated dogs finally die. Dogs usually began with diarrhea, irritation, and ataxia. The precedent of visiting infested areas and the presence of

Another example of disease caused by chiggers but without direct contact to vegetation is also a case of conjunctivitis induced by *N. autumnalis*, reported in a patient with no history of travelling, hill walking, gardening, or contact with vegetation [109]. There, the authors suggested mite infestation occurred by direct contact with the patient's cat. Nevertheless, there is no data about the cat in the manuscript. These cases suggested that close human contact with infected pets should be considered as an unusual route of trombiculiasis, so chigger transmission is possible without direct contact with infested soil or vegetation [36,109].

Previously, patients were rarely referred for dermatologist review unless symptoms were severe. Over the last 15 years, cases of severe trombiculiasis have increased in western Germany and in the United Kingdom [31,107]. The influence of climate and environmental variations, changes in leisure habits, and broader environmental awareness in the population

Chigger bites are initially painless, and frequently the only sign of exposure is a severe itching. Then small, red bite like lesions appears on the skin [1,19]. Typical 1–2 mm diameter, pruritic, erythematous papules appear at the sites of the bites 3–24 h after exposure (Figure 7).

a cause of severe itching and dermatitis in humans and dogs in South Africa [108].

"red points" in the dog's eyes are essential clues to guide the diagnosis [25]

have been speculated as possible explanations of this increase [26].

Germany not only in summer and autumn but also in early spring and in winter [31].

trombiculiasis in Japan [5].

190 An Overview of Tropical Diseases

**3.2. Clinical manifestation**

[10,28,37,101,103].

The presence of papulovesicles, which may gradually progress to pustules, crusty, scabby, eczematous, and ulcerated confluent forms of skin lesions, has also been described [17,26,103]. The pruritus is very intense, especially at night in bed. Although the chigger is not present, the papules and discomfort may persist up to 2–3 weeks, but regression of localized itching is generally observed in 1 week [26]. Since trombiculid mites share habitat with hard ticks, people may result coinfested. In fact, a patient suffering from trombiculiasis and having an "erythema migrans" (related to Lyme disease) was treated in our hospital. Furthermore, during an episode of trombiculiasis, two affected people and their dog had *R. felis* infection, possibly transmitted by fleas [110].

Chiggers usually "attack" in large numbers due to the clustering phenomenon, resulting in multiple grouped bites on infested hosts [32]. Given their preference for attaching where the skin is thin or in tighter contact with clothes, the bites tend to be concentrated around the knees, antecubital fossae, and ankles, thighs, axillary region, groins and genitalia, and wrists, and in areas constricted by clothing, such as along the belt line or the elastic borders or undergarments [1,17,26,28,101].

Trombiculiasis-causing chiggers do not survive more than 1–2 days feeding on humans due to the adverse host reaction and because they are remove by scratching [1,23]. The irritant effect of chiggers' saliva seems to induce both dermal inflammatory reaction of moderate intensity and an adaptive immune response. These salivary components generally reveal relatively moderate lytic properties and weak immunological characters [111]. The type of skin inflam‐ matory response during the feeding of trombiculid larvae is determined by concomitant factors such as the site of the parasite localization, condition of the host's skin, among others [39]. Repeated exposures result in a more rapid and intense adaptive immune response [102]. Anyway, permanent or long-term human residents in an infested area increase their immunity as a result of continued bites, and some people can develop a high degree of tolerance to the antigenic substances injected by chiggers. However, the occurrence of unusual outbreaks of urticaria, increasingly severe pruritus or bulla formation, are indications of hypersensitivity to such antigenic substances [5]. It is clear that the natural hosts of trombiculids have to be sensitized with respect to parasites that may lead the development of the strong specific inflammatory response [39, 111].

#### **3.3. Diagnosis and treatment**

Diagnosis is based on the clinical manifestations, taking into consideration the history of being in contact with vegetation and the seasonality. As the etiological agent of the trombiculiasis is rarely found in the skin of the patients, these reactions are often misinterpreted and has been wrongly associated to plant allergies, flea or mosquito bites, or even scabies [26]. Cutaneous findings are nonspecific, so clinical examination would probably lead to a wrong diagnosis of a nonspecific itchy dermatitis, leading to use inadequate or needless medications. Then an accurate anamnesis is essential for making such challenging diagnosis. Chigger bites should be considered whenever any unexplained skin eruption is presented to the physician.

Chiggers are not easily seen on human's skin with the naked eye, and common magnification lenses and even dermoscopy (×10 magnifications) have some limitations. Recently, videoder‐ matoscopy (×150 magnification) has been used to diagnose trombiculiasis caused by *N. autumnalis* in a man with a well-documented diagnosis of scabies [100].

Differential diagnosis includes infestations with other mite species (e.g., the itch mite *Sarcoptes scabiei*), or blood-sucking ectoparasites, such as bed bugs, fleas, ticks, and mosquitoes. Also, hypersensitivity to chemical substances or photoallergic skin reaction to contact with a plant (*Meadow dermatitis*) should be taken into consideration [26].

Treatment is primarily symptomatic and consists of antipruritics, antihistamines, and topical corticosteroids [112]. In our medical consultation, supportive measures such as oatmeal baths are also highly recommended. Antibiotics might be needed in case bacterial superinfection resulting from repeated scratching occurs.

After being in known areas of chigger activity, the dermatitis can be minimized, and the recovery time can be significantly shortened, by taking a hot soapy shower or bath and washing clothes with soap and hot water. These good practices are recommended immediately after exposure, in order to remove both unattached and attached chiggers, before they have firmly anchored to the skin (generally within 3–6 h following attachment) [1,26]. Once the papules are present, scratching should be avoided in order to prevent to excoriate the lesions and the infection.

Patients should be advised on preventive measures, including avoidance of high-risk areas when larvae are active. Since in many cases these results are unreasonable and contact with trombiculid mites is unavoidable, chigger infestation may be minimized by wearing protective clothing and soaking socks and trouser legs with insect repellents [112]. Usually, the use of repellent sprays and lotions containing benzyl benzoate or diethyltoluamide has been recommended [29]. Permethrin was successfully used as a clothing treatment for personal protection against chigger mites [113]. However, the active ingredient is no longer available for this purpose in the European Union [10,26].

Although better than before, our contemporary knowledge on the biology and ecology of these mites is still extremely limited. Currently, no reliable recommendations for the control of mites, except from personal protection, can be given [26].
