First Record of Indigenous Furuncular Myiasis Due to Cordylobia anthropophaga in Unusual Ecologic Niche, Makkah, Saudi Arabia

Department of Parasitology, Faculty of Medicine, Assiut University, Egypt. Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah 7607, Saudi Arabia. Department of Animal Hygiene and Zoonoses, Faculty of Veterinary Medicine, Assiut University, Egypt. Department of Medical Parasitology, Faculty of Medicine, Umm Al-Qura University, Makkah 7607, Saudi Arabia. Department of Medical Parasitology, Faculty of Medicine, El-Minia University, Egypt. Clinical Laboratory Diagnosis, Animal Medicine, Faculty of Veterinary Medicine, Assiut University, Assiut 71526, Egypt.


INTRODUCTION
Myiasis is defined as the infestation of human and animal tissues by the larvae of dipteran flies. In humans, myiasis is usually classified according to the clinical presentation into cutaneous myiasis, traumatic myiasis, and myiasis of body cavities [1]. While the term traumatic myiasis is used when maggots of dipteran flies infest open wounds, cutaneous myiasis always refers to penetration of intact skin by dipteran maggots [1][2][3].
Furuncular myiasis (FM) is one of the common forms of cutaneous myiasis in which a boil-like lesion, with one or more maggots, developed in affected skin. FM could be developed into what is called migratory myiasis when maggots migrate aimlessly through burrows in the skin and produce numerous furuncular lesions [4].

Cordylobia anthropophaga (tumbu fly) and
Dermatobia hominis (human botfly) are the most commonly associated dipteran flies with furuncular myiasis. However, these 2 types appears to have distinct geographical preferences, where C. anthropophaga is the common cause of FM and reportedly endemic in tropical sub-Saharan Africa, while Dermatobia hominis is endemic in Central and South America [5,6]. Tumbu fly-induced FM not only differs than that of human botfly in term of geographical location, but also in the mode of transmission. In human botfly, eggs are carried to the host by a blood-sucking insect, where the hatched larvae invade exposed skin of the trunks, head and limbs. On the other hand, eggs of the tumbu fly, are however deposited on the soil or wet and soiled clothes hung outside for drying where the hatched larvae invade unexposed skin of the buttocks, trunk and limbs in contact with the wet clothes [3,6].
Diagnosis of furuncular myiasis depends mainly on the epidemiological history of the case such as recent travel to endemic areas [7]. Clinical manifestations of FM are not specific and are often confused with other conditions such as actinomycosis, leishmaniasis, tuberculosis induced furuncular lesions, insect bite, cellulitis, and sebaceous cyst. However, diagnosis of FM is usually confirmed by the extraction and morphological identification of the larvae from the lesion [4,5].
Although C. anthropophaga itself has long been limited to tropical and subtropical sub-Saharan Africa [8], cases of tumbu fly-induced FM, are not uncommon in regions outside Africa. However, such cases are usually recorded in travelers returning from endemic areas [9,10]. In Saudi Arabia, human cutaneous myiasis in general, and C. anthropophaga infestation in particular are not very common. However, indigenous cases of tumbu fly-related FM were repeatedly reported in Saudi Arabia during the periods of 80s and early 90s of the last century in the province of Asir [11,12] and more recently in the province of Al-baha [13]. Both provinces are located at the South Western region of Saudi Arabia, a region with an ecology of great resemblances to that of subtropical Africa with a rainy, humid climate and surrounding forests environment [13], which make it a potential endemic focus of indigenous FM outside Africa. The current study described seven different cases of human cutaneous FM caused by maggots of Cordylobia anthropophaga in Makkah region, Midwest/Saudi Arabia. To the best of our knowledge these cases that were reported among children that never travelled to any of the known endemic regions represent the first record of indigenous furuncular myiasis outside the conventional ecologic niche of Cordylobia anthropophaga.

History and Clinical Examination
All cases were subjected to thorough clinical examination of suspected lesions to record site and shape of the lesions. In addition, all cases were subjected to complete history taking that included medical history, past lesions or trauma as well as travel history. Blood samples were collected from suspected cases for complete blood count.

Taxonomic Identification of Extracted Maggots
Suspected larvae were collected by gentle squeezing of the lesions and grasping of the maggots painlessly using strile forceps. Cephaloskeleton and posterior spiracles was dissected and examined microscopically after the standard procedures of fixation, dehydration and clearing. The extracted larvae were identified based on the size, body shape, cephaloskeleton, spine pattern and posterior spiracles morphology as previously described [8].

Clinical Presentation and History of Cases
Clinical examination of suspected cases revealed that suspected lesions had initially started as a painful itchy swelling in varies regions of the patient's body including face, shoulder, abdomen, back and limbs. No medical history of systemic malaise, trauma, bites or chronic disease as diabetes or history of wound in affected areas was recorded. History of previous travel to any of the known endemic areas was not evident. Upon clinical examination, there was a cutaneous boil-like lesion, associated with cellulitis spreading over their face, abdomen, back and the limb. Hematological parameters were within normal range and there was neither bleeding nor pus discharge from the crater, but there was what seemed like creamy contents at the bottom layer of the boil. Suspected maggots were obtained after squeezing -with or without the help of small surgical incisions-of the lesions. After removal of the maggots, the left sinus-shape wound was dressed using local anti-parasitic and antibiotic agents. Patients were placed on ampicillin/ cloxacillin capsules, tetanus toxoid injection, analgesics and daily wound dressing with EUSOL. One week post treatment, patients were seen in the clinic to ensure that all the furuncle had healed.
Seven cases belonging to 3 different households were presented on 3 distinctive incidents with a history of boil-like swellings and skin abscess. In the First incidence, an 11 years-old male child was referred to the Maternity and Children Hospital, Makkah province, Saudi Arabia the 3 rd of September, 2014 with 2 suspected lesions on the face and abdomen (Fig. 1A,B). In the second incidence, three siblings aged 2 month male, 5 years female and 16 years female children were referred to the Maternity and Children Hospital, Makkah province, Saudi Arabia the 23 rd of October, 2014 with a single suspected lesion on the abdomen and/or limb ( Fig. 1 C,D). In the third incidence, three siblings aged 5 years old female, 7 years old male and 15 years old male children were referred to the Maternity and Children Hospital, Makkah province, Saudi Arabia at 8 th of February, 2016 with multiple lesions. The 7 years old male child was presented with 4 lesions on the back (Fig. 1E). The 5-years old female child and the 15 years old male child were presented each with a single lesion at the limb (Fig. 1F).

Morphology and Identification of Extracted Maggots
Extracted larvae were identified as typical thirdinstars of C. anthropophaga based on the size, body shape, Cephaloskeleton, spine pattern and posterior spiracles morphology. Briefly, the maggots were oval in shape with a pointed anterior and a blunt posterior end, creamy white in color and with a size range of 7-12 mm ( Fig.  2A). The oral area contained a pair of toothed, spade-like hooks (Fig. 2B). The body consisted of twelve clearly marked segments with transverse black bands covered with backwardly directed black spines Spade-like hooks (Fig. 2C). Posterior spiracles were not widely separated and lacked a chitinous rim with a closed peritreme and three slightly sinuous slits (Fig. 2D).

DISCUSSION
Cordylobia anthropophaga-induced furuncular myiasis has long been endemic in tropical sub-Saharan Africa [14]. Although FM due to C. anthropophaga used to be restricted to the Afro-tropical regions with an autochthonous pattern of transmission, several reports have recently recorded multiple cases of FM in several countries as UK [15], USA [16], Spain [17], and China [7], outside the conventional endemic regions of the disease. Although most cases where reported among travellers returning from endemic areas [9,10,18], sporadically reported cases were also recorded among un-travellers in Spain and Portugal suggesting indigenously acquired cases in these non-endemic areas as well [19].
Despite of the little available information on epidemiology of myiasis in Saudi Arabia, few reports had already recorded furuncular myiasis among Saudi patients during the last decade.
Interestingly, most incidences of FM were recorded as being indigenous cases that were restricted to Aser Province, a region located southwest of Saudi Arabia [11,12]. The fact that ecological features of Asir region is quite similar to that of the tropical sub-Saharan Africa, have suggested it as the sole Saudi endemic focus outside Africa. More recently, a case of furuncular myiasis proved to be induced by C. anthropophaga where recorded in Al-Baha province, which is 300-Km north to Aser, yet sharing the same Afrotropic ecological features of Asir region [13,20,21].
In the current study, 7 cases of FM, belonging to 3 different households were recorded among local residents of Makkah region over a period extended from September, 2014 to February, 2016. All cases were recorded among children with age range from 2 Month up to 16-years where the high risk is probably due to relatively thin skin and lower immunity with the lack of exposure. This finding is in agreement with previous studies, which showed increased infective rate in infants and children as well as pregnant and nursing mothers with physiological impaired immunity [18]. Furuncular myiasis is usually presented as a nodular swelling that develops into a boil-like tender lesion with the symptoms of pruritus, pain, and movement sensation commonly reported [1,22]. Lesions tend to affect unexposed body regions as libs, back, abdomen, buttocks and shoulders and to lesser extend affecting face and other exposed skin regions [4,23,24]. The central pore of the lesions exude serous or purulent fluid and usually have one or more maggots that may protrude from the pore with its respiratory spiracle bearing posterior segment [1]. In the current study, the However, the fact that non of currently recorded cases had previously travelled to any of the known endemic areas of C. anthropophaga neither in Tropical Africa nor in southwest region of Saudi Arabia suggests indigenous acquisition of the disease. With the exclusion of the southwestern region, Saudi Arabia is considered one of the driest countries in the world. In fact Asir and Al-Baha provinces, as parts of the southwestern region, is considered by many authors part of the Afrotropical zone [25]. On the other hand, Makkah region is far from sharing the same ecological features of the Afrotropic zone with a more desert and water deficit conditions [26]. These facts make Mekkah environment far from being conventional permissive ecologic environment for C. anthropophaga. However the un-travelling history of the presented cases to any of the known C. anthropophaga endemic areas raise a very interesting question about the possibility of autochthonous pattern of transmission in this non-endemic region. A question that might denote a dramatic change in the geographical distribution of such myiasis causing flies, which indeed needs further investigations to document the inhabitance and successful life cycle completion of C. anthropophaga in Makkah region.

CONCLUSION
To the best of our knowledge, the current report is the first to record cases of indigenously acquired FM in Makkah region, Midwest of Saudi Arabia. The recording of indigenously acquired cases of FM in dry desert-climate region among patients that never travelled to any of the known endemic regions of C. anthropophaga might represent the first cases of autochthonous transmission pattern outside its conventional endemic niche. Indeed, the current report represent an interesting finding that clearly shows that Calliphorine species are not restricted to Afro-tropical regions, yet further epidemiological and ecological investigations are required to gain more insights on this interesting finding.

CONSENT
All participated persons has given, either via themselves or via their parents or legal guardians, a written consent that they acknowledge the inclusion of their data anonymously in the study and that they cannot be identified via the paper.

ETHICAL APPROVAL
It is not applicable.