Human dirofilariasis: an emerging zoonosis in India

Abstract

Human dirofilariasis is an uncommon zoonotic infection having a widespread geographical distribution. World over 800 cases of Dirofilaria are on record with highest numbers from Italy, Sri Lanka and republics of the ex-Soviet Union. Dirofilaria repens belongs to the subgenus Nochtiella and is the most common species identified in India. Topographically, the orbital/periorbital regions are the most common regions involved by Dirofilaria. We present a brief review of cases from India including two received in our own institute. This review focuses on the epidemiology of the disease including its geographical distribution and the probable causation of the recent increase in its incidence in Indian subcontinent.

Introduction

Dirofilaiasis is an uncommon zoonotic disease where man is the dead end host. Among nearly forty species of Dirofilaria identified, only a few give rise to human infection. There are two forms of the disease—(a) pulmonary dirofilariasis caused primarily by Dirofilaria immitis (the dog heartworm), and (b) subcutaneous dirofilariasis caused primarily by Dirofilaria tenuis and Dirofilaria repens, parasites of the raccoon and of dogs and cats respectively. In rare instances the parasite has also been recovered from deeper locations of peritoneal cavity, omentum, ligaments, breast and liver (Padmaja et al. 2005; Orihel and Eberhard 1998; Mrad et al. 1999; Kim et al. 2002).

Dirofilaria repens is the commonest species identified in India. It belongs to the subgenus Nochtiella. Transmission to humans is via the bite of zoo-anthropophilic vector—the mosquito of the Anopheles, Aedes and Culex species. Clinically infection is apparent as a solitary subcutaneous nodule commonly in the head and neck region with or without pain. Identifying its characteristic longitudinal cuticular ridges by wet mount study or histopathological examination in conjunction with the typical clinical features is usually sufficient for diagnosis in most of the cases (Orihel and Eberhard 1998; Khurana et al. 2010).

Case reports

Case 1

A 37 year old female a resident of Karnataka presented with a slowly enlarging mass over the left side of the neck for 2 months. The mass was preceeded by symptoms of itching, pain and fever. The mass measured 1.5 cm × 1 cm, was irregular, freely mobile and firm in consistency. The lesion was nontender and there was no local rise of temperature. Ultrasonography showed an oval hypoechoic lesion, 8 mm × 5 mm with tubular hyperechoic structure in the subcutaneous plane suggestive of inflammatory swelling due to parasitic infestation. The nodule was excised and the worm was delivered out of the cystic lesion. The worm measured 11.5 cm in length and was identified as D. repens (Fig. 1).

Fig. 1.

Wet mount of the worm showing characteristic longitudinal cuticular ridges

Case 2

A 40 year old male, resident of Dakshina Kannada district of coastal Karnataka presented with swelling of the right upper eyelid for 2 weeks. On examination the swelling was associated with periorbital edema and tenderness. Computed tomographic scan suggested an inflammatory/malignant mass. The excised mass consisted of an irregular grey pink nodule measuring about 1 cm × 0.8 mm. Cut section showed a whitish centre. Microscopy revealed several cross-sections of a slightly degenerated worm showing the cuticular and internal structures (Fig 2).

Fig. 2.

Photomicrograph of the slightly degenerated worm showing the multilayered cuticle, longitudinal ridges and the genital tube. H&E original magnification 40×

Discussion

Dirofilaria has widespread geographical distribution with cases recorded from over 30 countries. It has endemic foci in Southern and Eastern Europe, Asia Minor, Central Asia and Sri Lanka. World over around 800 cases of Dirofilaria are on record (Pampiglione et al. 1995, 1982; Pampiglione and Rivasi 2000).

Dirofilaria species isolated from humans are divided into two subgenera: Dirofilaria, with D. immitis as the type species, and Nochtiella, with D. repens as its type species. Nematodes in the former, have a smooth cuticle and are typically found in pulmonary arteries, whereas those in the latter (D. repens, D. ursi, D. tenuis and D. striata) exhibit longitudinal cuticular ridges and are usually found in subcutaneous tissues. Epidemiologically, the species recovered, depend upon the geographical location (Orihel and Eberhard 1998).

Dirofilaria is relatively rare in India with approximately 73 on record since 1977. Dirofilaria repens is the commonest species identified followed by D. immitis and D. tenius (Joseph et al. 1976; Bhat et al. 2003, 2012; Teerthanath and Hariprasad 2011; Badhe and Sane 1989; Senthivel and Pillai 1999). Two cases of D. repens were identified in our institute (Table 1).

Table 1.

Case reports of Dirofilaria in India with epidemiological details

Case No.	Author	Area	Location	Age	Sex	Worm sex	Number of worms	Length of the worm in cm	Species
1	Joseph et al. (1976)	Kera	Conjb	60	F	F	1	NMc	D. repens
2	(Badhe and Sane 1989)	Mahad	Pulmonary	Child	NM	NM	NM	NM	D. immitis
3	(Senthivel and Pillai 1999)	Ker	SCe	NM	NM	NM	NM	NM	NM
4	Sekhar et al. (2000)	Ker	Eyelid	26	F	NM	2	10.5 and 5	NM
5	Nadgir et al. (2001)	Karf	Conj	42	M	M	1	3.5	D. repens
6	Gautam et al. (2002)	Haryana	Sub conj	23	M	M	1	8.3	D. repens
7	Ittyerah and Mallik (2004)	Ker	Eyelid	14	F	F	1	10	D. repens
8	Bhat et al. (2003)	NM	Eyelid	70	F	NM	1	12	D. tenius
9	Padmaja et al. (2005)	TN	Lip	35	M	F	1	12.5	D. repens
10	Mahesh et al. (2005)	Asian	Eyelid	78	F	F	1	10	D. repens
11	Sathyan et al. (2006)	Ker	Subtenon	63	F	F	1	9.5	D. repens
12–20	Sabu et al. (2005)	Ker	9 Eye	NM	NM	11 F	Single	9–13.5	D. repens
21–23	Sabu et al. (2005)	Ker	3 SC	NM	NM	1 M	1	6	D. repens
24	Smitha et al. (2008)	Ker	Eyelid	40	F	NM	1	13.5	D. repens
25	Raju et al. (2008)	Ker	Eyelid	33	F	NM	1	9	D. repens
26	Raju et al. (2008)	Ker	Eyelid	46	F	NM	1	8	NM
27	(Dhar and Nambiar 2008)	Ker	Limbus	24	F	F	1	10.5	NM
28	(Chakrabarti et al. 2009)	Ker	Sub Conj	60	F	NM	1		D tenius
29	Singh et al. (2010)	Orissa	Scrotum	40	M	F	1	10.5	D. repens
30	Nath et al. (2010)	Assam	Eyelid	23	F	F	1	12	D. repens
31	Nath et al. (2010)	NM	Eyelid	30	M	F	1	13	D. repens
32	Nath et al. (2010)	NM	Conj	70	M	F	1	12	D. repens
33	Khurana et al. (2010)	Kar	AB Wallg	16	M	F	1	9	D. repens
34	Khurana et al. (2010)	Maha	Cheek	45	M	F	1	8	D. repens
35	Khurana et al. (2010)	Maha	Eyelid	15	F	F	1	11.5	D. repens
36	(Joseph et al. 2011a, b)	Ker	Face	53	F	NM	1	NM	D. repens in 17 cases
37	(Joseph et al. 2011a, b)	Ker	Chest	60	F	NM	1	NM	D. repens in 17 cases
38	(Joseph et al. 2011a, b)	Ker	Cheek R	45	F	NM	1	NM	D. repens in 17 cases
39	(Joseph et al. 2011a, b)	Ker	Arm	19	F	NM	1	NM	D. repens in 17 cases
40	(Joseph et al. 2011a, b)	Ker	AB wall	1	M	NM	1	NM	D. repens in 17 cases
41	(Joseph et al. 2011a, b)	Ker	Canthus	27	M	NM	1	NM	D. repens in 17 cases
42	(Joseph et al. 2011a, b)	Ker	Flank	65	M	NM	1	NM	D. repens in 17 cases
43	(Joseph et al. 2011a, b)	Ker	Thigh	28	F	NM	1	NM	D. repens in 17 cases
44	(Joseph et al. 2011a, b)	Ker	Neck	48	M	NM	1	NM	D. repens in 17 cases
45	(Joseph et al. 2011a, b)	Ker	AB wall	34	F	NM	1	NM	D. repens in 17 cases
46	(Joseph et al. 2011a, b)	Ker	Arm	35	F	NM	1	NM	D. repens in 17 cases
47	(Joseph et al. 2011a, b)	Ker	Inguinal	38	F	NM	1	NM	D. repens in 17 cases
48	(Joseph et al. 2011a, b)	Ker	Arm	22	F	NM	1	NM	D. repens in 17 cases
49	(Joseph et al. 2011a, b)	Ker	Axilla	14	M	NM	1	NM	D. repens in 17 cases
50	(Joseph et al. 2011a, b)	Ker	Chest	25	M	NM	1	NM	D. repens in 17 cases
51	(Joseph et al. 2011a, b)	Ker	Neck	56	F	NM	1	NM	D. repens in 17 cases
52	(Joseph et al. 2011a, b)	Ker	Chest wall	50	M	NM	1	NM	D. repens in 17 cases
53	(Joseph et al. 2011a, b)	Ker	Nasolabial	10	F	NM	1	NM	D. repens in 17 cases
54	(Joseph et al. 2011a, b)	Ker	Parotid	39	F	NM	1	NM	D. repens in 17 cases
55	(Joseph et al. 2011a, b)	Ker	Epididymis	1	M	NM	1	NM	D. repens in 17 cases
56	(Joseph et al. 2011a, b)	Ker	Infraorbit	24	F	NM	1	NM	D. repens in 17 cases
57	(Teerthanath and Hariprasad 2011)	Ker	Muscle	27	M	M	1	16	D. immitis
58	Kotian et al. (2011)		Supra orbit	52	F	F	1		D. repens
59	Kotian et al. (2011)		Below eyelid	34	F		1		D immitis
60	Permi et al. (2011)	Ker	Cheek	40	M	F	1	NM	D. repens
61	Permi et al. (2011)	Ker	Neck	45	M	NM	1	NM	D. repens
62	(Joseph et al. 2011a, b)	Ker	Orbit	50	F	F	1	12.5	D. repens
63	Sanjeev et al. (2011)	Ker	Neck	18	F	F	1	9	NM
64	Kotigadde et al. (2012)	Kar	Eyelid	47	F	F	1	10	D. repens
65	Chopra et al. (2012)	Bihar	Ant.h Chamber	25	M	F	1	10	NM
66	Bhat et al. (2012)	NM	Conjun	75	M	NM	1	NM	D. tenius
67	(Vaidya and Srikar 2012)	NM	AB wl	30	F	F	1	NM	D. repens
68	(Sangit and Haldipurkar 2012)	NM	Conjuc	48	M	F	2	3.5 cm	D. repens
69	Mukherjee et al. (2012)	Asian	Eyelid	61	M	NM	1	NM	NM
70	(Srinivasamurthy et al. 2012)	Indian	Neck	40	F	F	1	NM	NM
71	Sahdev et al. (2012)	Maha	Eye lid	3	M	NM	1	NM	D. repens
72	Case 1*	Kar	Neck	35	F	F	1		D. repens
73	Case 2*	Kar	Eyelid	45	M	NM	1		D. repens

M Male, F Female

^* Cases received in our institute (unpublished)

^aKerala

^bConjunctiva

^cNot mentioned

^dMaharashtra

^eSubcutaneous

^fKarnataka

^gabdominal

^hAnterior chamber

Dirofilaria repens is the most prevalent agent of zoonotic dirofilariasis in many parts of the world including Africa, Canada, Japan Kuwait France, Italy, Turkey, Africa, Thailand, USA and Southeast Asia (Athari 2003; Sekhar et al. 2000).

Dirofilaria repens was first reported in India by Joseph et al. who described a case of ocular Dirofilaria in a patient from southern coastal state of Kerala. Following this, isolated case reports of Dirofilaria were published throughout the nineties. It is probable that the sudden spurt in the cases seen over the last decade is not only indicative of greater awareness of this entity but also an actual increase in its incidence (Fig. 3).

Fig. 3.

Year-wise distribution of cases in India since 1977

The state of Kerala has so far been the main reservoir of infection. Its close geographical proximity to Srilanka, one of the most affected countries may be the cause. Out of the 70 odd case reports, more than half of the patients either were residents of or provided history of travels to Kerala. Recent trends however indicate a northward migration of the disease with cases being reported from Karnataka and Maharashtra and occasionally from Northern and Eastern states of Assam, Bihar Orissa and Haryana (Gautam et al. 2002; Singh et al. 2010; Nath et al. 2010; Chopra et al. 2012).

The prevalence of microfilaremia in dogs in Kerala and Karnataka is around 7 and 21 % respectively. This high prevalence in dogs—both domestic and stray explains the high incidence of disease in these regions. Moreover, India is endemic for malaria and lymphatic filariasis. The humid climate and recent industrialization have given rise to a conductive atmosphere for the breeding mosquitoes. Hence, it is not surprising that the incidence of Dirofilaria, which shares its arthropod vectors with these, should also rise (Pampiglione and Rivasi 2000; Sahdev et al. 2012; Rani et al. 2010).

Dirofilaria in India is more common in females with the age range from 1 to 75 years. The details of socio-economic status/living conditions and loco—regional details including local vector control measures if any, residence in rural/urban regions and contact history with animals were not available (Bhat et al. 2012; Nath et al. 2010).

A single case of pulmonary Dirofilaria has been reported from India in a child manifesting as portal cavernoma with pulmonary dirofilariasis detected at autopsy (Badhe and Sane 1989).

Orbital/periorbital Dirofilaria accounted for more than half the number of cases with worms located in the eyelid, subconjunctival region, canthus, limbus, subtenon space and anterior chamber. Preferred location for subcutaneous Dirofilaria was the head and neck, followed by face, arm and chest. The torso, thigh and scrotum were favoured locations in the lower half of the body. The distribution is similar to that observed by Orihel and Eberhard (1998). An isolated case of intramuscular Dirofilaria by D. immitus is reported (Teerthanath and Hariprasad 2011).

Where the sex of the worm was identified female worms were found with greater frequency than male worms (24 out of 27) which is in concurrence with the world literature. The male worms of D. repens ranged from 3.5 cm to 6 cm and female worms ranged from 10 cm to 13.5 cm. D. tenius was 12 cm to 16 cm.

Diagnosis of D repens is mainly by morphological examination of the worm. An adult male worm is 5–6 cm long with anal spicules. The female are 10–17 cm long and 460–650 μm wide with a vulva 1.15–1.62 cm from the anterior end. More important are the morphologic features seen in transverse- sections of the worms. The cuticle is multilayered and has transverse striations with prominent longitudinal ridges. On the inner surface of the cuticle in the lateral fields, a conspicuous cuticular ridge protrudes into the inner surface of the lateral chords. The muscle coat is characteristically well developed. The number of reproductive tubes and their contents (eggs, microfilariae, and sperm) help identify the sex of the worm (Orihel and Eberhard 1998).

Dirofilaria repens reproduces sexually, its lifecycle consisting of five developmental stages requiring a vertebrate main host (usually a dog or cat) and an arthropod intermediate host/vector. The immature filaria migrate subcutaneously, undergoes development into an adult worm and then dies inciting an inflammatory reaction of the Th2 type dominated by eosinophils. Blood counts including the white cell differentials are usually within normal limits (Orihel and Eberhard 1998).

Conclusion

We support the opinion that Dirofilaria is emerging zoonoses in Indian subcontinent. With its increasing incidence it becomes imperative for the regional pathologists and microbiologists to be well versed with its morphology and the surgeons and ophthalmologists be aware of this parasite. A DNA study may help in further epidemiological characterization of the Dirofilaria species.