• View in gallery

    Human ocular dirofilariasis caused by Dirofilaria repens. Surgical removal of the nematode from the patient's conjunctiva. A, incision of the bulbar conjunctiva cyst; B, the worm, in coiled shape, is clearly visible after the conjunctiva incision; C, D. repens emerging spontaneously from the conjunctiva cyst; D, the empty cyst remaining after nematode extraction.

  • View in gallery

    Scanning electron microscopy of external cuticular ridges of Dirofilaria repens (bar = 20 μm).

  • View in gallery

    Human cases of dirofilariasis caused by Dirofilaria repens during 1886–2000 and prevalence of D. repens infection in dogs in Sicily, Italy (*data obtained from Pampiglione and others, 199511 and Pampiglione and others, 20004; **data obtained from Giannetto and others, 2007).

  • 1.

    Anderson RC, 2000. Nematode parasites of vertebrates: their development and transmission. New York: CAB International, 417422.

  • 2.

    Orihel TC, Eberhard ML, 1998. Zoonotic filariasis. Clin Microbiol Rev 11: 366381.

  • 3.

    McCall JW, Genchi C, Kramer LH, Guerrero J, Venco L, 2008. Heartworm disease in animals and humans. Adv Parasitol 66: 193285.

  • 4.

    Pampiglione S, Rivasi F, 2000. Human dirofilariasis due to Dirofilaria (Nochtiella) repens: an update of world literature from 1995 to 2000. Parassitologia 42: 231254.

    • Search Google Scholar
    • Export Citation
  • 5.

    Pampiglione S, Rivasi F, Angeli G, Boldorini R, Incensati RM, Pastormerlo M, Pavesi M, Ramponi A, 2001. Dirofilariasis due to Dirofilaria repens in Italy, an emergent zoonosis: report of 60 new cases. Histopathology 38: 344354.

    • Search Google Scholar
    • Export Citation
  • 6.

    Pampiglione S, Rivasi F, Gustinelli A, 2009. Dirofilarial human cases in the Old World, attributed to Dirofilaria immitis: a critical analysis. Histopathology 54: 192204.

    • Search Google Scholar
    • Export Citation
  • 7.

    Ferri E, Barbuto M, Bain O, Galimberti A, Uni S, Guerrero R, Ferté H, Bandi C, Martin C, Casiraghi M, 2009. Integrated taxonomy: traditional approach and DNA barcoding for the identification of filarioid worms and related parasites (Nematoda). Front Zool 6: 1.

    • Search Google Scholar
    • Export Citation
  • 8.

    Otranto D, Sakru N, Testini G, Gürlü VP, Yakar K, Lia RP, Dantas-Torres F, Bain O, 2011. First evidence of human zoonotic infestation by Onchocerca lupi (Spirurida, Onchocercidae). Am J Trop Med Hyg 84: 5558.

    • Search Google Scholar
    • Export Citation
  • 9.

    Casiraghi M, Bazzocchi C, Mortarino M, Ottina E, Genchi C, 2006. A simple molecular method for discriminating common filarial nematodes of dogs (Canis familiaris). Vet Parasitol 141: 368372.

    • Search Google Scholar
    • Export Citation
  • 10.

    Anderson RC, Bain O, 1976. Diplotriaenoidea, Aproctoidea and Filarioidea. Anderson RC, Chabaud AG, Willmott S, eds. Keys to the Nematode Parasites of Vertebrates. New York: CAB International, 59116.

    • Search Google Scholar
    • Export Citation
  • 11.

    Pampiglione S, Azzaro S, Bongiorno A, Fioravanti ML, Garavelli PL, La Valle S, 1995. La dirofilariosi oculare umana in Italia: descrizione di 6 nuovi casi. Revisione della casistica Italiana. Ann Ottalmol Clin Ocul 121: 257277.

    • Search Google Scholar
    • Export Citation
  • 12.

    Pampiglione S, Canestri-Trotti G, Piro S, Maxia C, 1989. Dirofilariosi palpebrale nell'uomo: un caso in Sardegna. Pathologica 81: 5762.

  • 13.

    Therizol-Ferly M, Bain O, Reynouard F, Aimard I, Raymond JM, Rossazza C, Richard-Lenoble D, 1996. Ocular dirofilariosis in a French woman living in Sologne (France). Vet Res Commun 20: 345349.

    • Search Google Scholar
    • Export Citation
  • 14.

    Addario C, 1885. Su di un nematode dell'occhio umano. Ann Oftalmol 14: 135147.

  • 15.

    Pace A, 1886. Sopra un nuovo nematode. G Sci Nat Econ R Ist Tecn Palermo 2: 152154.

  • 16.

    Otranto D, Diniz DG, Dantas-Torres F, Casiraghi M, de Almeida IN, de Almeida LN, Nascimento dos Santos J, Penha Furtado A, de Almeida Sobrinho AF, Bain O, 2011. Human intraocular filariasis caused by Dirofilaria sp., Brazil. Emerg Infect Dis 17: doi: 10.3201/eid1705.100916.

    • Search Google Scholar
    • Export Citation
  • 17.

    Furtado AP, Do Carmo ES, Giese EG, Vallinoto AC, Lanfredi RM, Santos JN, 2009. Detection of dog filariasis in Marajo Island, Brazil by classical and molecular methods. Parasitol Res 105: 15091515.

    • Search Google Scholar
    • Export Citation
  • 18.

    Ciferri F, 1982. Human pulmonary dirofilariasis in the United States: a critical review. Am J Trop Med Hyg 31: 302308.

  • 19.

    Milanez de Campos JR, Barbas CS, Filomeno LT, Fernandez A, Minamoto H, Filho JV, Jatene FB, 1997. Human pulmonary dirofilariasis: analysis of 24 cases from São Paulo, Brazil. Chest 112: 729733.

    • Search Google Scholar
    • Export Citation
  • 20.

    Webber WAF, Hawking F, 1955. Experimental maintenance of Dirofilaria repens and D. immitis in dogs. Exp Parasitol 4: 143164.

  • 21.

    Cancrini G, Pietrobelli M, Frangipane di Regalbono A, Tampieri MP, Della Torre A, 1995. Development of Dirofilaria and Setaria nematodes in Aedes albopictus. Parassitologia 37: 141145.

    • Search Google Scholar
    • Export Citation
  • 22.

    Otranto D, Capelli G, Genchi C, 2009. Changing distribution patterns of canine vector borne diseases in Italy: leishmaniosis vs dirofilariosis. Parasit Vectors 2: S2.

    • Search Google Scholar
    • Export Citation

 

 

 

 

Human Ocular Infection with Dirofilaria repens (Railliet and Henry, 1911) in an Area Endemic for Canine Dirofilariasis

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  • Dipartimento di Sanità Pubblica e Zootecnia, Università degli Studi di Bari, Valenzano, Bari, Italy; Dipartimento di Sanità Pubblica Veterinaria, Facoltà di Medicina Veterinaria, Università degli Studi di Messina, Messina, Italy; Divisione di Oculistica, Ospedale Civile di Vittoria, Vittoria, Italy

Dirofilaria repens, which is usually found in canine subcutaneous tissues, is the main causative agent of human dirofilariasis in the Old Word. However, a relationship between animal and human cases of dirofilariasis caused by D. repens in a given area has never been demonstrated. The uneven distribution of D. repens in provinces in Sicily, Italy represented the foundation for this study. We report a human case of ocular infection with D. repens from Trapani Province, where canine dirofilariasis is endemic. The nematode was morphologically and molecularly identified and surgical removal of the parasite was documented. The relationship between the prevalence of D. repens in dogs and the occurrence of human cases of ocular dirofilariasis is discussed on the basis of a review of the historical literature.

Zoonotic filarioids are transmitted at larval stage by bloodsucking insects from infected animals to humans.1 Among several species of filarial worms, human infections are mostly caused by nematodes belonging to the genus Dirofilaria (Spirurida, Onchocercidae), which are located predominantly in the subcutaneous tissues and pulmonary vessels, but also in central nervous system, and cause a range of clinical manifestations from asymptomatic to more severe (e.g., cough, chest pains, eosinophilia, and hemoptysis).2 Although Dirofilaria immitis, the agent of cardio-pulmonary disease in dogs is considered with the filarioid of raccoons (Dirofilaria tenuis) the main agent of human dirofilariasis in the Americas,3 Dirofilaria repens, which is usually found in the subcutaneous tissue of dogs, is the main causative agent of human dirofilariasis in the Old Word.4 In most human cases of ocular dirofilariasis caused by D. repens, the parasites have been found in nodules or cysts in eye or in periocular tissues.2,4,5

Identification of nematodes at species level relies on microscopic examination of key characteristics (e.g., morphology of the body wall). A recent re-examination of 28 cases of human dirofilariasis reported in the past 30 years in the Old Word and erroneously attributed to D. immitis or Dirofilaria species other than D. repens indicated that D. repens was the prevalent species causing human infection.6 The DNA barcoding of cox1 and 12S mitochondrial markers has been shown to be useful for taxonomic identification of many filarioid species.7 This approach, coupled with morphologic identification, enabled us to describe the first case of human intraocular infection with Onchocerca lupi in Turkey.8 In spite of its reduced pathogenicity for dogs, D. repens is the species most frequently identified in human cases and it has been recently considered as an emerging metazoonosis in southern Europe.46 Although the relationship between animal and human cases of dirofilariasis in a given area could be expected, the correlation between infection rate in dogs and in humans has not been clearly documented.

A large survey was carried out on 2,512 dogs in nine provinces in Sicily, Italy to estimate the prevalence of microfilaremia of different filarial species (Giannetto S and others, unpublished data). In this study, although Acanthocheilonema reconditum infection was detected in dogs from all the provinces sampled, a significantly higher prevalence of D. repens (30.8%) was found in animals in Trapani Province than in those from other provinces (0.4–4.7%). The uneven distribution of D. repens in provinces in Sicily represented the foundation for the present work. We report a human case of ocular infection with D. repens in Trapani, an area to which canine dirofilariasis is endemic. The relationship between microfilaremic dogs and human cases of dirofilariasis by D. repens is also discussed on the basis of a review of the historical literature.

A 55 year-old man came to the Ospedale Riccardo Guzzardi Vittoria (Ragusa, Sicily) with intense pain and redness in the right eye. The patient reported eyelid swelling in the right eye, photophobia, conjunctiva irritation, and a history of painful insect bites on his forehead, five months earlier, at the beginning of summer (June) during a trip to Trapani.

Ophthalmologic examination showed a nematode under the bulbar conjunctiva of the right eye of the patient, and surgery for the removal of the nematode was recommended. After topical anesthesia, the palpebral fissure was kept open by using a blefarostat, and the nematode was gently extracted after incision of the conjunctiva membranes (Figure 1 and Supplemental Video). The patient recovered without complications within two weeks after surgery.

Figure 1.
Figure 1.

Human ocular dirofilariasis caused by Dirofilaria repens. Surgical removal of the nematode from the patient's conjunctiva. A, incision of the bulbar conjunctiva cyst; B, the worm, in coiled shape, is clearly visible after the conjunctiva incision; C, D. repens emerging spontaneously from the conjunctiva cyst; D, the empty cyst remaining after nematode extraction.

Citation: The American Society of Tropical Medicine and Hygiene 84, 6; 10.4269/ajtmh.2011.10-0719

After extraction, the nematode was morphologically studied by using light microscopy and scanning electron microscopy. A small section (approximately 3 mm) of the nematode was used for DNA extraction and subsequent amplification of cox1 gene fragments as described.9 After identification, the parasite was deposited at the Muséum National d'Histoire Naturelle, Parasitologie Comparée, Paris, France (MNHM accession no. 194 YU).

The parasite was a female Dirofilaria sp. that had a length of 117 mm and minimum and maximum widths of 170 μm and 530 μm (at the anus and vulva, respectively). The narrow hypodermal lateral chords were typical of Dirofilaria spp. In addition, scanning electron microscopy showed external cuticular ridges 7–12 μm apart, which are typical of D. repens (Figure 2). Other measurements were within the range of those for D. repens10 (length of the esophagus = 1,055 μm, a nerve ring 260 μm from the anterior edge, and the anus 120 μm from the posterior edge). In accordance with morphologic identification, BLAST analysis (http://blast.ncbi.nlm.nih.gov/Blast.cgi) of the cox1 gene was identical with those of D. repens genes available in GenBank (accession nos. AM749234 and AM749232).

Figure 2.
Figure 2.

Scanning electron microscopy of external cuticular ridges of Dirofilaria repens (bar = 20 μm).

Citation: The American Society of Tropical Medicine and Hygiene 84, 6; 10.4269/ajtmh.2011.10-0719

This case of ocular dirofilariasis was caused by D. repens. Anamnesis showed that the patient probably acquired the parasite in Trapani Province. Interestingly, as for previous cases of human ocular dirofilariasis caused by D. repens,11 the patient recalled a particularly painful insect bite, but it was impossible to say what insect was involved and whether the infection was transmitted at that time. In contrast to some human cases of dirofilariasis, no dermatologic signs (e.g., dermo-epidermal eruptive patches and itch) were recorded in the case reported herein. Cutaneous symptoms in human dirofilariasis has been attributed to the nematode tissue migration phase or, less frequently, by microfilariae in capillary vessels.12,13 The lack of dermatologic signs in our case might be explained by the absence of both events. Since the first reported case of nematode infection in the human eye as Filaria conjunctivae,14 D. repens has been implicated as the predominant causative agent of ocular dirofilariasis throughout the Old World.6 Most of the 492 cases reported in Europe have been in Italy (n = 117) and, in particular, from Sicily.4,11,13 However, these numbers are likely underestimated because of the lack of accurate etiologic diagnoses and because some cases are likely to go unreported in the literature.

The role of dogs as reservoirs of D. repens or the strict relationship between canine subcutaneous infection in a given area and human cases of dirofilariasis by D. repens have not been fully demonstrated. The patient in this study was likely infected with D. repens in Trapani Province, an area to which canine dirofilariasis is endemic and which has a prevalence of microfilaramic dogs up to 30.8% (Giannetto S and others, unpublished data). Accordingly, by reviewing the scientific literature on ocular dirofilariasis in Italy from 186615 through 2000, of the 14 patients in Sicily with ocular dirofilariasis, eight were from Trapani Province.4,11 The distribution of human dirofilariasis in Sicily overlaps the prevalence of D. repens infection observed by Giannetto and others (unpublished data) in dogs in the same provinces of Sicily (Figure 3). However, the role of dogs as reservoirs and transmitters (by mosquito bites) of human dirofilariasis and the correlation between infection rate in dogs and in humans should be further investigated by considering other factors that could affect the distribution of this human infection in a given area (e.g., species of mosquitoes, competent vectors).

Figure 3.
Figure 3.

Human cases of dirofilariasis caused by Dirofilaria repens during 1886–2000 and prevalence of D. repens infection in dogs in Sicily, Italy (*data obtained from Pampiglione and others, 199511 and Pampiglione and others, 20004; **data obtained from Giannetto and others, 2007).

Citation: The American Society of Tropical Medicine and Hygiene 84, 6; 10.4269/ajtmh.2011.10-0719

Similarly, the first case of human intraocular dirofilariasis by a Dirofilaria sp. closely related to D. immitis16 has recently been reported from Brazil in a region where canine dirofilariasis by D. immitis is endemic; prevalence of microfilaramic dogs up to 32.45%.17 A relationship between human dirofilariasis and endemicity of D. immitis in dog populations has been suggested in some areas of the United States18 and Brazil.19 Dogs represent a good source of D. immitis and D. repens for mosquitoes because these dogs remain microfilaremic for several months to more than three years, and female worms in these dogs produce up to 5,000 microfilariae/day.20

Thus, introduction and spread of Aedes albopictus in some countries in Europe, including southern Italy, increased the risk of human dirofilariasis transmission.21,22 Aedes albopictus is well established throughout regions where D. repens is endemic and has been demonstrated to be a competent vector of D. immitis and D. repens.21,22

ACKNOWLEDGMENTS:

We thank Odile Bain (Muséum National d'Histoire Naturelle, Parasitologie Comparée, Paris, France) for her critical discussions on human dirofilariasis, and Stefania Weigl (Università degli Studi di Bari, Valenzano, Bari, Italy) for her assistance with the laboratory work and data analysis. We dedicate this report to the memory of our colleague and friend Professor Silvio Pampiglione (April 18, 1925–October 5, 2008) who conducted several studies in the field of human dirofilariasis.

  • 1.

    Anderson RC, 2000. Nematode parasites of vertebrates: their development and transmission. New York: CAB International, 417422.

  • 2.

    Orihel TC, Eberhard ML, 1998. Zoonotic filariasis. Clin Microbiol Rev 11: 366381.

  • 3.

    McCall JW, Genchi C, Kramer LH, Guerrero J, Venco L, 2008. Heartworm disease in animals and humans. Adv Parasitol 66: 193285.

  • 4.

    Pampiglione S, Rivasi F, 2000. Human dirofilariasis due to Dirofilaria (Nochtiella) repens: an update of world literature from 1995 to 2000. Parassitologia 42: 231254.

    • Search Google Scholar
    • Export Citation
  • 5.

    Pampiglione S, Rivasi F, Angeli G, Boldorini R, Incensati RM, Pastormerlo M, Pavesi M, Ramponi A, 2001. Dirofilariasis due to Dirofilaria repens in Italy, an emergent zoonosis: report of 60 new cases. Histopathology 38: 344354.

    • Search Google Scholar
    • Export Citation
  • 6.

    Pampiglione S, Rivasi F, Gustinelli A, 2009. Dirofilarial human cases in the Old World, attributed to Dirofilaria immitis: a critical analysis. Histopathology 54: 192204.

    • Search Google Scholar
    • Export Citation
  • 7.

    Ferri E, Barbuto M, Bain O, Galimberti A, Uni S, Guerrero R, Ferté H, Bandi C, Martin C, Casiraghi M, 2009. Integrated taxonomy: traditional approach and DNA barcoding for the identification of filarioid worms and related parasites (Nematoda). Front Zool 6: 1.

    • Search Google Scholar
    • Export Citation
  • 8.

    Otranto D, Sakru N, Testini G, Gürlü VP, Yakar K, Lia RP, Dantas-Torres F, Bain O, 2011. First evidence of human zoonotic infestation by Onchocerca lupi (Spirurida, Onchocercidae). Am J Trop Med Hyg 84: 5558.

    • Search Google Scholar
    • Export Citation
  • 9.

    Casiraghi M, Bazzocchi C, Mortarino M, Ottina E, Genchi C, 2006. A simple molecular method for discriminating common filarial nematodes of dogs (Canis familiaris). Vet Parasitol 141: 368372.

    • Search Google Scholar
    • Export Citation
  • 10.

    Anderson RC, Bain O, 1976. Diplotriaenoidea, Aproctoidea and Filarioidea. Anderson RC, Chabaud AG, Willmott S, eds. Keys to the Nematode Parasites of Vertebrates. New York: CAB International, 59116.

    • Search Google Scholar
    • Export Citation
  • 11.

    Pampiglione S, Azzaro S, Bongiorno A, Fioravanti ML, Garavelli PL, La Valle S, 1995. La dirofilariosi oculare umana in Italia: descrizione di 6 nuovi casi. Revisione della casistica Italiana. Ann Ottalmol Clin Ocul 121: 257277.

    • Search Google Scholar
    • Export Citation
  • 12.

    Pampiglione S, Canestri-Trotti G, Piro S, Maxia C, 1989. Dirofilariosi palpebrale nell'uomo: un caso in Sardegna. Pathologica 81: 5762.

  • 13.

    Therizol-Ferly M, Bain O, Reynouard F, Aimard I, Raymond JM, Rossazza C, Richard-Lenoble D, 1996. Ocular dirofilariosis in a French woman living in Sologne (France). Vet Res Commun 20: 345349.

    • Search Google Scholar
    • Export Citation
  • 14.

    Addario C, 1885. Su di un nematode dell'occhio umano. Ann Oftalmol 14: 135147.

  • 15.

    Pace A, 1886. Sopra un nuovo nematode. G Sci Nat Econ R Ist Tecn Palermo 2: 152154.

  • 16.

    Otranto D, Diniz DG, Dantas-Torres F, Casiraghi M, de Almeida IN, de Almeida LN, Nascimento dos Santos J, Penha Furtado A, de Almeida Sobrinho AF, Bain O, 2011. Human intraocular filariasis caused by Dirofilaria sp., Brazil. Emerg Infect Dis 17: doi: 10.3201/eid1705.100916.

    • Search Google Scholar
    • Export Citation
  • 17.

    Furtado AP, Do Carmo ES, Giese EG, Vallinoto AC, Lanfredi RM, Santos JN, 2009. Detection of dog filariasis in Marajo Island, Brazil by classical and molecular methods. Parasitol Res 105: 15091515.

    • Search Google Scholar
    • Export Citation
  • 18.

    Ciferri F, 1982. Human pulmonary dirofilariasis in the United States: a critical review. Am J Trop Med Hyg 31: 302308.

  • 19.

    Milanez de Campos JR, Barbas CS, Filomeno LT, Fernandez A, Minamoto H, Filho JV, Jatene FB, 1997. Human pulmonary dirofilariasis: analysis of 24 cases from São Paulo, Brazil. Chest 112: 729733.

    • Search Google Scholar
    • Export Citation
  • 20.

    Webber WAF, Hawking F, 1955. Experimental maintenance of Dirofilaria repens and D. immitis in dogs. Exp Parasitol 4: 143164.

  • 21.

    Cancrini G, Pietrobelli M, Frangipane di Regalbono A, Tampieri MP, Della Torre A, 1995. Development of Dirofilaria and Setaria nematodes in Aedes albopictus. Parassitologia 37: 141145.

    • Search Google Scholar
    • Export Citation
  • 22.

    Otranto D, Capelli G, Genchi C, 2009. Changing distribution patterns of canine vector borne diseases in Italy: leishmaniosis vs dirofilariosis. Parasit Vectors 2: S2.

    • Search Google Scholar
    • Export Citation

Author Notes

*Address correspondence to Domenico Otranto, Dipartimento di Sanità Pubblica e Zootecnia, Università Degli Studi di Bari, Str. Prov.le per Casamassima, km 3, 70010 Valenzano, Bari, Italy. E-mail: d.otranto@veterinaria.uniba.it

Authors' addresses: Domenico Otranto and Filipe Dantas-Torres, Dipartimento di Sanità Pubblica e Zootecnia, Università degli Studi di Bari, Valenzano, Bari, Italy, E-mails: d.otranto@veterinaria.uniba.it and f.dantastorres@veterinaria.uniba.it. Emanuele Brianti, Gabriella Gaglio, and Salvatore Giannetto, Dipartimento di Sanità Pubblica Veterinaria, Facoltà di Medicina Veterinaria, Università degli Studi di Messina, Messina, Italy, E-mails: ebrianti@unime.it, ggaglio@unime.it, and sgiannetto@unime.it. Salvatore Azzaro, Divisione di Oculistica, Ospedale Civile di Vittoria, Vittoria (RG), Italy, E-mail: azzaro@ospedaleragusa.it.

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