International Journal of Infectious Diseases 16 (2012) e649–e662 Contents lists available at SciVerse ScienceDirect International Journal of Infectious Diseases jou rnal homepage: www.elsevier.com/locate/ijid Review Imported Loa loa filariasis: three cases and a review of cases reported in non-endemic countries in the past 25 years a, a b a a Spinello Antinori *, Luca Schifanella , Matthieu Million , Laura Galimberti , Laurenzia Ferraris , c d e e a Luca Mandia , Giuseppe Trabucchi , Viviana Cacioppo , Gaspare Monaco , Antonella Tosoni , b f f a Philippe Brouqui , Maria Rita Gismondo , Giuseppe Giuliani , Mario Corbellino a Department of Clinical Sciences L Sacco, Section of Infectious Diseases and Immunopathology, Universita` degli Studi di Milano, Via GB Grassi, 74, 20157 Milan, Italy b Service des Maladies Infectieuses et Tropicales, Hopital Nord, AP-HM, Faculte´ de Medecine, Universite´ de la Mediterrane´e, Marseille, France c Gynecology Unit, L Sacco Hospital, Milan, Italy d Unita` Operativa di Oculistica, Presidio Ospedaliero di Legnano, Milan, Italy e Unita` Operativa di Oculistica I, Ospedale Fatebenefratelli, Milan, Italy f Clinical Microbiology Unit, L Sacco Hospital, Milan, Italy A R T I C L E I N F O S U M M A R Y Article history: Objectives: The aim of this study was to highlight the increasing chance of Western physicians Received 6 December 2011 encountering patients (both immigrants and expatriates/travelers) seeking help for loiasis. Received in revised form 13 March 2012 Methods: We describe three cases of imported loiasis observed at two hospitals in Italy and France, and Accepted 11 May 2012 present a review of all previously published cases in the medical literature in the last 25 years (1986– Corresponding Editor: William Cameron, 2011). The search was performed using PubMed and Scopus databases using the terms ‘‘Loa loa’’ AND Ottawa, Canada ‘‘loiasis’’. Results: We reviewed 101 cases of imported loiasis of which 61 (60.4%) were reported from Europe and Keywords: 31 (30.7%) from the USA. Seventy-five percent of infestations were acquired in three countries: Loa loa Cameroon, Nigeria, and Gabon. Overall, peripheral blood microfilariae were detected in 61.4% of patients, African eye worm eosinophilia in 82.1%, eye worm migration in 53.5%, and Calabar swellings in 41.6%. However, Calabar Imported filariasis swellings and eosinophilia were more common among expatriates/travelers, whereas African Calabar swellings immigrants were more likely to have microfilaremia. Eye worm migration was observed in a similar Treatment proportion in the two groups. Only 35 patients (including the three described here) underwent clinical follow-up for a median period of 10.5 months (range 1–84 months); clinical relapse occurred in three of these patients and persistence or reappearance of blood microfilaria in another two. Conclusions: Due to increasing travel and the migration of people from the endemic countries of West Africa to Europe and the USA, we speculate on the possible emergence of loiasis. Western physicians should be aware of the typical (eye worm migration and Calabar swellings) as well as unusual clinical presentations. ß 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. 1. Introduction estimated that nearly 30 million people live in high to intermediate 2,3 risk areas with a prevalence of eye worm history exceeding 20%. Loiasis is a neglected nematode infestation that is endemic in In the medical literature loiasis is also referred to as ‘African eye the rainforests of western and central Africa, from a latitude of worm’ because one of its possible manifestations is the pathogno- 4 8–108 N to 58 S. The disease is transmitted to man by tabanid flies of monic migration of the adult worm under the conjunctiva. Several 1 the genus Chrysops. It is especially common in Cameroon, the local names, such as yolo li (yolo = worm; li = eye) and guilde´ guite´ Republic of Congo, the Democratic Republic of Congo, the Central (guilde´ = worm; guite´ = eye) are used by the different ethnic 1,2 5 African Republic, Gabon, Equatorial Guinea, and Nigeria. In a groups in eastern Cameroon to indicate the disease. The other recent survey using the rapid assessment procedure for loiasis most common clinical presentation of loiasis is the intermittent (identified with the acronym RAPLOA), which combines a history appearance of subcutaneous, non-pitting and non-tender edema, of eye worms with the level of endemicity of the infection, it was which is frequently localized to the extremities; these are also 1 known as ‘Calabar swellings’. We describe herein three patients with imported ocular loiasis (two African immigrants presenting over the course of 12 months * Corresponding author. Tel.: +39 0 2 39042688; fax: +39 0 2 50319758. E-mail address: [email protected] (S. Antinori). and one French traveler) managed at two medical centers, one in 1201-9712/$36.00 – see front matter ß 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijid.2012.05.1023 e650 S. Antinori et al. / International Journal of Infectious Diseases 16 (2012) e649–e662 Milan (Italy) and one in Marseille (France). Furthermore, we July 2009, complaining of a ‘foreign body sensation’ in her left eye, provide a discussion on the clinical management of the disease and which had started several hours before. On examination there was a review of all imported (in non-endemic countries) cases of loiasis a left conjunctival injection, and a subconjunctival yellowish 6–92 published from 1986 up to December 2011. Because of worm-like organism was seen moving in the inferior fornix increased immigration to Europe and the USA from areas endemic (Figure 1A). Following a telephone consultation, a provisional for loiasis and also an increase in travel to these endemic areas, diagnosis of ocular loiasis was made and the patient was physicians need to be familiar with the clinical manifestations and discharged from the ED and referred to our outpatient clinic. On the correct management of this neglected filariasis. evaluation 2 days later no worm was visible on gross examination or by slit lamp evaluation. On physical examination she appeared 2. Methods to be a healthy pregnant woman at week 16 of gestation. She had been living in Italy since 2002 and initially did not recall any We retrieved all articles published in the English, French, previous symptoms that could be relevant to the present diagnosis. German, Italian, and Spanish language literature over the last However, she subsequently referred to a similar episode of ocular 25 years (1986–2011) using PubMed and Scopus. The search was worm migration that had occurred when she was 17 years old and conducted using the terms ‘‘Loa loa’’ AND ‘‘loiasis’’. Additional living in Cameroon. cases were identified by reviewing the reference lists of the Additional investigations showed a white blood cell count of 9 original articles. Single case reports identified and published from 6.9 Â 10 /l with 13% eosinophils; liver enzymes and renal function countries endemic for loiasis were excluded. were normal. A peripheral blood smear drawn at 2 p.m. was For the purpose of the present study patients were defined as positive for the presence of sheathed microfilariae of Loa loa follows: (1) as immigrants when coming from endemic countries (Figure 1B). Subsequent examination of a wet peripheral blood and subsequently residing in non-endemic countries; (2) as sample under light microscopy confirmed these organisms to be expatriates when born and raised in non-endemic countries and viable and motile. In consideration of the early pregnancy we subsequently temporarily resident in endemic countries for decided not to treat the patient immediately. Instead we checked occupation or humanitarian purposes, and returning to their the patient at regular intervals (19, 24, 27, 31, and 34 weeks of original country when their assignment was completed; (3) as gestation) and on each occasion confirmed the persistence of blood travelers when traveling for less than 2 months in endemic microfilaremia and eosinophilia. During this time the patient countries. Eosinophilia was defined as an eosinophil count in the complained of another episode of ocular worm migration and two 9 blood exceeding 0.5 Â 10 cells/l, or a percentage 8% when an episodes of swelling of the right ankle. In January 2010 she had a absolute number was not available. normal labor and delivered a healthy female baby weighing In the three newly reported cases, the diagnosis of ocular loiasis 3900 g. Examinations of the cord and peripheral blood of the was based on the observation of the passage of the adult worm in newborn were negative for the presence of microfilariae. In the eyelid or under the conjunctiva. The presence of microfilariae contrast, rare microfilariae could be observed in the intervillar was determined by examining thin and thick blood smears vascular lacunae of the mother’s placenta (Figure 1C). obtained at noon and stained with Giemsa. After delivery, the patient was treated twice (1 month apart) 1 A nested PCR amplification was performed in two cases using with a single dose (200 mg/kg) of ivermectin (Stromectol , Merck the primers originally described by Toure´ et al., which amplify the Sharp & Dohme, Whitehouse Station, NJ, USA) associated with repeat 3 sequence (15r3) of the gene encoding the Loa loa 15-kD prednisone, but this therapy was unsuccessful in clearing the 93 polyprotein, with minor modifications. The presence and peripheral blood microfilariae. Four months after delivery, when integrity of human genomic DNA in each sample was assessed the patient had stopped breast-feeding, treatment with albenda- 1 by performing a simple PCR using human b-globin-specific zole (Zentel ) 400 mg twice daily for 4 weeks was attempted, but primers that amplify a 252-bp fragment.