Dirofilarial human cases in the Old World, attributed to Dirofilaria immitis : a critical analysis Silvio Pampiglione, Francesco Rivasi 1 & Andrea Gustinelli Department of Veterinary Public Health and Animal Pathology, University of Bologna, Ozzano Emilia, Bologna, and 1 Department of Pathologic Anatomy and Forensic Medicine, Section of Pathological Anatomy, University of Modena and Reggio Emilia, Modena, Italy Date of submission 6 May 2008 Accepted for publication 15 August 2008 Pampiglione S, Rivasi F & Gustinelli A (2009) Histopathology 54, 192–204 Dirofilarial human cases in the Old World, attributed to Dirofilaria immitis : a critical analysis Aims: To review 28 cases of human dirofilariasis reported in the last 30 years in the Old World and attributed, by their respective authors, to Dirofilaria immitis or a species of Dirofilaria other than D. repens. Methods and results: Each case was analysed by exam- ining the published accounts or by discussions with the authors, who were interviewed whenever possible. Conclusions: On the basis of these analyses we conclude that there is as yet no proof demonstrating with certainty that Old World D. immitis plays a pathogenic role in humans. It remains to be explained why D. immitis causes pulmonary infections in humans in the Americas while, in the Old World, this location appears, instead, to be always associated with D. repens, even though the former species is at times more frequent than the latter both in dogs and in the vectors. To explain this apparently different pathogenic power, two hypotheses are proposed: (i) there are perhaps twin populations with different genotypes on the two sides of the Atlantic, with different infective capacity for man and dog; (ii) the infective capacity to humans of the parasite could be modified, only in the Old World, by some unidentified factor, possibly inherent to the vector, that affects the complex mechanism of the vector–parasite relationship, affecting the survival of the larvae. Keywords: case analysis, Dirofilaria immitis, Dirofilaria repens, dirofilariasis, humans, lung, subconjunctival tissue, subcutaneous tissue Abbreviations: ECR, external cuticular ridge; ELISA, enzyme-linked immunosorbent assay; PCR, polymerase chain reaction Introduction Dirofilarial human infections in the Americas in pulmonary locations are generally assumed to be due to Dirofilaria immitis, 1,2 a nematode of dogs located in the host inside the blood vessels, in particular the pulmonary arterial network, widespread in the Old and the New World. Subcutaneous locations in the Amer- icas are attributed to another nematode, D. tenuis, parasite of the racoon, an American mammal restricted to the New World. In the Old World dirofilarial human cases, whether subcutaneous or in other locations, have, with the exception of Japan, 3 been identified mostly as due to D. repens, 4–6 another habitual parasitic nematode of the subcutaneous tissue of dogs, endemic in many parts of the world but absent from the Americas. Nevertheless, from the literature it can be seen that some authors are of different opinions, considering in fact that in almost 28 cases (20 pulmonary, five subcutaneous, one subconjunctival and one in the retroperitoneal fat tissue) D. repens is not the causal agent of the infections. They: (i) attribute the infection for the most part (23 cases) to D. immitis; (ii) in five Address for correspondence: Professor Francesco Rivasi, Department of Pathologic Anatomy and Forensic Medicine, Section of Pathological Anatomy, University of Modena and Reggio Emilia, Modena, via del Pozzo, 71, 4100 Modena, Italy. e-mail: francesco.rivasi@unimore.it Ó 2009 The Authors. Journal compilation Ó 2009 Blackwell Publishing Limited. Histopathology 2009, 54, 192–204. DOI: 10.1111/j.1365-2559.2008.03197_a.x