Acta Tropica

Background: Black fl y and sand fl y bites are related to the endemicity of pemphigus foliaceus (PF); however, an immune reaction against the salivary proteins from these fl ies still requires con fi rmation in the case of PF patients living in southeastern Brazil. Purpose: To georeference the distribution of Simuliidae (Diptera: Simuliidae) and Phlebotominae (Diptera: Psychodidae) and of PF cases in the northeastern region of São Paulo State, and to assess the humoral immune response against salivary gland extracts (SGEs) from biting fl ies in PF patients, relatives, and neighbours. Methods: PF patients ’ medical information recorded between 1965 and 2014 were obtained from the database of the University Hospital. Data on the distribution of fl y species were collected from scienti fi c reports and epidemiological databases. Spatial maps relating the distribution of biting fl ies with PF cases were plotted. Serum IgG antibodies against the SGEs from Simulium nigrimanum , Nyssomyia neivai , and Aedes aegypti (as control) were determined by ELISA. Results: Two hundred and eighty-fi ve PF cases were distributed in 60 municipalities with a prevalence of 57.5 per million inhabitants, revealing well-de fi ned geographical clusters. S. nigrimanum and N. neivai specimens were registered in eight (13.3%) and 26 (43.3%) of these municipalities, respectively. PF patients, and their relatives presented higher levels of IgG against the SGEs of S. nigrimanum and N. neivai ( P< 0.001 for both), but not against the SGE from A. aegypti ( P =0.115 and P =0.552, respectively), as compared to controls. IgG against the SGEs from S. nigrimanum and N. neivai but not against the SGE from A. aegypti correlated with levels of anti-Desmoglein 1 in PF patients (r=0.3848, P =0.039; and r=0.416, P =0.022, respectively). Conclusion: An epidemiological link between biting fl ies and PF in southeastern Brazil is proposed, implying a possible role of the salivary proteins from these fl ies in PF etiopathogenesis.

[1]  Luiz Eduardo Moschini,et al.  Spatial Distribution of Pemphigus Occurrence over Five Decades in Southeastern Brazil. , 2017, The American journal of tropical medicine and hygiene.

[2]  E. Donadi,et al.  Differential HLA class I and class II associations in pemphigus foliaceus and pemphigus vulgaris patients from a prevalent Southeastern Brazilian region. , 2016, Journal of autoimmunity.

[3]  J. Shaw,et al.  Distribution of Lutzomyia longipalpis Chemotype Populations in São Paulo State, Brazil , 2015, PLoS neglected tropical diseases.

[4]  J. Valenzuela,et al.  IgE anti-LJM11 sand fly salivary antigen may herald the onset of Fogo Selvagem in endemic Brazilian regions , 2014, The Journal of investigative dermatology.

[5]  M. Capurro,et al.  Effects of Aedes aegypti salivary components on dendritic cell and lymphocyte biology , 2013, Parasites & Vectors.

[6]  B. Qaqish,et al.  Cutting Edge: Brazilian Pemphigus Foliaceus Anti-Desmoglein 1 Autoantibodies Cross-React with Sand Fly Salivary LJM11 Antigen , 2012, The Journal of Immunology.

[7]  M. Mokni,et al.  Exposure to Phlebotomus papatasi and/or Leishmania major: possible etiologic link to Tunisian pemphigus. , 2012, The Journal of investigative dermatology.

[8]  J. Ribeiro,et al.  An insight into the sialotranscriptome of Simulium nigrimanum, a black fly associated with fogo selvagem in South America. , 2010, The American journal of tropical medicine and hygiene.

[9]  J. Valenzuela,et al.  Using Recombinant Proteins from Lutzomyia longipalpis Saliva to Estimate Human Vector Exposure in Visceral Leishmaniasis Endemic Areas , 2010, PLoS neglected tropical diseases.

[10]  I. J. Reason,et al.  Endemic pemphigus over a century: Part II , 2010, North American journal of medical sciences.

[11]  C. B. Marcondes.  A PROPOSAL OF GENERIC AND SUBGENERIC ABBREVIATIONS FOR PHLEBOTOMINE SANDFLIES (DIPTERA: PSYCHODIDAE: PHLEBOTOMINAE) OF THE WORLD , 2007 .

[12]  E. Galati,et al.  Nyssomyia intermedia (Lutz & Neiva, 1912) and Nyssomyia neivai (Pinto, 1926) (Diptera: Psychodidae: Phlebotominae) geographical distribution and epidemiological importance. , 2007, Memorias do Instituto Oswaldo Cruz.

[13]  A. Roselino,et al.  Endemic Pemphigus foliaceus ("Fogo selvagem"): a series from the Northeastern region of the State of São Paulo, Brazil, 1973-1998. , 2001, Revista do Instituto de Medicina Tropical de Sao Paulo.

[14]  A. de Castro Gomes,et al.  [Infestation of S. Paulo State, Brazil, by Aedes aegypti and Aedes albopictus]. , 2000, Revista de saude publica.

[15]  J. E. Tolezano.  Ecoepidemiological aspects of American cutaneous leishmaniasis in the state of São Paulo, Brazil. , 1994, Memorias do Instituto Oswaldo Cruz.

[16]  R. Millikan,et al.  Environmental risk factors in endemic pemphigus foliaceus (fogo selvagem). , 1992, The journal of investigative dermatology. Symposium proceedings.

[17]  M. Lerner,et al.  Isolation of maxadilan, a potent vasodilatory peptide from the salivary glands of the sand fly Lutzomyia longipalpis. , 1991, The Journal of biological chemistry.

[18]  J. Vieira.  PEMPHIGUS FOLIACEUS (FOGO SALVAGEM): AN ENDEMIC DISEASE OF THE STATE OF SÃO PAULO (BRAZIL) , 1940 .

[19]  Mateus Pepinelli.  Simuliidae (Diptera, Nematocera) do Estado de São Paulo , 2008 .

[20]  E. Lerner,et al.  Serum IgG from pemphigus foliaceus patients reacts against maxadilan , 2001 .

[21]  R. Hoffmann,et al.  Environmental risk factors in endemic pemphigus foliaceus (Fogo selvagem). "The Cooperative Group on Fogo Selvagem Research". , 1992, The Journal of investigative dermatology.

[22]  L. Diaz,et al.  Endemic pemphigus foliaceus (Fogo Selvagem): II. Current and historic epidemiologic studies. , 1989, The Journal of investigative dermatology.