• 1.

    Lacerda NB, Rachou RG, 1956. Filarioses humanas nas sedes municipais do Estado do Amazonas e territórios do Acre, Guaporé Rio Branco. Rev Bras Malariol Doencas Trop 8: 437442.

    • Search Google Scholar
    • Export Citation
  • 2.

    Shelley AJ, Coscarón S, 2001. Simuliid blackflies (Diptera: Simuliidae) and ceratopogonid midges (Diptera: Ceratopogonidae) as vectors of Mansonella ozzardi (Nematoda: Onchocercidae) in northern Argentina. Mem Inst Oswaldo Cruz 96: 451458.

    • Search Google Scholar
    • Export Citation
  • 3.

    Deane MP, 1949. Sobre a incidência de filárias humanas em Manaus, Estado do Amazonas. Rev Serv Esp Saude Publ 2: 849858.

  • 4.

    Batista D, Oliveira WR, Rabello VD, 1960. Estudo da patogenicidade da Mansonella ozzardi e da sintomatologia da mansonelose. Rev Inst Med Trop São Paulo 2: 281289.

    • Search Google Scholar
    • Export Citation
  • 5.

    Oliveira WR, 1961. Filarioses humanas na cidade de Manaus. Hosp (Lond) 56: 301303.

  • 6.

    Tavares AM, 1981. Estudo da Infecção por Mansonella ozzardi. MsD Thesis, Departamento de Medicina, Universidade de Brasília, Brasília, Brazil.

  • 7.

    Nutman TB, Nash TE, Ottesen EA, 1987. Ivermectin in the successful treatment of a patient with Mansonella ozzardi infection. J Infect Dis 156: 662665.

    • Search Google Scholar
    • Export Citation
  • 8.

    Chadee DD, Tilluckdharry CG, Doon R, Rawlins SC, Narayansingh V, Ariyanayagam DC, Teelucksingh S, Gaxote P, 1996. Ivermectin treatment of mansonellosis in Blanchisseuse, Trinidad, West Indies. Ann Trop Med Parasitol 90: 645649.

    • Search Google Scholar
    • Export Citation
  • 9.

    González AA, Chadee DD, Rawlins SC, 1999. Ivermectin treatment of mansonellosis in Trinidad. West Indian Med J 48: 231234.

  • 10.

    Basano SA, Fontes G, Medeiros JF, Camargo JSAA, Vera LJS, Araújo MPP, Parente MSP, Ferreira RGM, Crispim PTB, Camargo LMA, 2014. Sustained clearance of Mansonella ozzardi infection after treatment with ivermectin in the Brazilian Amazon. Am J Trop Med Hyg 90: 11701175.

    • Search Google Scholar
    • Export Citation
  • 11.

    Naquira C, Jimenez G, Guerra JG, Bernal R, Nalin DR, Neu D, Aziz M, 1989. Ivermectin for human strongyloidiasis and other intestinal helminths. Am J Trop Med Hyg 40: 304309.

    • Search Google Scholar
    • Export Citation
  • 12.

    Araújo CF, Fernanddez CL, 2005. Prevalência de parasitoses intestinais na cidade de Eirunepé, Amazonas. Rev Soc Bras Med Trop 38: 69.

  • 13.

    Bisoffi Z, Buonfrate D, Angheben A, Boscolo M, Anselmi M, Marocco S, Monteiro G, Gobbo M, Bisoffi G, Gobbi F, 2011. Randomized clinical trial on ivermectin versus thiabendazole for the treatment of strongyloidiasis. PLoS Negl Trop Dis 5: e1254.

    • Search Google Scholar
    • Export Citation
  • 14.

    IBGE–Instituto Brasileiro de Geografia e Estatística, 2017. Populações Estimadas–Brasil, Censo 2010. Available at: http://cidades.ibge.gov.br/v4/brasil/am/labrea/panorama. Accessed June 6, 2017.

  • 15.

    Connor RJ, 1987. Sample size for testing differences in proportions for the paired-sample design. Biometrics 43: 207211. Available at http://powerandsamplesize.com/Calculators/Compare-Paired-Proportions/McNemar-Z-test-2-Sided-Equality.

    • Search Google Scholar
    • Export Citation
  • 16.

    Chularerk P, Desowitz RS, 1970. A simplified membrane filtration technique for the diagnosis of microfilaraemia. J Parasitol 56: 623624.

  • 17.

    Ottesen EA, Campbell WC, 1994. Ivermectin in human medicine. J Antimicrob Chemother 34: 195203.

  • 18.

    Campos JRM, Barbas CSV, Filomeno LTB, Fernandez A, Minamoto H, Barbas Filho JV, Jatene FB, 1997. Human pulmonary dirofilariosis, analysis of 24 cases from São Paulo. Brazil Chest J 112: 729733.

    • Search Google Scholar
    • Export Citation
  • 19.

    França MS, 1985. Mansonelose No Estado do Amazonas: Contribuição ao Estudo Clínico e Epidemiológico. MsD Thesis, Departamento de Medicina, Universidade Federal do Rio de Janeiro, Brazil.

  • 20.

    Medeiros JF, Py-Daniel V, Barbosa UC, Farias ES, 2007. Epidemiological studies of Mansonella ozzardi (Nematoda, Onchocercidae) in indigenous communities of Pauini municipality, Amazonas, Brazil. Acta Amazon 37: 241245.

    • Search Google Scholar
    • Export Citation
  • 21.

    Medeiros JF, Py-Daniel V, Barbosa UC, Izzo TJ, 2009a. Mansonella ozzardi in Brazil: prevalence of infection in riverine communities in the Purus region, in the state of Amazonas. Mem Inst Oswaldo Cruz 104: 7480.

    • Search Google Scholar
    • Export Citation
  • 22.

    Medeiros JF, Py-Daniel V, Barbosa UC, Ogawa GM, 2009b. Ocorrência da Mansonella ozzardi (Nematoda, Onchocercidae) em comunidades ribeirinhas do rio Purus, Município de Boca do Acre, Amazonas, Brasil. Cad Saude Publica 25: 14211426.

    • Search Google Scholar
    • Export Citation
  • 23.

    Medeiros JF, Pessoa FAC, Martins M, 2010. Importância do método de gota espessa de sangue no diagnóstico de filárias simpátricas no Amazonas, Brasil. Acta Amazon 40: 779780.

    • Search Google Scholar
    • Export Citation
  • 24.

    Medeiros JF, Py-Daniel V, Barbosa UC, 2011. Prevalence of Mansonella ozzardi among riverine communities in the Lábrea municipality, State of Amazonas, Brazil. Rev Soc Bras Med Trop 44: 186190.

    • Search Google Scholar
    • Export Citation
  • 25.

    Medeiros JF, Costa CA, Lima AM, Pessoa FAC, 2014. Mansonella ozzardi (Nematoda: Onchocercidae) in the riverine population of the Tefé River, State of Amazonia, Brazil. Rev Soc Bras Med Trop 47: 113115.

    • Search Google Scholar
    • Export Citation
  • 26.

    Aziz MA, Diallo S, Diop IM, Lariviere M, Porta M, 1982. Efficacy and tolerance of ivermectin in human onchocerciasis. Lancet 2: 171173.

  • 27.

    WHO, 1995. Onchorcerciasis and Its Control Report of a WHO Expert Committee on onchorcerciasis Control. WHO Technical Report Series 852. Geneva, Switzerland: World Health Organization.

  • 28.

    Fischer P, Buttner DW, Bamuhiiga J, Willians SA, 1998. Detection of the filarial parasite Mansonella streptocerca in skin biopsies by nested polymerase chain reaction-based assay. Am J Trop Med Hyg 58: 816820.

    • Search Google Scholar
    • Export Citation
  • 29.

    Fischer P, Tukesiga E, Büttner DW, 1999. Long term suppression of Mansonella streptocerca microfilariae after treatment with ivermectina. J Infect Dis 180: 14031405.

    • Search Google Scholar
    • Export Citation
  • 30.

    Kyelem D, Sanou S, Boatin B, Medlock J, Coulibaly S, 2003. Impact of long-term ivermectina (Mectizan) on Wuchereria bancrofti and Mansonella perstans infections in Burkina Faso: strategic and policy implications. Ann Trop Med Parasitol 97: 827838.

    • Search Google Scholar
    • Export Citation
  • 31.

    Kyelem D, Medlock J, Sanou S, Bonkoungou M, Boatin B, Molyneux DH, 2005. Impact of long-term (14 years) bi-annual ivermectin on Wuchereria bancrofti microfilaraemia. Trop Med Int Health 10: 10021004.

    • Search Google Scholar
    • Export Citation
  • 32.

    Mas J, Ascaso C, Escaramis G, Abellana R, Duran E, 2006. Reduction in the prevalence and intensity of infection in Onchorcerca volvulus microfilariae according to ethnicity and community after 8 years of ivermectin treatment on the island of Bioko, Equatorial Guinea. Trop Med Int Health 11: 10821091.

    • Search Google Scholar
    • Export Citation
  • 33.

    Canga AG, Prieto MA, Liébana MJ, Martínez NF, Veja MS, 2008. The pharmacokinets and interactions of ivermectin in humans—a mini-review. AAPS J 10: 4246.

    • Search Google Scholar
    • Export Citation
  • 34.

    Krolewieck AJ, Cajal SP, Villalpando C, Gil JF, 2011. Invermectin-related adverse clinical events in patients treated for Mansonella ozzardi infections. Rev Arg Microb 43: 4850.

    • Search Google Scholar
    • Export Citation
  • 35.

    Biagi FF, 1956. Observaciones sobre mansonelosis en la província de Yucatan I. Frecuencia. Medicine 36: 521526.

  • 36.

    Romiti C, 1935. Filariasis in British Guyana. Trans R Soc Trop Med Hyg 28: 613626.

  • 37.

    Strong HP, 1945. Diagnosis Prevention and Treatment of Tropical Diseases, 7 edition, Vol. 2. Philadelphia, PA: Blakiston, 13391340.

  • 38.

    Brumpt E, 1949. Précis de Parasitologia, 6th edition, Vol. 1. Paris, France: Masson, 930993.

  • 39.

    Augustin DL, 1951. Filariasis. Gradwohl RBH, ed. Clinical Tropical Medicine. Sant Louis, MO: Mosby, 871873.

  • 40.

    Costa OR, 1956. Contribuição ao conhecimento da filariose na Amazônia. Rev Fund SESP 8: 329422.

  • 41.

    Branco BC, Chamon W, Belfort Neto R, Belfort R Jr, Costa AJA, 1998. Achados oculares entre habitantes do município de Pauini e possível associação entre lesões corneanas e mansonelose na Amazônia. Arq Bras Oftalmol 61: 674682.

    • Search Google Scholar
    • Export Citation
  • 42.

    Cohen JM, Ribeiro JAS, Martins M, 2008. Acometimento ocular em pacientes com mansonelose. Arq Bras Oftalmol 71: 167171.

  • 43.

    Martins M, Pessoa FAC, Medeiros MB, Andrade EV, Medeiros JF, 2010. Mansonella ozzardi in Amazonas, Brazil: prevalence and distribution in the municipality of Coari, in the middle Solimões River. Mem Inst Oswaldo Cruz 105: 246253.

    • Search Google Scholar
    • Export Citation
  • 44.

    Vianna LMM, Martins M, Cohen MJ, Cohen JM, Belfort R Jr, 2012. Mansonella ozzardi corneal lesions in the Amazon: a cross-sectional study. BMJ Open 27: 15.

    • Search Google Scholar
    • Export Citation

 

 

 

 

Phase III Clinical Trial to Evaluate Ivermectin in the Reduction of Mansonella ozzardi infection in the Brazilian Amazon

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  • 1 Secretaria de Saúde do Estado de Rondônia, Porto Velho, Brazil;
  • 2 Departamento de Medicina, Centro Universitário São Lucas, Porto Velho, Brazil;
  • 3 Universidade Federal de São João Del Rei, Campus Centro Oeste, Divinópolis, Brazil;
  • 4 Instituto Nacional de Epidemiologia na Amazônia Ocidental, Porto Velho, Brazil;
  • 5 Fiocruz-Rondônia, Fundação Oswaldo Cruz, Porto Velho, Brazil;
  • 6 Instituto de Ciências Biomédicas 5 (ICB5 USP), Universidade de São Paulo, Monte Negro, Brazil;
  • 7 Centro de Pesquisas em Medicina Tropical de Rondônia/SESAU, Porto Velho, Brazil

The treatment of mansonelliasis is still a challenge because there are few clinical trials for the treatment of the disease. This double-blind, randomized, placebo-controlled study (phase III clinical trial) was conducted to evaluate the effectiveness of a single oral dose of ivermectin (0.15 mg/kg) in the reduction of the Mansonella ozzardi microfilaraemia and the occurrence of adverse effects in infected people compared with the control group treated with placebo. A total of 49 microfilaraemic patients were randomly selected from the municipality of Lábrea, State of Amazonas, in the Brazilian Amazon. Among them, 40 patients have concluded the study, 19 treated with ivermectin and 21 treated with placebo. In the first and third days after the treatment, all the patients were clinically evaluated, and the diagnostic and quantification of blood microfilariae through blood filtration in polycarbonate membranes was performed. A significant reduction of the microfilaraemia (99.9%) was observed in the patients who received ivermectin. Slight changes in laboratory test results, without clinical importance, were seen in treated and control groups. Our results suggest that ivermectin is effective and safe for the treatment of infections caused by M. ozzardi.

Author Notes

Address correspondence to Luís Marcelo Aranha Camargo, Departamento de Parasitologia, Instituto de Ciências Biomédicas 5, Rua Francisco Prestes 1234, Monte Negro, Rondônia, CEP 76.888-000, Brazil. E-mail: spider@icbusp.org

Financial support: This study was supported by the University of São Paulo (USP) and Oswaldo Cruz Foundation–Fiocruz/Rondônia.

Authors’ addresses: Sergio de Almeida Basano, Secretaria de Saúde do Estado de Rondônia, Porto Velho, Brazil, and Departamento de Medicina, Centro Universitário São Lucas, Porto Velho, Brazil, E-mail: sergio@icbusp.org. Juliana de Souza Almeida Aranha Camargo and Mayara Costa de Oliveira Laudisse, Centro Universitário São Lucas, Porto Velho, Brazil, E-mails: juliana@icbusp.org and mayaralaudisse@icloud.com. Gilberto Fontes, Universidade Federal de São João Del Rei, Divinópolis, Brazil, and Ins6tituto Nacional de Epidemiologia na Amazônia Ocidental, Porto Velho, Brazil, E-mail: gilberto.fontes@pq.cnpq.br. Antonieta Relvas Pereira, Universidade Federal de São João Del Rei, Minas Gerais, Brazil, E-mail: antonietarp@hotmail.com. Jansen Fernandes Medeiros and Ricardo de Godoi Mattos Ferreira, Fundação Oswaldo Cruz, Fiocruz-Rondônia, Porto Velho, Brazil, and Instituto Nacional de Epidemiologia na Amazônia Ocidental, Porto Velho, Brazil, E-mails: jmedeiro@gmail.com and ricardogodoi@fiocruz.br. Luís Marcelo Aranha Camargo, Departamento de Medicina, Centro Universitário São Lucas, Porto Velho, Brazil, Instituto de Ciências Biomédicas 5 (ICB5 USP), Universidade de São Paulo, Monte Negro, Brazil, Instituto Nacional de Epidemiologia na Amazônia Ocidental, Porto Velho, Brazil, and Centro de Pesquisas em Medicina Tropical de Rondônia/SESAU, Porto Velho, Brazil, E-mail: spider@icbusp.org.

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