Volume 80, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


The treatment for hydrocele is expensive, invasive surgery—hydrocelectomy. A drug that could prevent or improve this condition could replace or supplement hydrocelectomy. In Ghana, 42 hydrocele patients participated in a double-blind, placebo-controlled trial of a six-week regimen of doxycycline, 200 mg/day. Four months after doxycycline treatment, patients received 150 μg/kg of ivermectin and 400 mg of albendazole, which is used for mass chemotherapy in this area. Patients were monitored for levels of sp., microfilaremia, antigenemia, plasma levels of vascular endothelial growth factor-A (VEGF-A) and stage/size of the hydrocele. sp. loads/microfilaria, microfilaremia, and antigenemia were significantly reduced in the doxycycline-treated patients compared with the placebo group. The mean plasma levels of VEGF-A were decreased significantly in the doxycycline-treated patients who had active infection. This finding preceded the reduction of the stage of hydrocele. A six-week regimen of doxycycline treatment against filariasis showed amelioration of pathologic conditions of hydrocele patients with active infection.


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  1. Ottesen EA, 2000. The global programme to eliminate lymphatic filariasis. Trop Med Int Health 5 : 591–594.
  2. Addiss DG, Brady MA, 2007. Morbidity management in the global programme to eliminate lymphatic filariasis: a review of the scientific literature. Filaria J 6 : 2.
  3. World Health Organization, 2006. Global programme to eliminate lymphatic filariasis. Wkly Epidemiol Rec 81 : 221–232.
  4. Eigege A, Richards FO Jr, Blaney DD, Miri ES, Gontor I, Ogah G, Umaru J, Jinadu MY, Mathai W, Amadiegwu S, Hopkins DR, 2003. Rapid assessment for lymphatic filariasis in central Nigeria: a comparison of the immunochromatographic card test and hydrocele rates in an area of high endemicity. Am J Trop Med Hyg 68 : 643–646.
  5. Jordan P, 1957. The fevers of Africa. 5. Clinical bancroftian disease in Tankanyika. Cent Afr J Med 3 : 18–23.
  6. Dreyer G, Nores J, Addis D, 1997. The silent burden of sexual disability associated with lymphatic filariasis. Acta Trop 63 : 57–60.
  7. Wegesa P, McMahon JE, Abaru DE, Hamilton PJ, Marshall TF, Vaughan JP, 1979. Tanzania filariasis project: survey methodology and clinical manifestations of bancroftian filariasis. Acta Trop 36 : 369–377.
  8. Mwobobia IK, Muniu EM, Kombe Y, Wamae CN, 2000. Hydrocelectomy: a proxy for hydrocele prevalence in coastal Kenya. Ann Trop Med Parasitol 94 : 479–484.
  9. DeVries CR, 2002. The role of the urologist in the treatment and elimination of lymphatic filariasis worldwide. BJU Int 89 (Suppl 1): 37–43.
  10. Ottesen EA, 1992. The Wellcome Trust Lecture. Infection and disease in lymphatic filariasis: an immunological perspective. Parasitology 104 (Suppl): S71–S79.
  11. Ottesen EA, 1980. Immunopathology of lymphatic filariasis in man. Springer Semin Immunopathol 2 : 373–385.
  12. Ottesen EA, Weller PF, Lunde MN, Hussain R, 1982. Endemic filariasis on a Pacific Island. II. Immunologic aspects: immunoglobulin, complement, and specific antifilarial IgG, IgM, and IgE antibodies. Am J Trop Med Hyg 31 : 953–961.
  13. Debrah AY, Mand S, Toliat RM, Marfo-Debrekyei Y, Batsa L, Nuernberg P, Lawson B, Adjei O, Hoerauf A, Pfarr K, 2007. Plasma vascular endothelial growth factor-A (VEGF-A) and VEGF-A gene polymorphism are associated with hydrocele development in lymphatic filariasis. Am J Trop Med Hyg 77 : 601–608.
  14. Ferrara N, 2000. Vascular endothelial growth factor and the regulation of angiogenesis. Recent Prog Horm Res 55 : 15–35.
  15. Carmeliet P, 2000. VEGF gene therapy: stimulating angiogenesis or angiomagenesis? Nat Med 6 : 1102–1103.
  16. Awata T, Inoue K, Kurihara S, Ohkubo T, Watanabe M, Inukai K, Inoue I, Katayama S, 2002. A common polymorphism in the 5′-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes. Diabetes 51 : 1635–1639.
  17. Ray D, Mishra M, Ralph S, Read I, Davies R, Brenchley P, 2004. Association of the VEGF gene with proliferative diabetic retinopathy but not proteinuria in diabetes. Diabetes 53 : 861–864.
  18. Dvorak HF, Brown LF, Detmar M, Dvorak AM, 1995. Vascular permeability factor/vascular endothelial growth factor, micro-vascular hyperpermeability, and angiogenesis. Am J Pathol 146 : 1029–1039.
  19. Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF, 1983. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219 : 983–985.
  20. Esterre P, Plichart C, Huin-Blondey MO, Nguyen LN, 2005. Soluble cellular adhesion molecules, selectins, VEGF and endothelin-1 in patients with Wuchereria bancrofti infection and association with clinical status. Parasite Immunol 27 : 9–16.
  21. Debrah AY, Mand S, Specht S, Marfo-Debrekyei Y, Batsa L, Pfarr K, Larbi J, Lawson B, Taylor M, Adjei O, Hoerauf A, 2006. Doxycycline reduces plasma VEGF-C/sVEGFR-3 and improves pathology in lymphatic filariasis. PLoS Pathog 2 : e92.
  22. Turner JD, Mand S, Debrah AY, Muehlfeld J, Pfarr K, McGarry HF, Adjei O, Taylor MJ, Hoerauf A, 2006. A randomized, double-blind clinical trial of a 3-week course of doxycycline plus albendazole and ivermectin for the treatment of Wuchereria bancrofti infection. Clin Infect Dis 42 : 1081–1089.
  23. Ristimaki A, Narko K, Enholm B, Joukov V, Alitalo K, 1998. Proinflammatory cytokines regulate expression of the lymphatic endothelial mitogen vascular endothelial growth factor-C. J Biol Chem 273 : 8413–8418.
  24. Rutkowski JM, Moya M, Johannes J, Goldman J, Swartz MA, 2006. Secondary lymphedema in the mouse tail: lymphatic hyperplasia, VEGF-C upregulation, and the protective role of MMP-9. Microvasc Res 72 : 161–171.
  25. Gyapong M, Gyapong J, Weiss M, Tanner M, 2000. The burden of hydrocele on men in northern Ghana. Acta Trop 77 : 287–294.
  26. Meyrowitsch DW, Simonsen PE, Makunde WH, 1996. Mass DEC chemotherapy for control of bancroftian filariasis: comparative efficacy of four strategies two years after start of treatment. Trans R Soc Trop Med Hyg 90 : 423–428.
  27. Bockarie MJ, Alexander ND, Hyun P, Dimber Z, Bockarie F, Ibam E, Alpers MP, Kazura JW, 1998. Randomised community-based trial of annual single-dose diethylcarbamazine with or without ivermectin against Wuchereria bancrofti infection in human beings and mosquitoes. Lancet 351 : 162–168.
  28. Bockarie MJ, Tisch DJ, Kastens W, Alexander ND, Dimber Z, Bockarie F, Ibam E, Alpers MP, Kazura JW, 2002. Mass treatment to eliminate filariasis in Papua New Guinea. N Engl J Med 347 : 1841–1848.
  29. Bernhard P, Magnussen P, Lemnge MM, 2001. A randomized, double-blind, placebo-controlled study with diethylcarbamazine for the treatment of hydrocoele in an area of Tanzania endemic for lymphatic filariasis. Trans R Soc Trop Med Hyg 95 : 534–536.
  30. Kyelem D, Sanou S, Boatin B, Medlock J, Coulibaly S, Molyneux DH, 2003. Impact of long-term ivermectin (Mectizan) on Wuchereria bancrofti and Mansonella perstans infections in Burkina Faso: strategic and policy implications. Ann Trop Med Parasitol 97 : 827–838.
  31. Hoerauf A, Mand S, Fischer K, Kruppa T, Marfo-Debrekyei Y, Debrah AY, Pfarr KM, Adjei O, Buttner DW, 2003. Doxycycline as a novel strategy against bancroftian filariasis-depletion of Wolbachia endosymbionts from Wuchereria bancrofti and stop of microfilaria production. Med Microbiol Immunol (Berl) 192 : 211–216.
  32. Mand S, Marfo-Debrekyei Y, Dittrich M, Fischer K, Adjei O, Hoerauf A, 2003. Animated documentation of the filaria dance sign (FDS) in bancroftian filariasis. Filaria J 2 : 3.
  33. Taylor MJ, Makunde WH, McGarry HF, Turner JD, Mand S, Hoerauf A, 2005. Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo-controlled trial. Lancet 365 : 2116–2121.
  34. World Health Organization, 1997. Chagas disease, leprosy, lymphatic filariasis, onchocerciasis: prospects for elimination. TDR/ Gen 97: 17–22.
  35. Michael E, Bundy DA, Grenfell BT, 1996. Re-assessing the global prevalence and distribution of lymphatic filariasis. Parasitol 112 : 409–428.
  36. Ottesen EA, Duke BO, Karam M, Behbehani K, 1997. Strategies and tools for the control/elimination of lymphatic filariasis. Bull World Health Organ 75 : 491–503.
  37. Addiss DG, Brady MA, 2007. Morbidity management in the global programme to eliminate lymphatic filariasis: a review of the scientific literature. Filaria J 6 : 2.
  38. Faris R, Hussain O, El Setouhy M, Ramzy RM, Weil GJ, 1998. Bancroftian filariasis in Egypt: visualization of adult worms and subclinical lymphatic pathology by scrotal ultrasound. Am J Trop Med Hyg 59 : 864–867.
  39. Jeltsch M, Kaipainen A, Joukov V, Meng X, Lakso M, Rauvala H, Swartz M, Fukumura D, Jain RK, Alitalo K, 1997. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science 276 : 1423–1425.
  40. Peixoto CA, Figueiredo-Silva J, 2001. Fine structure of intrascrotal lymphatic vessels infected by Wuchereria bancrofti adult worms. J Submicrosc Cytol Pathol 33 : 125–131.
  41. Norões J, Addiss D, Santos A, Medeiros Z, Coutinho A, Dreyer G, 1996. Ultrasonographic evidence of abnormal lymphatic vessels in young men with adult Wuchereria bancrofti infection in the scrotal area. J Urol 156 : 409–412.
  42. Saaristo A, Tammela T, Timonen J, Yla-Herttuala S, Tukiainen E, Asko-Seljavaara S, Alitalo K, 2004. Vascular endothelial growth factor-C gene therapy restores lymphatic flow across incision wounds. FASEB J 18 : 1707–1709.
  43. Yoon YS, Murayama T, Gravereaux E, Tkebuchava T, Silver M, Curry C, Wecker A, Kirchmair R, Hu CS, Kearney M, Ashare A, Jackson DG, Kubo H, Isner JM, Losordo DW, 2003. VEGF-C gene therapy augments postnatal lymphangiogenesis and ameliorates secondary lymphedema. J Clin Invest 111 : 717–725.
  44. Karkkainen MJ, Jussila L, Ferrell RE, Finegold DN, Alitalo K, 2001. Molecular regulation of lymphangiogenesis and targets for tissue oedema. Trends Mol Med 7 : 18–22.
  45. Ottesen E, Weil GJ, 2004. Towards a strategic plan for research to support the global programme to eliminate lymphatic filariasis. Am J Trop Med Hyg 71 (Suppl): 1–2.

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  • Received : 04 Dec 2007
  • Accepted : 26 Feb 2009

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