Onchocerca Volvulus Case Study

  • Burnham G. Onchocerciasis. Lancet. 1998 May 2. 351(9112):1341-6. [Medline].

  • Hoerauf A, Büttner DW, Adjei O, Pearlman E. Onchocerciasis. BMJ. 2003 Jan 25. 326(7382):207-10. [Medline].

  • Udall DN. Recent updates on onchocerciasis: diagnosis and treatment. Clin Infect Dis. 2007 Jan 1. 44(1):53-60. [Medline].

  • Pion SD, Kamgno J, Demanga-Ngangue, Boussinesq M. Excess mortality associated with blindness in the onchocerciasis focus of the Mbam Valley, Cameroon. Ann Trop Med Parasitol. 2002 Mar. 96(2):181-9. [Medline].

  • Enk CD. Onchocerciasis--river blindness. Clin Dermatol. 2006 May-Jun. 24 (3):176-80. [Medline]. [Full Text].

  • Hoerauf A, Mand S, Volkmann L, Büttner M, Marfo-Debrekyei Y, Taylor M, et al. Doxycycline in the treatment of human onchocerciasis: Kinetics of Wolbachia endobacteria reduction and of inhibition of embryogenesis in female Onchocerca worms. Microbes Infect. 2003 Apr. 5(4):261-73. [Medline].

  • Hoerauf A, Specht S, Büttner M, Pfarr K, Mand S, Fimmers R, et al. Wolbachia endobacteria depletion by doxycycline as antifilarial therapy has macrofilaricidal activity in onchocerciasis: a randomized placebo-controlled study. Med Microbiol Immunol. 2008 Sep. 197(3):295-311. [Medline].

  • Klion AD. Filarial infections in travelers and immigrants. Curr Infect Dis Rep. 2008 Mar. 10(1):50-7. [Medline].

  • Nguyen JC, Murphy ME, Nutman TB, Neafie RC, Maturo S, Burke DS. Cutaneous onchocerciasis in an American traveler. Int J Dermatol. 2005 Feb. 44(2):125-8. [Medline].

  • Richards F Jr, Rizzo N, Diaz Espinoza CE, Monroy ZM, Crovella Valdez CG, de Cabrera RM, et al. One Hundred Years After Its Discovery in Guatemala by Rodolfo Robles, Onchocerca volvulus Transmission Has Been Eliminated from the Central Endemic Zone. Am J Trop Med Hyg. 2015 Dec. 93 (6):1295-304. [Medline].

  • Onchocerciasis. WHO Media Center. Available at http://www.who.int/mediacentre/factsheets/fs374/en/. 01/2017; Accessed: 4/25/2017.

  • Richards F Jr, Rizzo N, Diaz Espinoza CE, Morales Monroy Z, Crovella Valdez CG, de Cabrera RM, et al. One Hundred Years After Its Discovery in Guatemala by Rodolfo Robles, Onchocerca volvulus Transmission Has Been Eliminated from the Central Endemic Zone. Am J Trop Med Hyg. 2015 Oct 26. [Medline].

  • Vlaminck J, Fischer PU, Weil GJ. Diagnostic Tools for Onchocerciasis Elimination Programs. Trends Parasitol. 2015 Oct 9. [Medline].

  • World Health Organization. Onchocerciasis (river blindness). Wkly Epidemiol Rec. 2001 Jul 6. 76(27):205-10. [Medline].

  • World Health Organization. Onchocerciasis and its control. Report of a WHO Expert Committee on Onchocerciasis Control. World Health Organ Tech Rep Ser. 1995. 852:1-104. [Medline].

  • World Health Organization. Onchocerciasis (river blindness). Report from the Fourteenth InterAmerican Conference on Onchocerciasis, Atlanta, Georgia, United States. Wkly Epidemiol Rec. 2005 Jul 29. 80(30):257-60. [Medline].

  • World Health Organization. Onchocerciasis (river blindness). Wkly Epidemiol Rec. 2001 Jul 6. 76(27):205-10. [Medline].

  • Dimomfu BL, Lubeji DK, Noma M, Sékétéli A, Boussinesq M. African Programme for Onchocerciasis Control (APOC): sociological study in three foci of central Africa before the implementation of treatments with ivermectin (Mectizan). Trans R Soc Trop Med Hyg. 2007 Jul. 101(7):674-9. [Medline].

  • Hotez PJ. Control of onchocerciasis--the next generation. Lancet. 2007 Jun 16. 369(9578):1979-80. [Medline].

  • Sauerbrey M. The Onchocerciasis Elimination Program for the Americas (OEPA). Ann Trop Med Parasitol. 2008 Sep. 102 Suppl 1:25-9. [Medline].

  • Amazigo U. The African Programme for Onchocerciasis Control (APOC). Ann Trop Med Parasitol. 2008 Sep. 102 Suppl 1:19-22. [Medline].

  • Boatin B. The Onchocerciasis Control Programme in West Africa (OCP). Ann Trop Med Parasitol. 2008 Sep. 102 Suppl 1:13-7. [Medline].

  • Krotneva SP, Coffeng LE, Noma M, Zouré HG, Bakoné L, Amazigo UV, et al. African Program for Onchocerciasis Control 1995-2010: Impact of Annual Ivermectin Mass Treatment on Off-Target Infectious Diseases. PLoS Negl Trop Dis. 2015 Sep. 9 (9):e0004051. [Medline].

  • Progress towards eliminating onchocerciasis in the WHO Region of the Americas: verification of elimination of transmission in Guatemala. Wkly Epidemiol Rec. 2016 Oct 28. 91 (43):501-5. [Medline].

  • Enk CD. Onchocerciasis--river blindness. Clin Dermatol. 2006 May-Jun. 24(3):176-80. [Medline].

  • Kayembe DL, Kasonga DL, Kayembe PK, Mwanza JC, Boussinesq M. Profile of eye lesions and vision loss: a cross-sectional study in Lusambo, a forest-savanna area hyperendemic for onchocerciasis in the Democratic Republic of Congo. Trop Med Int Health. 2003 Jan. 8(1):83-9. [Medline].

  • Timmann C, van der Kamp E, Kleensang A, König IR, Thye T, Büttner DW, et al. Human genetic resistance to Onchocerca volvulus: evidence for linkage to chromosome 2p from an autosome-wide scan. J Infect Dis. 2008 Aug 1. 198(3):427-33. [Medline].

  • Kayembe DL, Kasonga DL, Kayembe PK, Mwanza JC, Boussinesq M. Profile of eye lesions and vision loss: a cross-sectional study in Lusambo, a forest-savanna area hyperendemic for onchocerciasis in the Democratic Republic of Congo. Trop Med Int Health. 2003 Jan. 8(1):83-9. [Medline].

  • Colebunders R, Hendy A, van Oijen M. Nodding Syndrome in Onchocerciasis Endemic Areas. Trends Parasitol. 2016 Aug. 32 (8):581-3. [Medline].

  • Lipner EM, Dembele N, Souleymane S, Alley WS, Prevots DR, Toe L, et al. Field applicability of a rapid-format anti-Ov-16 antibody test for the assessment of onchocerciasis control measures in regions of endemicity. J Infect Dis. 2006 Jul 15. 194(2):216-21. [Medline].

  • Weil GJ, Steel C, Liftis F, Li BW, Mearns G, Lobos E. A rapid-format antibody card test for diagnosis of onchocerciasis. J Infect Dis. 2000 Dec. 182(6):1796-9. [Medline].

  • Nde PN, Pogonka T, Bradley JE, Titanji VP, Lucius R. Sensitive and specific serodiagnosis of onchocerciasis with recombinant hybrid proteins. Am J Trop Med Hyg. 2002 May. 66(5):566-71. [Medline].

  • Rodríguez-Pérez MA, Domínguez-Vázquez A, Méndez-Galván J, Sifuentes-Rincón AM, Larralde-Corona P, Barrera-Saldaña HA, et al. Antibody detection tests for Onchocerca volvulus: comparison of the sensitivity of a cocktail of recombinant antigens used in the indirect enzyme-linked immunosorbent assay with a rapid-format antibody card test. Trans R Soc Trop Med Hyg. 2003 Sep-Oct. 97(5):539-41. [Medline].

  • Guzmán GE, Lavebratt C, Luján R, Akuffo H. Diagnosis of onchocerciasis using highly specific and sensitive native proteins. Scand J Infect Dis. 2002. 34(8):583-90. [Medline].

  • Ayong LS, Tume CB, Wembe FE, Simo G, Asonganyi T, Lando G. Development and evaluation of an antigen detection dipstick assay for the diagnosis of human onchocerciasis. Trop Med Int Health. 2005 Mar. 10(3):228-33. [Medline].

  • Boatin BA, Toé L, Alley ES, Dembélé N, Weiss N, Dadzie KY. Diagnostics in onchocerciasis: future challenges. Ann Trop Med Parasitol. 1998 Apr. 92 Suppl 1:S41-5. [Medline].

  • Ozoh G, Boussinesq M, Bissek AC, Kobangue L, Kombila M, Mbina JR, et al. Evaluation of the diethylcarbamazine patch to evaluate onchocerciasis endemicity in Central Africa. Trop Med Int Health. 2007 Jan. 12(1):123-9. [Medline].

  • Toè L, Adjami AG, Boatin BA, Back C, Alley ES, Dembélé N. Topical application of diethylcarbamazine to detect onchocerciasis recrudescence in west Africa. Trans R Soc Trop Med Hyg. 2000 Sep-Oct. 94(5):519-25. [Medline].

  • Guderian RH. Effects of nodulectomy in onchocerciasis in Ecuador. Trop Med Parasitol. 1988 Dec. 39 Suppl 4:356-7. [Medline].

  • Kale, O. O. "Controlled studies on the effect of nodulectomy on the concentration of microfilariae in the skin of patients exposed o continuing transmission of Onchocerca volvulus in the rain-forest zone of Western Nigeria.". Tropenmedizin und Parasitologie. 1982. 40-42.

  • Basáñez MG, Pion SD, Boakes E, Filipe JA, Churcher TS, Boussinesq M. Effect of single-dose ivermectin on Onchocerca volvulus: a systematic review and meta-analysis. Lancet Infect Dis. 2008 May. 8(5):310-22. [Medline].

  • Reddy M, Gill SS, Kalkar SR, Wu W, Anderson PJ, Rochon PA. Oral drug therapy for multiple neglected tropical diseases: a systematic review. JAMA. 2007 Oct 24. 298(16):1911-24. [Medline].

  • Gutman J, Emukah E, Okpala N, Okoro C, Obasi A, Miri ES. Effects of annual mass treatment with ivermectin for onchocerciasis on the prevalence of intestinal helminths. Am J Trop Med Hyg. 2010 Sep. 83(3):534-41. [Medline].

  • Hoerauf A, Mand S, Adjei O, Fleischer B, Büttner DW. Depletion of wolbachia endobacteria in Onchocerca volvulus by doxycycline and microfilaridermia after ivermectin treatment. Lancet. 2001 May 5. 357(9266):1415-6. [Medline].

  • Taylor MJ, Hoerauf A, Townson S, Slatko BE, Ward SA. Anti-Wolbachia drug discovery and development: safe macrofilaricides for onchocerciasis and lymphatic filariasis. Parasitology. 2014 Jan. 141 (1):119-27. [Medline].

  • Linehan M, Hanson C, Weaver A, et al. Integrated implementation of programs targeting neglected tropical diseases through preventive chemotherapy: proving the feasibility at national scale. Am J Trop Med Hyg. 2011 Jan. 84(1):5-14. [Medline].

  • Turner JD, Tendongfor N, Esum M, et al. Macrofilaricidal activity after doxycycline only treatment of Onchocerca volvulus in an area of Loa loa co-endemicity: a randomized controlled trial. PLoS Negl Trop Dis. 2010 Apr 13. 4(4):e660. [Medline]. [Full Text].

  • Klarmann-Schulz U, Specht S, Debrah AY, Batsa L, Ayisi-Boateng NK, Osei-Mensah J, et al. Comparison of Doxycycline, Minocycline, Doxycycline plus Albendazole and Albendazole Alone in Their Efficacy against Onchocerciasis in a Randomized, Open-Label, Pilot Trial. PLoS Negl Trop Dis. 2017 Jan. 11 (1):e0005156. [Medline].

  • Specht S, Mand S, Marfo-Debrekyei Y, Debrah AY, Konadu P, Adjei O, et al. Efficacy of 2- and 4-week rifampicin treatment on the Wolbachia of Onchocerca volvulus. Parasitol Res. 2008 Nov. 103(6):1303-9. [Medline].

  • Hoerauf A, Marfo-Debrekyei Y, Büttner M, Debrah AY, Konadu P, Mand S, et al. Effects of 6-week azithromycin treatment on the Wolbachia endobacteria of Onchocerca volvulus. Parasitol Res. 2008 Jul. 103(2):279-86. [Medline].

  • Bah GS, Ward EL, Srivastava A, Trees AJ, Tanya VN, Makepeace BL. Efficacy of three-week oxytetracycline or rifampicin monotherapy compared with a combination regimen against the filarial nematode Onchocerca ochengi. Antimicrob Agents Chemother. 2013 Nov 18. [Medline].

  • Siva N. WHO researchers start trial on a new drug for river blindness. BMJ. 2009. 339:b2755. [Medline].

  • World Health Organization. Guidelines for Stopping Mass Drug Administration and Verifying Elimination of Human Onchocerciasis. 2016. [Medline]. [Full Text].

  • Report from the 2009 Inter-American Conference on Onchocerciasis: progress towards eliminating river blindness in the Region of the Americas. Wkly Epidemiol Rec. 2010 Aug 13. 85(33):321-6. [Medline].

  • Schneider MC, Aguilera XP, Barbosa da Silva Junior J, et al. Elimination of neglected diseases in latin america and the Caribbean: a mapping of selected diseases. PLoS Negl Trop Dis. 2011 Feb 15. 5(2):e964. [Medline]. [Full Text].

  • Abstract

    Recent progress in onchocerciasis research has led to improved understanding of the immunopathology of Onchocerca volvulus, as well as improvements in diagnosis and treatment of this morbid disease. This article reviews the recent literature, highlighting breakthroughs in sensitive means of antigen testing and an unusual new approach to therapy that targets an endosymbiotic bacterium required for filarial worm fecundity.

    Epidemiology

    Most widely known for causing “river blindness,” Onchocerca volvulus infection affects an estimated 17.7 million people worldwide in 34 countries in Africa, the Middle East, South America, and Central America. An estimated 500,000 people and 270,000 people experience secondary visual impairment and blindness, respectively [1]. Nations with the highest historical prevalence of onchocerciasis include 11 sub-Saharan West African nations, such as Ghana, Nigeria, Liberia, and parts of Mali; however, endemicity extends latitudinally across the entire continent of Africa and into Southwest Asia, with patchy foci in Yemen and Oman in the Arabian Peninsula. Small foci are also located in Ecuador, Venezuela, Colombia, Brazil, southern Mexico, and Guatemala [2]. Relationships between infection prevalence and individual infection intensity and between infection prevalence and transmission intensity appear to follow similar patterns in Africa and in Latin America, lending epidemiological support for Mesoamerican O. volvulus having a genetically recent relation to African O. volvulus [3]. In all, an estimated 123 million people live in areas where the disease is endemic. Onchocerciasis among nonimmigrant North Americans is almost entirely limited to travelers to areas of endemicity.

    Onchocerciasis as a human disease has been shown to have more than just an effect on the quality of life; it also appears to shorten it. Little et al. [4] found an association between O. volvulus microfilarial load and all-cause mortality, claiming that 5% of the deaths in the study' temporal and regional boundaries were attributable to O. volvulus infection. Blindness per se did not appear to have a significant effect on mortality when adjusted for microfilarial load. Recent data show that patients with glaucoma in Ghana had a higher prevalence of onchocerciasis (i.e., they had positive skin snip test results), even after adjustment for age, region, and sex (OR, 3.50; 95% CI, 1.10– 11.18) [5].

    Life Cycle

    O. volvulus has a 5-stage life cycle, in which the blackfly (genus Simulium) acts as obligate intermediate host ( figure 1). Humans are the sole definitive host. Infection occurs when a blackfly introduces an O. volvulus stage 3 larva into the host during a blood meal. The female nematode develops to adulthood and permanently incarcerates itself in a fibrous capsule, whereas male adults move freely throughout the skin and subcutaneous spaces. During adulthood, the female worm sheds hundreds of thousands of microfilariae measuring 220– 360 µ m [6] that migrate through the skin of the human host, with particular affinity for the eyes. The inflammatory response against dying microfilariae over years of repeated infection causes the gradual and eventually blinding sclerosal opacification of the anterior eye by local inflammation and of the posterior eye by autoimmune mechanisms [7]. The O. volvulus life cycle continues on uptake of microfilariae by the blackfly during a blood meal. Once inside, the microfilariae penetrate the fly' gut and migrate to the thoracic flight muscles, where they develop to third-stage larvae and then find their way to the blackfly' feeding apparatus. They then enter another human host during a blood meal, thus completing the cycle. Microfilariae persist in the human host for 3– 5 years, in contrast to the adult female worm life span, which is 2– 15 years [8, 9]. Filarial reproduction numbers and life spans are listed in table 1.

    During the late 1990s, it was discovered that a Wolbachia rickettsial bacterium inhabits the endodermis of female O. volvulus worms and various stages of its intrauterine embryos, and it appears to have coevolved with Onchocerca [10]. This obligative endosymbiont has confused past efforts to characterize worm proteins. Previous studies on “filarial” peptides obtained by homogenizing the entire worm— with only rudimentary purification steps— actually may have been detecting Wolbachia proteins and intrinsic worm antigens [13].

    Clinical Presentation and Pathogenesis

    Onchocerciasis most commonly presents as a diffuse papular dermatitis, often with intense pruritis. These recently infected patients tend to demonstrate a strong TH1-type immune response. In patients with chronic disease, however, the cutaneous manifestations can be differentiated across a spectrum, from pruritic lichenification on one end to asymptomatic depigmentation (the “leopard skin” pattern) on the other. Chronic papules and lichenification are associated with strong T helper lymphocyte (TH2) response, whereas depigmentation has been shown to correlate with a milder TH2 reactivity [11]. A subset of patients with chronic disease have papular disease that is similar in appearance to the acute papular eruption, but it is nevertheless TH2 predominant. Retinal and retinoic acids accumulate in tissues after the death of microfilariae and may be partially responsible for skin and ocular symptoms [14]. Exposure to Onchocerca breakdown products induces a strong eosinophilic response as well [15]. In contrast, the ocular pathology has been attributed to an immune reaction to Wolbachia antigens released as microfilariae undergo natural attrition over time [10, 16].

    Subdermal nodules called “onchocercomata,” which are most easily seen over bony prominences [17], are another commonly reported manifestation of onchocerciasis. The value and reliability of verbal diagnosis by eliciting a history of nodules in areas where the disease is highly endemic have been described elsewhere [18]. In Africa, onchocercomata are often found over the bony prominences of the torso and hips, whereas in South America, where it is sometimes called “Robles disease” [1], the predominant strains typically produce nodules in the head and shoulders [19]. Cases of onchocercoma presenting as a breast mass [20] or as deep nodules in the pelvis [17] have been described. An angiogenic protein produced by the adult female is thought to contribute to the formation of the nodules. Each adult worm is estimated to produce 1600 microfilariae per day [14], and estimates have indicated a total daily turnover of 10,000– 300,000 microfilariae at a steady state, with peak total body loads of 150 million [10, 12]. The presence of onchocercomata does not correlate with microfilarial load [17].

    Aside from exposure to infected blackfly bites, a dominant risk factor for onchocerciasis infection in children in areas of endemicity may be maternal onchocercal infection during the gestational period [21]. This is not thought to result from vertical transmission but, rather, from stimulation of a fetal shift toward a TH2 response to onchocercal infection that, on exposure later in life, favors tolerance of the presence of O. volvulus and, paradoxically, more-severe dermatological symptoms [11]. This conclusion has yet to be independently validated.

    Onchocerciasis and The Immune System

    It has been suggested that people with early O. volvulus infection have a significantly increased cell-mediated immune response, compared with patients who have chronic infection, who tend to have a blunted cellular immunity [22]. Prolonged infection promotes physiology more tolerant of the O. volvulus presence, although the mechanisms are not clear.

    Higher microfilarial loads have been associated with a lower severity of onchodermatitis. The degree of dermatitis is directly correlated with cytoadherence activity and cell proliferation in the host, and it is inversely correlated with microfilarial loads [23]. Thus, as is seen in Hansen disease and leishmaniasis, there appears to be a spectrum of disease with low-level infestations and highly symptomatic host reaction on one side, and concentrated infestation but less severe immune-mediated disease on the other. Whether this variability is inherent in the strains or is associated with host variability is not clear. In addition, the immune response to larval (L3) antigens appears to strengthen with age and duration of patency while developing an immune environment increasingly permissive to the presence of adult worms and microfilariae [24]. In other words, as the infected patient ages and develops a larger total worm load, the body becomes less susceptible to infection with new blackfly-transmitted L3 larvae.

    The predominant skin disease is thought to be a reaction to Onchocerca antigens, not Wolbachia antigens [11]. In contrast, both Wolbachia and Onchocerca antigens have an effect on the cornea. Wolbachia antigens released during microfilarial dying are largely responsible for the corneal inflammation that eventually leads to blindness [25, 26]. Wolbachia species do, however, seem to stimulate a systemic neutrophil response, which Brattig et al. [27] suggest may be part of the worm' adaptation to the competent host' immune environment and even a necessary condition for proper mating. In addition, a study that documented a cross-reaction between Ov39 antigen from Onchocerca volvulus and the human ocular tissue antigen hr44 implicated autoimmunity in the clinical ocular disease [28].

    Onchocerciasis and Hiv Infection

    If exposed to HIV, especially the macrophage-tropic HIV-1, patients with onchocerciasis have a greater likelihood of converting to HIV positivity than do those without onchocerciasis [29]. The same study also suggests that treatment of onchocerciasis in HIV-1– infected patients decreases viral replication. HIV infection may worsen the severity of onchodermatitis, although this aspect of the relationship has not been well studied [30, 31]. Recent work by Kipp et al. [32] reaffirms that it is safe to include HIV-infected patients in mass-treatment populations.

    Differential Diagnosis

    The differential diagnosis of the diffuse papular dermatitis seen in acute onchocerciasis is extensive and may include food allergies, leprosy, pinta, syphilis, vitamin A deficiency, and yaws [5]. Also, certain parasitic infestations can resemble onchocerciasis. Other Onchocerca species— Onchocerca gutturosa, in most cases— have been found to infect humans, but only 6 cases of infection have been reported, without evidence of transmission [33]. Rarely, O. volvulus infection can mimic dracunculiasis, the subcutaneous filaria emerging at the skin in 3 documented cases [34].

    Laboratory Diagnosis

    Perhaps the most important concept to understand when comparing diagnostic modalities is the lack of a reliable gold standard ( table 2). Onchocercomectomy with direct examination can be used to diagnose infestation, but not necessarily the potential to pass on infection (infectivity), which requires microfilaridermia [17]. Historically, the procedure of choice for the definitive diagnosis of onchocerciasis has been to use a sclerocorneal punch to obtain skin-tissue specimens from the iliac crests and search microscopically for microfilariae (skin-snip microscopy). It takes ∼ 1.5 years [39] for the worm to mature and release enough microfilariae to be detectable by skin-snip microscopy, and the sensitivity of skin-snip microscopy is too low to be useful in areas where there is a low prevalence of cases [35]. Testing for cure in treated populations, especially in those with a low prevalence of infection, presents a challenge. In patients repatriated from areas of endemicity, resolution of pruritic papular eruption is a better indicator of cure than is resolution of eosinophilia or IgE levels [40].

    Table 2

    0 thoughts on “Onchocerca Volvulus Case Study”

      -->

    Leave a Comment

    Your email address will not be published. Required fields are marked *