- Email: [email protected]
Fascinating factoids on the triatomine bugs!
Research Update
responses should be undertaken by surveying all possible available antigens. With the advent of antibiotic therapy (with presumed macrofilaristatic effects [20]), studies following the changes in immune responses should be executed. A broader and more systematic attempt to define immunity to the microfilarial stage should be made. Not only should stage-specific antigens be sought, but also identifying the effector mechanisms involved in microfilarial clearance should be attempted. Studies on the nature and the targets of concomitant immunity, and anti-larval immunity in the face of patent infection and microfilarial immunity should be undertaken. There is a growing awareness that, despite the major progress made in clinical studies in areas endemic for onchocerciasis and in expatriates with O. volvulus infection [21], better clinical definition must be used. Significantly improved clinical descriptions for patient classification must be used for all human studies. Other missing information that could best be answered with clinical studies includes a better understanding of the pathogenesis of important clinical outcomes of infection (hyperreactive onchcodermatitis, generalized onchodermatitis, lymphadenopathy and eye disease). Perspective
Beyond the impediments to the development of any vaccine (such as production, cost, adjuvants, stability, schedule and route of administration), vaccine development for onchocerciasis must be tempered by the knowledge that parasites (and helminths in particular) have achieved a unique evolutionary arrangement with mammalian immune systems, which defeats simple vaccine strategies previously successful against viral and bacterial targets. Nevertheless, our growing knowledge of the host–parasite interaction, the fundamental biology of O. volvulus including its genetic makeup, methods to examine human populations and perform clinical trials, and the development of an infrastructure (moving from the identification and production of candidate antigens to the early pre-clinical testing of possible vaccines) is a testament to the vision of the EMCF and the Oncho Task Force which advised the EMCF. The spirit of resource-sharing and broad international collaborations forged by the EMCF has allowed the scientific, http://parasites.trends.com
TRENDS in Parasitology Vol.18 No.6 June 2002
medical and public health community at large the luxury of envisaging the possibility of subverting O. volvulus infection through vaccination. We must continue to build on the EMCF’s foundation. Acknowledgements
The extraordinary contributions of the members of the Oncho Task Force that included Ted Bianco, Joe Cook, John Donelson, Brian Duke, Bruce Greene, Jeff Mecaskey, Eric Ottesen, Cathy Steel, Hugh Taylor and Steve Williams are gratefully acknowledged for providing the guiding vision toward the goal of a vaccine for onchocerciasis. References 1 Cook, J.A. et al. (2001) Towards a vaccine for onchocerciasis. Trends Parasitol. 17, 555–558 2 Abraham, D. et al. (2002) Immunity to Onchocerca spp. in animal hosts. Trends Parasitol. 18, 164–170 3 Hoerauf, A. and Brattig, N. (2002) Resistance and susceptibility in human onchocerciasis-beyond Th1 vs Th2. Trends Parasitol. 18, 25–31 4 Lustigman, S. et al. (2002) Towards a recombinant antigen vaccine against Onchocerca volvulus. Trends Parasitol. 18, 135–141 5 Richards, F.O. et al. (2001) Control of onchocerciasis today: status and challenges. Trends Parasitol. 17, 558–563 6 Williams, S.A. et al. (2002) The river blindness genome project. Trends Parasitol. 18, 86–90 7 Elbashir, S.M. et al. (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411, 494–498 8 Ware, J. et al. (2002) Sequencing and analysis of a 63 kb bacterial artificial chromosome insert from the Wolbachia endosymbiont of the human filarial parasite Brugia malayi. Int. J. Parasitol. 32, 159–166 9 Taylor, M.J. et al. (2000) Wolbachia bacteria of filarial nematodes: a target for control? Parasitol. Today 16, 179–180 10 Saint André, A. et al. (2002) The role of endosymbiotic Wolbachia bacteria in the pathogenesis of river blindness. Science 295, 1892–1895
239
11 Greene, B.M. (1987) Primate model for onchocerciasis research. Ciba Found. Symp. 127, 236–243 12 Taylor, M.D. and Else, K.J. (2002) Human Trichuris-specific antibody responses in vaccinated hu-PBL-SCID mice. Parasite Immunol. 24, 1–13 13 Kamhawi, S. et al. (2000) Protection against cutaneous leishmaniasis resulting from bites of uninfected sand flies. Science 290, 1351–1354 14 Cupp, E.W. and Cupp, M.S. (1997) Black fly (Diptera:Simuliidae) salivary secretions: importance in vector competence and disease. J. Med. Entomol. 34, 87–94 15 Meyer, C.G. et al. (1994) HLA-D alleles associated with generalized disease, localized disease, and putative immunity in Onchocerca volvulus infection. Proc. Natl. Acad. Sci. U. S. A. 91, 7515–7519 16 Hoerauf, A. et al. (2002) The variant Arg110Gln of human IL-13 is associated with an immunologically hyper-reactive form of onchocerciasis (sowda). Microbes Infect. 4, 37–42 17 Maizels, R.M. et al. (2001) Immunological genomics of Brugia malayi: filarial genes implicated in immune evasion and protective immunity. Parasite Immunol. 23, 327–344 18 Harnett, W. and Harnett, M.M. (2001) Modulation of the host immune system by phosphorylcholinecontaining glycoproteins secreted by parasitic filarial nematodes. Biochim. Biophys. Acta 1539, 7–15 19 Cooper, P.J. et al. (1998) Impaired tetanus-specific cellular and humoral responses following tetanus vaccination in human onchocerciasis: a possible role for interleukin-10. J. Infect. Dis. 178, 1133–1138 20 Hoerauf, A. et al. (2001) Depletion of Wolbachia endobacteria in Onchocerca volvulus by doxycycline and microfilaridermia after ivermectin treatment. Lancet 357, 1415–1416 21 Henry, N.L. et al. (2001) Onchocerciasis in a nonendemic population: clinical and immunologic assessment before treatment and at the time of presumed cure. J. Infect. Dis. 183, 512–516
Thomas B. Nutman Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0425, USA. e-mail: [email protected]
Fascinating factoids on the triatomine bugs! The largest blood-sucking insect is the triatomine bug, Dipetalogaster maxima, which can reach 4.5 cm long and can take up to 3 ml of blood in a single meal. [Ryckman, R.E. and Ryckman, A.E. (1967) J. Med. Entomol. 4, 180–188]. Each person in a triatomine-infested house could lose ~2.5 ml of blood per day and up to 17 ml per day in exceptional cases. [Rabinovich, J.E. et al. (1979) Trans. R. Soc. Trop. Med. Hyg. 73, 272–283; Schofield, C.J. (1981) Lancet 8233, 1316]. An expert meeting in a bar estimated that if a person experienced all possible parasite and vector causes of blood loss, then the average daily blood loss could reach ~200ml per person. (R. Shrimpton, N.M. Prescott and C.J. Schofield, unpublished). If you have any ‘fascinating factoids’ from the world of parasitology, then please forward them to the Editor at [email protected] 1471-4922/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII: S1471-4922(02)02328-0
responses should be undertaken by surveying all possible available antigens. With the advent of antibiotic therapy (with presumed macrofilaristatic effects [20]), studies following the changes in immune responses should be executed. A broader and more systematic attempt to define immunity to the microfilarial stage should be made. Not only should stage-specific antigens be sought, but also identifying the effector mechanisms involved in microfilarial clearance should be attempted. Studies on the nature and the targets of concomitant immunity, and anti-larval immunity in the face of patent infection and microfilarial immunity should be undertaken. There is a growing awareness that, despite the major progress made in clinical studies in areas endemic for onchocerciasis and in expatriates with O. volvulus infection [21], better clinical definition must be used. Significantly improved clinical descriptions for patient classification must be used for all human studies. Other missing information that could best be answered with clinical studies includes a better understanding of the pathogenesis of important clinical outcomes of infection (hyperreactive onchcodermatitis, generalized onchodermatitis, lymphadenopathy and eye disease). Perspective
Beyond the impediments to the development of any vaccine (such as production, cost, adjuvants, stability, schedule and route of administration), vaccine development for onchocerciasis must be tempered by the knowledge that parasites (and helminths in particular) have achieved a unique evolutionary arrangement with mammalian immune systems, which defeats simple vaccine strategies previously successful against viral and bacterial targets. Nevertheless, our growing knowledge of the host–parasite interaction, the fundamental biology of O. volvulus including its genetic makeup, methods to examine human populations and perform clinical trials, and the development of an infrastructure (moving from the identification and production of candidate antigens to the early pre-clinical testing of possible vaccines) is a testament to the vision of the EMCF and the Oncho Task Force which advised the EMCF. The spirit of resource-sharing and broad international collaborations forged by the EMCF has allowed the scientific, http://parasites.trends.com
TRENDS in Parasitology Vol.18 No.6 June 2002
medical and public health community at large the luxury of envisaging the possibility of subverting O. volvulus infection through vaccination. We must continue to build on the EMCF’s foundation. Acknowledgements
The extraordinary contributions of the members of the Oncho Task Force that included Ted Bianco, Joe Cook, John Donelson, Brian Duke, Bruce Greene, Jeff Mecaskey, Eric Ottesen, Cathy Steel, Hugh Taylor and Steve Williams are gratefully acknowledged for providing the guiding vision toward the goal of a vaccine for onchocerciasis. References 1 Cook, J.A. et al. (2001) Towards a vaccine for onchocerciasis. Trends Parasitol. 17, 555–558 2 Abraham, D. et al. (2002) Immunity to Onchocerca spp. in animal hosts. Trends Parasitol. 18, 164–170 3 Hoerauf, A. and Brattig, N. (2002) Resistance and susceptibility in human onchocerciasis-beyond Th1 vs Th2. Trends Parasitol. 18, 25–31 4 Lustigman, S. et al. (2002) Towards a recombinant antigen vaccine against Onchocerca volvulus. Trends Parasitol. 18, 135–141 5 Richards, F.O. et al. (2001) Control of onchocerciasis today: status and challenges. Trends Parasitol. 17, 558–563 6 Williams, S.A. et al. (2002) The river blindness genome project. Trends Parasitol. 18, 86–90 7 Elbashir, S.M. et al. (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411, 494–498 8 Ware, J. et al. (2002) Sequencing and analysis of a 63 kb bacterial artificial chromosome insert from the Wolbachia endosymbiont of the human filarial parasite Brugia malayi. Int. J. Parasitol. 32, 159–166 9 Taylor, M.J. et al. (2000) Wolbachia bacteria of filarial nematodes: a target for control? Parasitol. Today 16, 179–180 10 Saint André, A. et al. (2002) The role of endosymbiotic Wolbachia bacteria in the pathogenesis of river blindness. Science 295, 1892–1895
239
11 Greene, B.M. (1987) Primate model for onchocerciasis research. Ciba Found. Symp. 127, 236–243 12 Taylor, M.D. and Else, K.J. (2002) Human Trichuris-specific antibody responses in vaccinated hu-PBL-SCID mice. Parasite Immunol. 24, 1–13 13 Kamhawi, S. et al. (2000) Protection against cutaneous leishmaniasis resulting from bites of uninfected sand flies. Science 290, 1351–1354 14 Cupp, E.W. and Cupp, M.S. (1997) Black fly (Diptera:Simuliidae) salivary secretions: importance in vector competence and disease. J. Med. Entomol. 34, 87–94 15 Meyer, C.G. et al. (1994) HLA-D alleles associated with generalized disease, localized disease, and putative immunity in Onchocerca volvulus infection. Proc. Natl. Acad. Sci. U. S. A. 91, 7515–7519 16 Hoerauf, A. et al. (2002) The variant Arg110Gln of human IL-13 is associated with an immunologically hyper-reactive form of onchocerciasis (sowda). Microbes Infect. 4, 37–42 17 Maizels, R.M. et al. (2001) Immunological genomics of Brugia malayi: filarial genes implicated in immune evasion and protective immunity. Parasite Immunol. 23, 327–344 18 Harnett, W. and Harnett, M.M. (2001) Modulation of the host immune system by phosphorylcholinecontaining glycoproteins secreted by parasitic filarial nematodes. Biochim. Biophys. Acta 1539, 7–15 19 Cooper, P.J. et al. (1998) Impaired tetanus-specific cellular and humoral responses following tetanus vaccination in human onchocerciasis: a possible role for interleukin-10. J. Infect. Dis. 178, 1133–1138 20 Hoerauf, A. et al. (2001) Depletion of Wolbachia endobacteria in Onchocerca volvulus by doxycycline and microfilaridermia after ivermectin treatment. Lancet 357, 1415–1416 21 Henry, N.L. et al. (2001) Onchocerciasis in a nonendemic population: clinical and immunologic assessment before treatment and at the time of presumed cure. J. Infect. Dis. 183, 512–516
Thomas B. Nutman Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0425, USA. e-mail: [email protected]
Fascinating factoids on the triatomine bugs! The largest blood-sucking insect is the triatomine bug, Dipetalogaster maxima, which can reach 4.5 cm long and can take up to 3 ml of blood in a single meal. [Ryckman, R.E. and Ryckman, A.E. (1967) J. Med. Entomol. 4, 180–188]. Each person in a triatomine-infested house could lose ~2.5 ml of blood per day and up to 17 ml per day in exceptional cases. [Rabinovich, J.E. et al. (1979) Trans. R. Soc. Trop. Med. Hyg. 73, 272–283; Schofield, C.J. (1981) Lancet 8233, 1316]. An expert meeting in a bar estimated that if a person experienced all possible parasite and vector causes of blood loss, then the average daily blood loss could reach ~200ml per person. (R. Shrimpton, N.M. Prescott and C.J. Schofield, unpublished). If you have any ‘fascinating factoids’ from the world of parasitology, then please forward them to the Editor at [email protected] 1471-4922/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII: S1471-4922(02)02328-0