Of mice, cattle, and humans: the immunology and treatment of river blindness

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Annotation Summary

Term Occurence Count Dictionary
ivermectin 11 infectiousdiseasesdrugs
loiasis 1 infectiousdiseases
onchocerciasis 17 infectiousdiseases
oxytetracycline 2 infectiousdiseasesdrugs
tetracycline 4 infectiousdiseasesdrugs
doxycycline 2 infectiousdiseasesdrugs
filariasis 3 infectiousdiseases

Graph of close proximity drug and disease terms (within 200 characters).

Note: If this graph is empty, then there are no terms that meet the proximity constraint.

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Select Drug Character Offset Drug Term Instance
doxycycline 26116 Wolbachia numbers and is not macrofilaricidal [78]. In humans, 6 weeks of treatment with 100 mg per day of doxycycline has resulted in a complete inhibition of embryogenesis from between 18 [74],[79],[80] and 24 months
doxycycline 26676 should be considered a priority. Importantly, the most recent results show that increasing the dose of doxycycline to 200 mg also exhibits a strong macrofilaricidal effect in human onchocerciasis [81],[82]. However,
ivermectin 2679 Programme (OCP) reduced the burden of disease in savannah regions of West Africa [2],[3]. In 1987, ivermectin (Mectizan, Merck & Co.) was introduced for mass treatment of onchocerciasis either alone or in combination
ivermectin 2923 closed in December 2002, and control of onchocerciasis now relies on community-based treatment with ivermectin implemented through the African Programme for Onchocerciasis Control (APOC) [4]. The Onchocerciasis
ivermectin 5158 drug administration for several years [6]–[8]. Furthermore, early hopes that mass treatment with ivermectin would eradicate the disease by breaking transmission have not been realised [2] because of inadequate
ivermectin 5438 areas where treatment has been suspended. In addition, there is mounting evidence that resistance to ivermectin is emerging [9]–[13]. Such circumstances require development of complementary measures to sustain
ivermectin 25004 Targeting WolbachiaControl of onchocerciasis in Africa relies on mass distribution of microfilaricidal ivermectin . Given the impossibility of onchocerciasis eradication with ivermectin alone [2] and rising concerns
ivermectin 25075 distribution of microfilaricidal ivermectin. Given the impossibility of onchocerciasis eradication with ivermectin alone [2] and rising concerns about resistance to this drug [9]–[13], there is a more pressing need
ivermectin 27230 anti-wolbachial chemotherapy is being considered [81].Targeting Wolbachia may also resolve the problem of ivermectin use in areas where onchocerciasis and loiasis are co-endemic and where mass treatment is often discouraged
ivermectin 28773 response. In the meantime, the prospect of developing new drug regimes using antibiotics to complement ivermectin treatment and to achieve a macrofilaricidal activity may mitigate against problems of emerging drug
ivermectin 28932 activity may mitigate against problems of emerging drug resistance and offer new therapy in cases where ivermectin is contra-indicated.Box 2. MethodsSelection of the publications cited was based on four approaches:Direct
ivermectin 29494 information on a particular topic that may not be recalled by a “filaria*” search (for example, “ ivermectin resistance”).Review of the main Web sites that maintain up-to-date information on disease statistics
ivermectin 30026 Partnership to Eliminate Riverblindness: http://www.worldbank.org/afr/gper/Box 3. Learning PointsAlthough ivermectin has made an immense contribution to onchocerciasis control, it cannot abrogate transmission, and its
oxytetracycline 21311 following successful macrofilaricidal treatment of pre-existing patent infections with melarsomine [19] or oxytetracycline [61], cattle were fully susceptible to re-infection. These data suggest that parasite death is an insufficient
oxytetracycline 25773 least for 4 weeks is required [76]. In cattle, long-term, intermittent antibiotic chemotherapy with oxytetracycline is macrofilaricidal and worm death is preceded by a considerable reduction in Wolbachia[77]. In contrast,
tetracycline 21314 successful macrofilaricidal treatment of pre-existing patent infections with melarsomine [19] or oxy tetracycline [61], cattle were fully susceptible to re-infection. These data suggest that parasite death is an insufficient
tetracycline 25554 potential target [73],[74]. Studies with L. sigmodontis have established that both rifampicin [75] and tetracycline s cause growth retardation and sterilisation of adult worms, but in the latter case daily treatment for
tetracycline 25776 least for 4 weeks is required [76]. In cattle, long-term, intermittent antibiotic chemotherapy with oxy tetracycline is macrofilaricidal and worm death is preceded by a considerable reduction in Wolbachia[77]. In contrast,
tetracycline 26306 [74],[79],[80] and 24 months [73]. Logistical considerations and compliance will demand shorter regimes if tetracycline s are to find their way into routine use against onchocerciasis. One approach will be to identify combination
Select Disease Character Offset Disease Term Instance
filariasis 6248 subcutaneous chambers [14]. Mice are somewhat more permissive to Brugia species (causative agents of lymphatic filariasis ) but still do not allow natural tissue migration or development of circulating microfilariae. Patent
filariasis 20239 naïve animals challenged experimentally with normal larvae has been demonstrated in numerous models of filariasis [14],[58], including both the L. sigmodontis[21],[58],[59] and O. ochengi models [19]. The protective
filariasis 29181 manuscript regarding key papers or unpublished research.Searches online (predominantly PubMed) for filariasis and a relevant keyword. For example, filarial* and regulat* were used to ensure that we were aware of
loiasis 27279 [81].Targeting Wolbachia may also resolve the problem of ivermectin use in areas where onchocerciasis and loiasis are co-endemic and where mass treatment is often discouraged because of severe adverse reactions that
onchocerciasis 2029 and blindness (river blindness). Adult worms live in subcutaneous nodules; however, the pathology of onchocerciasis is primarily associated with death of microfilariae larvae in the skin and eyes (Figures 1 and 2). It
onchocerciasis 2361 Africa, although there are significant foci in South and Central America. Early attempts at control of onchocerciasis relied on treatment of water courses with insecticides to kill the larvae (larviciding) of the blackfly
onchocerciasis 2751 West Africa [2],[3]. In 1987, ivermectin (Mectizan, Merck & Co.) was introduced for mass treatment of onchocerciasis either alone or in combination with larviciding. The OCP closed in December 2002, and control of onchocerciasis
onchocerciasis 2863 onchocerciasis either alone or in combination with larviciding. The OCP closed in December 2002, and control of onchocerciasis now relies on community-based treatment with ivermectin implemented through the African Programme for
onchocerciasis 5712 disease. What are needed is a safe and effective macrofilaricide and a vaccine.A major obstacle facing onchocerciasis research and, particularly that concerned with vaccine development, has been the absence of good animal
onchocerciasis 9829 these model systems is that they do not allow the investigation of disease pathology relevant to human onchocerciasis . This work will continue to rely on either human field studies or experimental exposure of mice to Onchocerca
onchocerciasis 17964 the data from human field studies demonstrating that T regulatory (Treg) cells can be isolated from onchocerciasis patients [53], and generalised onchocerciasis is associated with antigen-specific Treg cells that can
onchocerciasis 18010 demonstrating that T regulatory (Treg) cells can be isolated from onchocerciasis patients [53], and generalised onchocerciasis is associated with antigen-specific Treg cells that can be found in nodules [54]. These studies demonstrate
onchocerciasis 23323 as well as potential immune regulators.Because disease is associated with the microfilarial stage in onchocerciasis and because this stage is the key to transmission, an anti-microfilarial vaccine also needs to be considered.
onchocerciasis 24931 settings and field settings under natural challenge.Alternative Treatments Targeting WolbachiaControl of onchocerciasis in Africa relies on mass distribution of microfilaricidal ivermectin. Given the impossibility of onchocerciasis
onchocerciasis 25043 onchocerciasis in Africa relies on mass distribution of microfilaricidal ivermectin. Given the impossibility of onchocerciasis eradication with ivermectin alone [2] and rising concerns about resistance to this drug [9]–[13],
onchocerciasis 26367 compliance will demand shorter regimes if tetracyclines are to find their way into routine use against onchocerciasis . One approach will be to identify combination therapies. Given that an added benefit of long-lasting
onchocerciasis 26754 increasing the dose of doxycycline to 200 mg also exhibits a strong macrofilaricidal effect in human onchocerciasis [81],[82]. However, it must also be recognised that there are restrictions on use of this class of antibiotics
onchocerciasis 27260 being considered [81].Targeting Wolbachia may also resolve the problem of ivermectin use in areas where onchocerciasis and loiasis are co-endemic and where mass treatment is often discouraged because of severe adverse reactions
onchocerciasis 29703 statistics for river blindness and related diseases. These include:○ The WHO: http://www.who.int/topics/ onchocerciasis /en/○ The Carter Center: http://www.cartercenter.org/health/river_blindness/index.html○ Sightsavers:
onchocerciasis 30073 http://www.worldbank.org/afr/gper/Box 3. Learning PointsAlthough ivermectin has made an immense contribution to onchocerciasis control, it cannot abrogate transmission, and its efficacy is threatened by emerging drug resistance.
onchocerciasis 30322 effective against adult worms, or a vaccine, is required.Progress on understanding protective immunity in onchocerciasis has been accelerated by two model systems in particular, Litomosoides sigmodontis in mice and Onchocerca

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